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2,334,800
Resting cells rely on the DNA helicase component MCM2 to build cilia.
Minichromosome maintenance (MCM) proteins facilitate replication by licensing origins and unwinding the DNA double strand. Interestingly, the number of MCM hexamers greatly exceeds the number of firing origins suggesting additional roles of MCMs. Here we show a hitherto unanticipated function of MCM2 in cilia formation in human cells and zebrafish that is uncoupled from replication. Zebrafish depleted of MCM2 develop ciliopathy-phenotypes including microcephaly and aberrant heart looping due to malformed cilia. In non-cycling human fibroblasts, loss of MCM2 promotes transcription of a subset of genes, which cause cilia shortening and centriole overduplication. Chromatin immunoprecipitation experiments show that MCM2 binds to transcription start sites of cilia inhibiting genes. We propose that such binding may block RNA polymerase II-mediated transcription. Depletion of a second MCM (MCM7), which functions in complex with MCM2 during its canonical functions, reveals an overlapping cilia-deficiency phenotype likely unconnected to replication, although MCM7 appears to regulate a distinct subset of genes and pathways. Our data suggests that MCM2 and 7 exert a role in ciliogenesis in post-mitotic tissues.
2,334,801
Effects of trace mineral amount and source on aspects of oxidative metabolism and responses to intramammary lipopolysaccharide challenge in midlactation dairy cows.
Trace minerals have important roles in immune function and oxidative metabolism; however, little is known about the relationships between supplementation level and source with outcomes in dairy cattle. Multiparous Holstein cows (n=48) beginning at 60 to 140 days in milk were utilized to determine the effects of trace mineral amount and source on aspects of oxidative metabolism and responses to intramammary lipopolysaccharide (LPS) challenge. Cows were fed a basal diet meeting National Research Council (NRC) requirements except for no added zinc (Zn), copper (Cu) or manganese (Mn). After a 4-week preliminary period, cows were assigned to one of four topdress treatments in a randomized complete block design with a 2×2 factorial arrangement of treatments: (1) NRC inorganic (NRC levels using inorganic (sulfate-based) trace mineral supplements only); (2) NRC organic (NRC levels using organic trace mineral supplements (metals chelated to 2-hydroxy-4-(methythio)-butanoic acid); (3) commercial inorganic (approximately 2×NRC levels using inorganic trace mineral supplements only; and (4) commercial organic (commercial levels using organic trace mineral supplements only). Cows were fed the respective mineral treatments for 6 weeks. Treatment effects were level, source and their interaction. Activities of super oxide dismutase and glutathione peroxidase in erythrocyte lysate and concentrations of thiobarbituric acid reactive substances (TBARS) and total antioxidant capacity (TAC) in plasma were measured as indices of oxidative metabolism. Effects of treatment on those indices were not significant when evaluated across the entire experimental period. Plasma immunoglobulin G level was higher in cows supplemented with organic trace minerals over the entire treatment period; responses assessed as differences of before and after Escherichia coli J5 bacterin vaccination at the end of week 2 of treatment period were not significant. Cows were administered an intramammary LPS challenge during week 5; during week 6 cows fed commercial levels of Zn, Cu and Mn tended to have higher plasma TAC and cows fed organic sources had decreased plasma TBARS. After the LPS challenge, the extent and pattern of response of plasma cortisol concentrations and clinical indices (rectal temperature and heart rate) were not affected by trace mineral level and source. Productive performance including dry matter intake and milk yield and composition were not affected by treatment. Overall, results suggest that the varying level and source of dietary trace minerals do not have significant short-term effects on oxidative metabolism indices and clinical responses to intramammary LPS challenge in midlactation cows.
2,334,802
Does Adding Lidocaine to Intrathecal Bupivacaine Affect Hemodynamic Parameters during Hip Fracture Surgery?
Hip fracture is one of the most common problems in elderly that needs surgical repair. As, the majority of these patients have chronic diseases, they are at increased risk of peri-operative mortality and morbidity. The purpose of this study was to evaluate spinal anesthesia with bupivacaine vs bupivacaine in combination with lidocaine in terms of hemodynamic changes in patients undergoing hip fracture surgery.</AbstractText>This double-blind clinical trial was conducted on 292 patients undergoing surgery for hip fracture under spinal anesthesia. Patients were allocated into two groups of B (10 mg of hyperbaric 0.5% Bupivacaine) and BL (5 mg hyperbaric Bupivacaine 0.5% plus 50 mg Lidocaine 5%). Sensory and motor block and hemodynamic changes were consecutively measured before spinal anesthesia (T0), immediately after spinal injection (T1), every 5 minutes for half an hour (T2- T7), and at 45 minutes (T8) and 60 minutes (T9) after injection.</AbstractText>Patients in the two groups were homogeneous in demographic characteristics including age, sex, BMI, ASA Class, baseline blood pressure and heart rate. The onsets of sensory and motor blocks in group BL were faster than group B (P=0.0001</i>). Also, the durations of sensory and motor blocks in group B were significantly longer than group BL (P=0.0001</i>). The BL group had a significantly lower systolic blood pressure in all periods (P&lt;0.05</i>). Although the heart rate in the BL group was lower than group B at all time points, this difference was only significant during T2-T3 (P=0.033</i> and P=0.0001</i>, respectively). Group BL had significantly more episodes of hypotension, bradycardia, nausea and vomiting (P=0.0001</i>, P=0.023</i>, P=0.003</i>, and P=0.033</i>, respectively).</AbstractText>According to our findings, using Lidocaine 50 mg in combination with Bupivacaine 5 mg, compared with Bupivacaine 10 mg alone for spinal anesthesia in hip fracture fixation surgeries was associated with more hypotension and bradycardia. As a result, combination of Bupivacaine with Lidocaine at this dose is not recommended for induction of anesthesia in these patients.</AbstractText>
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Intra-operative effect of interscalene brachial plexus block to arthroscopic rotator cuff repair surgery.
To determine whether the placement of an interscalene brachial plexus block (IBPB) with general anaesthesia before shoulder arthroscopy would be effective in establishing a clear visual field and in shortening the surgical procedure.</AbstractText>This prospective randomized control trial study included 152 patients who had undergone arthroscopic rotator cuff repair. Group A received IBPB and group B did not receive IBPB. A visual clarity scale (VCS) was determined by arthroscopic visualization. The systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), duration of surgical procedure, VCS, and medication that was administered for haemodynamic stability were recorded.</AbstractText>The VCS was improved in group A at stages 2 and 3 of the surgical procedures (p&#x2009;&lt;&#x2009;0.05), but there were no significant difference at stages 1 (p&#x2009;=&#x2009;0.288) and 4 (p&#x2009;=&#x2009;0.062). SBP, DBP, and HR were higher in group B during surgery (p&#x2009;&lt;&#x2009;0.05). The administered analgesics were higher in group B (p&#x2009;=&#x2009;0.003), but there were no differences in hypotensive agents (p&#x2009;=&#x2009;0.287). No significant difference was observed for the duration of surgery (p&#x2009;=&#x2009;0.704).</AbstractText>Pre-operative IBPB with general anaesthesia for arthroscopic rotator cuff repair was beneficial in maintaining haemodynamic stability and improving the VCS during surgery.</AbstractText>
2,334,804
Modulation of alternative splicing of trafficking genes by genome editing reveals functional consequences in muscle biology.
Alternative splicing is a regulatory mechanism by which multiple mRNA isoforms are generated from single genes. Numerous genes that encode membrane trafficking proteins are alternatively spliced. However, there is limited information about the functional consequences that result from these splicing transitions. Here, we developed appropriate tools to study the functional impact of alternative splicing in development within the most in vivo context. Secondly, we provided evidence of the physiological implications of splicing regulation during muscle development. Our previous work in mouse heart development identified three trafficking genes that are regulated by alternative splicing between birth and adulthood: the clathrin heavy chain, the clathrin light chain-a, and the trafficking kinesin binding protein-1. Here, we demonstrated that alternative splicing regulation of these three genes is tissue- and developmental stage-specific. To identify the functional consequences of splicing regulation in vivo, we used genome editing to block the neonatal-to-adult splicing transitions. We characterized the phenotype of one of these mouse lines and demonstrated that when splicing regulation of the clathrin heavy chain gene is prevented mice exhibit an increase in body and muscle weights which is due to an enlargement in myofiber size. The significance of this work has two components. First, we revealed novel roles of the clathrin heavy chain in muscle growth and showed that its regulation by alternative splicing contributes to muscle development. Second, the new mouse lines will provide a useful tool to study how splicing regulation of three trafficking genes affects tissue identity acquisition and maturation in vivo.
2,334,805
Patient Monitoring System Using Cognitive Internet of Things.
In this article, we ponder multi-user medical image transmission using Cognitive Multiple-input Multiple-output (MIMO) Multi-carrier Code-division-multiple-access (MC-CDMA) system to monitor patient information. We investigate the performance of such system in the communication layer and application layer of internet of things (IOT). Patient monitoring system plays vital role in the hospital particularly in the emergency ward to resolve certain problems such as maintaining glucose level in the body, maintaining minimum sugar levels under emergency conditions. IOT find tremendous application in the hospital to deal with certain issues such as injection of drug to the patients by doctor from remote places, monitoring patients heart beats, sugar level by the concerned doctors. MIMO finds many applications in medical field to enrich data rate while communication patient information at faster rate. We utilize MC-CDMA system to accommodate large user patients information and to transmit such information with high resolution by eliminating channel impairments. We are utilizing Cognitive spectrum for medical image transmission of higher bandwidth applications. We realize Double-space-time transmit diversity as MIMO profile to boost up throughput. We perform multi-carrier modulation using IDFT at the transmitter .we carryout demodulation employing DFT at the hospital. We introduce Multi-carrier communication to fulfil the need of bandwidth efficiency and to diminish frequency selectivity effects.In the application layer, we estimate patient's information with aid of block-nulling decoding algorithm. Moreover we analyze the quality of image of D-STTD MC-CDMA system with turbo style of channel encoder to manifest medical image with high resolution with less signal strength. We conclude that Cognitive D-STTD MC-CDMA system provides reliable communication for the application of IOT and also transfer high resolution medical image with less signal strength in order to observe patient status by doctor.
2,334,806
Muscle membrane integrity in Duchenne muscular dystrophy: recent advances in copolymer-based muscle membrane stabilizers.
The scientific premise, design, and structure-function analysis of chemical-based muscle membrane stabilizing block copolymers are reviewed here for applications in striated muscle membrane injury. Synthetic block copolymers have a rich history and wide array of applications from industry to biology. Potential for discovery is enabled by a large chemical space for block copolymers, including modifications in block copolymer mass, composition, and molecular architecture. Collectively, this presents an impressive chemical landscape to leverage distinct structure-function outcomes. Of particular relevance to biology and medicine, stabilization of damaged phospholipid membranes using amphiphilic block copolymers, classified as poloxamers or pluronics, has been the subject of increasing scientific inquiry. This review focuses on implementing block copolymers to protect fragile muscle membranes against mechanical stress. The review highlights interventions in Duchenne muscular dystrophy, a fatal disease of progressive muscle deterioration owing to marked instability of the striated muscle membrane. Biophysical and chemical engineering advances are presented that delineate and expand upon current understanding of copolymer-lipid membrane interactions and the mechanism of stabilization. The studies presented here serve to underscore the utility of copolymer discovery leading toward the therapeutic application of block copolymers in Duchenne muscular dystrophy and potentially other biomedical applications in which membrane integrity is compromised.
2,334,807
Comparison of the Efficacy of Ultrasound-Guided Serratus Anterior Plane Block, Pectoral Nerves II Block, and Intercostal Nerve Block for the Management of Postoperative Thoracotomy Pain After Pediatric Cardiac Surgery.
The aim of this study was to compare the relative efficacy of ultrasound-guided serratus anterior plane block (SAPB), pectoral nerves (Pecs) II block, and intercostal nerve block (ICNB) for the management of post-thoracotomy pain in pediatric cardiac surgery.</AbstractText>A prospective, randomized, single-blind, comparative study.</AbstractText>Single-institution tertiary referral cardiac center.</AbstractText>The study comprised 108 children with congenital heart disease requiring surgery through a thoracotomy.</AbstractText>Children were allocated randomly to 1 of the 3 groups: SAPB, Pecs II, or ICNB. All participants received 3 mg/kg of 0.2% ropivacaine for ultrasound-guided block after induction of anesthesia. Postoperatively, intravenous paracetamol was used for multimodal and fentanyl was used for rescue analgesia.</AbstractText>A modified objective pain score (MOPS) was evaluated at 1, 2, 4, 6, 8, 10, and 12 hours post-extubation. The early mean MOPS at 1, 2, and 4 hours was similar in the 3 groups. The late mean MOPS was significantly lower in the SAPB group compared with that of the ICNB group (p &lt; 0.001). The Pecs II group also had a lower MOPS compared with the ICNB group at 6, 8, and 10 hours (p &lt; 0.001), but the MOPS was comparable at hour 12 (p&#x202f;=&#x202f;0.301). The requirement for rescue fentanyl was significantly higher in ICNB group in contrast to the SAPB and Pecs II groups.</AbstractText>SAPB and Pecs II fascial plane blocks are equally efficacious in post-thoracotomy pain management compared with ICNB, but they have the additional benefit of being longer lasting and are as easily performed as the traditional ICNB.</AbstractText>Copyright &#xa9; 2018. Published by Elsevier Inc.</CopyrightInformation>
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Effect of lorcaserin on prevention and remission of type 2 diabetes in overweight and obese patients (CAMELLIA-TIMI 61): a randomised, placebo-controlled trial.
There is a direct relationship between bodyweight and risk of diabetes. Lorcaserin, a selective serotonin 2C receptor agonist that suppresses appetite, has been shown to facilitate sustained weight loss in obese or overweight patients. We aimed to evaluate the long-term effects of lorcaserin on diabetes prevention and remission.</AbstractText>In this randomised, double-blind, placebo-controlled trial done in eight countries, we recruited overweight or obese patients (body-mass index &#x2265;27 kg/m2</sup>) with or at high risk for atherosclerotic vascular disease. Eligible patients were aged 40 years or older; patients at high risk for atherosclerotic vascular disease had to be aged 50 years or older with diabetes and at least one other risk factor. Patients were randomly assigned to receive either lorcaserin (10 mg twice daily) or matching placebo. Additionally, all patients had access to a standardised weight management programme based on lifestyle modification. The prespecified primary metabolic efficacy endpoint of time to incident diabetes was assessed in patients with prediabetes at baseline. The prespecified secondary outcomes for efficacy were incident diabetes in all patients without diabetes, achievement of normoglycaemia in patients with prediabetes, and change in glycated haemoglobin (HbA1c</sub>) in patients with diabetes. Hypoglycaemia was a prespecified safety outcome. Analysis was by intention to treat, using Cox proportional hazard models for time-to-event analyses. This trial is registered with ClinicalTrials.gov, number NCT02019264.</AbstractText>Between Feb 7, 2014, and Nov 20, 2015, 12&#x2008;000 patients were randomly assigned to lorcaserin or placebo (6000 patients in each group) and followed up for a median of 3&#xb7;3 years (IQR 3&#xb7;0-3&#xb7;5). At baseline, 6816 patients (56&#xb7;8%) had diabetes, 3991 (33&#xb7;3%) prediabetes, and 1193 (9&#xb7;9%) normoglycaemia. At 1 year, patients treated with lorcaserin had a net weight loss beyond placebo of 2&#xb7;6 kg (95% CI 2&#xb7;3-2&#xb7;9) for those with diabetes, 2&#xb7;8 kg (2&#xb7;5-3&#xb7;2) for those with prediabetes, and 3&#xb7;3 kg (2&#xb7;6-4&#xb7;0) for those with normoglycaemia (p&lt;0&#xb7;0001 for all analyses). Lorcaserin reduced the risk of incident diabetes by 19% in patients with prediabetes (172 [8&#xb7;5%] of 2015 vs 204 [10&#xb7;3%] of 1976; hazard ratio 0&#xb7;81, 95% CI 0&#xb7;66-0&#xb7;99; p=0&#xb7;038) and by 23% in patients without diabetes (174 [6&#xb7;7%] of 2615 vs 215 [8&#xb7;4%] of 2569; 0&#xb7;77, 0&#xb7;63-0&#xb7;94; p=0&#xb7;012). Lorcaserin resulted in a non-significant increase in the rate of achievement of normoglycaemia in patients with prediabetes (185 [9&#xb7;2%] vs 151 [7&#xb7;6%]; 1&#xb7;20, 0&#xb7;97-1&#xb7;49; p=0&#xb7;093). In patients with diabetes, lorcaserin resulted in a reduction of 0&#xb7;33% (95% CI 0&#xb7;29-0&#xb7;38; p&lt;0&#xb7;0001) in HbA1c</sub> compared with placebo at 1 year from a mean baseline of 53 mmol/mol (7&#xb7;0%). In patients with diabetes at baseline, severe hypoglycaemia with serious complications was rare, but more common with lorcaserin (12 [0&#xb7;4%] vs four [0&#xb7;1%] events; p=0&#xb7;054).</AbstractText>Lorcaserin decreases risk for incident diabetes, induces remission of hyperglycaemia, and reduces the risk of microvascular complications in obese and overweight patients, supporting the role of lorcaserin as an adjunct to lifestyle modification for chronic management of weight and metabolic health.</AbstractText>Eisai.</AbstractText>Copyright &#xa9; 2018 Elsevier Ltd. All rights reserved.</CopyrightInformation>
2,334,809
Cranial nerves VII and XII palsy after shoulder surgery.
A 46-year-old man underwent a left shoulder surgery in the beach chair position with general anaesthesia and oro-tracheal intubation preceded by a left interscalenic block. Patient's head was attached to the headrest in a position of soft extension and moderate right rotation with adhesive tape surrounding his forehead and mandible. Surgery was marked by repeated vertical tractions on the left arm and by blood resorption of the arthroscopy's irrigation fluid, including epinephrine, which translated in a heart rate and arterial blood pressure rise. Upon waking the patient had severe headaches, left Horner's sign, left facial paresis and a left lingual paralysis. MRI and CT scan did not show any carotid dissection or parapharyngeal lesion. Electromyogram and neurological examination confirmed a VII and XII cranial nerve peripheral lesion, which took several months to regress. An ischaemic complication was suspected although the most probable cause of the patient's symptoms was subsequent to an Eagle's syndrome neurapraxia related to a long styloid process.
2,334,810
Ultrasound-guided quadratus lumborum block in pediatrics: trans-muscular versus intra-muscular approach.
Quadratus lumborum (QL) block has four approaches. However, there is difference between the four approaches regarding efficacy, safety and adverse effects. The primary objective of this study is to compare the analgesic effect between trans-muscular and intra-muscular approaches of the QL block in pediatric patients for elective lower abdominal surgery.</AbstractText>54 patients aged between 1 and 6&#xa0;years were enrolled. Patients of both genders were selected. The patients were randomly classified into two groups: Group TQL includes patients (27 patients) in whom bilateral QL block was performed using trans-muscular approach, and Group IQL (27 patients), which underwent bilateral QL block using an intra-muscular approach. The primary outcome measure was the number of patients who require rescue analgesia in the first 24&#xa0;h. The secondary outcome measures were FLACC score, heart rate, non-invasive blood pressure at 2, 4, 6, 12, and 24&#xa0;h postoperatively, and postoperative complications (e.g., quadriceps muscle weakness, local hematoma).</AbstractText>In the first 24&#xa0;h after surgery, 13 patients in the IQL group (48.1%) required rescue analgesia, whereas only five patients in the TQL group (18.5%) required rescue analgesia. The FLACC score was lower in the TQL group than the IQL group at all time intervals up to 24&#xa0;h postoperatively. In the TQL group, eight patients (29.6%) developed quadriceps weakness; whereas, only one patient (3.7%) in the IQL group developed quadriceps weakness.</AbstractText>TQL is better than IQL in the analgesic efficacy following the pediatric lower laparotomy.</AbstractText>
2,334,811
Supra-inguinal fascia iliaca block under ultrasound guidance for perioperative analgesia during bipolar hip arthroplasty in a patient with severe cardiovascular compromise: A case report.
The relief of selective hip pain may be difficult to attain. Therefore, a deep nerve block such as epidural anesthesia or lumbar plexus nerve block is required. However, deep nerve blocks may not be possible in patients with complications, including severe cardiovascular disease.</AbstractText>The patient in our report had coronary stents inserted previously and required continuous anticoagulant therapy owing to severe heart failure.</AbstractText>Bipolar hip arthroplasty was required in our patient because of a fracture of the neck of femur on the left side.</AbstractText>We decided to perform the surgery using a fascia iliaca block (block of the femoral and the lateral femoral cutaneous nerves) by the suprainguinal approach. The fascia iliaca nerve block was performed under ultrasound guidance, using 20 mL of levobupivacaine.</AbstractText>The surgery was performed successfully with adequate sensory block around the hip region.</AbstractText>Ultrasound-guided fascia iliaca nerve block by the supra-inguinal approach may be an effective anesthetic technique for patients undergoing surgery for fracture of the neck of femur.</AbstractText>
2,334,812
Developing agent-based models of complex health behaviour.
Managing non-communicable diseases requires policy makers to adopt a whole systems perspective that adequately represents the complex causal architecture of human behaviour. Agent-based modelling is a computational method to understand the behaviour of complex systems by simulating the actions of entities within the system, including the way these individuals influence and are influenced by their physical and social environment. The potential benefits of this method have led to several calls for greater use in public health research. We discuss three challenges facing potential modellers: model specification, obtaining required data, and developing good practices. We also present steps to assist researchers to meet these challenges and implement their agent-based model.
2,334,813
Modulation of Cardiac Alternans by Altered Sarcoplasmic Reticulum Calcium Release: A Simulation Study.
<b>Background:</b> Cardiac alternans is an important precursor to arrhythmia, facilitating formation of conduction block, and re-entry. Diseased hearts were observed to be particularly vulnerable to alternans, mainly in heart failure or after myocardial infarction. Alternans is typically linked to oscillation of calcium cycling, particularly in the sarcoplasmic reticulum (SR). While the role of SR calcium reuptake in alternans is well established, the role of altered calcium release by ryanodine receptors has not yet been studied extensively. At the same time, there is strong evidence that calcium release is abnormal in heart failure and other heart diseases, suggesting that these changes might play a pro-alternans role. <b>Aims:</b> To demonstrate how changes to intracellular calcium release dynamics and magnitude affect alternans vulnerability. <b>Methods:</b> We used the state-of-the-art Heijman-Rudy and O'Hara-Rudy computer models of ventricular myocyte, given their detailed representation of calcium handling and their previous utility in alternans research. We modified the models to obtain precise control over SR release dynamics and magnitude, allowing for the evaluation of these properties in alternans formation and suppression. <b>Results:</b> Shorter time to peak SR release and shorter release duration decrease alternans vulnerability by improved refilling of releasable calcium within junctional SR; conversely, slow release promotes alternans. Modulating the total amount of calcium released, we show that sufficiently increased calcium release may surprisingly prevent alternans via a mechanism linked to the functional depletion of junctional SR during release. We show that this mechanism underlies differences between "eye-type" and "fork-type" alternans, which were observed in human <i>in vivo</i> and <i>in silico</i>. We also provide a detailed explanation of alternans formation in the given computer models, termed "sarcoplasmic reticulum calcium cycling refractoriness." The mechanism relies on the steep SR load-release relationship, combined with relatively limited rate of junctional SR refilling. <b>Conclusion:</b> Both altered dynamics and magnitude of SR calcium release modulate alternans vulnerability. In particular, slow dynamics of SR release, such as those observed in heart failure, promote alternans. Therefore, acceleration of intracellular calcium release, e.g., via synchronization of calcium sparks, may inhibit alternans in failing hearts and reduce arrhythmia occurrence.
2,334,814
Caudal Analgesia for Hypospadias in Pediatrics: Comparative Evaluation of Adjuvants Dexamethasone and Dexmedetomidine Combination versus Dexamethasone or Dexmedetomidine to Bupivacaine: A Prospective, Double-Blinded, Randomized Comparative Study.
Caudal block is the most commonly used regional anesthetic technique in pediatric surgeries; different additives have been used for better and safer outcome.</AbstractText>The aim of this study is to compare the combination of dexamethasone and dexmedetomidine as adjuvants to bupivacaine versus using each agent solely with bupivacaine in pediatric caudal block as regards their efficiency in pain relief (the duration of postoperative analgesia, first time to request analgesia, and modified objective pain score [MOPS]).</AbstractText>This was a prospective, double-blinded, randomized study.</AbstractText>Patients and Methods: Sixty-three children scheduled for hypospadias surgery wererandomized into three groupsaccording to the adjuvant drug added to caudal bupivacaine : Group I (n = 21): dexamethasone 0.1 mg/kg + 0.5 mg/kg bupivacaine 0.25%, Group II (n = 21): dexmedetomidine0.01 &#x3bc;g/kg + 0.5 mg/kg bupivacaine 0.25% and Group III (n = 21): dexamethasone 0.1 mg/kg + dexmedetomidine 0.01 &#x3bc;g/kg + 0.5 mg/kgbupivacaine 0.25%. Intraoperative and postoperative hemodynamics were recorded. In postoperative anesthesia care unit and then the ward, MOPS and sedation score were recorded at 30 min and 1, 2, 3, 6 and 12 h. Further, the time of first analgesic request and side effects were recorded.</AbstractText>Categorical data were presented as frequencies (%) and analyzed using Chi-square test. Continuous data were presented as mean (standard deviation) and median (quartiles). Continuous data were analyzed using one-way analysis of variance for single measures and two-way mixed model for repeated measures. Kaplan-Meier analysis was performed for the duration of analgesia.</AbstractText>In Group III, MOPS was lower than Groups I and II at the study times. Further, Group III had prolonged time for first request of analgesic. Sedation scores were prolonged in Group III and Group II than in Group I. There was a reduction in heart rates in Group III more than Group I and Group II but with no significant difference. However, there was a significant reduction in mean arterial blood pressure 30 min intraoperatively and postoperatively in Group III as compared to Groups I and II.</AbstractText>The addition of combined dexmedetomidine at a dose of 1 &#x3bc;g/kg and dexamethasone 0.1 mg/kg to caudal bupivacaine seemed to be an attractive alternative to each drug if used alone with more prolonged analgesia and almost no adverse effects.</AbstractText>
2,334,815
Urgent cardiac resynchronization therapy is useful in patients with decompensated heart failure requiring inotropes and mechanical circulatory support.
Although cardiac resynchronization therapy (CRT) is beneficial in patients with heart failure (HF) and left ventricular dyssynchrony, its effectiveness has not been established in patients with decompensated HF on mechanical support. Here, we report two patients with decompensated HF depending on inotropes and intra-aortic balloon pumping (IABP), who were rescued by urgent CRT implantations. Both patients had non-ischemic cardiomyopathy with wide QRS of left bundle brunch block. IABP could be weaned just after introducing CRT. CRT can dramatically improve hemodynamics even in severely decompensated HF, and thus could be considered when left ventricular dyssynchrony is present. &lt;<b>Learning objective:</b> The efficacy of cardiac resynchronization therapy (CRT) for acutely decompensated heart failure (HF) is controversial. However, the patients with wide QRS complex with left bundle brunch block and non-ischemic etiology can be the candidates of CRT implantation in order to wean inotrope and mechanical circulatory support.&gt;.
2,334,816
[Chan-Chuang Qigong Improves Exercise Capacity, Depression, and Quality of Life in Patients With Heart Failure].
Evidence-based research has shown the effects of traditional Chinese exercise on exercise capacity, depression, and quality of life in patients with cardiovascular disease. However, the effects of Chan-Chuang qigong on the physical and psychological status and on the quality of life of these patients are unknown.</AbstractText>To investigate the effects of Chan-Chuang qigong on exercise capacity, depression, and quality of life in patients with heart failure.</AbstractText>A randomized controlled study with repeated measures was conducted. One hundred participants with heart failure were recruited from a teaching medical center in Taiwan. Permuted block randomization was used to randomly assign the participants to either the Chan-Chuang qigong group, which received Chan-Chuang qigong intervention for three-months, or the control group. The outcome variables included six-minute walk distance, depression, and quality of life.</AbstractText>Generalized estimating equation analyses showed that the Chan-Chuang qigong group achieved significantly greater improvements than the control group in terms of six-minute walk distance (p = .001, p &lt; .001, p &lt; .001, respectively) and quality of life (p = .016, p &lt; .001, p &lt; .001, respectively) at 2, 4, and 12 weeks after the intervention and depression at 12 weeks after the intervention (p = .016).</AbstractText><AbstractText Label="CONCLUSIONS / IMPLICATIONS FOR PRACTICE" NlmCategory="CONCLUSIONS">The results of this study indicate that Chan-Chuang qigong improves exercise capacity, depression, and quality of life in patients with heart failure without imposing harmful side effects.</AbstractText>
2,334,817
Trauma-Induced Conduction Disturbances.
Electrical disturbances following blunt cardiac injuries are rare but can be caused by electrical or structural damage to the heart. We present the case of a patient who had conduction abnormalities following blunt traumatic injury that were incidentally detected on telemetry.</AbstractText>A 64-year-old female with no history of cardiac disease was brought to the emergency department after a motor vehicle collision that resulted in chest wall bruising. The patient was found to have L-spine fractures and was admitted for observation. During her hospitalization, the patient had multiple episodes of heart block. A temporary pacemaker was inserted because of the recurrent episodes, and a dual-chamber permanent pacemaker was placed on day 4 of her hospitalization.</AbstractText>Heart block as a consequence of blunt cardiac injury is rare; however, it needs to be recognized as early as possible. Permanent pacemaker placement is usually indicated for patients with prolonged or recurrent episodes.</AbstractText>
2,334,818
The validation of smartphone applications for heart rate measurement.
The smartphone apps provide a user-friendly option for measurement of heart rate (HR) by detecting pulsatile photoplethysmographic signals with built-in cameras from the fingertips, however, the validation study is limited.</AbstractText>We compared HR detected by the smartphone apps (App1&#x2009;=&#x2009;Instant HR, App2&#x2009;=&#x2009;Cardiio: HR Monitor and App3&#x2009;=&#x2009;Runtastic HR Monitor) with simultaneous standard ECG monitoring in the adult patients at the critical care unit.</AbstractText>HR measurements were obtained from 140 patients with mean age 67.6&#x2009;&#xb1;&#x2009;15.3 years. Mean baseline HR was 89.1&#x2009;&#xb1;&#x2009;19.1&#xa0;bpm (range, 32-136&#xa0;bpm). Sinus rhythm was presented in 111 patients (79.3%), atrial fibrillation in 25 patients (17.9%), pacemaker rhythm in 3 patients (2.1%), and high-grade AV block in 1 patient (0.7%). The ECG-derived HR correlated well with App1 (r&#x2009;=&#x2009;0.98), App2 (r&#x2009;=&#x2009;0.97), and App3 (r&#x2009;=&#x2009;0.92). In patients with regular rhythm, mean absolute deviation was 0.8&#x2009;&#xb1;&#x2009;1, 0.7&#x2009;&#xb1;&#x2009;0.9, 1.0&#x2009;&#xb1;&#x2009;1.3&#xa0;bpm on App1, App2 and App3, respectively. In the patients with irregular rhythm, median absolute deviation (IQR) was 3 (2-5.5), 4 (1.5-11.5), and 6 (2-13)&#xa0;bpm. Skin colour did not affect with the HR measurement.</AbstractText>HR measurements from all applications were correlated well with ECG monitoring. However, it was less accurate in case of irregular rhythm such as atrial fibrillation. Key messages Several reports on inaccuracy of mobile health apps have been published. We conducted the validation study in the real patients by using popular mobile apps. Heart rate measurements from mobile apps were correlated well with standard ECG. The accuracy of HR from apps was worse at irregular rate and tachycardia.</AbstractText>
2,334,819
Prognostic value of Sj&#xf6;gren's syndrome autoantibodies.
Sj&#xf6;gren's syndrome is in part considered an autoimmune disease because patient sera contain antibodies binding self-structures. In fact, in addition to anti-Ro (or SSA) and anti-La (or SSB), which are included in the classification criteria, there are a wide variety of autoantibodies found among these patients. We reviewed English-language MEDLINE sources. Anti-Ro and anti-La found among healthy individuals, including mothers giving birth to infants with neonatal lupus, predicts future connective tissue disease. Those with Sj&#xf6;gren's syndrome can be divided into two groups; patients with only exocrine gland involvement and those with systemic disease. The presence of anti-Ro/La is associated with systemic, extraglandular disease. Rheumatoid factor is also associated with extraglandular disease while anti-cyclic citrullinated peptide (CCP) is likely associated with inflammatory arthritis and progression to rheumatoid arthritis. Anti-mitochondrial antibodies are uncommon but predict progression to primary biliary cirrhosis. Cryoglobulinemia is found in excess among those with non-Hodgkin's lymphoma. Determination of autoantibodies on the sera of Sj&#xf6;gren's syndrome patients has prognostic implications for Sj&#xf6;gren's syndrome itself as well as associated diseases.
2,334,820
Vascular smooth muscle cells activate PI3K/Akt pathway to attenuate myocardial ischemia/reperfusion-induced apoptosis and autophagy by secreting bFGF.
Vascular smooth muscle cells (VSMCs) has been reported to be implicated in atherosclerotic plaque instability and rupture. Recently, it has been demonstrated that VSMCs block the progression of cardiac remodeling and thus promoting cardiac function in a rat myocardial infarction model. However, the detailed molecular mechanism of how VSMCs contributes to recovery in myocardial ischemia/reperfusion remains not fully understood.</AbstractText>We have isolated, identified and cultured VSMCs from rats to co-culture with rat cardiomyocyte H9C2. To culture H9C2 cells under hypoxia, we utilized CoCl2</sub>-containing medium to culture for 8&#x202f;h and then was replaced with normal media for additional 16&#x202f;h. Cell viability was examined by MTT assay and apoptosis was determined by flow cytometry. Infarcted area of myocardial tissue was measured by TTC staining.</AbstractText>VSMCs was shown to promote cell viability and inhibit apoptosis of H9C2 cells under hypoxia, which exhibited upregulated anti-apoptotic protein Bcl-2 and autophagy-related protein p62, whereas pro-apoptotic protein cleaved caspase-3 and the level of LC3II/LC3I were downregulated. Then, we confirmed VSMCs played the contributory role in cell viability of H9C2 under hypoxia by secreting bFGF, which exerted its function through PI3K/Akt pathway. Finally, in vivo, the results demonstrated that VSMCs transplantation contributed to recovery of myocardial ischemia.</AbstractText>We determine that VSMCs promote recovery of infarcted cardiomyocyte through secretion of bFGF, which then activating PI3K/Akt pathway to inhibit apoptosis and autophagy. These findings provide more insights into the molecular mechanism underlying VSMCs contributing to recovery of myocardial I/R and facilitate developing therapeutical strategies for treating heart diseases.</AbstractText>Copyright &#xa9; 2018. Published by Elsevier Masson SAS.</CopyrightInformation>
2,334,821
Electro-vectorcardiographic demonstration of rate-independent transient left posterior fascicular block.
Left posterior fascicular block (LPFB) is a rare intraventricular conduction disorder of rare occurrence, especially as an isolated entity. Its transient form is even rarer and maybe rate-independent or rate-dependent intermittent LPFB (phase 3 block, tachycardia-dependent and phase 4 block or bradycardia-dependent). We present a case of a young adult male whose baseline ECG/VCG showed the typical LPFB pattern. A treadmill stress test revealed rate-independent intermittent LPFB with random occurrence. Imaging exams ruled out structural heart disease. To our knowledge, this is the first case in the literature of a rate-independent intermittent LPFB with no underlying structural heart disease.
2,334,822
Enantiomeric A&#x3b2; peptides inhibit the fluid shear stress response of PIEZO1.
Traumatic brain injury (TBI) elevates Abeta (A&#x3b2;) peptides in the brain and cerebral spinal fluid. A&#x3b2; peptides are amphipathic molecules that can modulate membrane mechanics. Because the mechanosensitive cation channel PIEZO1 is gated by membrane tension and curvature, it prompted us to test the effects of A&#x3b2; on PIEZO1. Using precision fluid shear stress as a stimulus, we found that A&#x3b2; monomers inhibit PIEZO1 at femtomolar to picomolar concentrations. The A&#x3b2; oligomers proved much less potent. The effect of A&#x3b2;s on Piezo gating did not involve peptide-protein interactions since the D and L enantiomers had similar effects. Incubating a fluorescent derivative of A&#x3b2; and a fluorescently tagged PIEZO1, we showed that A&#x3b2; can colocalize with PIEZO1, suggesting that they both had an affinity for particular regions of the bilayer. To better understand the PIEZO1 inhibitory effects of A&#x3b2;, we examined their effect on wound healing. We observed that over-expression of PIEZO1 in HEK293 cells increased cell migration velocity ~10-fold, and both enantiomeric A&#x3b2; peptides and GsMTx4 independently inhibited migration, demonstrating involvement of PIEZO1 in cell motility. As part of the motility study we examined the correlation of PIEZO1 function with tension in the cytoskeleton using a genetically encoded fluorescent stress probe. A&#x3b2; peptides increased resting stress in F-actin, and is correlated with A&#x3b2; block of PIEZO1-mediated Ca<sup>2+</sup> influx. A&#x3b2; inhibition of PIEZO1 in the absence of stereospecific peptide-protein interactions shows that A&#x3b2; peptides modulate both cell membrane and cytoskeletal mechanics to control PIEZO1-triggered Ca<sup>2+</sup> influx.
2,334,823
Neuraxial anaesthesia in parturient with cardiac disease.
Parturient with corrected or uncorrected cardiac problem may undergo neuraxial anaesthesia for several reasons and in different trimesters. The altered physiological state in a parturient is further deranged in the presence of a cardiovascular lesion, producing the added risk to the parturient undergoing a neuraxial block. A detailed evaluation, knowledge regarding cardiovascular disease state, more vigilant monitoring, and a team approach can lead to a successful outcome.
2,334,824
Fidelity and Feasibility of a Brief Emergency Department Intervention to Empower Adults With Serious Illness to Initiate Advance Care Planning Conversations.
Emergency department (ED) visits provide opportunities to empower patients to discuss advance care planning with their outpatient clinicians, but systematically developed, feasible interventions do not currently exist. Brief negotiated interview (BNI) interventions, which allow ED clinicians to efficiently motivate patients, have potential to meet this need.</AbstractText>We developed a BNI ED intervention to empower older adults with life-limiting illness to formulate and communicate medical care goals to their primary outpatient clinicians. This study assessed the fidelity and feasibility of this intervention in a high-volume ED.</AbstractText>We enrolled adult patients with serious illnesses (advanced cancer, congestive heart failure, chronic obstructive pulmonary disease, chronic kidney disease on dialysis, predicted survival &lt;12&#xa0;months) in an urban, tertiary care academic medical center ED. All participants received the BNI intervention. We video-recorded the encounters. Two reviewers assessed the recordings for intervention fidelity based on adherence to the BNI steps (Part I) and communication skills (Part II).</AbstractText>We reviewed 46 video recordings. The mean total adherence score was 21.07/27 (SD 3.68) or 78.04%. The Part I mean adherence score was 12.07/15 (SD 2.07) or 80.47%. The Part II mean adherence score was 9.0/12 (SD 2.51) or 75%. The majority (75.6%) of recordings met the prespecified threshold for high intervention fidelity.</AbstractText>ED clinicians can deliver a BNI intervention to increase advance care planning conversations with high fidelity. Future research is needed to study the intervention's efficacy in a wider patient population.</AbstractText>Copyright &#xa9; 2018 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.</CopyrightInformation>
2,334,825
Heat acclimatization blunts copeptin responses to hypertonicity from dehydrating exercise in humans.
Acclimatization favors greater extracellular tonicity from lower sweat sodium, yet hyperosmolality may impair thermoregulation during heat stress. Enhanced secretion or action of vasopressin could mitigate this through increased free water retention. Aims were to determine responses of the vasopressin surrogate copeptin to dehydrating exercise and investigate its relationships with tonicity during short and long-term acclimatization. Twenty-three participants completed a structured exercise programme following arrival from a temperate to a hot climate. A Heat Tolerance Test (HTT) was conducted on Day-2, 6, 9 and 23, consisting of 60-min block-stepping at 50% VO<sub>2</sub> peak, with no fluid intake. Resting sweat [Na<sup>+</sup> ] was measured by iontophoresis. Changes in body mass (sweat loss), core temperature, heart rate, osmolality (serum and urine) and copeptin and aldosterone (plasma) were measured with each Test. From Day 2 to Day 23, sweat [Na<sup>+</sup> ] decreased significantly (adjusted P&#xa0;&lt;&#xa0;0.05) and core temperature and heart rate fell. Over the same interval, HTT-associated excursions were increased for serum osmolality (5 [-1, 9] vs. 9 [5, 12] mosm&#xb7;kg<sup>-1</sup> ), did not differ for copeptin (9.6 [6.0, 15.0] vs. 7.9 [4.3, 14.7] pmol&#xb7;L<sup>-1</sup> ) and were reduced for aldosterone (602 [415, 946] vs. 347 [263, 537] pmol&#xb7;L<sup>-1</sup> ). Urine osmolality was unchanging and related consistently to copeptin at end-exercise, whereas the association between copeptin and serum osmolality was right-shifted (P&#xa0;=&#xa0;0.0109) with acclimatization. Unchanging urine:serum osmolality argued against increased renal action of vasopressin. In conclusion, where exercise in the heat is performed without fluid replacement, heat acclimatization does not appear to enhance AVP-mediated free water retention in humans.
2,334,826
Analysing the efficacy of the I-gel supraglottic airway device in the supine and lateral decubitus positions.
The advantages of the I-gel supraglottic airway device include ease and speed of insertion, reduced trauma incidence, an integral bite block, gastric access, a non-inflatable cuff and superior seal pressure. The primary goal of this study was to compare airway leak pressures and the fibreoptic view in the supine and lateral positions. Our secondary aim was to analyse the effects of I-gel insertion on haemodynamic parameters.</AbstractText>One hundred patients undergoing saturation biopsy due to prostatic hyperplasia were recruited to this prospective randomised study. An I-gel device was inserted in the supine position. Taking of measurements, patients were placed in the lateral decubitus position. Mean arterial pressure, heart rate, peripheral O&#x2082; saturation and end-tidal CO&#x2082; were recorded before and after insertion. We recorded the number of attempts and insertion time for the I-gel device. Oropharyngeal leak pressures and I-gel device positioning were scored in the lateral decubitus and supine positions.</AbstractText>It was possible to insert the I-gel device in 88 patients on the first attempt. The median time for insertion was 7.97 &#xb1; 2.18 sec. The mean arterial pressure and heart rate decreased 1 and 2 min after insertion. Oropharyngeal leak pressure was similar in the supine (27.45 &#xb1; 5.37 mm Hg) and lateral decubitus positions (26.04 &#xb1; 4.92 mm Hg) (P &gt; 0.05). On fibreoptic examination through the I-gel device, the scores of patients were comparable in different positions (P = 0.542).</AbstractText>As there was no significant difference in oropharyngeal leak pressure and fibreoptic view, we concluded that the I-gel device may be used safely in both the supine and lateral positions.</AbstractText>
2,334,827
Detrended fluctuation analysis detects altered coordination of running gait in athletes following a heavy period of training.
To investigate whether functional overreaching affects locomotor system behaviour when running at fixed relative intensities and if any effects were associated with changes in running performance.</AbstractText>Prospective intervention study.</AbstractText>Ten trained male runners completed three training blocks in a fixed order. Training consisted of one week of light training (baseline), two weeks of heavy training designed to induce functional overreaching, and ten days of light taper training designed to allow athletes to recover from, and adapt to, the heavy training. Locomotor behaviour, 5-km time trial performance, and subjective reports of training status (Daily Analysis of Life Demands for Athletes (DALDA) questionnaire) were assessed at the completion of each training block. Locomotor behaviour was assessed using detrended fluctuation analysis of stride intervals during running at speeds corresponding to 65% and 85% of maximum heart rate (HRmax</sub>) at baseline.</AbstractText>Time trial performance (effect size &#xb1;95% confidence interval (ES): 0.16&#xb1;0.06; p&lt;0.001), locomotor behaviour at 65% HRmax</sub> (ES: -1.12&#xb1;0.95; p=0.026), and DALDA (ES: 2.55&#xb1;0.80; p&lt;0.001) were all detrimentally affected by the heavy training. Time trial performance improved relative to baseline after the taper (ES: -0.16&#xb1;0.10; p=0.003) but locomotor behaviour at 65% HRmax</sub> (ES: -1.18&#xb1;1.17; p=0.048) and DALDA (ES: 0.92&#xb1;0.90; p=0.045) remained impaired.</AbstractText>Locomotor behaviour during running at 65% HRmax</sub> was impaired by functional overreaching and remained impaired after a 10-day taper, despite improved running performance. Locomotor changes may increase injury risk and should be considered within athlete monitoring programs independently of performance changes.</AbstractText>Copyright &#xa9; 2018 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.</CopyrightInformation>
2,334,828
The analgesic efficiency of transversus abdominis plane (TAP) block after caesarean delivery.
The ultrasound-guided transversus abdominis plane (TAP) block is a supporting method of pain relief after different types of surgical and gynecological procedures. The aim of the present study was to evaluate the analgesic effects of the TAP-block in patients undergoing caesarean section.</AbstractText>88 women undergoing elective caesarean section under spinal anaesthesia were prospectively randomized into two groups. In the first group, an ultrasound-guided bilateral TAP block was performed using 40 mL 0.25% bupivacaine, while the second group was treated without a regional nerve block. Both groups received a standard analgesia protocol with intravenous paracetamol administered every 6 hours and intravenous tramadol on-demand, delivered using the Patient Controlled Analgesia (PCA) method. Pain intensity was assessed according to the visual analogue scale (VAS) directly after the TAP block and at 3, 6 and 12 hours postoperatively. Any patient complaints and side-effects during the postoperative period were recorded.</AbstractText>The TAP block resulted in a significant reduction of pain intensity using the visual analogue scale after 3, 6 and 12 hours (p &lt; 0.05) and a significant decrease in tramadol administration (p &lt; 0.05) during the first 12 hours postoperatively. No significant differences in the heart rate and blood pressure were noted between groups (p &gt; 0.05). There were no complications related to the TAP block.</AbstractText>The TAP block is a safe and effective adjunctive method of pain relief after caesarean delivery.</AbstractText>
2,334,829
Genome-wide association meta-analysis of coronary artery disease and periodontitis reveals a novel shared risk locus.
Evidence for a shared genetic basis of association between coronary artery disease (CAD) and periodontitis (PD) exists. To explore the joint genetic basis, we performed a GWAS meta-analysis. In the discovery stage, we used a German aggressive periodontitis sample (AgP-Ger; 680 cases vs 3,973 controls) and the CARDIoGRAMplusC4D CAD meta-analysis dataset (60,801 cases vs 123,504 controls). Two SNPs at the known CAD risk loci ADAMTS7 (rs11634042) and VAMP8 (rs1561198) passed the pre-assigned selection criteria (P<sub>AgP-Ger</sub>&#x2009;&lt;&#x2009;0.05; P<sub>CAD</sub>&#x2009;&lt;&#x2009;5&#x2009;&#xd7;&#x2009;10<sup>-8</sup>; concordant effect direction) and were replicated in an independent GWAS meta-analysis dataset of PD (4,415 cases vs 5,935 controls). SNP rs1561198 showed significant association (PD[Replication]: P&#x2009;=&#x2009;0.008 OR&#x2009;=&#x2009;1.09, 95% CI&#x2009;=&#x2009;[1.02-1.16]; PD [Discovery&#x2009;+&#x2009;Replication]: P&#x2009;=&#x2009;0.0002, OR&#x2009;=&#x2009;1.11, 95% CI&#x2009;=&#x2009;[1.05-1.17]). For the associated haplotype block, allele specific cis-effects on VAMP8 expression were reported. Our data adds to the shared genetic basis of CAD and PD and indicate that the observed association of the two disease conditions cannot be solely explained by shared environmental risk factors. We conclude that the molecular pathway shared by CAD and PD involves VAMP8 function, which has a role in membrane vesicular trafficking, and is manipulated by pathogens to corrupt host immune defense.
2,334,830
A study of anaesthesia-related cardiac arrest from a Chinese tertiary hospital.
The present survey evaluated the incidence of perioperative cardiac arrests in a Chinese tertiary general teaching hospital over ten years.</AbstractText>The incidence of cardiac arrest that occurred within 24&#xa0;h of anaesthesia administration was retrospectively identified in the Third Affiliated Hospital of Sun Yat-Sen University between August 2007 and October 2017. Overall, 152,513 anaesthetics were included in the study period. Data collected included patient characteristics, American Society of Anaesthesiologists (ASA) physical status score, surgical specialty and anaesthesia technique. Cardiac arrests were assigned to one of three groups: "anaesthesia-related", "anaesthesia-contributing" or "anaesthesia-unrelated".</AbstractText>In total, 104 cardiac arrests (6.8:10,000) and 34 deaths (2.2:10,000) were obtained. Among them, eleven cardiac arrests events were anaesthesia-related, resulting in an incidence of 0.7 per 10,000 anaesthetics. Sixteen cardiac arrests events were found to be anaesthesia-contributing, resulting in an incidence of 1.0 per 10,000 anaesthetics. Cardiovascular adverse events were the major events that contributed to anaesthesia-related cardiac arrest. Differences were found between events related and unrelated to anaesthesia with regard to ASA physical status and anaesthesia technique (P&#xa0;&lt;&#x2009;0.05).</AbstractText>Anaesthesia-related cardiac arrest occurred in 11 of 104 cardiac arrests within 24&#xa0;h of anaesthesia administration. Most cardiac arrests related to anaesthesia were due to cardiovascular events, including arrhythmia and hypotension after intravenous narcotic, as well as haemorrhage. ASA physical status of at least 3 and subarachnoid block appeared to be relevant risk factors for anaesthesia-related cardiac arrest.</AbstractText>
2,334,831
Sensory nerves mediate spontaneous behaviors in addition to inflammation in a murine model of psoriasis.
Psoriasis is characterized by keratinocyte hyperproliferation, erythema, as well as a form of pruritus, involving cutaneous discomfort. There is evidence from both clinical and murine models of psoriasis that chemical or surgical depletion of small-diameter sensory nerves/nociceptors benefits the condition, but the mechanisms are unclear. Hence, we aimed to understand the involvement of sensory nerve mediators with a murine model of psoriasis and associated spontaneous behaviors, indicative of cutaneous discomfort. We have established an Aldara model of psoriasis in mice and chemically depleted the small-diameter nociceptors in a selective manner. The spontaneous behaviors, in addition to the erythema and skin pathology, were markedly improved. Attenuated inflammation was associated with reduced dermal macrophage influx and production of reactive oxygen/nitrogen species (peroxynitrite and protein nitrosylation). Subsequently, this directly influenced observed behavioral responses. However, the blockade of common sensory neurogenic mechanisms for transient receptor potential (TRP)V1, TRPA1, and neuropeptides (substance P and calcitonin gene-related peptide) using genetic and pharmacological approaches inhibited the behaviors but not the inflammation. Thus, a critical role of the established sensory TRP-neuropeptide pathway in influencing cutaneous discomfort is revealed, indicating the therapeutic potential of agents that block that pathway. The ongoing inflammation is mediated by a distinct sensory pathway involving macrophage activation.-Kodji, X., Arkless, K. L., Kee, Z., Cleary, S. J., Aubdool, A. A., Evans, E., Caton, P., Pitchford, S. C., Brain, S. D. Sensory nerves mediate spontaneous behaviors in addition to inflammation in a murine model of psoriasis.
2,334,832
Better Hemodynamics and Less Antihypertensive Medication: Comparison of Scalp Block and Local Infiltration Anesthesia for Skull-Pin Placement in Awake Deep Brain Stimulation Surgery.
In deep brain stimulation (DBS) surgery, acute high blood pressure (BP) is a risk factor for intracranial hemorrhage. To minimize pain and hypertensive conditions, sufficient local anesthesia is mandatory. We evaluated whether local instillation of anesthetics (LA) or a scalp block (SB) is superior concerning intraoperative hemodynamics and analgesia.</AbstractText>We retrospectively analyzed intraoperative cardiovascular parameters and perioperative medication in 47 patients (LA&#xa0;= 29, SB&#xa0;= 18) undergoing DBS surgery. Primary study end points were intraoperative systolic BP and heart rate. Secondary end points were use of intraoperative antihypertensives and perioperative analgesics.</AbstractText>Patients who had SB showed lower mean systolic BP and heart rate compared with patients who had LA. Patients who had LA required more antihypertensive medication to stabilize BP. BP was higher, particularly during the first 90 minutes of surgery, in patients who had LA. Thereafter, more antihypertensives were necessary to achieve sufficient BP control in the LA group. The dose of analgesics did not differ significantly between both groups during and after surgery.</AbstractText>Our data suggest that SB might be superior to LA for DBS surgery with respect to BP control and hemodynamics. The need for analgesics does not differ substantially between both anesthetic treatment options.</AbstractText>Copyright &#xa9; 2018 Elsevier Inc. All rights reserved.</CopyrightInformation>
2,334,833
Adjusted regularization of cortical covariance.
It is now common to record dozens to hundreds or more neurons simultaneously, and to ask how the network activity changes across experimental conditions. A natural framework for addressing questions of functional connectivity is to apply Gaussian graphical modeling to neural data, where each edge in the graph corresponds to a non-zero partial correlation between neurons. Because the number of possible edges is large, one strategy for estimating the graph has been to apply methods that aim to identify large sparse effects using an [Formula: see text] penalty. However, the partial correlations found in neural spike count data are neither large nor sparse, so techniques that perform well in sparse settings will typically perform poorly in the context of neural spike count data. Fortunately, the correlated firing for any pair of cortical neurons depends strongly on both their distance apart and the features for which they are tuned. We introduce a method that takes advantage of these known, strong effects by allowing the penalty to depend on them: thus, for example, the connection between pairs of neurons that are close together will be penalized less than pairs that are far apart. We show through simulations that this physiologically-motivated procedure performs substantially better than off-the-shelf generic tools, and we illustrate by applying the methodology to populations of neurons recorded with multielectrode arrays implanted in macaque visual cortex areas V1 and V4.
2,334,834
Biochemical characterization of the catecholaldehyde reactivity of L-carnosine and its therapeutic potential in human myocardium.
Oxidative deamination of norepinephrine (NE) and dopamine (DA) by monoamine oxidase (MAO) generates the catecholaldehydes 3,4-dihydroxyphenylglycolaldehyde (DOPEGAL) and 3,4-dihydroxyphenylacetaldehyde (DOPAL), respectively, and H<sub>2</sub>O<sub>2</sub>. Catecholaldehydes are highly reactive electrophiles that have been implicated as causal factors in the etiology of neurodegenerative diseases and cardiac injury from ischemia and diabetes. The reactivity of both catechol and aldehyde groups enables the catecholaldehdyes to cross-link proteins and other biological molecules. Carnosine is a &#x3b2;-alanyl-histidine dipeptide found in millimolar concentrations in brain and myocardium. It is well known to detoxify aldehydes formed from oxidized lipids and sugars, yet the reactivity of carnosine with catecholaldehydes has never been reported. Here, we investigated the ability of carnosine to form conjugates with DOPAL and DOPEGAL. Both catecholaldehydes were highly reactive towards L-cysteine (L-Cys), as well as carnosine; however, glutathione (GSH) showed essentially no reactivity towards DOPAL. In contrast, GSH readily reacted with the lipid peroxidation product 4-hydroxy-2-nonenal (4HNE), while carnosine showed low reactivity to 4HNE by comparison. To determine whether carnosine mitigates catecholaldehyde toxicity, samples of atrial myocardium were collected from patients undergoing elective cardiac surgery. Using permeabilized myofibers prepared from this tissue, mitochondrial respiration analysis revealed a concentration-dependent decrease in ADP-stimulated respiration with DOPAL. Pre-incubation with carnosine, but not GSH or L-Cys, significantly reduced this effect (p&#x2009;&lt;&#x2009;0.05). Carnosine was also able to block formation of catecholaldehyde protein adducts in isolated human cardiac mitochondria treated with NE. These findings demonstrate the unique reactivity of carnosine towards catecholaldehydes and, therefore, suggest a novel and distinct biological role for histidine dipeptides in this detoxification reaction. The therapeutic potential of carnosine in diseases associated with catecholamine-related toxicity is worthy of further examination.
2,334,835
Towards understanding aromatase inhibitory activity via QSAR modeling.
Aromatase is a rate-limiting enzyme for estrogen biosynthesis that is overproduced in breast cancer tissue. To block the growth of breast tumors, aromatase inhibitors (AIs) are employed to bind and inhibit aromatase in order to lower the amount of estrogen produced in the body. Although a number of synthetic aromatase inhibitors have been released for clinical use in the treatment of hormone-receptor positive breast cancer, these inhibitors may lead to undesirable side effects (e.g. increased rash, diarrhea and vomiting; effects on the bone, brain and heart) and therefore, the search for novel AIs continues. Over the past decades, there has been an intense effort in employing medicinal chemistry and quantitative structure-activity relationship (QSAR) to shed light on the mechanistic basis of aromatase inhibition. To the best of our knowledge, this article constitutes the first comprehensive review of all QSAR studies of both steroidal and non-steroidal AIs that have been published in the field. Herein, we summarize the experimental setup of these studies as well as summarizing the key features that are pertinent for robust aromatase inhibition.
2,334,836
Dorsal penile nerve block versus eutectic mixture of local anesthetics cream for pain relief in infants during circumcision: A meta-analysis.
To compare dorsal penile nerve block (DPNB) and eutectic mixture of local anesthetics (EMLA) cream for pain relief in infants during circumcision.</AbstractText>We systematically searched Medline via PubMed, Embase, CNKI and the Cochrane Library Center Register to identify randomized controlled trials up to March 2018. Effect estimates were performed in random effect models. Mean neonate infant pain scale (NIPS) scores, incidence of hematoma, edema and erythema, mean heart rate were conducted to assessed the effect of analgesia. We found that the EMLA had significantly higher pain scores compared to DPNB (SMD = 3.72, 95% CI 1.27-6.17, P = 0.003). In DPNB group, the incidence of hematoma was significantly higher than EMLA group, OR = 0.03, 95% CI 0.00-0.24, P = 0.001. The analysis did not show any significant differences in mean heart rate and the risk of edema and erythema between EMLA and DPNB group (SMD = 21.71, 95% CI = -0.88-44.30, P = 0.06 &amp; OR = 0.40, 95% CI 0.15-1.07, P = 0.07 &amp; OR = 7.33, 95% CI 0.84-64.07, P = 0.07).</AbstractText>Based on the pooled results from the included studies, we found that DPNB was significantly more effective in pain relief as indicated by mean NIPS score than EMLA in infants during circumcision. However, use of DPNB significantly increased the risk of hematoma.</AbstractText>
2,334,837
Effects of modest iron loading on iron indices in healthy individuals.
Intravenous iron administration is typically indicated in individuals who have iron deficiency refractory to oral iron. However, in certain chronic disease states such as heart failure, it may be beneficial to administer intravenous iron to individuals who are not strictly iron deficient. The purpose of this study was to define a dose-response relationship between clinical indices of iron status and modest loading with intravenous iron in healthy, iron-replete participants. This was a double-blind, controlled study involving 18 male participants. Participants were block-randomized 2:1 to the iron and saline (control) groups. Participants in the iron group received 3.75 mg/kg body wt up to a maximum of 250 mg of intravenous iron, once a month for 6 mo, provided that their ferritin remained measured &lt;300 &#xb5;g/l within the week before a dose was due and their transferrin saturation remained &lt;45%. Otherwise they received a saline infusion, as did the control participants. Iron indices were measured monthly during the study. The pulmonary vascular response to sustained hypoxia and total hemoglobin mass were measured before, at 3 mo (hemoglobin mass only), and at 6 mo as variables that may be affected by iron loading. Serum ferritin was robustly elevated by intravenous iron by 0.21 &#xb5;g&#xb7;l<sup>-1</sup>&#xb7;mg<sup>-1</sup> of iron delivered (95% confidence interval: 0.15-0.26 &#xb5;g&#xb7;l<sup>-1</sup>&#xb7;mg<sup>-1</sup>), but the effects on all other iron indices did not reach statistical significance. The pulmonary vascular response to sustained hypoxia was significantly suppressed by iron loading at 6 mo, but the hemoglobin mass was unaffected. We conclude that the robust effect on ferritin provides a quantitative measure for the degree of iron loading in iron-replete individuals.<b>NEW &amp; NOTEWORTHY</b> There has been an increasing interest in administering intravenous iron to patients to alter their iron status. Here, we explore various indices of iron loading and show that in healthy volunteers serum ferritin provides a robust indicator of the amount of iron loaded, with a value of 21 &#xb5;g/l increase in ferritin per 100 mg of iron loaded.
2,334,838
The cholinergic anti-inflammatory pathway ameliorates acute viral myocarditis in mice by regulating CD4<sup>+</sup> T cell differentiation.<Pagination><StartPage>1364</StartPage><EndPage>1376</EndPage><MedlinePgn>1364-1376</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1080/21505594.2018.1482179</ELocationID><Abstract><AbstractText>Many studies have found that abnormalities in the proportion and differentiation of CD4<sup>+</sup> T cells (Th cells) are closely related to the pathogenesis of viral myocarditis (VMC). Our previous research indicates that the cholinergic anti-inflammatory pathway (CAP) attenuates the inflammatory response of VMC and downregulates the expression of cytokines in Th1 and Th17 cells. This suggests that the cholinergic anti-inflammatory pathway likely attenuates the inflammatory response in VMC by altering Th cell differentiation. The aim of this study is to investigate the effect of CAP on CD4<sup>+</sup> T cell differentiation in VMC mice. CD4<sup>+</sup> T cells in the spleen of VMC mice were obtained and cultured in the presence of nicotine or methyllycaconitine (MLA). Cells were harvested and analyzed for the percentage of each Th cell subset by flow cytometry and transcription factor release by Western blot. Then, we detected the effect of CAP on the differentiation of Th cells in vivo. Nicotine or MLA was used to activate and block CAP, respectively, in acute virus-induced myocarditis. Nicotine treatment increased the proportion of Th2 and Treg cells, decreased the proportion of Th1 and Th17 cells in the spleen, reduced the level of proinflammatory cytokines, and attenuated the severity of myocardium lesions and cellular infiltration in viral myocarditis. MLA administration had the opposite effect. Our result demonstrated that CAP effectively protects the myocardium from virus infection, which may be attributable to the regulation of Th cell differentiation.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>De-Pu</LastName><ForeName>Zhou</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>a Department of Cardiology , The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University , Wenzhou , China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li-Sha</LastName><ForeName>Ge</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>b Department of Pediatric Emergency , The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University , Wenzhou , China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Guang-Yi</LastName><ForeName>Chen</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>a Department of Cardiology , The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University , Wenzhou , China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Xiaohong</LastName><ForeName>Gu</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>c Children's Heart Center and Department of Pediatrics , The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University , Wenzhou , China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chao</LastName><ForeName>Xing</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>d Department of Clinical Laboratory , The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University , Wenzhou , China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cheng</LastName><ForeName>Zheng</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>a Department of Cardiology , The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University , Wenzhou , China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wen-Wu</LastName><ForeName>Zhang</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>e Department of Intensive Care Unit , The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University , Wenzhou , China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jia</LastName><ForeName>Li</ForeName><Initials>L</Initials><Identifier Source="ORCID">0000-0002-7191-1181</Identifier><AffiliationInfo><Affiliation>a Department of Cardiology , The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University , Wenzhou , China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jia-Feng</LastName><ForeName>Lin</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>a Department of Cardiology , The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University , Wenzhou , China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Maoping</LastName><ForeName>Chu</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>c Children's Heart Center and Department of Pediatrics , The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University , Wenzhou , China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yue-Chun</LastName><ForeName>Li</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>a Department of Cardiology , The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University , Wenzhou , China.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Virulence</MedlineTA><NlmUniqueID>101531386</NlmUniqueID><ISSNLinking>2150-5594</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D018678">Cholinergic Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D018733">Nicotinic Antagonists</NameOfSubstance></Chemical><Chemical><RegistryNumber>21019-30-7</RegistryNumber><NameOfSubstance UI="C054634">methyllycaconitine</NameOfSubstance></Chemical><Chemical><RegistryNumber>6M3C89ZY6R</RegistryNumber><NameOfSubstance UI="D009538">Nicotine</NameOfSubstance></Chemical><Chemical><RegistryNumber>X8YN71D5WC</RegistryNumber><NameOfSubstance UI="D000157">Aconitine</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000157" MajorTopicYN="N">Aconitine</DescriptorName><QualifierName UI="Q000031" MajorTopicYN="N">analogs &amp; derivatives</QualifierName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000208" MajorTopicYN="N">Acute Disease</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D015496" MajorTopicYN="N">CD4-Positive T-Lymphocytes</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002454" MajorTopicYN="Y">Cell Differentiation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D018678" MajorTopicYN="N">Cholinergic Agents</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D003384" MajorTopicYN="N">Coxsackievirus Infections</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName><QualifierName UI="Q000517" MajorTopicYN="N">prevention &amp; control</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005434" MajorTopicYN="N">Flow Cytometry</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007249" MajorTopicYN="N">Inflammation</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008213" MajorTopicYN="N">Lymphocyte Activation</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008807" MajorTopicYN="N">Mice, Inbred BALB C</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009205" MajorTopicYN="N">Myocarditis</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName><QualifierName UI="Q000517" MajorTopicYN="N">prevention &amp; control</QualifierName><QualifierName UI="Q000821" MajorTopicYN="Y">virology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D009206" MajorTopicYN="N">Myocardium</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D009538" MajorTopicYN="N">Nicotine</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D018733" MajorTopicYN="N">Nicotinic Antagonists</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D013154" MajorTopicYN="N">Spleen</DescriptorName><QualifierName UI="Q000166" MajorTopicYN="N">cytology</QualifierName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D018417" MajorTopicYN="N">Th1 Cells</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D058504" MajorTopicYN="N">Th17 Cells</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">CD4+ T cells</Keyword><Keyword MajorTopicYN="N">Cholinergic anti-inflammatory pathway</Keyword><Keyword MajorTopicYN="N">Th cell subsets</Keyword><Keyword MajorTopicYN="N">inflammatory cytokines</Keyword><Keyword MajorTopicYN="N">viral myocarditis</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2018</Year><Month>9</Month><Day>4</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2018</Year><Month>9</Month><Day>4</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2019</Year><Month>4</Month><Day>19</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">30176160</ArticleId><ArticleId IdType="pmc">PMC6141146</ArticleId><ArticleId IdType="doi">10.1080/21505594.2018.1482179</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Fairweather D, Rose NR.. 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Many studies have found that abnormalities in the proportion and differentiation of CD4<sup>+</sup> T cells (Th cells) are closely related to the pathogenesis of viral myocarditis (VMC). Our previous research indicates that the cholinergic anti-inflammatory pathway (CAP) attenuates the inflammatory response of VMC and downregulates the expression of cytokines in Th1 and Th17 cells. This suggests that the cholinergic anti-inflammatory pathway likely attenuates the inflammatory response in VMC by altering Th cell differentiation. The aim of this study is to investigate the effect of CAP on CD4<sup>+</sup> T cell differentiation in VMC mice. CD4<sup>+</sup> T cells in the spleen of VMC mice were obtained and cultured in the presence of nicotine or methyllycaconitine (MLA). Cells were harvested and analyzed for the percentage of each Th cell subset by flow cytometry and transcription factor release by Western blot. Then, we detected the effect of CAP on the differentiation of Th cells in vivo. Nicotine or MLA was used to activate and block CAP, respectively, in acute virus-induced myocarditis. Nicotine treatment increased the proportion of Th2 and Treg cells, decreased the proportion of Th1 and Th17 cells in the spleen, reduced the level of proinflammatory cytokines, and attenuated the severity of myocardium lesions and cellular infiltration in viral myocarditis. MLA administration had the opposite effect. Our result demonstrated that CAP effectively protects the myocardium from virus infection, which may be attributable to the regulation of Th cell differentiation.</Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>De-Pu</LastName><ForeName>Zhou</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>a Department of Cardiology , The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University , Wenzhou , China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li-Sha</LastName><ForeName>Ge</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>b Department of Pediatric Emergency , The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University , Wenzhou , China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Guang-Yi</LastName><ForeName>Chen</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>a Department of Cardiology , The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University , Wenzhou , China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Xiaohong</LastName><ForeName>Gu</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>c Children's Heart Center and Department of Pediatrics , The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University , Wenzhou , China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chao</LastName><ForeName>Xing</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>d Department of Clinical Laboratory , The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University , Wenzhou , China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cheng</LastName><ForeName>Zheng</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>a Department of Cardiology , The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University , Wenzhou , China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wen-Wu</LastName><ForeName>Zhang</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>e Department of Intensive Care Unit , The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University , Wenzhou , China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jia</LastName><ForeName>Li</ForeName><Initials>L</Initials><Identifier Source="ORCID">0000-0002-7191-1181</Identifier><AffiliationInfo><Affiliation>a Department of Cardiology , The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University , Wenzhou , China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jia-Feng</LastName><ForeName>Lin</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>a Department of Cardiology , The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University , Wenzhou , China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Maoping</LastName><ForeName>Chu</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>c Children's Heart Center and Department of Pediatrics , The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University , Wenzhou , China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yue-Chun</LastName><ForeName>Li</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>a Department of Cardiology , The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University , Wenzhou , China.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Virulence</MedlineTA><NlmUniqueID>101531386</NlmUniqueID><ISSNLinking>2150-5594</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D018678">Cholinergic Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D018733">Nicotinic Antagonists</NameOfSubstance></Chemical><Chemical><RegistryNumber>21019-30-7</RegistryNumber><NameOfSubstance UI="C054634">methyllycaconitine</NameOfSubstance></Chemical><Chemical><RegistryNumber>6M3C89ZY6R</RegistryNumber><NameOfSubstance UI="D009538">Nicotine</NameOfSubstance></Chemical><Chemical><RegistryNumber>X8YN71D5WC</RegistryNumber><NameOfSubstance UI="D000157">Aconitine</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000157" MajorTopicYN="N">Aconitine</DescriptorName><QualifierName UI="Q000031" MajorTopicYN="N">analogs &amp; derivatives</QualifierName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000208" MajorTopicYN="N">Acute Disease</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D015496" MajorTopicYN="N">CD4-Positive T-Lymphocytes</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002454" MajorTopicYN="Y">Cell Differentiation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D018678" MajorTopicYN="N">Cholinergic Agents</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D003384" MajorTopicYN="N">Coxsackievirus Infections</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName><QualifierName UI="Q000517" MajorTopicYN="N">prevention &amp; control</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005434" MajorTopicYN="N">Flow Cytometry</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007249" MajorTopicYN="N">Inflammation</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008213" MajorTopicYN="N">Lymphocyte Activation</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008807" MajorTopicYN="N">Mice, Inbred BALB C</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009205" MajorTopicYN="N">Myocarditis</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName><QualifierName UI="Q000517" MajorTopicYN="N">prevention &amp; control</QualifierName><QualifierName UI="Q000821" MajorTopicYN="Y">virology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D009206" MajorTopicYN="N">Myocardium</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D009538" MajorTopicYN="N">Nicotine</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D018733" MajorTopicYN="N">Nicotinic Antagonists</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D013154" MajorTopicYN="N">Spleen</DescriptorName><QualifierName UI="Q000166" MajorTopicYN="N">cytology</QualifierName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D018417" MajorTopicYN="N">Th1 Cells</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D058504" MajorTopicYN="N">Th17 Cells</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">CD4+ T cells</Keyword><Keyword MajorTopicYN="N">Cholinergic anti-inflammatory pathway</Keyword><Keyword MajorTopicYN="N">Th cell subsets</Keyword><Keyword MajorTopicYN="N">inflammatory cytokines</Keyword><Keyword MajorTopicYN="N">viral myocarditis</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2018</Year><Month>9</Month><Day>4</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2018</Year><Month>9</Month><Day>4</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2019</Year><Month>4</Month><Day>19</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">30176160</ArticleId><ArticleId IdType="pmc">PMC6141146</ArticleId><ArticleId IdType="doi">10.1080/21505594.2018.1482179</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Fairweather D, Rose NR.. 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J Cardiovasc Pharmacol. 2008;51:92&#x2013;98.</Citation><ArticleIdList><ArticleId IdType="pubmed">18209574</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM" IndexingMethod="Curated"><PMID Version="1">30176007</PMID><DateCompleted><Year>2018</Year><Month>10</Month><Day>15</Day></DateCompleted><DateRevised><Year>2020</Year><Month>08</Month><Day>19</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">1940-087X</ISSN><JournalIssue CitedMedium="Internet"><Issue>138</Issue><PubDate><Year>2018</Year><Month>Aug</Month><Day>19</Day></PubDate></JournalIssue><Title>Journal of visualized experiments : JoVE</Title><ISOAbbreviation>J Vis Exp</ISOAbbreviation></Journal><ArticleTitle>Acellular and Cellular Lung Model to Study Tumor Metastasis.</ArticleTitle><ELocationID EIdType="pii" ValidYN="Y">58145</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.3791/58145</ELocationID><Abstract>It is difficult to isolate tumor cells at different points of tumor progression. We created an ex vivo lung model that can show the interaction of tumor cells with a natural matrix and continual flow of nutrients, as well as a model that shows the interaction of tumor cells with normal cellular components and a natural matrix. The acellular ex vivo lung model is created by isolating a rat heart-lung block and removing all the cells using the decellularization process. The right main bronchus is tied off and tumor cells are placed in the trachea by a syringe. The cells move and populate the left lung. The lung is then placed in a bioreactor where the pulmonary artery receives a continual flow of media in a closed circuit. The tumor grown on the left lung is the primary tumor. The tumor cells that are isolated in the circulating media are circulating tumor cells and the tumor cells in the right lung are metastatic lesions. The cellular ex vivo lung model is created by skipping the decellularization process. Each model can be used to answer different research questions.
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A randomized, open-label, single-visit, crossover study simulating triple-drug delivery with Ellipta compared with dual inhaler combinations in patients with COPD.
Administering maintenance COPD therapy with a combination of multiple inhalers may increase inhaler errors. This study evaluated the potential benefits of using a single Ellipta dry powder inhaler (DPI) compared with two combinations of DPIs commonly used to deliver triple maintenance therapy.</AbstractText>Patients receiving inhaled COPD medication were enrolled in this multicenter, randomized, open-label, placebo-device, crossover study with a 2&#xd7;2 complete block design (NCT0298218), which comprised two substudies: Ellipta vs Diskus + HandiHaler (substudy 1) or Turbuhaler + HandiHaler (substudy 2). Patients demonstrated inhaler use after reading the relevant patient information leaflet (PIL). A trained investigator assessed user errors (critical errors [errors likely to result in no or significantly reduced medication being inhaled] and overall errors). The primary endpoint was the proportion of patients making &#x2265;1 critical error after reading the PIL. The secondary endpoints included error rates during &#x2264;2 reassessments following investigator instruction (if required), instruction time, and patient preference.</AbstractText>After reading the PIL, significantly fewer patients made critical errors with Ellipta compared with Diskus + HandiHaler (9% [7/80] vs 75% [60/80], respectively; P</i>&lt;0.001) or Turbuhaler + HandiHaler (9% [7/79] vs 73% [58/79], respectively; P</i>&lt;0.001). The number of patients making overall errors was also lower with Ellipta vs tested inhaler combinations (P</i>&lt;0.001 for each substudy). The median instruction time needed for error-free use was shorter with Ellipta in substudies 1 and 2 (2.7 and 2.6 minutes, respectively) vs either combination (10.6 [Diskus + HandiHaler] and 11.3 minutes [Turbuhaler + HandiHaler], respectively). Significantly more patients preferred Ellipta over Diskus + HandiHaler or Turbuhaler + HandiHaler overall for taking their COPD medication (81% vs 9% and 84% vs 4%, respectively) and per the number of steps for taking their COPD medication (89% vs 8% and 91% vs 5%, respectively).</AbstractText>Fewer patients with COPD made critical errors with the single DPI, and patients required less instruction time, compared with each dual DPI combination.</AbstractText>
2,334,840
Anaesthetic Management of a Patient with Left Ventricular Non-Compaction Undergoing Laparotomy.
We report a case of left ventricular non-compaction as patient underwent laparotomy for ovarian cystectomy. Left ventricular non-compaction is a rare congenital cardiomyopathy with clinical features of heart failure, systemic thromboembolic events and arrhythmias. Perioperative management of these patients can be very challenging. We used general anaesthesia with subarachnoid block for our patient. We used perioperative, goal-directed, fluid therapy using LiDCO rapid in this case. Patient was monitored in high dependency unit for the risk of perioperative arrhythmias and discharged home in next 24 hours.
2,334,841
Epidural analgesia versus paravertebral block in video-assisted thoracoscopic surgery.
A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was: In patients undergoing video-assisted thoracoscopic surgery, is paravertebral block (PVB) superior to epidural analgesia (EP) in terms of pain control and its postoperative complication rates? Altogether, 153 papers were found using the reporting search, of which 4 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. At present, there are a limited number of studies directly comparing pain control and postoperative outcomes between PVB and EP, and no large-scale randomized trials have been reported. Three of the 4 papers are small prospective randomized trials, with a small cohort study featuring as the final piece of literature. There is no conclusive body of evidence to recommend either route as more efficacious from a pain control perspective; one study demonstrated significantly lower levels of pain with EP (P&#x2009;=&#x2009;0.01), with a second study demonstrating significantly better pain control with PVB (P&#x2009;&lt;&#x2009;0.01) and a third failing to demonstrate any significant difference (P&#x2009;=&#x2009;0.899). The frequency of requiring supplemental analgesia was similar between the PVB and EP cohorts (56% vs 48%, P&#x2009;=&#x2009;0.26). PVB is associated with lower rates of postoperative complications compared to EP, specifically urinary retention (64% vs 34.6%, P&#x2009;=&#x2009;0.0036) and hypotension (32% vs 7%, P&#x2009;=&#x2009;0.0031; 21% vs 3%, P&#x2009;=&#x2009;0.02). In summary, PVBs appear to offer an equivalent level of analgesic effect following video-assisted thoracoscopic surgery, with a more favourable side-effect profile, compared to EP. This does need to be contextualized in light of the scarcity of published material, with the available studies each containing a small number of participants.
2,334,842
Endothelial SIRT1 prevents age-induced impairment of vasodilator responses by enhancing the expression and activity of soluble guanylyl cyclase in smooth muscle cells.
Aged arteries are characterized by attenuated vasodilator and enhanced vasoconstrictor responses, which contribute to the development of diseases such as arterial hypertension, atherosclerosis, and heart failure. SIRT1 is a longevity regulator exerting protective functions against vascular ageing, although the underlying mechanisms remain largely unknown. This study was designed to elucidate the signalling pathways involved in endothelial SIRT1-mediated vasodilator responses in the arteries of young and old mice. In particular, the contributions of nitric oxide (NO), endothelial NO synthase (eNOS), cyclooxygenase (COX), and/or soluble guanylyl cyclase (sGC) were examined.</AbstractText>Wild type (WT) or eNOS knockout (eKO) mice were cross-bred with those overexpressing human SIRT1 selectively in the vascular endothelium (EC-SIRT1). Arteries were collected from the four groups of mice (WT, EC-SIRT1, eKO, and eKO-SIRT1) to measure isometric relaxations/contractions in response to various pharmacological agents. Reduction of NO bioavailability, hyper-activation of COX signalling, and down-regulation of sGC collectively contributed to the decreased vasodilator and increased vasoconstrictor responses in arteries of old WT mice. Overexpression of endothelial SIRT1 did not block the reduction in NO bioavailability but attenuated the hyper-activation of COX-2, thus protecting mice from age-induced vasoconstrictor responses in arteries of EC-SIRT1 mice. Deficiency of eNOS did not affect endothelial SIRT1-mediated anti-contractile activities in arteries of eKO-SIRT1 mice. Mechanistic studies revealed that overexpression of endothelial SIRT1 enhanced Notch signalling to up-regulate sGC&#x3b2;1 in smooth muscle cells. Increased expression and activity of sGC prevented age-induced hyper-activation of COX-2 as well as the conversion of endothelium-dependent relaxations to contractions in arteries of EC-SIRT1 mice.</AbstractText>Age-induced down-regulation of sGC and up-regulation of COX-2 in arteries are at least partly attributable to the loss-of-endothelial SIRT1 function. Enhancing the endothelial expression and function of SIRT1 prevents early vascular ageing and maintains vasodilator responses, thus representing promising drug targets for cardiovascular diseases.</AbstractText>Published on behalf of the European Society of Cardiology. All rights reserved. &#xa9; The Author(s) 2018. For permissions, please email: [email protected].</CopyrightInformation>
2,334,843
Deletion of mitochondrial calcium uniporter incompletely inhibits calcium uptake and induction of the permeability transition pore in brain mitochondria.
Ca<sup>2+</sup> influx into mitochondria is mediated by the mitochondrial calcium uniporter (MCU), whose identity was recently revealed as a 40-kDa protein that along with other proteins forms the mitochondrial Ca<sup>2+</sup> uptake machinery. The MCU is a Ca<sup>2+</sup>-conducting channel spanning the inner mitochondrial membrane. Here, deletion of the MCU completely inhibited Ca<sup>2+</sup> uptake in liver, heart, and skeletal muscle mitochondria. However, in brain nonsynaptic and synaptic mitochondria from neuronal somata/glial cells and nerve terminals, respectively, the MCU deletion slowed, but did not completely block, Ca<sup>2+</sup> uptake. Under resting conditions, brain MCU-KO mitochondria remained polarized, and in brain MCU-KO mitochondria, the electrophoretic Ca<sup>2+</sup> ionophore ETH129 significantly accelerated Ca<sup>2+</sup> uptake. The residual Ca<sup>2+</sup> uptake in brain MCU-KO mitochondria was insensitive to inhibitors of mitochondrial Na<sup>+</sup>/Ca<sup>2+</sup> exchanger and ryanodine receptor (CGP37157 and dantrolene, respectively), but was blocked by the MCU inhibitor Ru360. Respiration of WT and MCU-KO brain mitochondria was similar except that for mitochondria that oxidized pyruvate and malate, Ca<sup>2+</sup> more strongly inhibited respiration in WT than in MCU-KO mitochondria. Of note, the MCU deletion significantly attenuated but did not completely prevent induction of the permeability transition pore (PTP) in brain mitochondria. Expression level of cyclophilin D and ATP content in mitochondria, two factors that modulate PTP induction, were unaffected by MCU-KO, whereas ADP was lower in MCU-KO than in WT brain mitochondria. Our results suggest the presence of an MCU-independent Ca<sup>2+</sup> uptake pathway in brain mitochondria that mediates residual Ca<sup>2+</sup> influx and induction of PTP in a fraction of the mitochondrial population.
2,334,844
Ondansetron and teratogenicity in rats: Evidence for a mechanism mediated via embryonic hERG blockade.
The potent hERG channel blocking drug ondansetron is used off-label for treatment of nausea and vomiting in early pregnancy. Some human epidemiological studies have associated ondansetron with fetal cardiovascular defects and orofacial clefts. This study investigated the effects of ondanestron on embryonic heart rhythm of gestational day (GD) 13 rat embryos in vitro and then integrated the results with published animal teratology, and animal and human pharmacokinetic studies to perform a risk evaluation. Ondansetron caused concentration dependent bradycardia and arrhythmia. Cardiovascular malformations in rats occurred at exposures slightly higher than those in early human pregnancy. Together the results suggest that ondansetron can have teratogenic potential in rats and humans mediated via hERG block and severe heart rhythm disturbances in the embryo. The risk may be increased in human pregnancy if additional risk factors are present such as hypokalemia.
2,334,845
ARAP2 inhibits Akt independently of its effects on focal adhesions.
ARAP2, an Arf GTPase-activating protein (Arf GAP) that binds to adaptor protein with PH domain, PTB domain and leucine zipper motifs 1 (APPL1), regulates focal adhesions (FAs). APPL1 affects FA dynamics by regulating Akt. Here, we tested the hypothesis that ARAP2 affects FAs in part by regulating Akt through APPL1.</AbstractText>We found that ARAP2 controlled FA dynamics dependent on its enzymatic Arf GAP activity. In some cells, ARAP2 also regulated phosphoAkt (pAkt) levels. However, ARAP2 control of FAs did not require Akt and conversely, the effects on pAkt were independent of FAs. Reducing ARAP2 expression reduced the size and number of FAs in U118, HeLa and MDA-MB-231 cells. Decreasing ARAP2 expression increased pAkt in U118 cells and HeLa cells and overexpressing ARAP2 decreased pAkt in U118 cells; in contrast, ARAP2 had no effect on pAkt in MDA-MB-231 cells. An Akt inhibitor did not block the effect of reduced ARAP2 on FAs in U118. Furthermore, the effect of ARAP2 on Akt did not require Arf GAP activity, which is necessary for effects on FAs and integrin traffic. Altering FAs by other means did not induce the same changes in pAkt as those seen by reducing ARAP2 in U118 cells. In addition, we discovered that ARAP2 and APPL1 had co-ordinated effects on pAkt in U118 cells. Reduced APPL1 expression, as for ARAP2, increased pAkt in U118 and the effect of reduced APPL1 expression was reversed by overexpressing ARAP2. Conversely, the effect of reduced ARAP2 expression was reversed by overexpressing APPL1. ARAP2 is an Arf GAP that has previously been reported to affect FAs by regulating Arf6 and integrin trafficking and to bind to the adaptor proteins APPL1. Here, we report that ARAP2 suppresses pAkt levels in cells co-ordinately with APPL1 and independently of GAP activity and its effect on the dynamic behaviour of FAs.</AbstractText>We conclude that ARAP2 affects Akt signalling in some cells by a mechanism independent of FAs or membrane traffic.</AbstractText>Our results highlight an Arf GAP-independent function of ARAP2 in regulating Akt activity and distinguish the effect of ARAP2 on Akt from that on FAs and integrin trafficking, which requires regulation of Arf6.</AbstractText>&#xa9; 2018 Soci&#xe9;t&#xe9; Fran&#xe7;aise des Microscopies and Soci&#xe9;t&#xe9; de Biologie Cellulaire de France. Published by John Wiley &amp; Sons Ltd.</CopyrightInformation>
2,334,846
[Changes in the tumor necrosis factor-&#x3b1; level after an ultrasound-guided femoral nerve block in elderly patients with a hip fracture].
An ultrasound guided femoral nerve block is an established analgesic method in patients with a hip fracture. Elevated cytokine levels correlate with poor patient outcomes after surgery. Hence, the aim of the study was to describe the levels of tumor necrosis factor-&#x3b1; after an ultrasound-guided femoral nerve block in elderly patients having a femoral neck fracture.</AbstractText>A total of 32 patients were allocated into two treatment groups: 16 patients (femoral nerve block group; ultrasound-guided femoral nerve block with up to 20&#xa0;mL of 0.3&#xa0;mL.kg&#x2212;1</sup> of 0.5% bupivacaine and intravenous tramadol) and 16 patients (standard management group; up to 3&#xa0;mL of 0.9% saline in the femoral sheath and intravenous tramadol). Tumor necrosis factor-&#x3b1; and visual analogue scale scores were evaluated immediately before the femoral nerve block and again at 4, 24, and 48&#xa0;h after the femoral nerve block. All surgery was performed electively after 48&#xa0;h of femoral nerve block.</AbstractText>The femoral nerve block group had a significantly lower mean tumor necrosis factor-&#x3b1; level at 24 (4.60 vs. 8.14, p</i>&#xa0;&lt;&#xa0;0.001) and 48&#xa0;h (5.05 vs. 8.56, p</i>&#xa0;&lt;&#xa0;0.001) after the femoral nerve block, compared to the standard management group. The femoral nerve block group showed a significantly lower mean visual analogue scale score at 4 (3.63 vs. 7.06, p</i>&#xa0;&lt;&#xa0;0.001) and 24&#xa0;h (4.50 vs. 5.75, p</i>&#xa0;&lt;&#xa0;0.001) after the femoral nerve block, compared to the standard management group.</AbstractText>Ultrasound-guided femoral nerve block using 0.3&#xa0;mL.kg&#x2212;1</sup> of 0.5% bupivacaine up to a maximum of 20&#xa0;mL resulted in a significant lower tumor necrosis factor-&#x3b1; level.</AbstractText>Copyright &#xa9; 2018 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.</CopyrightInformation>
2,334,847
Effect of dexmedetomidine added to ropivicaine for caudal anesthesia in patients undergoing hemorrhoidectomy: A prospective randomized controlled trial.
To assess the effect of dexmedetomidine added to ropivaccaine on the onset and duration of sensory block, as well as postoperative analgesia during caudal anesthesia in patients undergoing hemorrhoidectomy.</AbstractText>Fifty adult patients scheduled for hemorrhoidectomy were divided into 2 groups. The group R received caudal anesthesia using 18 mL 0.3% ropivacaine plus 2 mL normal saline. The group RD received 18 mL 0.3% ropivacaine plus 2 mL 1&#x200a;&#x3bc;g/kg dexmedetomidine. Heart rate, mean blood pressure, onset time and duration of sensory block, and duration of analgesia were observed.</AbstractText>The onset time of sensory block was shortened (9.2&#x200a;&#xb1;&#x200a;1.3 vs 7.2&#x200a;&#xb1;&#x200a;1.2), and the duration of sensory block (3.0&#x200a;&#xb1;&#x200a;0.7 vs 3.8&#x200a;&#xb1;&#x200a;0.8) and duration of analgesia (3.9&#x200a;&#xb1;&#x200a;0.7 vs 5.3&#x200a;&#xb1;&#x200a;0.8) were prolonged in group RD compared with group R (P&#x200a;&lt;&#x200a;.05). The heart rate and the mean blood pressure were also lower in the group RD compared with group R at each observation time points, except the baseline (P&#x200a;&lt;&#x200a;.05). No bradycardia or hypotension was reported.</AbstractText>Dexmedetomidine as an adjuvant to ropivacaine prolonged the duration of caudal block and improved postoperative analgesia without significant side effects in adult patients undergoing hemorrhoidectomy.</AbstractText>
2,334,848
Erucic acid, a component of Lorenzo's oil and PPAR-&#x3b4; ligand modifies C6 glioma growth and toxicity of doxorubicin. Experimental data and a comprehensive literature analysis.
PPAR-&#x3b4; is a transcription factor which has crucial roles in stimulating oligodendroglial differentiation and myelination and its activation was also shown to differentiate malignant C6 glioma cells into oligodendrocytes.</AbstractText>One of the ligands of PPAR-&#x3b4; is erucic acid (EA), an edible omega-9 fatty acid consumed more by Asian populations and exists highly in Chinese womens milk. There exist epidemiological evidence that pediatric brain tumor incidence is among the lowest in the Chinese population. EA is also an ingredient of Lorenzo's oil used against adrenoleukodystrophy, a pediatric demyelinating disease. EA was inappropriately assumed as a strong cardiotoxin based on Spanish oil syndrome, caused by toxic-aniline dye refined rapeseed oil. In this study, we studied whether EA is capable to block growth of C6 glioma cells and modify cardiotoxicity of doxorubicin.</AbstractText>We studied effects of EA on the 3-dimensional appearance of the adherent cells, soft agar colony formation and S-phase in the 3-dimensional spheroids in C6 glioma cell cultures. We also investigated the effects of EA on hepatic and cardiac toxicity of doxorubicin.</AbstractText>EA decreased in vitro growth of C6 glioma cells at therapeutically achievable concentrations. EA effects were more prominent in 3D-assays (soft agar colonies and spheroids) and induced cell fusions in monolayer cultures. EA decreased S-phase inhibitory potency of doxorubicin (DOX), yet augmented its efficacy to induce a senescent morphology (as assessed by scanning electron microscopy) in monolayer and to increase iNOS and eNOS expression in spheroids. In our study, EA reduced DOX-induced necrosis in mice heart and liver and induced healthier morphology of heart mitochondria (as assessed by transmission electron microscopy); yet intercalated disks (ID) were more disturbed with DOX&#xa0;+&#xa0;EA.</AbstractText>Both the antitumor and cardiac effects of EA may associate with the cell-to-cell contact mechanisms. Combining systemic EA with intrathecal DOX-chemotherapy via Ommaya reservoirs may reduce DOX concentrations in systemic circulation, hinder toxic interactions with EA and induce selective kill of glioma cells.</AbstractText>Copyright &#xa9; 2018. Published by Elsevier B.V.</CopyrightInformation>
2,334,849
Comparative Evaluation of Dexmedetomidine and Propofol Along With Scalp Block on Haemodynamic and Postoperative Recovery for Chronic Subdural Haematoma Evacuation Under Monitored Anaesthesia Care.
Chronic subdural haematoma (CSDH) is a common neurosurgical problem, and treatment includes evacuation of the haematoma by burr hole drainage. Commonly, these procedures are performed under local anaesthesia, general anaesthesia or, recently, with monitored anaesthesia care (MAC). We compared dexmedetomidine- and propofol-based sedation along with scalp nerve block for burr hole evacuation of CSDH.</AbstractText>In this prospective randomised study, 62 patients were divided into the following two groups of 31 patients each: Group D and Group P. Group D received dexmedetomidine 1 &#x3bc;g kg-1</sup> over 10 minutes as a loading dose, followed by 0.2-0.7 &#x3bc;g kg-1</sup> hr-1</sup>. Group P received propofol 1 mg kg-1</sup> over 10 minutes as a loading dose, followed by 1-3 mg kg-1</sup> hr-1</sup>. The heart rate (HR) and blood pressure were measured at different intervals. The recovery parameter and satisfaction score were also recorded.</AbstractText>There were no significant differences noted in the demographic profile. A significant decrease in HR compared to preoperative value was seen in Group D compared to Group P. Blood pressure values were statistically significantly lower in both study groups, compared to preoperative values during the whole procedure and after surgery (p&lt;0.05). Time to achieve modified Aldrete score of 9-10 was not significantly different between the groups (p=0.354). Surgeon satisfaction was significantly better in Group D compared to Group P (p&lt;0.05), but patient satisfaction was similar between the groups (p=0.364).</AbstractText>Dexmedetomidine-based sedation compared to propofol, along with scalp block for MAC in patients undergoing burr hole evacuation of CSDH is associated with haemodynamic stability and greater surgeon satisfaction.</AbstractText>
2,334,850
The comparison of short-term prognostic value of T1 mapping with feature tracking by cardiovascular magnetic resonance in patients with severe dilated cardiomyopathy.<Pagination><StartPage>171</StartPage><EndPage>178</EndPage><MedlinePgn>171-178</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1007/s10554-018-1444-8</ELocationID><Abstract><AbstractText>To evaluate and compare the prognostic value of T1 mapping with feature tracking cardiovascular magnetic resonance (FT-CMR) imaging in patients with severe dilated cardiomyopathy (DCM) during short-term follow-up. A total of 46 patients with severe DCM (LVEF&#x2009;&lt;&#x2009;35%) underwent 3.0-T CMR with T1 mapping and FT-CMR analysis. The study end-point was defined as a combination of cardiac death, heart transplantation, and hospitalization due to cardiovascular events. The significance of the risk factors was mainly evaluated by univariate and multivariate Cox model analyses. During the median follow-up of 13&#xa0;months (interquartile range 7-17&#xa0;months), two patients died of heart failure, one received a heart transplantation, and six were hospitalized for heart failure. In the univariate analysis, extracellular volume fraction (ECV) showed significant predictive association with cardiovascular events (hazard ratio [HR] 1.35; 95% confidence interval [CI] 1.13-1.62; P&#x2009;=&#x2009;0.001). No strain parameters in FT-CMR differed significantly between patients with or without events (all P&#x2009;&gt;&#x2009;0.05). In the multivariate analyses, ECV was the sole independent predictor of cardiovascular events (HR, 1.48; 95% CI 1.13-1.94; P&#x2009;=&#x2009;0.005). The area under the curve of the time-dependent receiver operating characteristic in leave-one-out cross-validation (all &gt;&#x2009;0.70) further confirmed the predictive significance of ECV. In patients with severe DCM, ECV was not only a strong independent predictor of adverse cardiovascular events but also provided prognostic value prior to strain parameters of the FT-CMR in the short term.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Chen</LastName><ForeName>Rui</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>School of Medicine, South China University of Technology, Guangzhou, 510006, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Radiology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhong Shan Er Lu, Guangzhou, 510080, Guangdong, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Jingjing</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>School of Medicine, South China University of Technology, Guangzhou, 510006, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Radiology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhong Shan Er Lu, Guangzhou, 510080, Guangdong, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Du</LastName><ForeName>Zhicheng</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>Department of Medical Statistics and Epidemiology, Health Information Research Center, Guangdong Key Laboratory of Medicine, School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Juan</LastName><ForeName>Yu-Hsiang</ForeName><Initials>YH</Initials><AffiliationInfo><Affiliation>Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital, Linkou, Chang Gung University, Taoyuan, Taiwan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chan</LastName><ForeName>Carmen Wing-Sze</ForeName><Initials>CW</Initials><AffiliationInfo><Affiliation>Division of Cardiology, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Rm 1929b, Block K, Hong Kong, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fei</LastName><ForeName>Hongwen</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Department of Cardiology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Xie</LastName><ForeName>Jiajun</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Radiology, The Second Affiliated Hospital, South China University of Technology, Guangzhou, Guangdong, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wu</LastName><ForeName>Wanjia</ForeName><Initials>W</Initials><AffiliationInfo><Affiliation>Department of Radiology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhong Shan Er Lu, Guangzhou, 510080, Guangdong, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhu</LastName><ForeName>Yulei</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>School of Medicine, South China University of Technology, Guangzhou, 510006, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Radiology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhong Shan Er Lu, Guangzhou, 510080, Guangdong, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Liwen</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Department of Cardiology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Meng</LastName><ForeName>Jinxiu</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Cardiology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wu</LastName><ForeName>Shulin</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Cardiology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Liang</LastName><ForeName>Changhong</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>School of Medicine, South China University of Technology, Guangzhou, 510006, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Radiology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhong Shan Er Lu, Guangzhou, 510080, Guangdong, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yu</LastName><ForeName>Zhuliang</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>School of Medicine, South China University of Technology, Guangzhou, 510006, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>College of Automation Science and Technology, South China University of Technology, Guangzhou, Guangdong, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Liu</LastName><ForeName>Hui</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>School of Medicine, South China University of Technology, Guangzhou, 510006, China. [email protected].</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Radiology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhong Shan Er Lu, Guangzhou, 510080, Guangdong, China. [email protected].</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Cardiology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China. [email protected].</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>81771799</GrantID><Agency>National Natural Science Foundation of China</Agency><Country/></Grant><Grant><GrantID>2014A020212676</GrantID><Agency>Guangdong Provincial Science and Technology Planning Project</Agency><Country/></Grant><Grant><GrantID>201707010306</GrantID><Agency>Science and Technology Program of Guangzhou, China</Agency><Country/></Grant></GrantList><PublicationTypeList><PublicationType UI="D003160">Comparative Study</PublicationType><PublicationType UI="D023362">Evaluation Study</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2018</Year><Month>08</Month><Day>21</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Int J Cardiovasc Imaging</MedlineTA><NlmUniqueID>100969716</NlmUniqueID><ISSNLinking>1569-5794</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000328" MajorTopicYN="N">Adult</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002311" MajorTopicYN="N">Cardiomyopathy, Dilated</DescriptorName><QualifierName UI="Q000000981" MajorTopicYN="Y">diagnostic imaging</QualifierName><QualifierName UI="Q000401" MajorTopicYN="N">mortality</QualifierName><QualifierName UI="Q000503" MajorTopicYN="N">physiopathology</QualifierName><QualifierName UI="Q000601" MajorTopicYN="N">surgery</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002423" MajorTopicYN="N">Cause of Death</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D018450" MajorTopicYN="N">Disease Progression</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016027" MajorTopicYN="N">Heart Transplantation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007090" MajorTopicYN="N">Image Interpretation, Computer-Assisted</DescriptorName><QualifierName UI="Q000379" MajorTopicYN="Y">methods</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D019028" MajorTopicYN="N">Magnetic Resonance Imaging, Cine</DescriptorName><QualifierName UI="Q000379" MajorTopicYN="Y">methods</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010343" MajorTopicYN="N">Patient Admission</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011237" MajorTopicYN="N">Predictive Value of Tests</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011379" MajorTopicYN="N">Prognosis</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012307" MajorTopicYN="N">Risk Factors</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012720" MajorTopicYN="N">Severity of Illness Index</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013997" MajorTopicYN="N">Time Factors</DescriptorName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Cardiovascular magnetic resonance</Keyword><Keyword MajorTopicYN="N">Feature tracking</Keyword><Keyword MajorTopicYN="N">Severe dilated cardiomyopathy</Keyword><Keyword MajorTopicYN="N">Short-term prognostic values</Keyword><Keyword MajorTopicYN="N">T1 mapping</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2018</Year><Month>4</Month><Day>16</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2018</Year><Month>8</Month><Day>17</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2018</Year><Month>8</Month><Day>23</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2019</Year><Month>3</Month><Day>15</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2018</Year><Month>8</Month><Day>23</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">30132161</ArticleId><ArticleId IdType="doi">10.1007/s10554-018-1444-8</ArticleId><ArticleId IdType="pii">10.1007/s10554-018-1444-8</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>N Engl J Med. 2000 Apr 13;342(15):1077-84</Citation><ArticleIdList><ArticleId IdType="pubmed">10760308</ArticleId></ArticleIdList></Reference><Reference><Citation>Biometrics. 2000 Jun;56(2):337-44</Citation><ArticleIdList><ArticleId 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Version="1">30131043</PMID><DateCompleted><Year>2019</Year><Month>05</Month><Day>16</Day></DateCompleted><DateRevised><Year>2019</Year><Month>05</Month><Day>16</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0022-9040</ISSN><JournalIssue CitedMedium="Print"><Issue>8</Issue><PubDate><Year>2018</Year><Month>Aug</Month></PubDate></JournalIssue><Title>Kardiologiia</Title><ISOAbbreviation>Kardiologiia</ISOAbbreviation></Journal>[Clinical Value of Algorithms of Minimization of Right Ventricular Pacing in Patients With Sick Sinus Syndrome and History of Atrial Fibrillation].
To evaluate and compare the prognostic value of T1 mapping with feature tracking cardiovascular magnetic resonance (FT-CMR) imaging in patients with severe dilated cardiomyopathy (DCM) during short-term follow-up. A total of 46 patients with severe DCM (LVEF&#x2009;&lt;&#x2009;35%) underwent 3.0-T CMR with T1 mapping and FT-CMR analysis. The study end-point was defined as a combination of cardiac death, heart transplantation, and hospitalization due to cardiovascular events. The significance of the risk factors was mainly evaluated by univariate and multivariate Cox model analyses. During the median follow-up of 13&#xa0;months (interquartile range 7-17&#xa0;months), two patients died of heart failure, one received a heart transplantation, and six were hospitalized for heart failure. In the univariate analysis, extracellular volume fraction (ECV) showed significant predictive association with cardiovascular events (hazard ratio [HR] 1.35; 95% confidence interval [CI] 1.13-1.62; P&#x2009;=&#x2009;0.001). No strain parameters in FT-CMR differed significantly between patients with or without events (all P&#x2009;&gt;&#x2009;0.05). In the multivariate analyses, ECV was the sole independent predictor of cardiovascular events (HR, 1.48; 95% CI 1.13-1.94; P&#x2009;=&#x2009;0.005). The area under the curve of the time-dependent receiver operating characteristic in leave-one-out cross-validation (all &gt;&#x2009;0.70) further confirmed the predictive significance of ECV. In patients with severe DCM, ECV was not only a strong independent predictor of adverse cardiovascular events but also provided prognostic value prior to strain parameters of the FT-CMR in the short term.</Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Chen</LastName><ForeName>Rui</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>School of Medicine, South China University of Technology, Guangzhou, 510006, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Radiology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhong Shan Er Lu, Guangzhou, 510080, Guangdong, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Jingjing</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>School of Medicine, South China University of Technology, Guangzhou, 510006, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Radiology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhong Shan Er Lu, Guangzhou, 510080, Guangdong, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Du</LastName><ForeName>Zhicheng</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>Department of Medical Statistics and Epidemiology, Health Information Research Center, Guangdong Key Laboratory of Medicine, School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Juan</LastName><ForeName>Yu-Hsiang</ForeName><Initials>YH</Initials><AffiliationInfo><Affiliation>Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital, Linkou, Chang Gung University, Taoyuan, Taiwan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chan</LastName><ForeName>Carmen Wing-Sze</ForeName><Initials>CW</Initials><AffiliationInfo><Affiliation>Division of Cardiology, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Rm 1929b, Block K, Hong Kong, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fei</LastName><ForeName>Hongwen</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Department of Cardiology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Xie</LastName><ForeName>Jiajun</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Radiology, The Second Affiliated Hospital, South China University of Technology, Guangzhou, Guangdong, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wu</LastName><ForeName>Wanjia</ForeName><Initials>W</Initials><AffiliationInfo><Affiliation>Department of Radiology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhong Shan Er Lu, Guangzhou, 510080, Guangdong, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhu</LastName><ForeName>Yulei</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>School of Medicine, South China University of Technology, Guangzhou, 510006, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Radiology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhong Shan Er Lu, Guangzhou, 510080, Guangdong, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Liwen</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Department of Cardiology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Meng</LastName><ForeName>Jinxiu</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Cardiology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wu</LastName><ForeName>Shulin</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Cardiology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Liang</LastName><ForeName>Changhong</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>School of Medicine, South China University of Technology, Guangzhou, 510006, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Radiology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhong Shan Er Lu, Guangzhou, 510080, Guangdong, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yu</LastName><ForeName>Zhuliang</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>School of Medicine, South China University of Technology, Guangzhou, 510006, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>College of Automation Science and Technology, South China University of Technology, Guangzhou, Guangdong, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Liu</LastName><ForeName>Hui</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>School of Medicine, South China University of Technology, Guangzhou, 510006, China. [email protected].</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Radiology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhong Shan Er Lu, Guangzhou, 510080, Guangdong, China. [email protected].</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Cardiology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China. [email protected].</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>81771799</GrantID><Agency>National Natural Science Foundation of China</Agency><Country/></Grant><Grant><GrantID>2014A020212676</GrantID><Agency>Guangdong Provincial Science and Technology Planning Project</Agency><Country/></Grant><Grant><GrantID>201707010306</GrantID><Agency>Science and Technology Program of Guangzhou, China</Agency><Country/></Grant></GrantList><PublicationTypeList><PublicationType UI="D003160">Comparative Study</PublicationType><PublicationType UI="D023362">Evaluation Study</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2018</Year><Month>08</Month><Day>21</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Int J Cardiovasc Imaging</MedlineTA><NlmUniqueID>100969716</NlmUniqueID><ISSNLinking>1569-5794</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000328" MajorTopicYN="N">Adult</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002311" MajorTopicYN="N">Cardiomyopathy, Dilated</DescriptorName><QualifierName UI="Q000000981" MajorTopicYN="Y">diagnostic imaging</QualifierName><QualifierName UI="Q000401" MajorTopicYN="N">mortality</QualifierName><QualifierName UI="Q000503" MajorTopicYN="N">physiopathology</QualifierName><QualifierName UI="Q000601" MajorTopicYN="N">surgery</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002423" MajorTopicYN="N">Cause of Death</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D018450" MajorTopicYN="N">Disease Progression</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016027" MajorTopicYN="N">Heart Transplantation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007090" MajorTopicYN="N">Image Interpretation, Computer-Assisted</DescriptorName><QualifierName UI="Q000379" MajorTopicYN="Y">methods</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D019028" MajorTopicYN="N">Magnetic Resonance Imaging, Cine</DescriptorName><QualifierName UI="Q000379" MajorTopicYN="Y">methods</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010343" MajorTopicYN="N">Patient Admission</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011237" MajorTopicYN="N">Predictive Value of Tests</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011379" MajorTopicYN="N">Prognosis</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012307" MajorTopicYN="N">Risk Factors</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012720" MajorTopicYN="N">Severity of Illness Index</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013997" MajorTopicYN="N">Time Factors</DescriptorName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Cardiovascular magnetic resonance</Keyword><Keyword MajorTopicYN="N">Feature tracking</Keyword><Keyword MajorTopicYN="N">Severe dilated cardiomyopathy</Keyword><Keyword MajorTopicYN="N">Short-term prognostic values</Keyword><Keyword MajorTopicYN="N">T1 mapping</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2018</Year><Month>4</Month><Day>16</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2018</Year><Month>8</Month><Day>17</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2018</Year><Month>8</Month><Day>23</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2019</Year><Month>3</Month><Day>15</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2018</Year><Month>8</Month><Day>23</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">30132161</ArticleId><ArticleId IdType="doi">10.1007/s10554-018-1444-8</ArticleId><ArticleId IdType="pii">10.1007/s10554-018-1444-8</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>N Engl J Med. 2000 Apr 13;342(15):1077-84</Citation><ArticleIdList><ArticleId IdType="pubmed">10760308</ArticleId></ArticleIdList></Reference><Reference><Citation>Biometrics. 2000 Jun;56(2):337-44</Citation><ArticleIdList><ArticleId 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Jan;9(1):40-50</Citation><ArticleIdList><ArticleId IdType="pubmed">26762873</ArticleId></ArticleIdList></Reference><Reference><Citation>Eur Heart J Cardiovasc Imaging. 2016 Dec;17(12):1321-1360</Citation><ArticleIdList><ArticleId IdType="pubmed">27422899</ArticleId></ArticleIdList></Reference><Reference><Citation>Radiology. 2017 Jun;283(3):681-691</Citation><ArticleIdList><ArticleId IdType="pubmed">28156200</ArticleId></ArticleIdList></Reference><Reference><Citation>Circulation. 2017 Jul 11;136(2):215-231</Citation><ArticleIdList><ArticleId IdType="pubmed">28696268</ArticleId></ArticleIdList></Reference><Reference><Citation>N Engl J Med. 1994 Dec 8;331(23):1564-75</Citation><ArticleIdList><ArticleId IdType="pubmed">7969328</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM" IndexingMethod="Curated"><PMID Version="1">30131043</PMID><DateCompleted><Year>2019</Year><Month>05</Month><Day>16</Day></DateCompleted><DateRevised><Year>2019</Year><Month>05</Month><Day>16</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0022-9040</ISSN><JournalIssue CitedMedium="Print"><Issue>8</Issue><PubDate><Year>2018</Year><Month>Aug</Month></PubDate></JournalIssue><Title>Kardiologiia</Title><ISOAbbreviation>Kardiologiia</ISOAbbreviation></Journal><ArticleTitle>[Clinical Value of Algorithms of Minimization of Right Ventricular Pacing in Patients With Sick Sinus Syndrome and History of Atrial Fibrillation].</ArticleTitle><Pagination><StartPage>58</StartPage><EndPage>63</EndPage><MedlinePgn>58-63</MedlinePgn></Pagination><Abstract><AbstractText Label="PURPOSE" NlmCategory="OBJECTIVE">to assess effectiveness of algorithms of minimization of right ventricular pacing (MRVP) for prevention of progression of atrial fibrillation (AF), lowering of frequency of hospitalizations due to cardiovascular causes, and mortality in patients with sick sinus syndrome (SSS) and history of paroxysmal AF compared with standard compared with dual-chamber pacing (DDDR).<AbstractText Label="MATERIALS AND METHODS" NlmCategory="METHODS">We included in this single-center prospective study 74 consecutive patients with indications to permanent DDDR pacing because of SSS combined with documented history of paroxysmal AF. Patients were randomized in the groups of DDDR pacing (n=36) and with activated algorithms of MRVP (n=38). Pacemaker check up was made after 6 months during 1 year after device implantation. Primary composite endpoint included development of persistent AF, hospitalization due to cardiovascular causes, and all cause death.<AbstractText Label="RESULTS" NlmCategory="RESULTS">During follow-up there was no statistically significant difference in achievement of the primary endpoint (27.8 and 18.4% in groups of DDDR pacing and activated algorithms of MRVP respectively (relative risk 1.29% confidence interval 0.43 to 3.86; p=0.25). Rate of development of persistent AF in both groups was comparable (8.6 and 5.3% in DDDR and MRVP groups, respectively; p=0.47). Median AF burden was 6.0 (0;42) and 6.0 (0;42) min/day in DDDR and MRVP groups, respectively (p=0.67).<AbstractText Label="CONCLUSION" NlmCategory="CONCLUSIONS">Our study failed to demonstrate advantages of the use of algorithms of decreasing "unmotivated" right ventricular pacing over standard regimen of standard DDDR pacing in patients with SSS and history of paroxysmal AF.
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Neuromuscular block monitoring after the administration of 1&#xa0;mg/kg intravenous cis-atracurium in the anaesthetized pig.
Neuromuscular blocking agents should be included as part of a balanced anaesthetic protocol to improve anaesthetic management, although doses are not always established for each species. Cis-atracurium is a benzylisoquinolinium neuromuscular blocking agent with an intermediate duration of action devoid of significant adverse effects previously used in pigs with a wide dosage range. Cis-atracurium was administered at 1&#xa0;mg/kg bolus to sixteen pigs to establish its time profile and effects. The pigs were premedicated intramuscularly with 4&#xa0;mg/kg azaperone, 8&#xa0;mg/kg ketamine and 0.2&#xa0;mg/kg morphine IM and maintained with isoflurane in oxygen. After cis-atracurium administration, neuromuscular monitoring via acceleromyography was started until the recovery of the 90% of the train of four ratio. Complete decrease in the train of four ratio was accomplished in eleven pigs. Onset of action was 70&#xa0;s, with a recovery of the fourth twitch at 26&#xa0;min and a recovery of a train of four ratio greater than 90% in 60&#xa0;min. In conclusion, 1&#xa0;mg/kg intravenous cis-atracurium in the pig allowed for a rapid onset of action and a complete recovery after 60&#xa0;min although high variability in the time profile is seen.
2,334,852
Impact of local administration of various doses of dexmedetomidine on ropivacaine-induced lumbar plexus-sciatic nerve block.
The present study aimed to investigate the impact of various doses of dexmedetomidine (DEX) on ropivacaine (ROP)-induced lumbar plexus-sciatic nerve block (LSB). A total of 80 patients who underwent ankle surgery under LSB were divided into group R (applied with 30 ml 5% ROP), Dex1 (30 ml 0.5% ROP + 1 &#xb5;g/kg DEX), Dex2 (30 ml 0.5% ROP + 1.5 &#xb5;g/kg DEX) and Dex3 (30 ml 0.5% ROP + 2 &#xb5;g/kg DEX), with 20 cases in each group. The onset time and duration of sensory and motor block, mean arterial pressure (MAP), heart rate (HR), oxygen saturation, Ramsay score, serum vascular endothelial growth factor (VEGF) level and adverse reactions in the four groups were observed. Results demonstrated that the durations of sensory and motor block in group R were shorter than those in groups Dex1-3 (P&lt;0.01), followed by the sequence of group Dex1&lt;Dex2&lt;Dex3 (P&lt;0.05). MAP and HR in groups Dex1-3 at T2-T5 were significantly lower than those in group R (P&lt;0.01), and HR in group Dex3 at T3 and T4 was significantly lower than that in groups Dex1 and Dex2 (P&lt;0.05). Ramsay scores in groups Dex1-3 at T2-T4 were significantly higher than those in group R (P&lt;0.05). Serum VEGF levels in groups Dex2 and Dex3 at T2-T5 were significantly higher than those in group R (P&lt;0.01). The incidences of over-sedation, bradycardia and dry mouth in group Dex3 were notably higher than those in the other groups. In conclusion, 1.5 &#xb5;g/kg DEX exhibits a superior effect in improving ROP-induced LSB.
2,334,853
Metacognitive therapy home-based self-help for cardiac rehabilitation patients experiencing anxiety and depressive symptoms: study protocol for a feasibility randomised controlled trial (PATHWAY Home-MCT).
Anxiety and depression are common among patients attending cardiac rehabilitation services. Currently available pharmacological and psychological interventions have limited effectiveness in this population. There are presently no psychological interventions for anxiety and depression integrated into cardiac rehabilitation services despite emphasis in key UK National Health Service policy. A new treatment, metacognitive therapy, is highly effective at reducing anxiety and depression in mental health settings. The principal aims of the current study are (1) to evaluate the acceptability of delivering metacognitive therapy in a home-based self-help format (Home-MCT) to cardiac rehabilitation patients experiencing anxiety and depressive symptoms and conduct a feasibility trial of Home-MCT plus usual cardiac rehabilitation compared to usual cardiac rehabilitation; and (2) to inform the design and sample size for a full-scale trial.</AbstractText>The PATHWAY Home-MCT trial is a single-blind feasibility randomised controlled trial comparing usual cardiac rehabilitation (control) versus usual cardiac rehabilitation plus home-based self-help metacognitive therapy (intervention). Economic and qualitative evaluations will be embedded within the trial. Participants will be assessed at baseline and followed-up at 4 and 12&#xa0;months. Patients who have been referred to cardiac rehabilitation programmes and have a score of &#x2265;&#x2009;8 on the anxiety and/or depression subscales of the Hospital Anxiety and Depression Scale will be invited to take part in the study and written informed consent will be obtained. Participants will be recruited from the National Health Service in the UK. A minimum of 108 participants will be randomised to the intervention and control arms in a 1:1 ratio.</AbstractText>The Home-MCT feasibility randomised controlled trial will provide evidence on the acceptability of delivering metacognitive therapy in a home-based self-help format for cardiac rehabilitation patients experiencing symptoms of anxiety and/or depression and on the feasibility and design of a full-scale trial. In addition, it will provide provisional point estimates, with appropriately wide measures of uncertainty, relating to the effectiveness and cost-effectiveness of the intervention.</AbstractText>ClinicalTrials.gov, NCT03129282 , Submitted to Registry: 11 April 2017.</AbstractText>
2,334,854
Analgesic effect of Ropivacaine combined with Dexmedetomidine on brachial plexus block.
This randomized controlled study investigated the analgesic effect of ropivacaine in combination with dexmedetomidine versus ropivacaine alone on brachial plexus block to provide alternative anesthetic means for upper limb trauma surgery.</AbstractText>Totally 114 patients who received upper limb surgeries under brachial plexus block anesthesia in our hospital from February 2013 to July 2015 were enrolled. The patients were randomized to ropivacaine alone (the control group) or ropivacaine combined with dexmedetomidine (the combination group). The blocking effect on sensory and motor neurons, visual analog scale (VAS) score, heart rate (HR), mean arterial pressure (MAP), peripheral capillary oxygen saturation (SPO2</sub>) and adverse reactions were compared between the two groups.</AbstractText>The time to onset of sensory and motor nerve blockade was significantly shorter in the combination group than in the control group (8.9&#xa0;min vs. 12.4&#xa0;min for sensation blockade; 7.5&#xa0;min vs. 12.8&#xa0;min for motor blockade, P&#x2009;&lt;&#x2009;0.05 for both comparisons), and the duration of the blockade was significantly longer in the combination group (590.2&#xa0;min vs. 532.1&#xa0;min, P&#x2009;&lt;&#x2009;0.05). There was no significant difference in VAS scores between the two groups immediately and 4&#xa0;h after surgery; however, 8, 12 and 24&#xa0;h after surgery, the VAS scores were all significantly lower in the combination group than the control group (2.4 vs. 3.0 for 8&#xa0;h; 2.2 vs. 4.2 for 12&#xa0;h, and 2.1 vs. 5.4 for 24&#xa0;h, respectively, P&#x2009;&lt;&#x2009;0.05 for all comparisons). There was no statistical difference in HR, MAP and SPO2</sub> between the two groups before anesthesia, but after anesthesia, the MAP and HR were significantly lower, and the SPO2</sub> was significantly higher in the combination group than the control group (78 vs. 84 for MAP; 72 vs. 79 for HR; and 95.1 vs. 88.2 for SPO2</sub>, P&#x2009;&lt;&#x2009;0.05 for all comparisons). The rates of adverse reaction was significantly lower in the combination group than the control group (3.6 vs. 7.2, P&#x2009;&lt;&#x2009;0.05).</AbstractText>The brachial plexus blocking effect of ropivacaine combined with dexmedetomidine was superior to that of ropivacaine alone, mainly intra-operatively and postoperatively.</AbstractText>Analgesic Effect of Ropivacaine Combined with Dexmedetomidine on Brachial Plexus Block, ChiCTR1800017372, retrospectively registered on July 26, 2018.</AbstractText>
2,334,855
Curcumin-loaded PLGA-PEG nanoparticles conjugated with B6 peptide for potential use in Alzheimer's disease.
Alzheimer's disease is a neurodegenerative disorder mainly characterized by &#x3b2;-amyloid deposit and tau hyperphosphorylation with no curative treatments. Curcumin (Cur) has been proved to have potential use in Alzheimer's disease with its anti-amyloid, anti-inflammatory, and anti-oxidant properties, etc. However, its hydrophobicity and low bioavailability hinder its application. In this paper, we designed a novel brain-target nanoparticle, poly(lactide-co-glycolide)-block-poly(ethylene glycol) (PLGA-PEG) conjugated with B6 peptide and was loaded with Cur (PLGA-PEG-B6/Cur) and administered it into HT22 cells and APP/PS1 Al transgenic mice. The in vitro assays including dynamic light scattering (DLS), flow cytometry (FCM), red blood cell (RBC) lysis, and thromboelastography (TEG) analysis indicated that this nanoparticle could narrow the diameter of Cur, increase its cellular uptake and possess good blood compatibility. The results from Morris water maze proved that PLGA-PEG-B6/Cur could tremendously improve the spatial learning and memory capability of APP/PS1 mice, compared with native Cur. The ex vivo assays including Bielschowsky silver staining, immunostaining, and western blotting demonstrated that PLGA-PEG-B6/Cur could reduce hippocampal &#x3b2;-amyloid formation and deposit and tau hyperphosphorylation. Thus, we suggested that PLGA-PEG-B6/Cur nanoparticles would be of potential and promising use for the treatment of Alzheimer's disease.
2,334,856
Highly conductive, stretchable and biocompatible Ag-Au core-sheath nanowire composite for wearable and implantable bioelectronics.
Wearable and implantable devices require conductive, stretchable and biocompatible materials. However, obtaining composites that simultaneously fulfil these requirements is challenging due to a trade-off between conductivity and stretchability. Here, we report on Ag-Au nanocomposites composed of ultralong gold-coated silver nanowires in an elastomeric block-copolymer matrix. Owing to the high aspect ratio and percolation network of the Ag-Au nanowires, the nanocomposites exhibit an optimized conductivity of 41,850&#x2009;S&#x2009;cm<sup>-1</sup> (maximum of 72,600&#x2009;S&#x2009;cm<sup>-1</sup>). Phase separation in the Ag-Au nanocomposite during the solvent-drying process generates a microstructure that yields an optimized stretchability of 266% (maximum of 840%). The thick gold sheath deposited on the silver nanowire surface prevents oxidation and silver ion leaching, making the composite biocompatible and highly conductive. Using the nanocomposite, we successfully fabricate wearable and implantable soft bioelectronic devices that can be conformally integrated with human skin and swine heart for continuous electrophysiological recording, and electrical and thermal stimulation.
2,334,857
Design of high performance QRS complex detector for wearable healthcare devices using biorthogonal spline wavelet transform.
A high performance QRS complex detector applicable for wearable healthcare devices is proposed in the present work. Since, higher SNR results in better detection accuracy and lesser number of coefficients reduces the hardware resources as well as power dissipation during on chip implementation. Biorthogonal spline wavelet transform is chosen for the proposed detector as it has high signal to noise ratio (SNR) and uses only four coefficients for decomposition. In the proposed approach, a Biorthogonal wavelet filter bank with fourth level decomposition is first used to separate the different frequency components and then a fourth level wavelet filter bank is used to get the denoised electrocardiogram (ECG) signals. Wavelet filter bank outputs are multiplied and soft threshold method is applied to get the QRS complex peaks by the QRS complex peak detector block. Add and shift multiplier used in the earlier designs has been replaced by a Booth multiplier in our approach to achieve the higher performance. Booth multiplier and QRS complex peak detector blocks have been designed for low hardware complexity, high performance and accurate detection of the QRS complex peaks. Time interval between the consecutive QRS peaks is calculated using the R-R peak time calculator block and the heart rate (HR) by the HR calculator block. Heart Rate Variability (HRV) and arrhythmia are detected based on these heart rate calculations. Proposed design has been tested for its robustness on multiple datasets (namely, MIT-BIH arrhythmia, MIT-BIH noise stress test, and MIT-BIH atrial fibrillation databases). Sensitivity of 99.31%, positive predictivity of 99.19% and the Detection Error Rate (DER) of 1.49% shown by the proposed design makes it preferable for QRS complex detectors used in wearable healthcare devices.
2,334,858
Growth performance, organ weights, and blood parameters of nursery pigs fed diets containing increasing levels of cold-pressed canola cake.
Oilseed cakes have high oil content, and thus their inclusion in swine can lead to reduced dietary inclusion of oil, and hence reduced cost of feed. An experiment was conducted to determine effects of including Brassica napus-derived cold-pressed canola cake (CPCC) in diets for nursery pigs on growth performance, organ weights relative to live body weight (BW), and blood parameters. A total of 160 pigs (initial BW: 7.8 &#xb1; 0.9 kg), which had been weaned at 21 d of age were housed in 40 pens (4 pigs/pen) and fed 4 diets (10 pens/diet) in a randomized complete block design for 35 d. The 4 diets were corn-soybean meal (SBM)-based basal diet and the basal diet with corn and SBM replaced by 20, 30, or 40% of CPCC. The diets were fed in 2 phases, Phase 1 from day 0 to 14 and Phase 2 from day 14 to 35; and were formulated to meet NRC (2012) nutrient recommendations for nursery pigs and to have the same net energy, standardized ileal digestible amino acid, and digestible P contents. Increasing inclusion of CPCC in diets was achieved by partial replacement of corn, SBM, limestone, and mono-calcium phosphate. Growth performance was determined by phase. On day 35, 1 pig from each pen was euthanized for determining organ weights and blood parameters. The CPCC contained 7.63% moisture, and on a dry matter basis, it (CPCC) contained 39.6% crude protein, 2.32% Lys, 0.74% Met, 1.63% Thr, 0.50% Trp, 16.0% ether extract, 20.7% neutral detergent fiber, and 14.9 &#xb5;mol/g of glucosinolates. Increasing dietary CPCC from 0 to 40% linearly reduced (P &lt; 0.05) overall (day 0 to 35) average daily gain and average daily feed intake (0.440 to 0.288 kg/d and 0.739 to 0.522 kg/d, respectively). Increasing dietary CPCC from 0 to 40% resulted in a linear increase (P &lt; 0.05) in liver weight by 0.1 g/kg of BW and in thyroid gland weight by 2.2 mg/kg of BW, but in a linear reduction (P &lt; 0.05) in serum tetraiodothyronine (T4) level by 0.2 ng/mL for each 1% increase in CPCC at 35 d of age. No differences were observed in heart and kidney weights relative to live BW, and in serum triiodothyronine (T3) concentration. In conclusion, increasing dietary CPCC from 0 to 40% by reducing corn and SBM levels resulted in depressed growth performance, increased metabolic activity in liver and thyroid gland, and reduced serum T4 level of pigs. Thus, the amounts of CPCC included in nursery pig diets should be based on targeted growth performance and cost of other feedstuffs in relation to that of CPCC.
2,334,859
Use of an automaton model to suggest methods for cessation of intractable fibrillatory activity.
Atrial fibrillation (AF) is the most common heart arrhythmia, and permanent AF is an intractable medical problem. If cessation of permanent AF were possible, via extensive substrate ablation or multisite stimulation, it could significantly improve the public health.</AbstractText>A cellular automaton composed of 576&#x202f;&#xd7;&#x202f;576 computerized grid nodes, described in detail previously, was used to test hypotheses concerning the cessation of fibrillatory electrical activity. A refractory period gradient across the grid, and addition of randomly located nonconducting fibers, were utilized as conditions leading to fibrillatory activity. A premature S1-S2 stimulus was applied to one grid corner, resulting in unidirectional conduction block at some locations, followed by rotational activity and random propagation of activation wavelets throughout the grid, none of which terminated spontaneously. Simulated ablation lesions of dimension 20&#x202f;&#xd7;&#x202f;20 grid nodes, imparted at core locations of rotational activity, and multisite electrode stimulation (MES) applied at nodes where recovery of excitability had occurred, were used in attempts to terminate fibrillatory activity. Six impositions of random fiber location were utilized in separate trials.</AbstractText>Simulated ablation lesions eliminated the targeted swirling vortices; however, additional vortices then often appeared at other locations. After ablating approximately one third of the grid area, localized vortices were eliminated, but individual wavelets continued to propagate about longer viable pathways forming at ablation lesions. Thus extensive ablation was unsuccessful in terminating arrhythmia. However, MES applied uniformly throughout the grid, with a coupling interval slightly longer than the maximum refractory period, terminated fibrillatory activity in some trials. More efficaciously, application of MES with a coupling interval half the maximum refractory period of the grid succeeded in capture of activation at all nodes, and when followed by a doubling of the MES coupling interval, resulted in cessation of all fibrillatory activity.</AbstractText>It is possible to terminate simulated fibrillatory activity in a computerized grid that would otherwise be intractable, using multisite stimulation with a coupling interval related to the maximum refractory period of the substrate. If each MES stimulating electrode could be individually controlled, it would be possible to apply a stimulation pattern mimicking the normal heart activation sequence.</AbstractText>Copyright &#xa9; 2018. Published by Elsevier Ltd.</CopyrightInformation>
2,334,860
FNAC Versus CNB: Who Wins the Match in Breast Lesions?
The triple test lies at the heart of preoperative diagnosis of breast lesions. Raised awareness and self-assessment have significantly increased the rate of detection of breast pathologies. The managing clinicians usually decide the imaging and pathological modalities to the best interest of the patients. Core needle biopsy (CNB), cell-block studies, and fine needle aspiration cytology (FNAC) coupled with rapid on-site evaluation (ROSE) have significantly increased the accuracy of preoperative diagnosis. Immunocytochemistry, immunohistochemistry on cell blocks, and other ancillary studies give confidence to the clinicians to decide the best treatment strategies.
2,334,861
High-mobility group box 1 protein-mediated necroptosis contributes to dasatinib-induced cardiotoxicity.
Dasatinib shows remarkable activity against imatinib-refractory chronic myelogenous leukemia (CML) and Philadelphia chromosome positive acute lymphoblastic leukemia (Ph<sup>+</sup>ALL). However, severe cardiovascular toxicity limits the clinical applications of dasatinib. Since the underlying mechanism of dasatinib-induced cardiotoxicity is still elusive, we aim to clarify this. Recent studies have shown that necroptosis and apoptosis participate in multiple toxicity development. Here, we first report that dasatinib could directly induce cardiomyocytes death, as analyzed by the Sulforhodamine B (SRB) assay. This type of cardiomyocytes death was mediated by the necrosis pathway rather than apoptosis, as determined by using flow cytometry to characterize the mode of dasatinib-induced cell death. Inhibition of receptor-interacting protein kinase 1 (RIP1)activity and knockdown of receptor-interacting protein kinase 3 (RIP3)expression can block dasatinib-evoked cardiotoxicity, which further confirmed the involvement of necroptosis. We next found that the classic substrates of RIP3, mixed lineage kinase domain-like protein (MLKL) and Ca<sup>2+</sup>-calmodulin-dependent protein kinase II (CaMKII) were not involved in dasatinib-induced cardiomyocytes necroptosis. What's more, unlike the inflammation-associated necroptosis, dasatinib-triggered necroptosis was dependent on intracellular instead of secreted High-mobility group box 1 (HMGB1) protein. Collectively, our study revealed that dasatinib-induced cardiotoxicity acted via leading cardiomyocytes to HMGB1-mediated necroptosis, indicating a viable strategy for prevention of dasatinib-induced cardiotoxicity.
2,334,862
Circadian-based Treatment Strategy Effective in the BACHD Mouse Model of Huntington's Disease.
Huntington's disease (HD) patients suffer from progressive neurodegeneration that results in cognitive, psychiatric, cardiovascular, and motor dysfunction. Disturbances in sleep-wake cycles are common among HD patients with reports of delayed sleep onset, frequent bedtime awakenings, and excessive fatigue. The BACHD mouse model exhibits many HD core symptoms including circadian dysfunction. Because circadian dysfunction manifests early in the disease in both patients and mouse models, we sought to determine if early interventions that improve circadian rhythmicity could benefit HD symptoms and delay disease progression. We evaluated the effects of time-restricted feeding (TRF) on the BACHD mouse model. At 3 months of age, the animals were divided into 2 groups: ad lib and TRF. The TRF-treated BACHD mice were exposed to a 6-h feeding/18-h fasting regimen that was designed to be aligned with the middle (ZT 15-21) of the period when mice are normally active (ZT 12-24). Following 3 months of treatment (when mice reached the early disease stage), the TRF-treated BACHD mice showed improvements in their locomotor activity and sleep behavioral rhythms. Furthermore, we found improved heart rate variability, suggesting that their autonomic nervous system dysfunction was improved. On a molecular level, TRF altered the phase but not the amplitude of the PER2::LUC rhythms measured in vivo and in vitro. Importantly, treated BACHD mice exhibited improved motor performance compared with untreated BACHD controls, and the motor improvements were correlated with improved circadian output. It is worth emphasizing that HD is a genetically caused disease with no known cure. Lifestyle changes that not only improve the quality of life but also delay disease progression for HD patients are greatly needed. Our study demonstrates the therapeutic potential of circadian-based treatment strategies in a preclinical model of HD.
2,334,863
Fatality Following Intentional Ingestion of <i>Cerbera odollam</i> Seeds.
Seeds from the mangrove plant <i>Cerbera (C.) odollam</i>, known as the "suicide tree," are responsible for a significant number of plant deaths worldwide but are not well recognized in Western medicine. Cerberin is a cardiac glycoside concentrated in the plant's seeds, which causes disrupted cardiac electrical activity leading to fatal dysrhythmias. We present a fatal case of intentional <i>C. odollam</i> seed ingestion. The patient experienced high-degree heart block and cardiac arrest despite supportive treatment and digoxin immune fab administration. Clinicians should be aware of the potential morbidity and mortality associated with <i>C. odollam</i> poisoning and be prepared for resuscitative interventions.
2,334,864
Assessing the Effectiveness of Curative Benznidazole Treatment in Preventing Chronic Cardiac Pathology in Experimental Models of Chagas Disease.
Chagasic heart disease develops in 30% of those infected with the protozoan parasite <i>Trypanosoma cruzi</i>, but can take decades to become symptomatic. Because of this, it has been difficult to assess the extent to which antiparasitic therapy can prevent the development of pathology. We sought to address this question using experimental murine models, exploiting highly sensitive bioluminescent imaging to monitor curative efficacy. Mice were inoculated with bioluminescent parasites and then cured in either the acute or chronic stage of infection with benznidazole. At the experimental endpoint (5 to 6 months postinfection), heart tissue was removed and assessed for inflammation and fibrosis, two widely used markers of cardiac pathology. Infection of BALB/c and C3H/HeN mice with distinct <i>T. cruzi</i> lineages resulted in greatly increased myocardial collagen content at a group level, indicative of fibrotic pathology. When mice were cured by benznidazole in the acute stage, the development of pathology was completely blocked. However, if treatment was delayed until the chronic stage, cardiac fibrosis was observed in the BALB/c model, although the protective effect was maintained in the case of C3H/HeN mice. These experiments therefore demonstrate that curative benznidazole treatment early in murine <i>T. cruzi</i> infections can prevent the development of cardiac fibrosis. They also show that treatment during the chronic stage can block pathology but the effectiveness varies between infection models. If these findings are extendable to humans, it implies that widespread chemotherapeutic intervention targeted at early-stage infections could play a crucial role in reducing Chagas disease morbidity at a population level.
2,334,865
Cardiorespiratory effects of a 7&#xb0; reverse Trendelenburg position in anaesthetized horses: a randomized clinical trial.
To evaluate the cardiorespiratory effects of a 7&#xb0; reverse Trendelenburg position (RTP) in anaesthetized horses.</AbstractText>Randomized, non-blinded clinical trial.</AbstractText>A total of 125 horses undergoing elective surgery in dorsal recumbency.</AbstractText>Horses were allocated to one of three weight classes and assigned to be positioned either on a horizontal table or on a table in 7&#xb0; RTP, according to a randomized block design. In all horses, anaesthesia was maintained with isoflurane in oxygen and a constant rate infusion of romifidine. All horses were mechanically ventilated throughout anaesthesia, and routine cardiovascular monitoring and arterial blood gas analysis were performed at 15-minute intervals and relevant variables calculated. Data from the first 60 minutes of anaesthesia were compared between both positions using a mixed model analysis of variance.</AbstractText>A significant interaction was found between position and weight class for the alveolar to arterial oxygen tension gradient and F-shunt: these variables were lower in RTP than in horizontal position in the two lowest weight classes and vice versa in the highest weight class. Arterial oxygen tension and oxygenation indices were significantly worse in the horses in the higher weight classes.</AbstractText>A 7&#xb0; RTP did not result in clinically relevant changes in gas exchange or cardiovascular function. Horses with a higher body weight are at increased risk for hypoxaemia during anaesthesia in dorsal recumbency.</AbstractText>Copyright &#xa9; 2018 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.</CopyrightInformation>
2,334,866
Contribution of the neighborhood environment to cross-sectional variation in long-term CVD risk scores in the Framingham Heart Study.
Few studies of the health impact of the built environment have examined downstream outcomes, such as cardiovascular disease. We analyzed the neighborhood-level proportional variance in the 10- and 30-year Framingham risk scores (FRS) in the Framingham Heart Study. Our analysis included 3,103 Offspring- and Generation 3 cohort participants 20-74 years old, inhabiting private residences in Massachusetts geocoded to neighborhoods (defined as 2000 US Census block groups) containing the residences of &#x2265;5 participants. The outcome variables were log-transformed to mitigate the effects of the non-normal distributions. In order to remove the possible effects of neighborhood clustering by age and sex, we analyzed residuals of the transformed FRS regressed upon age and sex. Neighborhood-level intraclass correlations (ICCs) and 95% confidence intervals (CIs) of age- and sex-independent, log-transformed FRS were estimated using multilevel linear regression. Individual- and neighborhood-level variables were then added to models to evaluate their influence on ICCs. Analyses were repeated stratified by sex. Among 2,888 participants living in 187 neighborhoods, 1.73% (95% CI: 0.62, 4.72%) of the variance in 10-year FRS was explained at the neighborhood level. The neighborhood ICC was 2.70% (95% CI: 0.93, 7.56) among women but 0.23% (95% CI: 0.00, 99.47%) among men. In the analysis of the neighborhood-level variances in 30-year FRS among 2,317 participants residing in 164 neighborhoods, the ICCs were 3.31% (95% CI: 1.66, 6.47%), 6.47% (95% CI: 3.22, 12.58), and 0.74% (95% CI: 0.01, 33.31), among all participants, women, and men, respectively. In our homogenous middle-class white population in Massachusetts, residential neighborhoods explained a small proportion of the variance in CVD risk.
2,334,867
Pharmacological Signatures of the Exenatide Nanoparticles Complex Against Myocardial Ischemia Reperfusion Injury.
<AbstractText Label="BACKGROUND/AIMS" NlmCategory="OBJECTIVE">Myocardial ischemia/reperfusion (I/R) injury (MI/RI) is a critical cause of death in patients with heart disease. However, the pharmaco-therapeutical outcome for MI/RI remains unsatisfactory. Innovative approaches for enhancing drug sensitivity and recovering myocardial function in MI/RI treatment are urgently needed. The purpose of this study was to evaluate the protective effects of exenatide-loaded poly(L-lysine)-poly(ethylene glycol)-poly(L-lysine) (PLL-PEG-PLL) nanoparticles (NPs) against MI/RI.</AbstractText>The size of PLL-PEG-PLL NPs and the loading and release rates of exenatide were determined. The in vitro NP cytotoxicity was evaluated using newborn rat cardiomyocytes. Rats pretreated with free exenatide or exenatide/PLL-PEG-PLL polyplexes were subjected to 0.5-h ischemia and 2-h reperfusion in the left anterior descending coronary artery. The histopathologic lesions were assessed using hematoxylin-eosin staining. The general physiological indices, including blood pressure (BP), heart rate (HR), the left ventricular ejection fraction (LVEF) and end-diastolic pressure (LEVDP), and the left ventricular pressure maximal rate of rising (dp/dtmax), were monitored using a non-invasive blood pressure analyzer and color Doppler echocardiography. The antioxidative activity in the myocardial tissue was measured. The myocardial enzymatic activity was further estimated by determining the serum levels of creatine kinase (CK), lactate dehydrogenase (LDH), cardiac troponin T (cTnT), and glucagon-like peptide-1 (GLP-1), as well as the expression of GLP-1R in the myocardial tissue.</AbstractText>Exenatide preconditioning attenuated the oxidative stress injury and promoted the myocardial function in I/R-induced myocardial injury, while the application of block copolymer PLL-PEG-PLL as a potential exenatide nanocarrier with sustained release significantly enhanced the bioavailability of exenatide.</AbstractText>The block copolymer PLL-PEG-PLL may function as a potent exenatide nanocarrier for augmenting pharmacotherapy against MI/RI with unprecedented clinical benefits. Further study is needed to better clarify the underlying mechanisms.</AbstractText>&#xa9; 2018 The Author(s). Published by S. Karger AG, Basel.</CopyrightInformation>
2,334,868
Factors affecting pain during outpatient clinic based surgical procedures in gynecologic oncology.
Colposcopy-directed punch biopsy (punch biopsy) and endocervical curettage (ECC) are accompanied by considerable pain. However, many physicians perform these procedures without adequate pain management. Therefore, identification of factors affecting pain experienced during the procedures may encourage physician effort in selective pain management. This study investigated factors affecting the severity of pain experienced during punch biopsy and ECC in an outpatient clinic of gynecologic oncology department.In this retrospective, exploratory study, a total of 101 Korean patients with abnormal cervical cytology underwent punch biopsy and ECC under a paracervical block performed for pain relief. Residents under training performed these procedures and recorded patient-reporting maximum Numeric Rating Scale (NRS) scores experienced during the procedures. Residents were classified into four outpatient clinic training groups (1st-4th); the group designators correspond to the resident's experience in performing these procedures. A linear mixed model adjusted for physician factors such as either residents or outpatient clinic training groups was used to analyze the association between each variable and maximum NRS score.Among the outpatient clinic training groups, maximum NRS scores significantly decreased in the 4th group, compared with those in the 1st group although those were not different among groups when adjusted for residents. Some of cervical cytology findings and discrepancies between the severity of cervical cytology results and those of punch biopsy or ECC showed significant associations with maximum NRS scores. However, when adjusted for either residents or outpatient clinic training groups, maximum NRS scores were not different by age, body mass index, presence of menopause, cervical cytology findings, discrepancies between the severity of cervical cytology results and those of punch biopsy or ECC, and tissue volume.There are no significant factors affecting the severity of pain experienced during punch biopsy and ECC.
2,334,869
Blinded and unblinded sample size reestimation in crossover trials balanced for period.
The determination of the sample size required by a crossover trial typically depends on the specification of one or more variance components. Uncertainty about the value of these parameters at the design stage means that there is often a risk a trial may be under- or overpowered. For many study designs, this problem has been addressed by considering adaptive design methodology that allows for the re-estimation of the required sample size during a trial. Here, we propose and compare several approaches for this in multitreatment crossover trials. Specifically, regulators favor reestimation procedures to maintain the blinding of the treatment allocations. We therefore develop blinded estimators for the within and between person variances, following simple or block randomization. We demonstrate that, provided an equal number of patients are allocated to sequences that are balanced for period, the proposed estimators following block randomization are unbiased. We further provide a formula for the bias of the estimators following simple randomization. The performance of these procedures, along with that of an unblinded approach, is then examined utilizing three motivating examples, including one based on a recently completed four-treatment four-period crossover trial. Simulation results show that the performance of the proposed blinded procedures is in many cases similar to that of the unblinded approach, and thus they are an attractive alternative.
2,334,870
Twin Brothers with Carnitine Membrane Transporter Deficiency: A Case Study.
Carnitine membrane transporter deficiency or primary carnitine deficiency (PCD) is an autosomal recessive disorder of fatty acid oxidation, in which the transport of carnitine into cells is impaired. Carnitine plays an important role in transporting fatty acids into the mitochondria and carnitine deficiency block oxidation of long-chain fatty acids in the mitochondria that leads to heart and hepatic disease, myopathy, nonketotic hypoglycemia, and neurological complications. PCD has a wide range of symptoms and can reveal itself as symptomatic cardiomyopathy or even asymptomatic. In this study, we reported twin brothers with PCD. One of them had symptoms of disease and cardiomyopathy and was under treatment with carnitine. Another twin was asymptomatic and was diagnosed during follow-up period of his brother.
2,334,871
Initial Changes in the Heart Conduction System Illustrated by Difference Map Patterns in Adolescent Patients After Kidney Transplantation: A Pilot Study.
Cardiovascular complications (CVCs) in patients with end-stage renal disease (ESRD) often require hospitalization and are associated with an increased risk of fatality. Although kidney transplantation (KTx) improves a patient's status, CVCs are still a serious risk factor, so early identification is very important for final therapeutic outcome.</AbstractText>This study included 5 post-KTx patients (age, 20.8 &#xb1; 1.16 years), dialyzed before KTx, and followed up for 6.7 &#xb1; 1.71 years. Body surface potential mapping (BSPM) was performed 4 times: twice before and twice after KTx. Electrocardiographic data were processed into map plotting to illustrate differences in ventricular activation times (VATs).</AbstractText>A comparative analysis of difference maps, both of dialyzed patients and normal subjects, highlighted certain specificities in the distribution of VAT changes for the left anterior fascicle block (LAFB). The maps clearly showed a significant correlation between the intensity of changes and duration of dialysis before KTx. After KTx, VATs seemed to be similar to those in normal subjects; however, this was true only for patients dialyzed for&#xa0;&lt;1 year. The patients dialyzed for &gt;1 year showed persistent conduction abnormalities on their VAT maps.</AbstractText>Summary differences in VAT maps can enable diagnostics of initial activation propagation abnormalities in the heart. Short-term dialysis therapy before KTx imposes positive effects with regression of heart conduction changes. These observations need to be verified in a larger study population.</AbstractText>Copyright &#xa9; 2018. Published by Elsevier Inc.</CopyrightInformation>
2,334,872
An incretin-based tri-agonist promotes superior insulin secretion from murine pancreatic islets via PLC activation.
Recently, a unimolecular tri-agonist with activity at glucagon-like peptide 1 receptor (GLP-1R), glucose dependent insulinotropic receptor, and the glucagon receptor was reported to improve glycemic control in mice. Here, we defined the underlying molecular mechanisms of enhanced insulin secretion in murine pancreatic islets for a specific tri-agonist. The tri-agonist induced an increase in insulin secretion from murine islets compared to the respective mono-agonists. GLP-1R mainly signals via activation of the G&#x3b1;<sub>s</sub> pathway, but inhibition of protein kinase A (H89) and exchange protein activation by cAMP (EPAC) (ESI-09) could not completely block insulin release induced by tri-agonist. Electrophysiological observations identified a strong increase of intracellular Ca<sup>2+</sup> concentration and whole-cell currents induced by tri-agonist via transient receptor potential channels (TRPs). Although, EPAC activation mobilizes intracellular Ca<sup>2+</sup> via TRPs, the TRPs blockers (La<sup>3+</sup> and Ruthenium Red) had a larger inhibitory impact than ESI-09 on tri-agonist stimulatory effects. To test for other potential mechanisms, we blocked PLC activity (U73122) which reduced the superior effect of tri-agonist to induce insulin secretion, and partially inhibited the induced Ca<sup>2+</sup> influx. This result suggests that the relative effect of tri-agonist on insulin secretion caused by GLP-1R agonism is mediated mainly via G&#x3b1;<sub>s</sub> signaling and partially by activation of PLC. Therefore, the large portion of the increased intracellular Ca<sup>2+</sup> concentration and the enhanced whole-cell currents induced by tri-agonist might be attributable to TRP channel activation resulting from signaling through multiple G-proteins. Here, we suggest that broadened intracellular signaling may account for the superior in vivo effects observed with tri-agonism.
2,334,873
PACAP-Induced PAC1 Receptor Internalization and Recruitment of Endosomal Signaling Regulate Cardiac Neuron Excitability.
Pituitary adenylate cyclase-activating polypeptide (PACAP, Adcyap1) activation of PAC1 receptors (Adcyap1r1) significantly increases excitability of guinea pig cardiac neurons. This modulation of excitability is mediated in part by plasma membrane G protein-dependent activation of adenylyl cyclase and downstream signaling cascades, as well as by endosomal signaling mechanisms. PACAP/PAC1 receptor-mediated activation of plasma membrane adenylyl cyclase (AC) and the resulting increase in cellular cAMP enhances a hyperpolarization-induced nonselective cationic current I<sub>h</sub>, which contributes to the PACAP-induced increase in cardiac neuron excitability. Further, PACAP-mediated AC/cAMP/PKA downstream signaling also appears to enhance cardiac neuron I<sub>T</sub> to facilitate the excitatory responses. PACAP activation of PAC1 receptors rapidly stimulates receptor internalization, and reducing ambient temperature or treatments with the clathrin inhibitor Pitstop2 or the dynamin I/II inhibitor dynasore to block endocytic events can suppress PACAP-enhanced neuronal excitability. Thus, endocytosis inhibitors essentially eliminate PACAP-enhanced excitability suggesting that endosomal platforms represent a primary signaling mechanism. Endosomal signaling is associated canonically with ERK activation and in accord, PACAP-enhanced cardiac neuron excitability is reduced by MEK inhibitor pretreatments. PACAP activation of MEK/ERK signaling can enhance currents through voltage-dependent Nav1.7 channels. Hence, PACAP-induced PAC1 receptor internalization/endosomal signaling, recruitment of MEK/ERK signaling, and modulation of Nav1.7 are implicated as key mechanisms contributing to the PACAP-enhanced neuronal excitability. PACAP/PAC1 receptor-mediated endosomal ERK signaling in central circuits can play key roles in development of chronic pain and anxiety-related responses; thus, PAC1 endosomal signaling likely participates in a variety of homeostatic responses within neuronal circuits in the CNS.
2,334,874
Identification of an I<sub>Na</sub>-dependent and I<sub>to</sub>-mediated proarrhythmic mechanism in cardiomyocytes derived from pluripotent stem cells of a Brugada syndrome patient.
Brugada syndrome (BrS) is an inherited cardiac arrhythmia commonly associated with SCN5A mutations, yet its ionic mechanisms remain unclear due to a lack of cellular models. Here, we used human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from a BrS patient (BrS1) to evaluate the roles of Na<sup>+</sup> currents (I<sub>Na</sub>) and transient outward K<sup>+</sup> currents (I<sub>to</sub>)&#xa0;in BrS induced action potential (AP) changes. To understand the role of these current changes in repolarization we employed dynamic clamp to "electronically express" I<sub>K1</sub> and restore normal resting membrane potentials and allow normal recovery of the inactivating currents, I<sub>Na</sub>, I<sub>Ca</sub> and I<sub>to</sub>. HiPSC-CMs were generated from BrS1 with a compound SCN5A mutation (p. A226V &amp; p. R1629X) and a healthy sibling control (CON1). Genome edited hiPSC-CMs (BrS2) with a milder p. T1620M mutation and a commercial control (CON2) were also studied. CON1, CON2 and BrS2, had unaltered peak I<sub>Na</sub> amplitudes, and normal APs whereas BrS1, with over 75% loss of I<sub>Na</sub>, displayed a loss-of-I<sub>Na</sub> basal AP morphology (at 1.0&#x2009;Hz) manifested by a reduced maximum upstroke velocity (by ~80%, p&#x2009;&lt;&#x2009;0.001) and AP amplitude (p&#x2009;&lt;&#x2009;0.001), and an increased phase-1 repolarization pro-arrhythmic AP morphology (at 0.1&#x2009;Hz) in ~25% of cells characterized by marked APD shortening (~65% shortening, p&#x2009;&lt;&#x2009;0.001). Moreover, I<sub>to</sub> densities of BrS1 and CON1 were comparable and increased from 1.0&#x2009;Hz to 0.1&#x2009;Hz by ~ 100%. These data indicate that a repolarization deficit could be a mechanism underlying BrS.
2,334,875
Clopidogrel Pharmacokinetics in Malaysian Population Groups: The Impact of Inter-Ethnic Variability.
Malaysia is a multi-ethnic society whereby the impact of pharmacogenetic differences between ethnic groups may contribute significantly to variability in clinical therapy. One of the leading causes of mortality in Malaysia is cardiovascular disease (CVD), which accounts for up to 26% of all hospital deaths annually. Clopidogrel is used as an adjunct treatment in the secondary prevention of cardiovascular events. CYP2C19 plays an integral part in the metabolism of clopidogrel to the active metabolite clopi-H4. However, CYP2C19 genetic polymorphism, prominent in Malaysians, could influence target clopi-H4 plasma concentrations for clinical efficacy. This study addresses how inter-ethnicity variability within the Malaysian population impacts the attainment of clopi-H4 target plasma concentration under different CYP2C19 polymorphisms through pharmacokinetic (PK) modelling. We illustrated a statistically significant difference (<i>P</i> &lt; 0.001) in the clopi-H4 C<sub>max</sub> between the extensive metabolisers (EM) and poor metabolisers (PM) phenotypes with either Malay or Malaysian Chinese population groups. Furthermore, the number of PM individuals with peak clopi-H4 concentrations below the minimum therapeutic level was partially recovered using a high-dose strategy (600 mg loading dose followed by a 150 mg maintenance dose), which resulted in an approximate 50% increase in subjects attaining the minimum clopi-H4 plasma concentration for a therapeutic effect.
2,334,876
Development of an Orthogonal Tie2 Ligand Resistant to Inhibition by Ang2.
Angiopoietin-1 (Ang1) is a vascular protective ligand that acts through the receptor tyrosine kinase Tie2 to enhance endothelial survival and quiescence. In sepsis, diabetic retinopathy, and a range of other diseases, Ang2, an antagonist of Tie2, increases markedly. This antagonist suppresses Ang1 protective effects leading to vascular destabilization, inflammation, and endothelial death. Administration of recombinant Ang1 can counter Ang2 antagonism and restore vascular function. However, recombinant Ang1 is needed at sufficiently high concentrations to block Ang2, and the protein is difficult to produce, requires mammalian expression systems, and is prone to aggregation. Here we present an engineered synthetic Tie2 ligand that is not antagonized by Ang2 but is easy to produce and more robust than Ang1. Using a peptide phage display, we isolated a heptameric sequence that binds Tie2-ectodomain and fused this to the coiled:coil domain of cartilage oligomeric matrix protein. This pentameric protein is 60 kDa in size, expressed in E. coli, and facile to purify. The protein, designated TSL1, binds to Tie2-ectodomain in vitro and on the cell surface. TSL1 inhibits endothelial apoptosis. Crucially, TSL1 binds at a site on Tie2 distinct from the angiopoietin-binding site and is resistant to antagonism by Ang2. This engineered ligand has several advantages over recombinant Ang1 for potential therapeutic applications. The study also highlights the value of orthogonal ligands for regulating cellular receptors without being subject to antagonism or modulation by endogenous ligands.
2,334,877
A Case of Complete Heart Block With Diagnostic Challenge and Therapeutic Dilemma.
Permanent pacemaker implantation is a class I indication for all symptomatic patients with complete heart block either congenital or acquired. However, certain portions of patients with congenital complete heart block are asymptomatic. Those patients are often very young, and implanting a permanent pacemaker is not always an easy decision. A therapeutic dilemma arises when a select patient population does not meet certain criteria to gain the maximum benefits out of prophylactic pacemaker therapy. Most asymptomatic patients with congenital complete heart block will eventually become symptomatic and require pacemakers at some point in their life but the definitive answer for the ideal time to initiate pacemaker therapy in such population has not been established. We present a case of asymptomatic congenital complete heart block with junctional escape rhythm, which is capable of incrementing the heart rate with physical activity to result in a challenge in diagnosis as well as the treatment strategy.
2,334,878
Automated detection of atrial fibrillation using long short-term memory network with RR interval signals.
Atrial Fibrillation (AF), either permanent or intermittent (paroxysnal AF), increases the risk of cardioembolic stroke. Accurate diagnosis of AF is obligatory for initiation of effective treatment to prevent stroke. Long term cardiac monitoring improves the likelihood of diagnosing paroxysmal AF. We used a deep learning system to detect AF beats in Heart Rate (HR) signals. The data was partitioned with a sliding window of 100 beats. The resulting signal blocks were directly fed into a deep Recurrent Neural Network (RNN) with Long Short-Term Memory (LSTM). The system was validated and tested with data from the MIT-BIH Atrial Fibrillation Database. It achieved 98.51% accuracy with 10-fold cross-validation (20 subjects) and 99.77% with blindfold validation (3 subjects). The proposed system structure is straight forward, because there is no need for information reduction through feature extraction. All the complexity resides in the deep learning system, which gets the entire information from a signal block. This setup leads to the robust performance for unknown data, as measured with the blind fold validation. The proposed Computer-Aided Diagnosis (CAD) system can be used for long-term monitoring of the human heart. To the best of our knowledge, the proposed system is the first to incorporate deep learning for AF beat detection.
2,334,879
Inhibition of Btk by Btk-specific concentrations of ibrutinib and acalabrutinib delays but does not block platelet aggregation mediated by glycoprotein VI.
Ibrutinib and acalabrutinib are irreversible inhibitors of Bruton tyrosine kinase used in the treatment of B-cell malignancies. They bind irreversibly to cysteine 481 of Bruton tyrosine kinase, blocking autophosphorylation on tyrosine 223 and phosphorylation of downstream substrates including phospholipase C-&#x3b3;2. In the present study, we demonstrate that concentrations of ibrutinib and acalabrutinib that block Bruton tyrosine kinase activity, as shown by loss of phosphorylation at tyrosine 223 and phospholipase C-&#x3b3;2, delay but do not block aggregation in response to a maximally-effective concentration of collagen-related peptide or collagen. In contrast, 10- to 20-fold higher concentrations of ibrutinib or acalabrutinib block platelet aggregation in response to glycoprotein VI agonists. <i>Ex vivo</i> studies on patients treated with ibrutinib, but not acalabrutinib, showed a reduction of platelet aggregation in response to collagen-related peptide indicating that the clinical dose of ibrutinib but not acalabrutinib is supramaximal for Bruton tyrosine kinase blockade. Unexpectedly, low concentrations of ibrutinib inhibited aggregation in response to collagen-related peptide in patients deficient in Bruton tyrosine kinase. The increased bleeding seen with ibrutinib over acalabrutinib is due to off-target actions of ibrutinib that occur because of unfavorable pharmacodynamics.
2,334,880
AMPK blunts chronic heart failure by inhibiting autophagy.
AMP-activated protein kinase (AMPK), a serine/threonine protein kinase, has been shown to exert a protective effect against cardiac hypertrophy and heart failure. Our previous reports have demonstrated that AMPK can inhibit cardiac hypertrophy and block the development of heart failure by promoting autophagy. However, other investigators have demonstrated that overactive and dysregulated autophagy may also contribute to the onset and exacerbation of heart failure. Thus, a major goal of the present investigation is to explore how AMPK regulates autophagy in heart failure. First, heart failure was induced in mice by 4 weeks of pressure overload; AMPK activation was subsequently induced by injecting 5-aminoimidazole-4-carboxamide 1-&#x3b2;-d-ribonucleotide (AICAR) after the establishment of chronic heart failure. We showed that AMPK activation significantly attenuated the progression of heart failure and improved cardiac function, which was accompanied by decreased autophagy levels in the failing hearts. Additionally, we demonstrated that the treatment with AICAR inhibited phosphorylation of the mammalian target of rapamycin (mTOR) complex 1 (mTORC1) downstream effectors 4E-binding protein1 (4EBP1), and ribosomal protein S6 kinase (p70S6K). A major action of AICAR was significantly to activate AKT (Ser<sup>473</sup>), the downstream substrate of mTOR complex 2 (mTORC2). In conclusion, the data suggest that AMPK improved cardiac function during the development of chronic heart failure by attenuating autophagy, potentially via mTORC2 activation and the downstream effects.
2,334,881
Aberrant Deactivation-Induced Gain of Function in TRPM4 Mutant Is Associated with Human Cardiac Conduction Block.
A gain-of-function mutation in the Ca<sup>2+</sup>-activated transient receptor potential melastatin member 4 (TRPM4<sup>A432T</sup>) is linked to life-threatening cardiac conduction disturbance, but the underlying mechanism is unclear. For deeper insights, we used photolysis of caged Ca<sup>2+</sup>, quantitative Ca<sup>2+</sup>, and electrophysiological measurements. TRPM4<sup>A432T</sup>'s 2-fold larger membrane current was associated with 50% decreased plasma membrane expression. Kinetic analysis unveiled 4-fold slower deactivation that was responsible for the augmented membrane current progressively rising during repetitive human cardiac action potentials. Rational mutagenesis of TRPM4 at position 432 revealed that the bulkiness of the amino acid was key to TRPM4<sup>A432T</sup>'s aberrant gating. Charged amino acids rendered the channel non-functional. The slow deactivation caused by an amino acid substitution at position 432 from alanine to the bulkier threonine represents a key contributor to the gain of function in TRPM4<sup>A432T</sup>. Thus, our results add a mechanism in the etiology of TRP channel-linked human cardiac channelopathies.
2,334,882
Mechanistic implication of decreased plasma atrial natriuretic peptide level for transient rise in the atrial capture threshold early after ICD or CRT-D implantation.
Despite the use of steroid-eluting leads, a transient but not persistent rise in the atrial/ventricular capture threshold (TRACT/TRVCT) can occur early after pacemaker implantation in patients with sick sinus syndrome. This study aimed to assess the prevalence, predictors, and mechanisms of TRACT/TRVCT in patients with heart failure undergoing implantable cardioverter defibrillator (ICD) or cardiac resynchronization therapy (CRT) implantation.</AbstractText>One hundred twenty consecutive patients underwent ICD (N&#x2009;=&#x2009;70) or CRT (N&#x2009;=&#x2009;50) implantation. Capture threshold was measured at implantation, 7-day, 1-month, and 6-month post-implantation. TRACT/TRVCT was defined as a threshold rise at 7&#xa0;days by more than twice the height of the threshold at implantation, with full recovery during follow-up. Atrial and brain natriuretic peptide (ANP and BNP) levels were measured before implantation.</AbstractText>TRACT and TRVCT were observed in 13 (11%) and 10 (8%) patients, respectively. Patients with TRACT had lower ANP level (median 72 [42-105] vs. 99 [49-198] pg/mL, P&#x2009;=&#x2009;0.06), lower ANP/BNP ratio (0.29 [0.20-0.36] vs. 0.50 [0.33-0.70], P&#x2009;&lt;&#x2009;0.01), lower atrial sensing amplitude (2.0&#x2009;&#xb1;&#x2009;0.8 vs. 2.7&#x2009;&#xb1;&#x2009;1.3&#xa0;mV, P&#x2009;=&#x2009;0.02), and lower left ventricular ejection fraction (32&#x2009;&#xb1;&#x2009;12 vs. 40&#x2009;&#xb1;&#x2009;14%, P&#x2009;=&#x2009;0.04) than those without TRACT. TRACT recovered within 1&#xa0;month, whereas TRVCT recovered within 6&#xa0;months. In multivariable analysis, ANP/BNP ratio was the only independent predictor of TRACT (OR, 0.018; 95% CI, 0.001-0.734; P&#x2009;=&#x2009;0.034).</AbstractText>Atrial degenerative change characterized by lower ANP/BNP ratio was associated with the occurrence of TRACT in patients with heart failure. TRVCT could also occur, but it required a longer recovery time than TRACT.</AbstractText>
2,334,883
Inhibition of Angiopoietin-2 Production by Myofibrocytes Inhibits Neointimal Hyperplasia After Endoluminal Injury in Mice.
Fibrocytes are myeloid lineage cells implicated in wound healing, repair, and fibrosis. We previously showed that fibrocytes are mobilized into the circulation after vascular injury, including the immune-mediated injury that occurs after allogeneic transplantation. A common response to inflammatory vascular injury is intimal hyperplasia (IH), which, alongside vascular remodeling, results in progressive loss of blood flow, downstream ischemia, and end-organ fibrosis. This forms the pathological basis of transplant arteriosclerosis and other diseases including post-angioplasty re-stenosis. In investigating whether fibrocytes contribute to IH, we previously showed that subpopulations expressing smooth muscle actin and CD31 are recruited to the site of injury and accumulate in the neointima. Expression of tissue factor (TF) by these "CD31+ myofibrocytes" is needed for progressive neointimal expansion, such that TF inhibition limits the neointima to a single layer of cells by day 28 post-injury. The aim of this study was to determine pathophysiological mediators downstream of TF that contribute to myofibrocyte-orchestrated IH. We first show that myofibrocytes make up a significant component of the neointima 28&#x2009;days following injury. Using a previously defined adoptive transfer model, we then show that CD31+ myofibrocytes get recruited early to the site of injury; this model allows manipulations of the adoptively transferred cells to study how IH develops. Having confirmed that inhibition of TF on adoptively transferred cells prevents IH, we then show that TF, primarily through the generation of thrombin, induces secretion of angiopoietin-2 by myofibrocytes and this directly stimulates proliferation, inhibits apoptosis, and induces CXCL-12 production by neointimal cells, including non-fibrocytes, all of which promote progressive IH <i>in vivo</i>. Prior incubation to inhibit angiopoietin-2 secretion by or block TIE-2 signaling on adoptively transferred fibrocytes inhibits IH. These novel data indicate that angiopoietin-2 production by early recruited myofibrocytes critically influences the development of IH after vascular injury and suggest new therapeutic avenues for exploration.
2,334,884
Musculoskeletal health of Indigenous Australians.
Research on non-communicable diseases (NCD) in Indigenous Australians has mostly focused on diabetes mellitus and chronic kidney or cardiovascular disease. Osteoporosis, characterised by low bone mass and structural deterioration of bone tissue, and sarcopenia, the age-related loss of muscle mass and strength, often co-exist with these common NCDs-the combination of which will disproportionately increase bone fragility and fracture risk and negatively influence cortical and trabecular bone. Furthermore, the social gradient of NCDs, including osteoporosis and fracture, is well-documented, meaning that specific population groups are likely to be at greater risk of poorer health outcomes: Indigenous Australians are one such group.</AbstractText>This review summarises the findings reported in the literature regarding the muscle and bone health of Indigenous Australians.</AbstractText>There are limited data regarding the musculoskeletal health of Indigenous Australians; however, areal bone mineral density (aBMD) measured by dual-energy X-ray absorptiometry (DXA) is reported to be greater at the hip compared to non-Indigenous Australians. Falls are the leading cause of injury-related hospitalisations in older Australians, particularly Indigenous Australians, with a great proportion suffering from fall-related fractures. Despite sparse data, it appears that Indigenous men and women have a substantially higher risk of hip fracture at a much younger age compared to non-Indigenous Australians.</AbstractText>Data on more detailed musculoskeletal health outcomes are required in Indigenous Australians to better understand fracture risk and to formulate evidence-based strategies for fracture prevention and to minimise the risk of falls.</AbstractText>
2,334,885
Blocking CCL5-CXCL4 heteromerization preserves heart function after myocardial infarction by attenuating leukocyte recruitment and NETosis.
Myocardial infarction (MI) is a major cause of death in Western countries and finding new strategies for its prevention and treatment is thus of high priority. In a previous study, we have demonstrated a pathophysiologic relevance for the heterophilic interaction of CCL5 and CXCL4 in the progression of atherosclerosis. A specifically designed compound (MKEY) to block this CCL5-CXCR4 interaction is investigated as a potential therapeutic in a model of myocardial ischemia/reperfusion (I/R) damage. 8 week-old male C57BL/6 mice were intravenously treated with MKEY or scrambled control (sMKEY) from 1 day before, until up to 7 days after I/R. By using echocardiography and intraventricular pressure measurements, MKEY treatment resulted in a significant decrease in infarction size and preserved heart function as compared to sMKEY-treated animals. Moreover, MKEY treatment significantly reduced the inflammatory reaction following I/R, as revealed by specific staining for neutrophils and monocyte/macrophages. Interestingly, MKEY treatment led to a significant reduction of citrullinated histone 3 in the infarcted tissue, showing that MKEY can prevent neutrophil extracellular trap formation in vivo. Disrupting chemokine heterodimers during myocardial I/R might have clinical benefits, preserving the therapeutic benefit of blocking specific chemokines, and in addition, reducing the inflammatory side effects maintaining normal immune defence.
2,334,886
Obstruction of ventricular Ca<sup>2+</sup> -dependent arrhythmogenicity by inositol 1,4,5-trisphosphate-triggered sarcoplasmic reticulum Ca<sup>2+</sup> release.
Augmented inositol 1,4,5-trisphosphate (IP3</sub> ) receptor (IP3</sub> R2) expression has been linked to a variety of cardiac pathologies. Although cardiac IP3</sub> R2 function has been in the focus of research for some time, a detailed understanding of its potential role in ventricular myocyte excitation-contraction coupling under pathophysiological conditions remains elusive. The present study focuses on mechanisms of IP3</sub> R2-mediated sarcoplasmic reticulum (SR)-Ca2+</sup> release in ventricular excitation-contraction coupling under IP3</sub> R2-overexpressing conditions by studying intracellular Ca2+</sup> events. We report that, upon IP3</sub> R2 overexpression in ventricular myocytes, IP3</sub> -induced Ca2+</sup> release (IP3</sub> ICR) modulates the SR-Ca2+</sup> content via "eventless" SR-Ca2+</sup> release, affecting the global SR-Ca2+</sup> leak. Thus, IP3</sub> R2 activation could act as a SR-Ca2+</sup> gateway mechanism to escape ominous SR-Ca2+</sup> overload. Our approach unmasks a so far unrecognized mechanism by which "eventless" IP3</sub> ICR plays a protective role against ventricular Ca2+</sup> -dependent arrhythmogenicity.</AbstractText>Augmented inositol 1,4,5-trisphosphate (IP3</sub> ) receptor (IP3</sub> R2) function has been linked to a variety of cardiac pathologies including cardiac arrhythmias. The functional role of IP3</sub> -induced Ca2+</sup> release (IP3</sub> ICR) within ventricular excitation-contraction coupling (ECC) remains elusive. As part of pathophysiological cellular remodelling, IP3</sub> R2s are overexpressed and have been repeatedly linked to enhanced Ca2+</sup> -dependent arrhythmogenicity. In this study we test the hypothesis that an opposite scenario might be plausible in which IP3</sub> ICR is part of an ECC protecting mechanism, resulting in a Ca2+</sup> -dependent anti-arrhythmogenic response on the cellular scale. IP3</sub> R2 activation was triggered via endothelin-1 or IP3</sub> -salt application in single ventricular myocytes from a cardiac-specific IP3</sub> R type&#xa0;2 overexpressing mouse model. Upon IP3</sub> R2 overexpression, IP3</sub> R activation reduced Ca2+</sup> -wave occurrence (46 vs. 21.72%; P&#xa0;&lt;&#xa0;0.001) while its block increased SR-Ca2+</sup> content (&#x223c;29.4% 2-aminoethoxydiphenyl borate, &#x223c;16.4% xestospongin C; P&#xa0;&lt;&#xa0;0.001), suggesting an active role of IP3</sub> ICR in SR-Ca2+</sup> content regulation and anti-arrhythmogenic function. Pharmacological separation of ryanodine receptor RyR2 and IP3</sub> R2 functions and two-dimensional Ca2+</sup> event analysis failed to identify local IP3</sub> ICR events (Ca2+</sup> puffs). SR-Ca2+</sup> leak measurements revealed that under pathophysiological conditions, "eventless" SR-Ca2+</sup> efflux via enhanced IP3</sub> ICR maintains the SR-Ca2+</sup> content below Ca2+</sup> spark threshold, preventing aberrant SR-Ca2+</sup> release and resulting in a protective mechanism against SR-Ca2+</sup> overload and arrhythmias. Our results support a so far unrecognized modulatory mechanism in ventricular myocytes working in an anti-arrhythmogenic fashion.</AbstractText>&#xa9; 2018 The Authors. The Journal of Physiology &#xa9; 2018 The Physiological Society.</CopyrightInformation>
2,334,887
Gain without pain: Glucose promotes cognitive engagement and protects positive affect in older adults.
When faced with a cognitively demanding task, older adults tend to disengage and withdraw effort. At the same time, their usual processing preference for positive information disappears. Providing glucose as an energy resource is known to improve cognitive performance and reinstate older adults' positivity preference. Here, we examined whether glucose can help older adults to exert more effort under high difficulty conditions, and if so, whether such increase is accompanied by a change in positive affect. Fifty-three young and 58 older adults consumed a glucose or a placebo drink and completed a memory-search task at three levels of difficulty. Cognitive engagement was measured through changes in heart rate (HR) and self-reported effort. After each memory-search block, participants completed an implicit emotion-assessment task. In both age groups, glucose produced increased HR (indicating higher task engagement) relative to placebo. In older but not in young adults, glucose also improved cognitive performance and increased positive affect. Subjective effort, in contrast, did not differ between the older-glucose and older-placebo groups. These results suggest that in older adults, glucose improves cognitive performance by promoting higher cognitive engagement while mitigating the subjective costs of effortful exertion. (PsycINFO Database Record
2,334,888
Small doses of epinephrine prolong the recovery from a rocuronium-induced neuromuscular block: a case report.
During anaesthesia it is not uncommon to administer epinephrine in patients blocked by non-depolarizing muscle relaxants. However, there are few reports on possible interaction of epinephrine with neuromuscular transmission in humans.</AbstractText>An otherwise healthy 74-yr-old man underwent transurethral resection of a benign prostatic hyperplasia under total intravenous anaesthesia. Because of repeated drop in heart rate and blood pressure the patient received in total three bolus of epinephrine 5&#xa0;&#x3bc;g, respectively. Each time this small dose of epinephrine intensified a rocuronium-induced neuromuscular block verified by acceleromygraphy. Further anaesthetic course was uneventful.</AbstractText>In this case reported here small doses of intravenously administered epinephrine markedly prolonged a rocuronium-induced neuromuscular block. Given the widely used co-administration of epinephrine and muscle relaxants possible adrenergic interference with neuromuscular transmission would have implications for daily anaesthetic practice.</AbstractText>
2,334,889
Heartbeats Based Biometric Random Binary Sequences Generation to Secure Wireless Body Sensor Networks.
Heartbeats based random binary sequences (RBSs) are the backbone for several security aspects in wireless body sensor networks (WBSNs). However, current heartbeats based methods require a lot of processing time (&#x223c;25-30 s) to generate 128-bit RBSs in real-time healthcare applications. In order to improve time efficiency, a biometric RBSs generation technique using interpulse intervals (IPIs) of heartbeats is developed in this study. The proposed technique incorporates a finite monotonic increasing sequences generation mechanism of IPIs and a cyclic block encoding procedure that extracts a high number of entropic bits from each IPI. To validate the proposed technique, 89 ECG recordings including 25 healthy individuals in a laboratory environment, 20 from MIT-BIH Arrhythmia Database, and 44 cardiac patients from the clinical environment are considered. By applying the proposed technique on the ECG signals, at most 16 random bits can be extracted from each heartbeat to generate 128-bit RBSs via concatenation of eight consecutive IPIs. And the randomness and distinctiveness of generated 128-bit RBSs are measured based on the National Institute of Standards and Technology statistical tests and hamming distance, respectively. From the experimental results, the generated 128-bit RBSs from both healthy subjects and patients can potentially be used as keys for encryption or entity identifiers to secure WBSNs. Moreover, the proposed approach is examined to be up to four times faster than the existing heartbeat-based RBSs generation schemes. Therefore, the developed technique necessitates less processing time (0-8 s) in real-time health monitoring scenarios to construct 128-bit RBSs in comparisons with current methods.
2,334,890
Thyroid Storm and Complete Heart Block after Treatment with Radioactive Iodine.
Thyroid storm is a rare endocrine emergency characterized by dysfunction of multiple organ systems. Thyroid storm is more common in Graves' disease and can be precipitated by surgery, trauma, infection, metabolic abnormalities, iodine load, and parturition. We present a diagnostically challenging case of thyroid storm precipitated by radioiodine therapy and accompanied by bradycardia, a rare but life-threatening complication related to treatment for hyperthyroidism.
2,334,891
Optimising genetic transformation of Trypanosoma cruzi using hydroxyurea-induced cell-cycle synchronisation.
The limited flexibility and time-consuming nature of the genetic manipulation procedures applicable to Trypanosoma cruzi continue to restrict the functional dissection of this parasite. We hypothesised that transformation efficiency could be enhanced if electroporation was timed to coincide with DNA replication. To test this, we generated epimastigote cultures enriched at the G1/S boundary using hydroxyurea-induced cell-cycle synchronisation, and then electroporated parasites at various time points after release from the cell-cycle block. We found a significant increase in transformation efficiency, with both episomal and integrative constructs, when cultures were electroporated 1&#x202f;h after hydroxyurea removal. It was possible to generate genetically modified populations in less than 2 weeks, compared to the normal 4-6 weeks, with a 5 to 8-fold increase in the number of stably transformed clones. This straightforward optimisation step can be widely applied and should help streamline functional studies in T. cruzi.
2,334,892
Contact force and ablation assessment of surgical bipolar radiofrequency clamps in the treatment of atrial fibrillation.
Atrial fibrillation is treated surgically by creating conduction block lesions. Radiofrequency (RF) lesions have reduced efficacy compared to 'cut-and-sew'. Catheter ablation studies demonstrate a relationship between lesion depth and contact force. We hypothesized that contact force and lesion depth are dependent on design of the bipolar surgical RF clamps.</AbstractText>Hinged and parallel jaw style RF clamps were studied. Muscle samples were clamped with pressure-sensitive film at increasing tissue thicknesses. Films were analysed determining clamp pressure profiles. A sheep model was utilized for ablation testing using each clamp style until the device indicated transmurality. Separate muscle areas had 1, 2 or 3 burns applied. The muscle was excised, sectioned every 1&#x2009;cm and stained for lesion depth and fat thickness analysis.</AbstractText>Pressure profiling comparing the proximal and distal segments of each clamp style demonstrated only one statistically significant difference in the parallel clamp; the hinged clamp had statistically significant differences (P&#x2009;&#x2264;&#x2009;0.03) for all tissue thicknesses. There was no evidence for differences in the proximal lesion depth of both clamps (P&#x2009;=&#x2009;0.13) but deeper distally in the parallel clamp (10.17&#x2009;mm vs 8.02&#x2009;mm, P&#x2009;=&#x2009;0.003). The logistic regression analysis demonstrated increased odds of transmurality with parallel clamps at 1, 2 or 3 burns (P&#x2009;=&#x2009;0.03, P&#x2009;=&#x2009;0.003 and P&#x2009;=&#x2009;0.002). Every 1&#x2009;mm increase in overlying fat decreased likelihood of transmurality by 11% (P&#x2009;&lt;&#x2009;0.05).</AbstractText>The parallel and hinged clamps have different pressure profiles with higher likelihood of transmurality using the parallel clamp. Fat reduces the ability of RF to deliver a transmural lesion. These findings have implications for optimal surgical RF ablation technique.</AbstractText>
2,334,893
Knee Joint Tissues Effectively Separate Mixed Sized Molecules Delivered in a Single Bolus to the Heart.
The role of molecular size selectivity in the onset and progression of osteoarthritis (OA), a degenerative disease of the musculoskeletal system and the most common cause of disability in aging adults, is unknown. Here we delivered a mixture of Texas-red (70&#x2009;kDa), and Rhodamine-green (10&#x2009;kDa) tagged, dextrans of neutral charge in a single bolus via heart injection to middle aged (8-10 months) and aged (17-19 months) Dunkin-Hartley Guinea pigs, a natural model for OA. We quantified tracer transport in serial-sectioned, cryofixed block specimens after five minutes' circulation. A remarkable separation of the molecules was observed in serial fluorescent images of whole joint sections. The larger, 70&#x2009;kDa red tracer was abundant in the marrow cavity albeit less prevalent or absent in the bone, cartilage, meniscus and other tissues of the joint. Tissues of the meniscus, ligament, and tendon exhibited abundant 10&#x2009;kDa tracer; volumes of tissue containing this molecular tracer were significantly lower in older than in younger animals. Surprisingly, muscle fiber bundles exhibited little fluorescence, while their bounding fasciae fluoresced either red or green. Small caliber channels through the articular cartilage appeared to show a degree of green fluorescence not observed in the surrounding cartilage matrix. This study opens up new avenues for study of musculoskeletal physiology in health and disease as well as new strategies for drug delivery.
2,334,894
Neuromuscular blockade of atracurium in permissive hypercapnic versus normocapnic swine undergoing laparoscopy.
Neuromuscular blocking agents (NMBAs) are commonly used in experimental laparoscopy in swine undergoing carbon dioxide pneumoperitoneum. Hypercapnia may be present and may prolong NMBAs' pharmacologic activity. The aim of this study is to evaluate the effect of permissive hypercapnia on the neuromuscular blockade of atracurium in swine. Six Large White swine weighing 30.5 &#xb1; 1.6 kg were sedated with intramuscular ketamine and medetomidine, after which anaesthesia was induced with propofol and maintained with sevoflurane. Atracurium 0.4 mg/kg was administered intravenously and the neuromuscular block monitored by acceleromyography during normocapnic and hypercapnic conditions (PaCO2 range 35-45 mmHg and 60-70 mmHg, respectively). Onset time and time to reach a train of four ratio (TOFR) of 0.7 and 0.9 were recorded. Cardiorespiratory parameters, electrolytes and acid-base status were measured under both conditions. Onset time was similar between the two conditions. Time to reach a TOFR of 0.7 and 0.9 (duration of the neuromuscular block) was longer in hypercapnic compared to normocapnic animals being 1325 &#xb1; 300 vs 855 &#xb1;111 (p = 0.002) and 1823 &#xb1; 434 vs 1218 &#xb1; 210 seconds (p = 0.005), respectively. Three hypercapnic swine had a TOF count of 2 and 1 instead of a count of 4 with fade. Permissive hypercapnia was associated with a decrease in pH from 7.444 &#xb1; 0.039 to 7.257 &#xb1; 0.025 (p &lt; 0.001). No differences were observed for heart rate, end-tidal concentration of sevoflurane, body temperature and arterial haemoglobin saturation. Nonetheless, hypercapnic swine had a statistically significant increase in mean arterial pressure (p = 0.020) and plasma potassium concentration (p = 0.003). The values of PaCO2 achieved during hypercapnia were well tolerated in swine undergoing CO2 pneumoperitoneum for laparoscopy. Permissive hypercapnia increased the duration of the atracurium effect and caused an increase in the intensity of the neuromuscular block in few swine.
2,334,895
The relationship between circulating adiponectin, ADIPOQ variants and incident cardiovascular disease in type 2 diabetes: The Fremantle Diabetes Study.
To investigate the relationship between serum adiponectin, ADIPOQ variants and haplotypes, and cardiovascular disease (CVD) in type 2 diabetes (T2D).</AbstractText>Baseline data including serum total adiponectin and 21 ADIPOQ polymorphisms were available for 1076 participants (mean age 64.0&#x202f;years, 49.4% males) in a community-based cohort followed for an average of 12&#x202f;years.</AbstractText>During 8843 patient-years of follow-up for coronary heart disease (CHD), 13,494 patient-years for ischaemic stroke (IS) and 12,028 patient-years for heart failure (HF), 40.4%, 11.8% and 31.9% of patients experienced a first episode of CHD, IS or HF, respectively. In Cox regression after adjustment for the most parsimonious models, loge</sub>(serum adiponectin) and the ADIPOQ variant rs12495941 were inversely associated with incident CHD (hazard ratio [95% confidence interval] 0.79 [0.65-0.98] and 0.64 [0.44-0.94], respectively), while rs1648707 was positively associated with incident IS (2.05 [1.37-3.06]; all P&#x202f;&#x2264;&#x202f;0.028). In males, rs9860747 and rs17366568 predicted CHD (0.22 [0.05-0.92] and 1.50 [1.01-2.20]; P&#x202f;&#x2264;&#x202f;0.042), while rs1648707 and rs1063537 predicted IS (2.36 [1.32-4.23] and 2.09 [1.17-3.72]; P&#x202f;&#x2264;&#x202f;0.012). In females, rs10937273 predicted CHD via an interaction with serum adiponectin (0.43 [0.21-0.91]; P&#x202f;=&#x202f;0.027), while rs864265 predicted IS (0.43 [0.21-0.88], P&#x202f;=&#x202f;0.021). The associations between ADIPOQ variants and outcomes were supported by haplotype block analysis. Neither serum adiponectin nor ADIPOQ variants predicted HF.</AbstractText>Serum total adiponectin and gender-specific ADIPOQ variants predict CHD and IS, but not HF, independently of other risk factors in community-based patients with T2D. In contrast to some previous studies, there was no relationship between a high serum total adiponectin and CVD.</AbstractText>Copyright &#xa9; 2018 Elsevier B.V. All rights reserved.</CopyrightInformation>
2,334,896
Random-amplitude sinusoidal linear acceleration causes greater vestibular modulation of skin sympathetic nerve activity than constant-amplitude acceleration.
We tested the hypothesis that random variations in the magnitude of sinusoidal linear acceleration cause greater modulation of skin sympathetic nerve activity (SSNA), but not muscle sympathetic nerve activity (MSNA), than sinusoidal stimuli of the same frequency but constant amplitude. Subjects (n&#x2009;=&#x2009;22) were seated in a sealed room mounted on a linear motor that could deliver peak sinusoidal accelerations of 30&#xa0;mG in the antero-posterior direction. Subjects sat on a padded chair with their neck and head supported vertically, thereby minimizing somatosensory cues, facing the direction of motion in the anterior direction. Each block of sinusoidal motion was delivered at 0.2&#xa0;Hz, either with a constant-amplitude (root mean square 14 mG) or randomly fluctuating amplitudes of the same mean amplitude. MSNA (n&#x2009;=&#x2009;12) and SSNA (n&#x2009;=&#x2009;10) were recorded via tungsten microelectrodes inserted into muscle or cutaneous fascicles of the common peroneal nerve. Cross-correlation analysis was used to measure the magnitude of vestibular modulation. The modulation index for SSNA was significantly higher during delivery of random vs constant-amplitude acceleration (31.4&#x2009;&#xb1;&#x2009;1.9 vs 24.5&#x2009;&#xb1;&#x2009;2.5%), but there was no significant difference in the modulation indices for MSNA (28.8&#x2009;&#xb1;&#x2009;2.9 vs 33.4&#x2009;&#xb1;&#x2009;4.1%). We conclude that the pattern of vestibular stimulation affects the magnitude of modulation of sympathetic outflow to skin but not to muscle. Presumably, this is related to the subperceptual development of nausea, which is known to be associated with greater vestibular modulation of SSNA but not MSNA.
2,334,897
Study on Clinical Profile and Predictors of Mortality in <i>Cerbera odollam</i> Poisoning.
Cerbera odollam</i> is a tree native to South Asia. It belongs to the poisonous Apocynaceae family. Deliberate self-harm with fruit of this plant is a major clinical problem in the developing world. Ingestion of C. odollam</i> kernels is the cause of deaths in more than half of Kerala's plant poisoning deaths. The data on clinical features and complications of C. odollam poisoning are sparse, apart from a few case reports and limited studies.</AbstractText>The present study was done to find the mode of presentation, complications, need for cardiac pacing, inhospital mortality, and the predictors of mortality in patients with C. odollam</i> poisoning.</AbstractText>This was a retrospective study conducted in the department of general medicine in a tertiary care center in Alappuzha district, Kerala. The study period was for 1 year from January 1, 2016, to December 31, 2016.</AbstractText>All the patients admitted with a history of ingestion of odollam during the study period were included in the study. Data were collected from case records. The study was approved by the institutional ethics committee and research committee (IEC/TDMCA/EC3.dated29/11/201).</AbstractText>The data were analyzed using SPSS 16 for Windows (SPSS Inc., Chicago, IL, USA).</AbstractText>In this study, 102 patients were identified with C. odollam</i> poisoning, and the mortality rate was 16.7%. Electrocardiogram (ECG) changes were common in our patients, and we observed different types of heart block in the same ECG itself. Ingestion of more than two kernels of odollam, late presentation to hospital, vomiting, bradycardia, hypotension, hyperkalemia, and more severe ECG changes were associated with significantly higher mortality in this study.</AbstractText>C. odollam</i> poisoning is a common method of deliberate self-harm in Kerala. It carries a high mortality rate, and the predictors of mortality include vomiting, bradycardia, hypotension, hyperkalemia, and the presence of severe ECG changes.</AbstractText>
2,334,898
Comparison of Two Doses of Dexmedetomidine for Supraclavicular Brachial Plexus Block: A Randomized Controlled Trial.
Dexmedetomidine is commonly used as an additive in supraclavicular brachial plexus block (SBPB). Due to its adverse effects such as bradycardia and hypotension, finding the appropriate dose of dexmedetomidine is the question.</AbstractText>We aimed to compare two commonly used doses of dexmedetomidine (1 &#x3bc;g/kg and 2 &#x3bc;g/kg) added to levobupivacaine in ultrasound-guided SBPB in terms of its effect on duration of analgesia, hemodynamics, and associated adverse effects.</AbstractText>This randomized, double-blinded prospective study was conducted over a period of 1.5 years in our tertiary care hospital.</AbstractText>Clearance from the Institutional Ethical Committee and Clinical Trial Registry of India was taken. Ninety patients' physical status American Society of Anesthesiologists Classes I and II undergoing upper limb surgeries under SBPB were included in this study. Patients in Group I received 1 &#x3bc;g/kg dexmedetomidine, whereas patients in Group II received 2 &#x3bc;g/kg dexmedetomidine added to 20 cc levobupivacaine. The primary outcome measure was the duration of analgesia after administering the block. Secondary outcomes included effect on hemodynamics, duration of blockade, and adverse effects.</AbstractText>Statistical analysis was carried out using Stata Version 10. Unpaired t</i>-test and Chi-square test were used.</AbstractText>The duration of analgesia and sensory and motor blockade were similar in both the groups. The heart rate (HR) and mean arterial pressure were statistically lower in Group II. The incidence of bradycardia and hypotension was more in Group II.</AbstractText>Increasing the dose of dexmedetomidine does not prolong the duration of analgesia, but it is associated with lower HR and blood pressure. Incidence of hypotension and bradycardia is also more. Hence, a lower dose of 1 &#x3bc;g/kg dexmedetomidine added to 0.5% levobupivacaine is a good balance between safety and efficacy.</AbstractText>
2,334,899
A Comparative Study of Two Different Intravenous Bolus Doses of Phenylephrine Used Prophylactically for Preventing Hypotension after Subarachnoid Block in Cesarean Sections.
Hypotension occurs in most of the cases following subarachnoid block in for cesarean sections. Studies comparing different bolus doses of phenylephrine for preventing hypotension induced by subarachnoid block in cesarean sections are sparse.</AbstractText>This study was conducted to compare the efficacy of two different bolus doses of phenylephrine for preventing subarachnoid block-induced hypotension in cesarean sections.</AbstractText>Sixty parturients undergoing cesarean section were allocated into two groups. Group A (n</i> = 30) received 150 mcg phenylephrine intravenously (IV) and Group B (n</i> = 30) received 200 mcg phenylephrine IV prophylactically immediately after subarachnoid block. Then, for every 2 min, systolic blood pressure, diastolic blood pressure, mean arterial pressure (MAP), and heart rate (HR) were measured for 20 min, and APGAR scores were measured.</AbstractText>The observations are expressed as mean &#xb1; standard deviation and were compared using unpaired t</i>-test. The statistical significance of difference between groups was based on P</i> value. P</i> &lt; 0.05 was considered statistically significant.</AbstractText>There was no difference in preventing hypotension in both the groups, the incidence in Group A being 16.6% and Group B also 16.6%. However, the rise in systolic pressure in Group B was higher than Group A in the first 2-6 min. The incidence of bradycardia was higher in Group B (43.3%) than Group A (20%).</AbstractText>Both the doses of phenylephrine were equally efficient in prevention of hypotension after subarachnoid block. Lower prophylactic bolus phenylephrine 150 mcg IV is better in the prevention of hypotension after subarachnoid block in cesarean sections as the incidence of bradycardia is higher with phenylephrine 200 mcg.</AbstractText>