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2,335,500
Impaired Sarcoplasmic Reticulum Calcium Uptake and Release Promote Electromechanically and Spatially Discordant Alternans: A Computational Study.
Cardiac electrical dynamics are governed by cellular-level properties, such as action potential duration (APD) restitution and intracellular calcium (Ca) handling, and tissue-level properties, including conduction velocity restitution and cell-cell coupling. Irregular dynamics at the cellular level can lead to instabilities in cardiac tissue, including alternans, a beat-to-beat alternation in the action potential and/or the intracellular Ca transient. In this study, we incorporate a detailed single cell coupled map model of Ca cycling and bidirectional APD-Ca coupling into a spatially extended tissue model to investigate the influence of sarcoplasmic reticulum (SR) Ca uptake and release properties on alternans and conduction block. We find that an intermediate SR Ca uptake rate and larger SR Ca release resulted in the widest range of stimulus periods that promoted alternans. However, both reduced SR Ca uptake and release promote arrhythmogenic spatially and electromechanically discordant alternans, suggesting a complex interaction between SR Ca handling and alternans characteristics at the cellular and tissue level.
2,335,501
Holistic ultrasound in trauma: An update.
Holistic ultrasound is a total body examination using an ultrasound device aiming to achieve immediate patient care and decision making. In the setting of trauma, it is one of the most fundamental components of care of the injured patients. Ground-breaking imaging software allows physicians to examine various organs thoroughly, recognize imaging signs early, and potentially foresee the onset or the possible outcome of certain types of injuries. Holistic ultrasound can be performed on a routine basis at the bedside of the patients, at admission and during the perioperative period. Trauma care physicians should be aware of the diagnostic and guidance benefits of ultrasound and should receive appropriate training for the optimal management of their patients. In this paper, the findings of holistic ultrasound in trauma patients are presented, with emphasis on the lungs, heart, cerebral circulation, abdomen, and airway. Additionally, the benefits of ultrasound imaging in interventional anaesthesia techniques such as ultrasound-guided peripheral nerve blocks and central vein catheterization are described.
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Suppression of APC/CCdh1 has subtype specific biological effects in acute myeloid leukemia.
The E3 ubiquitin ligase and tumor suppressor APC/CCdh1 is crucial for cell cycle progression, development and differentiation in many cell types. However, little is known about the role of Cdh1 in hematopoiesis. Here we analyzed Cdh1 expression and function in malignant hematopoiesis. We found a significant decrease of Cdh1 in primary acute myeloid leukemia (AML) blasts compared to normal CD34+ cells. Thus, according to its important role in connecting cell cycle exit and differentiation, decreased expression of Cdh1 may be a mechanism contributing to the differentiation block in leukemogenesis. Indeed, knockdown (kd) of Cdh1 in HL-60 cell line (AML with maturation, FAB M2) led to less differentiated cells and a delay in PMA-induced differentiation. Acute promyelocytic leukemia (APL, FAB M3) is an AML subtype which is highly vulnerable to differentiation therapy with all-trans retinoic acid (ATRA). Accordingly, we found that APL is resistant to a Cdh1-kd mediated differentiation block. However, further depletion of Cdh1 in APL significantly reduced viability of leukemia cells upon ATRA-induced differentiation. Thus, low Cdh1 expression may be important in AML biology by contributing to the differentiation block and response to therapy depending on differences in the microenvironment and the additional genetic background.
2,335,503
A gap junction inhibitor, carbenoxolone, induces spatiotemporal dispersion of renal cortical perfusion and impairs autoregulation.
Renal autoregulation dynamics originating from the myogenic response (MR) and tubuloglomerular feedback (TGF) can synchronize over large regions of the kidney surface, likely through gap junction-mediated electrotonic conduction and reflecting distributed operation of autoregulation. We tested the hypotheses that inhibition of gap junctions reduces spatial synchronization of autoregulation dynamics, abrogates spatial and temporal smoothing of renal perfusion, and impairs renal autoregulation. In male Long-Evans rats, we infused the gap junction inhibitor carbenoxolone (CBX) or the related glycyrrhizic acid (GZA) that does not block gap junctions into the renal artery and monitored renal blood flow (RBF) and surface perfusion by laser speckle contrast imaging. Neither CBX nor GZA altered RBF or mean surface perfusion. CBX preferentially increased spatial and temporal variation in the distribution of surface perfusion, increased spatial variation in the operating frequencies of the MR and TGF, and reduced phase coherence of TGF and increased its dispersion. CBX, but not GZA, impaired dynamic and steady-state autoregulation. Separately, infusion of the Rho kinase inhibitor Y-27632 paralyzed smooth muscle, grossly impaired dynamic autoregulation, and monotonically increased spatial variation of surface perfusion. These data suggest CBX inhibited gap junction communication, which in turn reduced the ability of TGF to synchronize among groups of nephrons. The results indicate that impaired autoregulation resulted from degraded synchronization, rather than the reverse. We show that network behavior in the renal vasculature is necessary for effective RBF autoregulation.
2,335,504
Infrared inhibition of embryonic hearts.
Infrared control is a new technique that uses pulsed infrared lasers to thermally alter electrical activity. Originally developed for nerves, we have applied this technology to embryonic hearts using a quail model, previously demonstrating infrared stimulation and, here, infrared inhibition. Infrared inhibition enables repeatable and reversible block, stopping cardiac contractions for several seconds. Normal beating resumes after the laser is turned off. The block can be spatially specific, affecting propagation on the ventricle or initiation on the atrium. Optical mapping showed that the block affects action potentials and not just calcium or contraction. Increased resting intracellular calcium was observed after a 30-s exposure to the inhibition laser, which likely resulted in reduced mechanical function. Further optimization of the laser illumination should reduce potential damage. Stopping cardiac contractions by disrupting electrical activity with infrared inhibition has the potential to be a powerful tool for studying the developing heart.
2,335,505
The Efficacy of Femoral Block and Unilateral Spinal Anaesthesia on Analgesia, Haemodynamics and Mobilization in Patients undergoing Endovenous Ablation in the Lower Extremity.
This study aimed to investigate the efficacy of femoral block and unilateral spinal anaesthesia on analgesia, haemodynamics and mobilization during endovenous ablation in patients with lower extremity venous insufficiency.</AbstractText>Forty patients of ASA physical status I and II, with ages ranging between 30 and 45 years, and who were scheduled for endovenous laser ablation for varicose veins were prospectively enrolled in this study. Patients were randomized into a unilateral spinal anaesthesia group (group HS, n=20) or a femoral block group (group F, n=20). Group HS received 7.5-10 mg of heavy bupivacaine for unilateral spinal anaesthesia, while group F received 100 mg prilocaine for femoral block with ultrasound guidance. The level of motor blockage (Bromage score), visual pain score, mean heart rate and mean arterial pressures were recorded at postoperative 0, 1, 2, 3d and 6 h, respectively.</AbstractText>Perioperative visual pain score values in both groups were &lt;4. None of the groups required an additional analgesic agent. Bromage scores were significantly lower in group F than in group HS during the postoperative period (p&lt;0.01). Motor function returned to normal in all patients at 3 h in group F and at 6 h in group HS. Postoperative mean heart rate and arterial pressure did not differ between the groups (p&gt;0.05).</AbstractText>In patients with lower extremity venous insufficiency who were undergoing endovenous laser ablation, an ultrasound-guided femoral block provided similar analgesia with that of unilateral spinal anaesthesia. In group F, the duration of anaesthesia and mobilization time was shorter.</AbstractText>
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Association of Polymorphisms in Connective Tissue Growth Factor and Epidermal Growth Factor Receptor Genes With Human Longevity.
Growth pathways play key roles in longevity. The present study tested single-nucleotide polymorphisms (SNPs) in the connective tissue growth factor gene (CTGF) and the epidermal growth factor receptor gene (EGFR) for association with longevity. Comparison of allele and genotype frequencies of 12 CTGF SNPs and 41 EGFR SNPs between 440 American men of Japanese ancestry aged &#x2265;95 years and 374 men of average life span revealed association with longevity at the p &lt; .05 level for 2 SNPs in CTGF and 7 in EGFR. Two in CTGF and two in EGFR remained significant after Bonferroni correction. The SNPs of both CTGF and EGFR were in a haplotype block in each respective gene. Haplotype analysis confirmed the suggestive association found by &#x3c7;2 analysis. We noted an excess of heterozygotes among the longevity cases, consistent with heterozygote advantage in living to extreme old age. No associations of the most significant SNPs were observed in whites or Koreans. In conclusion, the present findings indicate that genetic variation in CTGF and EGFR may contribute to the attainment of extreme old age in Japanese. More research is needed to confirm that genetic variation in CTGF and EGFR contributes to the attainment of extreme old age across human populations.
2,335,507
Kinases as Novel Therapeutic Targets in Asthma and Chronic Obstructive Pulmonary Disease.
Multiple kinases play a critical role in orchestrating the chronic inflammation and structural changes in the respiratory tract of patients with asthma and chronic obstructive pulmonary disease (COPD). Kinases activate signaling pathways that lead to contraction of airway smooth muscle and release of inflammatory mediators (such as cytokines, chemokines, growth factors) as well as cell migration, activation, and proliferation. For this reason there has been great interest in the development of kinase inhibitors as anti-inflammatory therapies, particular where corticosteroids are less effective, as in severe asthma and COPD. However, it has proven difficult to develop selective kinase inhibitors that are both effective and safe after oral administration and this has led to a search for inhaled kinase inhibitors, which would reduce systemic exposure. Although many kinases have been implicated in inflammation and remodeling of airway disease, very few classes of drug have reached the stage of clinical studies in these diseases. The most promising drugs are p38 MAP kinases, isoenzyme-selective PI3-kinases, Janus-activated kinases, and Syk-kinases, and inhaled formulations of these drugs are now in development. There has also been interest in developing inhibitors that block more than one kinase, because these drugs may be more effective and with less risk of losing efficacy with time. No kinase inhibitors are yet on the market for the treatment of airway diseases, but as kinase inhibitors are improved from other therapeutic areas there is hope that these drugs may eventually prove useful in treating refractory asthma and COPD.
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The analgesic effect of clonidine as an adjuvant in dorsal penile nerve block.
Dorsal penile nerve block (DPNB) is a commonly performed regional anesthetic technique for male circumcision. The aim of this study was to assess the analgesic effect of the adjunction of clonidine to bupivacaine 0.5% in this block.</AbstractText>It was a prospective randomized double-blind clinical trial including 40 ASA1 boys aged from 1 to 4 years undergoing elective circumcision. Dorsal penile nerve block was performed under general Anesthesia. Patients were randomized in two groups: Group 1 (G1): received 0.1 ml/Kg of bupivacaine 0.5% with 1&#xb5;g/kg of clonidine in each side. Group 2 (G2): received 0.1 ml/kg of bupivacaine 0.5% with placebo in each side. The failure of the DNPB was defined by the increase of heart rate by more than 25% comparing to baseline and in his case an intravenous injection of 20 &#xb5;g/kg of alfentanyl was given. Post-operative pain was assessed by CHEOPS score.</AbstractText>A total of 40 patients were enrolled. Demographic parameters were similar in both groups. We noted no case of DNPB failure in this study. The supply for additional analgesia was seen in 12 patients in group 2 versus 3 cases in group 1. CHEOPS (Children's Hospital of Eastern Ontario Pain Scale) was significantly lower in group 1 from 2nd post operative hour until the 24th hour.</AbstractText>Clonidine can be used in dorsal penile nerve block to improve and to prolong its analgesic effects after male circumcision.</AbstractText>
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Pain after sternotomy - review.
Adequate analgesia after sternotomy reduces postoperative adverse events. There are various methods of treating pain after heart surgery, such as infiltration with a local anesthetic, nerve block, opioids, non-steroidal anti-inflammatory drugs, alpha-adrenergic agents, intrathecal and epidural techniques, and multimodal analgesia.</AbstractText>A review of the epidemiology, pathophysiology, prevention and treatment of pain after sternotomy. We also discuss the various analgesic therapeutic modalities, emphasizing advantages and disadvantages of each technique.</AbstractText>Heart surgery is performed mainly via medium sternotomy, which results in significant postoperative pain and a non-negligible incidence of chronic pain. Effective pain control improves patient satisfaction and clinical outcomes. There is no clearly superior technique. It is believed that a combined multimodal analgesic regimen (using different techniques) is the best approach for treating postoperative pain, maximizing analgesia and reducing side effects.</AbstractText>Copyright &#xa9; 2015 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.</CopyrightInformation>
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The association of maternal vitamin D status with infant birth outcomes, postnatal growth and adiposity in the first 2 years of life in a multi-ethnic Asian population: the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort study.
Maternal vitamin D status during pregnancy has been associated with infant birth and postnatal growth outcomes, but reported findings have been inconsistent, especially in relation to postnatal growth and adiposity outcomes. In a mother-offspring cohort in Singapore, maternal plasma vitamin D was measured between 26 and 28 weeks of gestation, and anthropometric measurements were obtained from singleton offspring during the first 2 years of life with 3-month follow-up intervals to examine birth, growth and adiposity outcomes. Associations were analysed using multivariable linear regression. Of a total of 910 mothers, 13&#xb7;2 % were vitamin D deficient (&lt;50 nmol/l) and 26&#xb7;5 % were insufficient (50-75 nmol/l). After adjustment for potential confounders and multiple testing, no statistically significant associations were observed between maternal vitamin D status and any of the birth outcomes - small for gestational age (OR 1&#xb7;00; 95 % CI 0&#xb7;56, 1&#xb7;79) and pre-term birth (OR 1&#xb7;16; 95 % CI 0&#xb7;64, 2&#xb7;11) - growth outcomes - weight-for-age z-scores, length-for-age z-scores, circumferences of the head, abdomen and mid-arm at birth or postnatally - and adiposity outcomes - BMI, and skinfold thickness (triceps, biceps and subscapular) at birth or postnatally. Maternal vitamin D status in pregnancy did not influence infant birth outcomes, postnatal growth and adiposity outcomes in this cohort, perhaps due to the low prevalence (1&#xb7;6 % of the cohort) of severe maternal vitamin D deficiency (defined as of &lt;30&#xb7;0 nmol/l) in our population.
2,335,511
Effect of addition of dexmedetomidine to ropivacaine 0.2% for femoral nerve block in patients undergoing unilateral total knee replacement: A randomised double-blind study.
Total knee replacement (TKR) patients experience considerable post-operative pain. We evaluated whether addition of perineural dexmedetomidine to ropivacaine 0.2% in the femoral nerve block would enhance post-operative analgesia in patients undergoing unilateral TKR under spinal anaesthesia.</AbstractText>Fifty patients were allocated randomly to two groups of 25 each. Group D received ropivacaine (0.2%) with dexmedetomidine (1.5 &#x3bc;g/kg), and Group C received ropivacaine (0.2%) with normal saline. Pain scores, time to the first request for analgesia and total consumption of ropivacaine in 48 h, along with haemodynamic parameters and sedation scores, were recorded. Quantitative data were compared using t-test, categorical data using Chi-square or Fisher's exact test and time variables using ANOVA.</AbstractText>The mean pain scores were significantly low till 2 h post-operatively in Group D. Time to the first demand for analgesia after initial loading dose was statistically prolonged in Group D, with mean duration of 346.8 &#xb1; 240 min, compared to 150 &#xb1; 115.2 min in Group C (P = 0.001). Total local anaesthetic consumption was also decreased over 24 and 48 h in Group D (P = 0.001). Haemodynamically, there was no significant variation in heart rate from their baseline mean values in either group (P &gt; 0.05). However, the drop in systolic and mean blood pressure post-surgery was significant till 4 (P = 0.002) and 8 h (P = 0.02), respectively, in Group D. Group D patients were also significantly more sedated till 4 h post-operatively (P &lt; 0.005).</AbstractText>Adding dexmedetomidine to ropivacaine 0.2% in the femoral nerve block in patients undergoing unilateral TKR improves the quality and prolongs the duration of post-operative analgesia.</AbstractText>
2,335,512
Toxicity of single-wall carbon nanotubes functionalized with polyethylene glycol in zebrafish (Danio rerio) embryos.
Single-wall carbon nanotubes functionalized with polyethylene glycol (SWCNT-PEG) are promising materials for biomedical applications such as diagnostic devices and controlled drug-release systems. However, several questions about their toxicological profile remain unanswered. Thus, the aim of this study was to investigate the action of SWCNT-PEG in Danio rerio zebrafish embryos at the molecular, physiological and morphological levels. The SWCNT used in this study were synthesized by the high-pressure carbon monoxide process, purified and then functionalized with distearoyl phosphatidylethanolamine block copolymer-PEG (molecular weight 2&#x2009;kDa). The characterization process was carried out with low-resolution transmission electron microscopy, thermogravimetric analysis and Raman spectroscopy. Individual zebrafish embryos were exposed to the SWCNT-PEG. Toxic effects occurred only at the highest concentration tested (1&#x2009;ppm) and included high mortality rates, delayed hatching and decreased total larval length. For all the concentrations tested, the alkaline comet assay revealed no genotoxicity, and Raman spectroscopy measurements on the histological slices revealed no intracellular nanotubes. The results shown here demonstrate that SWCNT-PEG has low toxicity in zebrafish embryos, but more studies are needed to understand what mechanisms are involved. However, the presence of residual metals is possibly among the primary mechanisms responsible for the toxic effects observed, because the purification process was not able to remove all metal contamination, as demonstrated by the thermogravimetric analysis. More attention must be given to the toxicity of these nanomaterials before they are used in biomedical applications. Copyright &#xa9; 2016 John Wiley &amp; Sons, Ltd.
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Reactive oxygen species facilitate the EDH response in arterioles by potentiating intracellular endothelial Ca(2+) release.
There is abundant evidence that H2O2 can act as an endothelium-derived hyperpolarizing factor in the resistance vasculature. However, whilst scavenging H2O2 can abolish endothelial dependent hyperpolarization (EDH) and the associated vascular relaxation in some arteries, EDH-dependent vasorelaxation can often be mimicked only by using relatively high concentrations of H2O2. We have examined the role of H2O2 in EDH-dependent vasodilatation by simultaneously measuring vascular diameter and changes in endothelial cell (EC) [Ca(2+)]i during the application of H2O2 or carbachol, which triggers EDH. Carbachol (10&#xb5;M) induced dilatation of phenylephrine-preconstricted rat cremaster arterioles was largely (73%) preserved in the presence of indomethacin (3&#xb5;M) and l-NAME (300&#xb5;M). This residual NO- and prostacyclin-independent dilatation was reduced by 89% upon addition of apamin (0.5&#xb5;M) and TRAM-34 (10&#xb5;M), and by 74% when an extracellular ROS scavenging mixture of SOD and catalase (S&amp;C; 100Uml(-1) each) was present. S&amp;C also reduced the carbachol-induced EC [Ca(2+)]i increase by 74%. When applied in Ca(2+)-free external medium, carbachol caused a transient increase in EC [Ca(2+)]i. This was reduced by catalase, and was enhanced when 1&#xb5;M H2O2 was present in the bath. H2O2 -induced dilatation, which occurred only at concentrations &#x2265;100&#xb5;M, was reduced by a blocking antibody to TRPM2, which had no effect on carbachol-induced responses. Similarly, iberotoxin and Rp-8bromo cGMP reduced the vasodilatation induced by H2O2, but not by carbachol. Inhibiting PLC, PLA2 or CYP450 2C9 each greatly reduced the carbachol-induced increase in EC [Ca(2+)]i and vasodilatation, but adding 10&#xb5;M H2O2 during PLA2 or CYP450 2C9 inhibition completely restored both responses. The nature of the effective ROS species was investigated by using Fe(2+) chelators to block the formation of &#x2219;OH. A cell permeant chelator was able to inhibit EC Ca(2+) store release, but cell impermeant chelators reduced both the vasodilatation and EC Ca(2+) influx, implying that &#x2219;OH is required for these responses. The results indicate that rather than mediating EDH by acting directly on smooth muscle, H2O2 promotes EDH by acting within EC to enhance Ca(2+) release.
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[Efficacy of Ultrasound-guided Caudal Epidural Block for Transrectal Ultrasound-guided Prostate Biopsy].
We investigated the efficacy of ultrasound (US)-guided caudal epidural block for transrectal ultrasound (TRUS)-guided prostate biopsy.</AbstractText>Sixty adult patients (ASA I or II) were enrolled in this study and randomized into two groups: group S receiving spinal block (n = 30) and group C receiving US-guided caudal epidural block (n = 30). We measured systolic blood pressure (SBP), heart rate (HR), and degrees of sensory and motor blockade. Procedural time for regional anesthesia was recorded.</AbstractText>Six patients in group C were excluded from analysis because of insufficient block effect. Spinal block caused a significant decrease in SBP compared to that with US-guided caudal epidural block (P &lt; 0.05). Degrees of sensory and motor blockade were significantly greater in group S than in group C (P &lt; 0.05).</AbstractText>US-guided caudal epidural block provided hemodynamic stability during TRUS-guided prostate biopsy. Furthermore, US-guided caudal epidural block effectively produced appropriate sensory blockade for TRUS-guided prostate biopsy with minimum motor blockade.</AbstractText>
2,335,515
Rising trend of cardiovascular risk factors between 1991-1994 and 2010-2012: A repeat cross sectional survey in urban and rural Vellore.
Repeat cross sectional surveys document the trend of prevalence rates for non-communicable diseases and their risk factors. In this study, we compare the prevalence rates for risk factors for cardiovascular disease in urban and rural Vellore between 1991-1994 and 2010-2012.</AbstractText>Cross sectional survey was carried out in 1991-1994 in a rural block in Vellore district and in Vellore town, to study the prevalence of cardiovascular risk factors among adults aged 30-60 years. A repeat survey was done in 2010-2012 using the WHO STEPS method. In both surveys, socio-demographic and behavioral history, physical measurements, biochemical measurements, and medical history were obtained. Age adjusted rates were used to compare the rates in the two surveys.</AbstractText>In the rural areas, there was a three times increase in diabetes and body mass index (BMI) &#x2265;25kg/m(2) (overweight/obese) with a doubling of the prevalence of hypertension. In urban areas there was a tripling of diabetes, doubling of proportion with BMI&#x2265;25kg/m(2) and 50% increase in prevalence of hypertension. While the proportion of male current smokers reduced by 50% in both rural and urban Vellore, lifetime abstainers to alcohol decreased in the rural area from 46.8% to 37.5% (p&lt;0.001).</AbstractText>There has been an alarming rise in diabetes, hypertension, and overweight/obese with an even greater increase in rural areas. Alcohol use is increasing while smoking is on the decline. Primary prevention programs are required urgently to stem the rising incidence of non-communicable diseases in India.</AbstractText>Copyright &#xa9; 2015 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.</CopyrightInformation>
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Effects of arthroscopy-guided suprascapular nerve block combined with ultrasound-guided interscalene brachial plexus block for arthroscopic rotator cuff repair: a randomized controlled trial.
The aim of this study was to compare the pain relieving effect of ultrasound-guided interscalene brachial plexus block (ISB) combined with arthroscopy-guided suprascapular nerve block (SSNB) with that of ultrasound-guided ISB alone within the first 48&#xa0;h after arthroscopic rotator cuff repair.</AbstractText>Forty-eight patients with rotator cuff tears who had undergone arthroscopic rotator cuff repair were enrolled. The 24 patients in group 1 received ultrasound-guided ISB and arthroscopy-guided SSNB; the remaining 24 patients in group 2 underwent ultrasound-guided ISB alone. Visual analogue scale pain score and patient satisfaction score were checked at 1, 3, 6, 12, 18, 24, and 48&#xa0;h post-operatively.</AbstractText>Group 1 had a lower visual analogue scale pain score at 3, 6, 12, 18, 24, and 48&#xa0;h post-operatively (1.7&#xa0;&lt;&#xa0;2.6, 1.6&#xa0;&lt;&#xa0;4.0, 3.5&#xa0;&lt;&#xa0;5.8, 3.6&#xa0;&lt;&#xa0;5.2, 3.2&#xa0;&lt;&#xa0;4.2, 1.3&#xa0;&lt;&#xa0;2.0), and a higher patient satisfaction score at 6, 12, 18, 24, and 36&#xa0;h post-operatively than group 2 (7.8&#xa0;&gt;&#xa0;6.0, 6.2&#xa0;&gt;&#xa0;4.3, 6.4&#xa0;&gt;&#xa0;5.1, 6.9&#xa0;&gt;&#xa0;5.9, 7.9&#xa0;&gt;&#xa0;7.1). Six patients in group 1 developed rebound pain twice, and the others in group 1 developed it once. All of the patients in group 2 had one rebound phenomenon each (p&#xa0;=&#xa0;0.010). The mean timing of rebound pain in group 1 was later than that in group 2 (15.5&#xa0;&gt;&#xa0;9.3&#xa0;h, p&#xa0;&lt;&#xa0;0.001), and the mean size of rebound pain was smaller in group 1 than that in group 2 (2.5&#xa0;&gt;&#xa0;4.0, p&#xa0;=&#xa0;0.001).</AbstractText>Arthroscopy-guided SSNB combined with ultrasound-guided ISB resulted in lower visual analogue scale pain scores at 3-24 and 48&#xa0;h post-operatively, and higher patient satisfaction scores at 6-36&#xa0;h post-operatively with the attenuated rebound pain compared to scores in patients who received ultrasound-guided ISB alone after arthroscopic rotator cuff repair. The combined blocks may relieve post-operative pain more effectively than the single block within 48&#xa0;h after arthroscopic cuff repair.</AbstractText>Randomized controlled trial, Level I. ClinicalTrials.gov Identifier: NCT02424630.</AbstractText>
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A systematic review of the clinical effectiveness and cost-effectiveness of pharmacological and psychological interventions for the management of obsessive-compulsive disorder in children/adolescents and adults.
Obsessive-compulsive disorder (OCD) is a relatively common and disabling condition.</AbstractText>To determine the clinical effectiveness, acceptability and cost-effectiveness of pharmacological and psychological interventions for the treatment of OCD in children, adolescents and adults.</AbstractText>We searched the Cochrane Collaboration Depression, Anxiety and Neurosis Trials Registers, which includes trials from routine searches of all the major databases. Searches were conducted from inception to 31 December 2014.</AbstractText>We undertook a systematic review and network meta-analysis (NMA) of the clinical effectiveness and acceptability of available treatments. Outcomes for effectiveness included mean differences in the total scores of the Yale-Brown Obsessive-Compulsive Scale or its children's version and total dropouts for acceptability. For the cost-effectiveness analysis, we developed a probabilistic model informed by the results of the NMA. All analyses were performed using OpenBUGS version 3.2.3 (members of OpenBUGS Project Management Group; see www.openbugs.net ).</AbstractText>We included 86 randomised controlled trials (RCTs) in our systematic review. In the NMA we included 71 RCTs (54 in adults and 17 in children and adolescents) for effectiveness and 71 for acceptability (53 in adults and 18 in children and adolescents), comprising 7643 and 7942 randomised patients available for analysis, respectively. In general, the studies were of medium quality. The results of the NMA showed that in adults all selective serotonin reuptake inhibitors (SSRIs) and clomipramine had greater effects than drug placebo. There were no differences between SSRIs, and a trend for clomipramine to be more effective did not reach statistical significance. All active psychological therapies had greater effects than drug placebo. Behavioural therapy (BT) and cognitive therapy (CT) had greater effects than psychological placebo, but cognitive-behavioural therapy (CBT) did not. BT and CT, but not CBT, had greater effects than medications, but there are considerable uncertainty and methodological limitations that should be taken into account. In children and adolescents, CBT and BT had greater effects than drug placebo, but differences compared with psychological placebo did not reach statistical significance. SSRIs as a class showed a trend for superiority over drug placebo, but the difference did not reach statistical significance. However, the superiority of some individual drugs (fluoxetine, sertraline) was marginally statistically significant. Regarding acceptability, all interventions except clomipramine had good tolerability. In adults, CT and BT had the highest probability of being most cost-effective at conventional National Institute for Health and Care Excellence thresholds. In children and adolescents, CBT or CBT combined with a SSRI were more likely to be cost-effective. The results are uncertain and sensitive to assumptions about treatment effect and the exclusion of trials at high risk of bias.</AbstractText>The majority of psychological trials included patients who were taking medications. There were few studies in children and adolescents.</AbstractText>In adults, psychological interventions, clomipramine, SSRIs or combinations of these are all effective, whereas in children and adolescents, psychological interventions, either as monotherapy or combined with specific SSRIs, were more likely to be effective. Future RCTs should improve their design, in particular for psychotherapy or combined interventions.</AbstractText>The study is registered as PROSPERO CRD42012002441.</AbstractText>The National Institute for Health Research Health Technology Assessment programme.</AbstractText>
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Augmented Renal Clearance in Traumatic Brain Injury: A Single-Center Observational Study of Atrial Natriuretic Peptide, Cardiac Output, and Creatinine Clearance.
Augmented renal clearance (ARC) is being increasingly described in neurocritical care practice. The mechanisms driving this phenomenon are largely unknown. The aim of this project was therefore to explore changes in renal function, cardiac output (CO), and atrial natriuretic peptide (ANP) concentrations in patients with isolated traumatic brain injury (TBI). This prospective observational cohort study was conducted in a tertiary-level, university-affiliated intensive care unit (ICU). Patients with normal plasma creatinine concentrations (&lt;120&#x2009;&#x3bc;mol/L) at admission and no history of chronic kidney disease, admitted with isolated TBI, were eligible for enrollment. Continuous CO measures were obtained using arterial pulse waveform analysis. Eight-hour urinary creatinine clearances (CL<sub>CR</sub>) were used to quantify renal function. ANP concentrations in plasma were measured on alternate days. Data were collected from study enrollment until ICU discharge, death, or day 15, which ever came first. Eleven patients, contributing 100 ICU days of physiological data, were enrolled into the study. Most participants were young men, requiring mechanical ventilation. Median ICU length of stay was 9.6 [7.8-13.0] days. Elevated CL<sub>CR</sub> measures (&gt;150&#x2009;mL/min) were frequent and appeared to parallel changes in CO. Plasma ANP concentrations were also significantly elevated over the study period (minimum value&#x2009;=&#x2009;243&#x2009;pg/mL). These data suggest that ARC is likely to complicate the care of TBI patients with normal plasma creatinine concentrations, and may be driven by associated cardiovascular changes and/or elevated plasma ANP concentrations. However, significant additional research is required to further understand these findings.
2,335,519
CHADS<sub>2</sub> and CHA<sub>2</sub>DS<sub>2</sub>-VASc Scores Predict the Risk of Ischemic Stroke Outcome in Patients with Interatrial Block without Atrial Fibrillation.
To evaluate the role of CHADS2</sub> and CHA2</sub>DS2</sub>-VASc scores in predicting the risk of ischemic stroke or transient ischemic attack (TIA) outcomes in patients with interatrial block (IAB) without a history of atrial fibrillation (AF).</AbstractText>A retrospective study was conducted, including 1,046 non-anticoagulated inpatients (612 males, 434 females; mean age: 63&#xb1;10 years) with IAB and without AF. IAB was defined as P-wave duration &#xff1e;120 ms using a 12-lead electrocardiogram. CHADS2</sub> and CHA2</sub>DS2</sub>-VASc scores were retrospectively calculated. The primary outcomes evaluated were ischemic stroke or TIA.</AbstractText>During the mean follow-up period of 4.9&#xb1;0.7 years, 55 (5.3%) patients had an ischemic stroke or TIA. Receiver operating characteristic (ROC) curve analysis showed that the CHADS2</sub> score [area under the curve (AUC), 0.638; 95% confidence interval (CI), 0.562-0.715; P=0.001] and the CHA2</sub>DS2</sub>-VASc score (AUC, 0.671; 95% CI, 0.599-0.744; P&#xff1c;0.001) were predictive of ischemic strokes or TIA. Cut-off point analysis showed that a CHADS2</sub> score &#x2265;3 (sensitivity=0.455 and specificity=0.747) and a CHA2</sub>DS2</sub>-VASc score &#x2265;4 (sensitivity=0.564 and specificity=0.700) provided the highest predictive value for ischemic stroke or TIA. The multivariate Cox regression analysis showed that CHADS2</sub> [hazard ratio (HR), 1.442; 95% CI, 1.171-1.774; P=0.001] and CHA2</sub>DS2</sub>-VASc (HR, 1.420; 95% CI, 1.203-1.677; P&#xff1c;0.001) scores were independently associated with ischemic stroke or TIA following adjustment for smoking, left atrial diameter, antiplatelet agents, angiotensin inhibitors, and statins.</AbstractText>CHADS2</sub> and CHA2</sub>DS2</sub>-VASc scores may be predictors of risk of ischemic stroke or TIA in patients with IAB without AF.</AbstractText>
2,335,520
Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes.
The cardiovascular effect of liraglutide, a glucagon-like peptide 1 analogue, when added to standard care in patients with type 2 diabetes, remains unknown.</AbstractText>In this double-blind trial, we randomly assigned patients with type 2 diabetes and high cardiovascular risk to receive liraglutide or placebo. The primary composite outcome in the time-to-event analysis was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The primary hypothesis was that liraglutide would be noninferior to placebo with regard to the primary outcome, with a margin of 1.30 for the upper boundary of the 95% confidence interval of the hazard ratio. No adjustments for multiplicity were performed for the prespecified exploratory outcomes.</AbstractText>A total of 9340 patients underwent randomization. The median follow-up was 3.8 years. The primary outcome occurred in significantly fewer patients in the liraglutide group (608 of 4668 patients [13.0%]) than in the placebo group (694 of 4672 [14.9%]) (hazard ratio, 0.87; 95% confidence interval [CI], 0.78 to 0.97; P&lt;0.001 for noninferiority; P=0.01 for superiority). Fewer patients died from cardiovascular causes in the liraglutide group (219 patients [4.7%]) than in the placebo group (278 [6.0%]) (hazard ratio, 0.78; 95% CI, 0.66 to 0.93; P=0.007). The rate of death from any cause was lower in the liraglutide group (381 patients [8.2%]) than in the placebo group (447 [9.6%]) (hazard ratio, 0.85; 95% CI, 0.74 to 0.97; P=0.02). The rates of nonfatal myocardial infarction, nonfatal stroke, and hospitalization for heart failure were nonsignificantly lower in the liraglutide group than in the placebo group. The most common adverse events leading to the discontinuation of liraglutide were gastrointestinal events. The incidence of pancreatitis was nonsignificantly lower in the liraglutide group than in the placebo group.</AbstractText>In the time-to-event analysis, the rate of the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke among patients with type 2 diabetes mellitus was lower with liraglutide than with placebo. (Funded by Novo Nordisk and the National Institutes of Health; LEADER ClinicalTrials.gov number, NCT01179048.).</AbstractText>
2,335,521
Effects of ultrasound-guided stellate ganglion block on autonomic nervous function during CO2-pneumoperitoneum: A randomized double-blind control trial.
CO2-pneumoperitoneum can cause sympathetic nerve activity increased and is likely to causes severe stress-related homeostatic disorders.</AbstractText>Patients undergoing elective laparoscopic cholecystectomy were administered type-B ultrasound-guided stellate ganglion block (SGB) to observe the effects on autonomic nervous system during CO2- pneumoperitoneum.</AbstractText>A randomized, double-blinded, and placebo-controlled study.</AbstractText>University-affiliated teaching hospital.</AbstractText>Eighty patients (aged 32-75 years; weight, 45-80 kg; American Society of Anesthesiologists (ASA) physical status classification, class I or II) undergoing elective laparoscopic cholecystectomy.</AbstractText>The RSGB group was administered lidocaine 1% 7 ml under ultrasound guidance.</AbstractText>The low frequency (LF), high frequency (HF), total power (TP) and LF/HF ratio were recorded before the block (T0), 5 min (T1) and 30 min (T2) following pneumoperitoneum, 5 min after deflation of pneumoperitoneum (T3) and after surgery (T4). The low-frequency normalized unit (LFnu) and high-frequency normalized units (HFnu) were calculated.</AbstractText>Compared with T0, LF, LFnu and LF/HF ratio were significantly elevated at T1-4 (all P&lt; .05 or .01). HFnu was significantly decreased at T2-4 in control group (P&lt; .05) while HF was significantly elevated (P&lt; .01). The LF/HF ratio was significantly decreased (P&lt; .05) at T1-4 in RSGB group. Compared with control group, the LF, LFnu and LF/HF ratio were significantly decreased (P&lt; .05) and HF and HFnu was significantly elevated (P&lt; .05 or .01) at T1-4 in RSGB group.</AbstractText>Ultrasound-guided RSGB inhibited CO2-pneumoperitoneum-induced sympathetic neural excitation, upregulated vagal nerve stimulation and maintained stable autonomic nervous function.</AbstractText>Copyright &#xa9; 2016 Elsevier Inc. All rights reserved.</CopyrightInformation>
2,335,522
Identifying rural food deserts: Methodological considerations for food environment interventions.
<b>OBJECTIFS :</b> L&#x2019;ins&#xe9;curit&#xe9; alimentaire est une probl&#xe9;matique de sant&#xe9; publique qui atteint pr&#xe8;s de 13 % des m&#xe9;nages canadiens. Elle est associ&#xe9;e &#xe0; une faible accessibilit&#xe9; &#xe0; des produits alimentaires frais, diversifi&#xe9;s et abordables. Cependant, la mesure de l&#x2019;environnement alimentaire demeure un d&#xe9;fi important en milieu rural puisque les sources d&#x2019;approvisionnement alimentaire sont distribu&#xe9;es de fa&#xe7;on in&#xe9;gale sur le territoire. L&#x2019;objectif de cette &#xe9;tude &#xe9;tait de d&#xe9;velopper une m&#xe9;thodologie pour identifier les d&#xe9;serts alimentaires potentiels en milieu rural. <b>M&#xc9;THODES :</b> L&#x2019;&#xe9;valuation de 25 produits alimentaires a &#xe9;t&#xe9; r&#xe9;alis&#xe9;e pour tous les magasins d&#x2019;alimentation de quatre municipalit&#xe9;s r&#xe9;gionales de comt&#xe9; rurales qu&#xe9;b&#xe9;coises. La qualit&#xe9; des produits alimentaires fut estim&#xe9;e par quatre indices: la fra&#xee;cheur, l&#x2019;abordabilit&#xe9;, la diversit&#xe9; et la disponibilit&#xe9; relative. La distance r&#xe9;ticulaire entre toutes les r&#xe9;sidences et le magasin d&#x2019;alimentation le plus proche ayant un indice favorable pour les quatre indices fut cartographi&#xe9;e pour localiser les regroupements de r&#xe9;sidences localis&#xe9;s dans une communaut&#xe9; d&#xe9;favoris&#xe9;e n&#x2019;ayant pas un acc&#xe8;s &#xe0; une &#xab; bonne &#xbb; source d&#x2019;approvisionnement alimentaire. Le r&#xe9;sultat fut compar&#xe9; aux param&#xe8;tres d&#x2019;identification d&#x2019;un d&#xe9;sert alimentaire propos&#xe9;s par le USDA, ainsi qu&#x2019;&#xe0; la perception d&#x2019;un groupe d&#x2019;acteurs r&#xe9;gionaux. <b>R&#xc9;SULTATS :</b> Lorsque la qualit&#xe9; de l&#x2019;alimentation &#xe9;tait consid&#xe9;r&#xe9;e, la pr&#xe9;sence de d&#xe9;serts alimentaires potentiels &#xe9;tait beaucoup plus importante qu&#x2019;avec la d&#xe9;finition propos&#xe9;e par le USDA. La mesure objective de l&#x2019;environnement alimentaire concordait avec la perception des acteurs r&#xe9;gionaux. <b>CONCLUSION :</b> Les caract&#xe9;ristiques des magasins d&#x2019;alimentation sont diff&#xe9;rentes en milieu rural et n&#xe9;cessitent une &#xe9;valuation directe pour identifier les d&#xe9;serts alimentaires potentiels. Les mesures objectives de l&#x2019;environnement alimentaire conjugu&#xe9;es avec les connaissances des acteurs r&#xe9;gionaux pourraient contribuer &#xe0; d&#xe9;velopper des arguments plus solides pour obtenir le support des d&#xe9;cideurs afin d&#x2019;&#xe9;laborer des interventions adapt&#xe9;es au milieu.
2,335,523
Apolipoprotein E: from cardiovascular disease to neurodegenerative disorders.
Apolipoprotein (apo) E was initially described as a lipid transport protein and major ligand for low density lipoprotein (LDL) receptors with a role in cholesterol metabolism and cardiovascular disease. It has since emerged as a major risk factor (causative gene) for Alzheimer's disease and other neurodegenerative disorders. Detailed understanding of the structural features of the three isoforms (apoE2, apoE3, and apoE4), which differ by only a single amino acid interchange, has elucidated their unique functions. ApoE2 and apoE4 increase the risk for heart disease: apoE2 increases atherogenic lipoprotein levels (it binds poorly to LDL receptors), and apoE4 increases LDL levels (it binds preferentially to triglyceride-rich, very low density lipoproteins, leading to downregulation of LDL receptors). ApoE4 also increases the risk for neurodegenerative diseases, decreases their age of onset, or alters their progression. ApoE4 likely causes neurodegeneration secondary to its abnormal structure, caused by an interaction between its carboxyl- and amino-terminal domains, called domain interaction. When neurons are stressed or injured, they synthesize apoE to redistribute cholesterol for neuronal repair or remodeling. However, because of its altered structure, neuronal apoE4 undergoes neuron-specific proteolysis, generating neurotoxic fragments (12-29&#xa0;kDa) that escape the secretory pathway and cause mitochondrial dysfunction and cytoskeletal alterations, including tau phosphorylation. ApoE4-associated pathology can be prevented by small-molecule structure correctors that block domain interaction by converting apoE4 to a molecule that resembles apoE3 both structurally and functionally. Structure correctors are a potential therapeutic approach to reduce apoE4 pathology in both cardiovascular and neurological disorders.
2,335,524
Postoperative analgesia in children: A comparison of three different doses of caudal epidural morphine.
Caudal epidural block is the most commonly used neuraxial block in children. Morphine has been used as a caudal additive for more than three decades. The aim of our study was to evaluate the efficacy and duration of analgesia of three different doses of caudal epidural morphine (CEM), and to find out the incidence of side effects.</AbstractText>This study was conducted on 75 patients of American Society of Anesthesiologists grades I and II, aged 2-12 years, undergoing lower abdominal and urogenital surgeries. Patients were randomly allocated to one of the three groups according to the dose of morphine. Group I received 30 &#x3bc;g/kg, group II 50 &#x3bc;g/kg, and group III 70 &#x3bc;g/kg. Heart rate, blood pressure, oxygen saturation, electrocardiogram, pain score, sedation score, duration of analgesia, and side-effects were noted.</AbstractText>The mean duration of analgesia was 8.63 h in group I, 13.36 h in group II and 19.19 h in group III. Respiratory depression was noted in three patients in group III. One patient in group I had itching. One patient each in groups I, II, and III had nausea/vomiting.</AbstractText>CEM significantly prolongs the duration of analgesia, though with a higher dose the risk of respiratory depression should always be kept in mind.</AbstractText>
2,335,525
The Effects of Kangaroo Mother Care and Swaddling on Venipuncture Pain in Premature Neonates: A Randomized Clinical Trial.
Hospitalized premature babies often undergo various painful procedures. Kangaroo mother care (KMC) and swaddling are two pain reduction methods.</AbstractText>This study was undertaken to compare the effects of swaddling and KMC on pain during venous sampling in premature neonates.</AbstractText>This study was performed as a randomized clinical trial on 90 premature neonates. The neonates were divided into three groups using a random allocation block. The three groups were group A (swaddling), group B (KMC), and group C (control). In all three groups, the heart rate and arterial oxygen saturation were measured and recorded in time intervals of 30 seconds before, during, and 30, 60, 90, and 120 seconds after blood sampling. The neonate's face was video recorded and assessed using the premature infant pain profile (PIPP) at time intervals of 30 seconds. The data was analyzed using the t-test, chi-square test, Repeated Measure analysis of variance (ANOVA), Kruskal-Wallis, Post-hoc, and Bonferroni test.</AbstractText>The findings revealed that pain was reduced to a great extent in the swaddling and KMC methods compared to the control group. However, there was no significant difference between KMC and swaddling (P &#x2265; 0.05).</AbstractText>The results of this study indicate that there is no meaningful difference between swaddling and KMC on physiological indexes and pain in neonates. Therefore, the swaddling method may be a good substitute for KMC.</AbstractText>
2,335,526
Anesthetic management of patient with Sjogren's syndrome who underwent cesarean section: a case report.
Sjogren's syndrome is one of the most common autoimmune disorders and has a female predominance. Maternal circulating autoantibodies such as anti-Ro/SSA and anti-La/SSB antibodies can cause congenital heart block of fetus, and in severe case, emergency pacemaker implantation may be needed for neonate. Therefore, it is very important to understand maternal and fetal condition and pay attention to the status of the neonate during delivery. In this paper, we present a case of patient with Sjogren's syndrome who underwent cesarean section under spinal anesthesia.
2,335,527
[The Effect of Different Positions on Block Plane of Isobaric Bupivacaine for Caesarean Section with Combined Spinal-Eqidural Analgesia].
To evaluate the effect of horizontal and trendelenburg left lateral position on the onset time and the spread of intrathecal isobaric bupivacaine for elective cesarean delivery.</AbstractText>180 parturients were enrolled to undergo elective cesarean delivery with combined spinal-epidural anesthesia (CSE). They were randomly divided into 3 groups (n = 60) according to the different positions during anesthesia: Group I horizontal position, Group II trendelenburg position 5 degrees, Group III trendelenburg position 10 degrees. A combined spinal-eqidural (CSE) analgesia was performed at the L3-4 interspace in either horizontal or trendelenburg left lateral position, according to randomization. 2 mL of 0.5% isobaric bupivacaine was injected into subarachnoid space when cerebrospinal fluid outflew. Then the patient was placed in a supine position. The success criteria of anesthesia was: T6 sensory block, Bromage grade 2 or 3 (motor block), anesthesia effect &#x2265; grade III. The systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), sensory block, motor block and adverse reactions such as hypotension, bradycardia, chest distress were observed after the 3 groups parturients entered into operating room. The numbers and success rate of Group I, II and III which got T6 sensory block in ten minutes were observed.</AbstractText>Among Group I, II and III, there were no significant differences in onset time of sensory block and motor block (P &gt; 0.05). The cold and pinprick sensation level in 10 min of Group I1 and Group III were higher than that of Group I (P &lt; 0.05). The success rate of Group II or III was higher than Group I (P &lt; 0.05). The success rate of Group III was higher than that of Group II, but not with significant difference (P &gt; 0.05). There were no significant differences in hemodynamics, adverse reactions such as hypotension, bradycardia, chest distress among three groups (P &gt; 0.05).</AbstractText>The trendelenburg 5 degrees position can meet the requirement of operation without high anesthesia level.</AbstractText>
2,335,528
Interactions between amiodarone and the hERG potassium channel pore determined with mutagenesis and in silico docking.
The antiarrhythmic drug amiodarone delays cardiac repolarisation through inhibition of hERG-encoded potassium channels responsible for the rapid delayed rectifier potassium current (IKr). This study aimed to elucidate molecular determinants of amiodarone binding to the hERG channel. Whole-cell patch-clamp recordings were made at 37&#xb0;C of ionic current (IhERG) carried by wild-type (WT) or mutant hERG channels expressed in HEK293 cells. Alanine mutagenesis and ligand docking were used to investigate the roles of pore cavity amino-acid residues in amiodarone binding. Amiodarone inhibited WT outward IhERG tails with a half-maximal inhibitory concentration (IC50) of &#x223c;45nM, whilst inward IhERG tails in a high K(+) external solution ([K(+)]e) of 94mM were blocked with an IC50 of 117.8nM. Amiodarone's inhibitory action was contingent upon channel gating. Alanine-mutagenesis identified multiple residues directly or indirectly involved in amiodarone binding. The IC50 for the S6 aromatic Y652A mutation was increased to &#x223c;20-fold that of WT IhERG, similar to the pore helical mutant S624A (&#x223c;22-fold WT control). The IC50 for F656A mutant IhERG was &#x223c;17-fold its corresponding WT control. Computational docking using a MthK-based hERG model differentiated residues likely to interact directly with drug and those whose Ala mutation may affect drug block allosterically. The requirements for amiodarone block of aromatic residues F656 and Y652 within the hERG pore cavity are smaller than for other high affinity IhERG inhibitors, with relative importance to amiodarone binding of the residues investigated being S624A&#x223c;Y652A&gt;F656A&gt;V659A&gt;G648A&gt;T623A.
2,335,529
Carvedilol inhibits cADPR- and IP<sub>3</sub>-induced Ca<sup>2+</sup> release.
Spontaneous Ca<sup>2+</sup> waves, also termed store-overload-induced Ca<sup>2+</sup> release (SOICR), in cardiac cells can trigger ventricular arrhythmias especially in failing hearts. SOICR occurs when RyRs are activated by an increase in sarcoplasmic reticulum (SR) luminal Ca<sup>2+</sup>. Carvedilol is one of the most effective drugs for preventing arrhythmias in patients with heart failure. Furthermore, carvedilol analogues with minimal &#x3b2;-blocking activity also block SOICR showing that SOICR-inhibiting activity is distinct from that for &#x3b2;-block. We show here that carvedilol is a potent inhibitor of cADPR-induced Ca<sup>2+</sup> release in sea urchin egg homogenate. In addition, the carvedilol analog VK-II-86 with minimal &#x3b2;-blocking activity also suppresses cADPR-induced Ca<sup>2+</sup> release. Carvedilol appeared to be a non-competitive antagonist of cADPR and could also suppress Ca<sup>2+</sup> release by caffeine. These results are consistent with cADPR releasing Ca<sup>2+</sup> in sea urchin eggs by sensitizing RyRs to Ca<sup>2+</sup> involving a luminal Ca<sup>2+</sup> activation mechanism. In addition to action on the RyR, we also observed inhibition of inositol 1,4,5-trisphosphate (IP<sub>3</sub>)-induced Ca<sup>2+</sup> release by carvedilol suggesting a common mechanism between these evolutionarily related and conserved Ca<sup>2+</sup> release channels.
2,335,530
Persistence of Amygdala-Hippocampal Connectivity and Multi-Voxel Correlation Structures During Awake Rest After Fear Learning Predicts Long-Term Expression of Fear.
After encoding, memories undergo a process of consolidation that determines long-term retention. For conditioned fear, animal models postulate that consolidation involves reactivations of neuronal assemblies supporting fear learning during postlearning "offline" periods. However, no human studies to date have investigated such processes, particularly in relation to long-term expression of fear. We tested 24 participants using functional MRI on 2 consecutive days in a fear conditioning paradigm involving 1 habituation block, 2 acquisition blocks, and 2 extinction blocks on day 1, and 2 re-extinction blocks on day 2. Conditioning blocks were preceded and followed by 4.5-min rest blocks. Strength of spontaneous recovery of fear on day 2 served as a measure of long-term expression of fear. Amygdala connectivity primarily with hippocampus increased progressively during postacquisition and postextinction rest on day 1. Intraregional multi-voxel correlation structures within amygdala and hippocampus sampled during a block of differential fear conditioning furthermore persisted after fear learning. Critically, both these main findings were stronger in participants who exhibited spontaneous recovery 24 h later. Our findings indicate that neural circuits activated during fear conditioning exhibit persistent postlearning activity that may be functionally relevant in promoting consolidation of the fear memory.
2,335,531
Detection and treatment of atherosclerosis using nanoparticles.
Atherosclerosis is the key pathogenesis of cardiovascular disease, which is a silent killer and a leading cause of death in the United States. Atherosclerosis starts with the adhesion of inflammatory monocytes on the activated endothelial cells in response to inflammatory stimuli. These monocytes can further migrate into the intimal layer of the blood vessel where they differentiate into macrophages, which take up oxidized low-density lipoproteins and release inflammatory factors to amplify the local inflammatory response. After accumulation of cholesterol, the lipid-laden macrophages are transformed into foam cells, the hallmark of the early stage of atherosclerosis. Foam cells can die from apoptosis or necrosis, and the intracellular lipid is deposed in the artery wall forming lesions. The angiogenesis for nurturing cells is enhanced during lesion development. Proteases released from macrophages, foam cells, and other cells degrade the fibrous cap of the lesion, resulting in rupture of the lesion and subsequent thrombus formation. Thrombi can block blood circulation, which represents a major cause of acute heart events and stroke. There are generally no symptoms in the early stages of atherosclerosis. Current detection techniques cannot easily, safely, and effectively detect the lesions in the early stages, nor can they characterize the lesion features such as the vulnerability. While the available therapeutic modalities cannot target specific molecules, cells, and processes in the lesions, nanoparticles appear to have a promising potential in improving atherosclerosis detection and treatment via targeting the intimal macrophages, foam cells, endothelial cells, angiogenesis, proteolysis, apoptosis, and thrombosis. Indeed, many nanoparticles have been developed in improving blood lipid profile and decreasing inflammatory response for enhancing therapeutic efficacy of drugs and decreasing their side effects. WIREs Nanomed Nanobiotechnol 2017, 9:e1412. doi: 10.1002/wnan.1412 For further resources related to this article, please visit the WIREs website.
2,335,532
K201 (JTV519) is a Ca2+-Dependent Blocker of SERCA and a Partial Agonist of Ryanodine Receptors in Striated Muscle.
K201 (JTV-519) may prevent abnormal Ca(2+) leak from the sarcoplasmic reticulum (SR) in the ischemic heart and skeletal muscle (SkM) by stabilizing the ryanodine receptors (RyRs; RyR1 and RyR2, respectively). We tested direct modulation of the SR Ca(2+)-stimulated ATPase (SERCA) and RyRs by K201. In isolated cardiac and SkM SR microsomes, K201 slowed the rate of SR Ca(2+) loading, suggesting potential SERCA block and/or RyR agonism. K201 displayed Ca(2+)-dependent inhibition of SERCA-dependent ATPase activity, which was measured in microsomes incubated with 200, 2, and 0.25 &#xb5;M Ca(2+) and with the half-maximal K201 inhibitory doses (IC50) estimated at 130, 19, and 9 &#xb5;M (cardiac muscle) and 104, 13, and 5 &#xb5;M (SkM SR). K201 (&#x2265;5 &#xb5;M) increased RyR1-mediated Ca(2+) release from SkM microsomes. Maximal K201 doses at 80 &#xb5;M produced &#x223c;37% of the increase in SkM SR Ca(2+) release observed with the RyR agonist caffeine. K201 (&#x2265;5 &#xb5;M) increased the open probability (Po) of very active ("high-activity") RyR1 of SkM reconstituted into bilayers, but it had no effect on "low-activity" channels. Likewise, K201 activated cardiac RyR2 under systolic Ca(2+) conditions (&#x223c;5 &#xb5;M; channels at Po &#x223c;0.3) but not under diastolic Ca(2+) conditions (&#x223c;100 nM; Po &lt; 0.01). Thus, K201-induced the inhibition of SR Ca(2+) leak found in cell-system studies may relate to potentially potent SERCA block under resting Ca(2+) conditions. SERCA block likely produces mild SR depletion in normal conditions but could prevent SR Ca(2+) overload under pathologic conditions, thus precluding abnormal RyR-mediated Ca(2+) release.
2,335,533
Ultrasound guided continuous paravertebral block in a patient with coronary heart disease and sleep apnea syndrome.
The case of a 77-year-old patient with severe coronary heart disease who underwent radical mastectomy with axillary lymph node dissection by ultrasound-guided continuous paravertebral block (CPVB) is described in the present report. Radical mastectomy with axillary dissection is a surgical procedure that necessitates endotracheal intubation and is usually performed under general anesthesia, which carries heightened risk for patients with coronary heart disease (CHD) and sleep apnea syndrome (SAS). Ultrasound-guided CPVB is a simple and safe alternative technique that allows for the use of anesthesia and postoperative analgesia with minimal side effects.
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Deficiency of myeloid-related proteins 8 and 14 (Mrp8/Mrp14) does not block inflammaging but prevents steatosis.
The Mrp8 and Mrp14 proteins (calprotectin) accumulate within tissues during aging and may contribute to chronic inflammation. To address this possibility, we evaluated female calprotectin-deficient Mrp14-KO and wild-type (WT) mice at 5 and 24 months of age. However, there was no evidence that age-related inflammation is blunted in KO mice. Inflammation markers were in fact elevated in livers from old KO mice, and microarray analysis revealed more consistent elevation of genes specifically expressed by B-cells and T-cells. Adipose-specific genes, however, were less consistently elevated in aged KO mice, suggesting an anti-steatosis effect of Mrp8/14 deficiency. Consistent with this, genes decreased by the anti-steatosis agent SRT1720 were decreased in old KO compared to old WT mice. Expression of lipid metabolism genes was altered in KO mice at 5 months of age, along with genes associated with development, biosynthesis and immunity. These early-age effects of Mrp8/14 deficiency, in the absence of any external stressor, were unexpected. Taken together, our findings demonstrate a pro-steatosis rather than pro-inflammatory role of calprotectin within the aging liver. This appears to reflect a developmental-metabolic phenotype of Mrp14-KO mice that is manifest at a young age in the absence of pro-inflammatory stimuli.
2,335,535
Non-image forming effects of illuminance level: Exploring parallel effects on physiological arousal and task performance.
This study investigated diurnal non-image forming (NIF) effects of illuminance level on physiological arousal in parallel to NIF effects on vigilance and working memory performance. We employed a counterbalanced within-subjects design in which thirty-nine participants (mean age=21.2; SD=2.1; 11 male) completed three 90-min sessions (165 vs. 600lx vs. 1700lx at eye level) either in the morning (N=18) or afternoon (N=21). During each session, participants completed four measurement blocks (incl. one baseline block) each consisting of a 10-min Psychomotor Vigilance Task (PVT) and a Backwards Digit-Span Task (BDST) including easy trials (4-6 digits) and difficult trials (7-8 digits). Heart rate (HR), skin conductance level (SCL) and systolic blood pressure (SBP) were measured continuously. The results revealed significant improvements in performance on the BDST difficult trials under 1700lx vs. 165lx (p=0.01), while illuminance level did not affect performance on the PVT and BDST easy trials. Illuminance level impacted HR and SCL, but not SBP. In the afternoon sessions, HR was significantly higher under 1700lx vs. 165lx during PVT performance (p=0.05), while during BDST performance, HR was only slightly higher under 600 vs. 165lx (p=0.06). SCL was significantly higher under 1700lx vs. 165lx during performance on BDST easy trials (p=0.02) and showed similar, but nonsignificant trends during the PVT and BDST difficult trials. Although both physiology and performance were affected by illuminance level, no consistent pattern emerged with respect to parallel changes in physiology and performance. Rather, physiology and performance seemed to be affected independently, via unique pathways.
2,335,536
Optimization-Based Speckle Tracking Algorithm for Left Ventricle Strain Estimation: A Feasibility Study.
Speckle tracking echocardiography (STE) is a widespread method for calculating myocardial strains and estimating left ventricle function. Since echocardiographic clips are corrupted by speckle decorrelation noise, resulting in irregular, nonphysiological tissue displacement fields, smoothing is performed on the displacement data, affecting the strain results. Thus, strain results may depend on the specific implementations of 2-D STE, as well as other systems' characteristics of the various vendors. A novel algorithm (called K-SAD) is introduced, which integrates the physiological constraint of smoothness of the displacement field into an optimization process. Simulated B-mode clips, modeling healthy and abnormal cases, were processed by K-SAD. Peak global and subendocardial longitudinal strains, as well as regional strains, were calculated. In addition, 410 healthy subjects were also processed. The results of K-SAD are compared with those of one of the leading commercial product. K-SAD provides global mid-wall strain values, as well as subendocardial and regional strain values, all in good agreement with the ground-truth-simulated phantom data. K-SAD peak global longitudinal systolic strain values for 410 healthy subjects are quite similar for the different regions: - 17.02 &#xb1; 4.02%, - 19.00 &#xb1; 3.45%, and - 19.72 &#xb1; 5.06% at the basal, mid, and apical regions, respectively. Improved performance under noisy conditions was demonstrated by comparing a subgroup of 40 subjects with the best image quality with the remaining 370 cohort: K-SAD provides statistically similar global and regional results for the two cohorts. Our study indicates that the sensitivity of strain values to speckle noise, caused by the post block-matching weighted smoothing, can be significantly reduced and accuracy enhanced by employing an integrated one-stage, physiologically constrained optimization process.
2,335,537
Comparison of Video-Assisted Thoracoscopic Surgery and Robotic Approaches for Clinical Stage I and Stage II Non-Small Cell Lung Cancer Using The Society of Thoracic Surgeons Database.
Data from selected centers show that robotic lobectomy is safe and effective and has 30-day mortality comparable to that of video-assisted thoracoscopic surgery (VATS). However, widespread adoption of robotic lobectomy is controversial. We used The Society of Thoracic Surgeons General Thoracic Surgery (STS-GTS) Database to evaluate quality metrics for these 2 minimally invasive lobectomy techniques.</AbstractText>A database query for primary clinical stage I or stage II non-small cell lung cancer (NSCLC) at high-volume centers from 2009 to 2013 identified 1,220 robotic lobectomies and 12,378 VATS procedures. Quality metrics evaluated included operative morbidity, 30-day mortality, and nodal upstaging, defined as cN0 to pN1. Multivariable logistic regression was used to evaluate nodal upstaging.</AbstractText>Patients undergoing robotic lobectomy were older, less active, and less likely to be an ever smoker and had higher body mass index (BMI) (all p &lt; 0.05). They were also more likely to have coronary heart disease or hypertension (all p &lt; 0.001) and to have had preoperative mediastinal staging (p &lt; 0.0001). Robotic lobectomy operative times were longer (median 186 versus 173 minutes; p &lt; 0.001); all other operative measurements were similar. All postoperative outcomes were similar, including complications and 30-day mortality (robotic lobectomy, 0.6% versus VATS, 0.8%; p&#xa0;= 0.4). Median length of stay was 4 days for both, but a higher proportion of patients undergoing robotic lobectomy had hospital stays less than 4 days (48% versus 39%; p &lt; 0.001). Nodal upstaging overall was similar (p&#xa0;= 0.6) but with trends favoring VATS in the cT1b group and robotic lobectomy in the cT2a group.</AbstractText>Patients undergoing robotic lobectomy had more comorbidities and robotic lobectomy operative times were longer, but quality outcome measures, including complications, hospital stay, 30-day mortality, and nodal upstaging, suggest that robotic lobectomy and VATS are equivalent.</AbstractText>Copyright &#xa9; 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.</CopyrightInformation>
2,335,538
Neural response patterns in spider, blood-injection-injury and social fearful individuals: new insights from a simultaneous EEG/ECG-fMRI study.
In the present simultaneous EEG/ECG-fMRI study we compared the temporal and spatial characteristics of the brain responses and the cardiac activity during fear picture processing between spider, blood-injection-injury (BII) and social fearful as well as healthy (non-fearful) volunteers. All participants were presented with two neutral and six fear-related blocks of pictures: two social, two spider and two blood/injection fear blocks. In a social fear block neutral images were occasionally interspersed with photographs of angry faces and social exposure scenes. In spider and blood/injection fear blocks neutral pictures were interspersed with spider fear-relevant and blood/injection pictures, respectively. When compared to healthy controls the social fear group responded with increased activations in the anterior orbital, middle/anterior cingulate and middle/superior temporal areas for pictures depicting angry faces and with a few elevated superior frontal activations for social exposure scenes. In the blood/injection fear group, heart rate was decreased and the activity in the middle/inferior frontal and visual processing regions was increased for blood/injection pictures. The HR decrease for blood/injection pictures correlated with increased frontal responses. In the spider fear group, spider fear-relevant pictures triggered increased activations within a broad subcortical and cortical neural fear network. The HR response for spider fear-relevant stimuli was increased and correlated with an increased insula and hippocampus activity. When compared to healthy controls, all fear groups showed higher LPP amplitudes for their feared cues and an overall greater P1 hypervigilance effect. Contrasts against the fear control groups showed that the increased responses for fear-specific stimuli are mostly related to specific fears and not to general anxiety proneness. The results suggest different engagement of cognitive evaluation and down-regulation strategies and an overall increased sensitization of the fear system in the three fear groups.
2,335,539
Subcutaneous Phaeohyphomycosis Cyst Associated with Medicopsis romeroi in an Immunocompromised Host.
An 88-year-old man, receiving prednisolone for sarcoidosis, presented with a discrete keratotic lesion on the dorsum of his right hand following the placement of an intravenous cannula a month prior to its appearance. Medicopsis romeroi was isolated from the tissue and identified by sequencing the internal transcribed spacer region ITS-1 and the D1-2 fragment of the 28S rDNA gene. Histopathological examination showed fungal hyphae in the internal inflammatory cells layer and within the histocyte-macrophage layer, highly suggestive of deep mycosis. The patient was successfully treated with surgical excision of the cyst. M. romeroi exhibited high MIC values for echinocandin drugs in vitro, but appeared susceptible to newer triazole agents, amphotericin B and terbinafine. This is the first report of a subcutaneous phaeohyphomycotic cyst occurring following the placement of an intravenous cannula. This report highlights the potential role of M. romeroi as an emerging cause of deep, non-mycetomatous infection in immunocompromised patients.
2,335,540
Pregnancy and primary Sj&#xf6;gren's syndrome: management and outcomes in a multicentre retrospective study of 54 pregnancies.
Primary Sj&#xf6;gren's syndrome (pSS) is one of the most common autoimmune diseases, mainly affecting women during the fourth decade of life. During pregnancy, the presence of anti-Ro/SSa and anti-La/SSb antibodies increases the risk of congenital heart block (CHB). Foetal and pregnancy outcomes in pregnant women with pSS compared with the general population are difficult to evaluate because of confounding factors including age and body mass index (BMI).</AbstractText>The aim of this case-control study was to analyse the impact of pSS in pregnant women on foetal and pregnancy outcomes.</AbstractText>We enrolled 19 women with pSS (54 pregnancies) matched by age and BMI to 216 controls. Patients with pSS delivered significantly earlier (38 weeks&#xa0;+&#xa0;3 days vs. 39&#xa0;weeks&#xa0;+&#xa0;2&#xa0;days) and experienced more spontaneous abortions [&lt; 22&#xa0;weeks of gestation (WG)] than the controls [n&#xa0;=&#xa0;16/54 (30.0%) vs. n&#xa0;=&#xa0;1/216 (0.4%); p&#xa0;&lt;&#xa0;0.00001]. Preterm delivery (&#x2264; 37+6</sup> WG) was significantly higher in the pSS group than in the control group (29% vs. 12%, p&#xa0;=&#xa0;0.04). pSS activity significantly affected the birthweight percentile, which was lower in pregnancies occurring after the diagnosis of pSS than in those occurring before (32.43&#xa0;&#xb1;&#xa0;21.57 vs. 60.46&#xa0;&#xb1;&#xa0;27.37; p&#xa0;=&#xa0;0.008). No case of CHB was observed.</AbstractText>pSS is responsible for an increased risk of spontaneous abortion. The duration of pregnancy is lower in patients with than without pSS, with more premature deliveries. Pregnancies that occur after the onset of the disease result in lower birthweight percentile children than when pSS is not clinically overt.</AbstractText>
2,335,541
Acetyl L-carnitine targets adenosine triphosphate synthase in protecting zebrafish embryos from toxicities induced by verapamil and ketamine: An in vivo assessment.
Verapamil is a Ca<sup>2</sup><sup>+</sup> channel blocker and is highly prescribed as an anti-anginal, antiarrhythmic and antihypertensive drug. Ketamine, an antagonist of the Ca<sup>2</sup><sup>+</sup> -permeable N-methyl-d-aspartate-type glutamate receptors, is a pediatric anesthetic. Previously we have shown that acetyl l-carnitine (ALCAR) reverses ketamine-induced attenuation of heart rate and neurotoxicity in zebrafish embryos. Here, we used 48&#x2009;h post-fertilization zebrafish embryos that were exposed to relevant drugs for 2 or 4&#x2009;h. Heart beat and overall development were monitored in vivo. In 48&#x2009;h post-fertilization embryos, 2&#x2009;mm ketamine reduced heart rate in a 2 or 4&#x2009;h exposure and 0.5&#x2009;mm ALCAR neutralized this effect. ALCAR could reverse ketamine's effect, possibly through a compensatory mechanism involving extracellular Ca<sup>2</sup><sup>+</sup> entry through L-type Ca<sup>2</sup><sup>+</sup> channels that ALCAR is known to activate. Hence, we used verapamil to block the L-type Ca<sup>2</sup><sup>+</sup> channels. Verapamil was more potent in attenuating heart rate and inducing morphological defects in the embryos compared to ketamine at specific times of exposure. ALCAR reversed cardiotoxicity and developmental toxicity in the embryos exposed to verapamil or verapamil plus ketamine, even in the presence of 3,4,5-trimethoxybenzoic acid 8-(diethylamino)octyl ester, an inhibitor of intracellular Ca<sup>2</sup><sup>+</sup> release suggesting that ALCAR acts via effectors downstream of Ca<sup>2</sup><sup>+</sup> . In fact, ALCAR's protective effect was blunted by oligomycin A, an inhibitor of adenosine triphosphate synthase that acts downstream of Ca<sup>2</sup><sup>+</sup> during adenosine triphosphate generation. We have identified, for the first time, using in vivo studies, a downstream effector of ALCAR that is critical in abrogating ketamine- and verapamil-induced developmental toxicities. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.
2,335,542
Comparative Efficacy of Intrathecal Bupivacaine Alone and Combination of Bupivacaine with Clonidine in Spinal Anaesthesia.
Clonidine is an &#x3b1;2 agonist agent that has been used as an adjuvant to local anaesthetics in regional anaesthesia.</AbstractText>This study compared two combinations of bupivacaine and clonidine with bupivacaine alone for surgeries below the level of umbilicus in spinal anaesthesia.</AbstractText>We conducted a randomized double blind study on 90 patients of ASA I and ASA II aged 20-60 years, 30 in each group, undergoing surgery below the level of umbilicus in spinal anaesthesia. For intrathecal block, Group 1 received bupivacaine hydrochloride 12.5mg (2.5ml) in 8% dextrose (0.5% sensorcaine heavy) + 1ml (150&#x3bc;g) of preservative free clonidine. Group 2 received bupivacaine hydrochloride 12.5mg (2.5ml) in dextrose (0.5% sensorcaine heavy) + 0.5ml (75&#x3bc;g) of preservative free clonidine + 0.5ml of normal saline to make the volumes of all the groups same. Group 3 received bupivacaine hydrochloride 2.5ml in 8% dextrose (0.5% sensorcaine heavy) + 1ml of normal saline to make the volumes of all the groups same. Heart rate, NIBP, oxygen saturation and respiratory rate were monitored. The onset and duration of sensory block, the highest dermatomal level of sensory block, motor block, time to complete motor block recovery and duration of spinal anaesthesia were recorded.</AbstractText>The data of the study was recorded in the record chart and results were evaluated using statistical tests (ANOVA test, post-hoc turkey hsd test, paired t-test and chi-square test).</AbstractText>Demographic data, the incidence and duration of bradycardia were comparable amongst the groups. The duration of sensory and motor block were greatest in group 1, followed by group 2 and group 3 (p &lt;0.01). Decrease in the systolic blood pressure of group 2 and group 3 was noted as compared to group 1. No significant sedation or respiratory depression was observed in any group.</AbstractText>Addition of clonidine to bupivacaine intrathecally is although a reliable method to prolong spinal anaesthesia but close monitoring for hypotension is desirable.</AbstractText>
2,335,543
Major complications of regional anesthesia in 11 teaching hospitals of China: a prospective survey of 106,569 cases.
To determine the incidence of major complications in patients undergoing regional anesthesia (RA) in China.</AbstractText>Multicenter prospective survey.</AbstractText>Eleven teaching hospitals in China.</AbstractText>A total of 106,569 patients undergoing RA from April 1, 2009, to April 30, 2011, were involved.</AbstractText>Information on patients, types of surgery, and RA techniques was collected with a standardized chart. After RA, the patients were followed up by an investigator in each center for 1 to 3 weeks according to the patient's condition. Data were integrated and analyzed with a structured query language server system.</AbstractText>Among the patients undergoing RA, 37 developed major complications, including Horner syndrome (n = 9; 0.84/10,000), recurrent laryngeal nerve blockade (n = 6; 0.56/10,000), cardiac arrest (n = 1; 0.09/10,000), hematoma (n = 2; 0.19/10,000), seizures (n = 5; 0.46/10,000), catheter break (n = 1; 0.09/10,000), paraplegia (n = 1; 0.09/10,000), cauda equina syndrome (n = 2; 0.19/10,000), and extensive neuraxial block (n = 10; 0.94/10,000). The incidence of major RA complications varied from 0.8/10,000 to 18.8/10,000 among centers and was highest in cervical plexum block. Plastic surgery had the highest incidence of complications (19.0/10,000), most of which were recurrent extensive neuraxial block. The total incidence of major RA complications was 3.47/10,000.</AbstractText>This large, multicenter, prospective survey revealed the incidence of major complications after RA in China's hospitals. Although severe complication like cardiac arrest is rare, it is distressing and challenging. Hence, there is still a room to improve on daily basis to further reduce complications related to RA.</AbstractText>Copyright &#xa9; 2016 Elsevier Inc. All rights reserved.</CopyrightInformation>
2,335,544
Changes in vagal afferent drive alter tracheobronchial coughing in anesthetized cats.
Unilateral cooling of the vagus nerve (&lt;5&#xb0;C, blocking mainly conductivity of myelinated fibers) and unilateral vagotomy were employed to reduce cough afferent drive in order to evaluate the effects of these interventions on the temporal features of the cough reflex. Twenty pentobarbitone anesthetized, spontaneously breathing cats were used. Cough was induced by mechanical stimulation of the tracheobronchial airways. The number of coughs during vagal cooling was significantly decreased (p&lt;0.001). Inspiratory cough efforts were reduced by approximately 30% (p&lt;0.001) and expiratory motor drive by more than 80% (p&lt;0.001). Temporal analysis showed prolonged inspiratory and expiratory phases, the total cycle duration, its active portion, and the interval between maxima of the diaphragm and the abdominal activity during coughing (p&lt;0.001). There was no significant difference in the average effects on the cough reflex between cooling of the left or the right vagus nerve. Compared to control, vagal cooling produced no significant difference in heart rate and mean arterial blood pressure (p&gt;0.05), however, cold block of vagal conduction reduced respiratory rate (p&lt;0.001). Unilateral vagotomy significantly reduced cough number, cough-related diaphragmatic activity, and relative values of maximum expiratory esophageal pressure (all p&lt;0.05). Our results indicate that reduced cough afferent drive (lower responsiveness) markedly attenuates the motor drive to respiratory pump muscles during coughing and alters cough temporal features. Differences in the effects of unilateral vagal cooling and vagotomy on coughing support an inhibitory role of sensory afferents that are relatively unaffected by cooling of the vagus nerve to 5&#xb0;C on mechanically induced cough.
2,335,545
Gleaning structural and functional information from correlations in protein multiple sequence alignments.
The availability of vast amounts of protein sequence data facilitates detection of subtle statistical correlations due to imposed structural and functional constraints. Recent breakthroughs using Direct Coupling Analysis (DCA) and related approaches have tapped into correlations believed to be due to compensatory mutations. This has yielded some remarkable results, including substantially improved prediction of protein intra- and inter-domain 3D contacts, of membrane and globular protein structures, of substrate binding sites, and of protein conformational heterogeneity. A complementary approach is Bayesian Partitioning with Pattern Selection (BPPS), which partitions related proteins into hierarchically-arranged subgroups based on correlated residue patterns. These correlated patterns are presumably due to structural and functional constraints associated with evolutionary divergence rather than to compensatory mutations. Hence joint application of DCA- and BPPS-based approaches should help sort out the structural and functional constraints contributing to sequence correlations.
2,335,546
Anaesthetic efficacy of lidocaine/clonidine for inferior alveolar nerve block in patients with irreversible pulpitis.
This prospective, randomized, double-blind study aimed to compare the efficacy of lidocaine with epinephrine versus lidocaine with clonidine for inferior alveolar nerve block (IANB) and hemodynamic stability (heart rate, systolic blood pressure, diastolic blood pressure and mean arterial pressure) in patients with irreversible pulpitis.</AbstractText>One hundred patients with irreversible pulpitis in mandibular molar teeth randomly received 1.8 mL of 2% lidocaine with clonidine (15&#xa0;&#x3bc;g&#xa0;mL-1</sup> ) or 1.8 mL of 2% lidocaine with epinephrine (12.5&#xa0;&#x3bc;g&#xa0;mL-1</sup> ), using a conventional IANB technique. Endodontic access cavities were prepared 15&#xa0;min after solution deposition, and all patients were required to have profound lip numbness. Success was defined as no or mild pain (visual analog scale recording) upon endodontic access cavity preparation or initial canal instrumentation. The hemodynamic parameters were measured before, during and 5, 10 and 30&#xa0;min after administration. Finally, the collected data were subjected to independent t-test, chi-square and Fisher's exact test using spss software ver.20 at a significant level of 0.05.</AbstractText>The success rates for IANB using lidocaine with epinephrine and lidocaine with clonidine solutions were 29% and 59%, respectively. The clonidine group exhibited a significantly higher success rate (P&#xa0;&lt;&#xa0;0.05). Five minutes after drug administration, systolic blood pressure and heart rate significantly increased in the lidocaine with epinephrine group and insignificantly decreased in lidocaine with clonidine group.</AbstractText>For mandibular molars with irreversible pulpitis, addition of clonidine to lidocaine improved the success rate of IANB compared to a standard lidocaine/epinephrine solution.</AbstractText>&#xa9; 2016 International Endodontic Journal. Published by John Wiley &amp; Sons Ltd.</CopyrightInformation>
2,335,547
Hypotensive Epidural Anesthesia Reduces Blood Loss in Pelvic and Sacral Bone Tumor Resections.
Resection of pelvic and sacral tumors can cause severe blood loss, complications, and even postoperative death. Hypotensive epidural anesthesia has been used to mitigate blood loss after elective arthroplasty, but to our knowledge, it has not been studied as an approach that might make resection of pelvic and sacral tumors safer.</AbstractText><AbstractText Label="QUESTIONS/PURPOSES" NlmCategory="OBJECTIVE">The purposes of this study were (1) to compare the blood loss and blood product use for patients undergoing pelvic and sacral tumor surgery under standard anesthesia or hypotensive epidural anesthesia; (2) to assess the frequency of end-organ damage with the two techniques; and (3) to compare 90-day mortality between the two techniques.</AbstractText>Between 2000 and 2014, 285 major pelvic and sacral resections were performed at one center. A total of 174 (61%) had complete data sets for analysis of blood loss, transfusion use, complications, and mortality at 90 days. Of those, 102 (59%) underwent hypotensive epidural anesthesia, whereas the remainder received standard anesthetic care. The anesthetic approach was determined by the anesthetists in charge of the case with hypotensive epidural anesthesia exclusively performed by one of two subspecialty trained anesthetists as their routine for major pelvic or sacral surgery. The groups were comparable in terms of potential confounding variables such as age, gender, tumor volume, and operation performed. Hypotensive epidural anesthesia was defined as a technique using an extensive epidural block up to T2-3 dermatome, peripherally administered low-concentration intravenous adrenaline infusion, and using unimpeded spontaneous respiration to achieve controlled hypotension, precise rate control of the heart, and enhanced velocity of venous return, all aggregated thus to minimize blood loss during pelvic surgery while preserving vital perfusion. The groups were assessed for perioperative blood loss calculated from pre- and postsurgery hemoglobin and transfusion use as well as postoperative complications, morbidity, and mortality at 90 days.</AbstractText>There was less mean blood loss in the hypotensive epidural anesthesia group (1457 mL, SD 1721, 95% confidence interval [CI], 1114-1801 versus 2421 mL, SD 2297, 95% CI, 1877-2965; p = 0.003). Patients in the hypotensive epidural anesthesia group on average received fewer packed red cell transfusions (2.7 units, SD 2.9, 95% CI, 2.1-3.2 versus 3.9 units, SD 4.4, 95% CI, 2.9-5.0; p = 0.03). There were no differences in the proportions of patients experiencing end-organ injury (7%, n = seven of 102 versus 6%, n = four of 72; p = 0.72). With the numbers available, there was no difference in 90-day mortality rate between groups (1.9%, n = two of 102 versus 1.3%, n = one of 72; p = 0.77).</AbstractText>We found that hypotensive epidural anesthesia resulted in less blood loss, fewer transfusions, and no apparent increase in serious complications in pelvic and sacral tumor surgery performed in the setting of a high-volume tertiary sarcoma referral hospital. We recommend that further collaborative studies be undertaken to confirm our results with hypotensive epidural anesthesia in surgery for pelvic tumors.</AbstractText>Level III, therapeutic study.</AbstractText>
2,335,548
Multiplex cytokine analyses in patients with rheumatoid arthritis require use of agents blocking heterophilic antibody activity.
Heterophilic antibodies, such as rheumatoid factor (RF), are known to interfere with enzyme-linked immunosorbent assays (ELISAs). Treatment of rheumatoid arthritis (RA) with tumour necrosis factor (TNF)-&#x3b1; blockers is well established. The aims of this study were to develop a protocol for blocking the interaction of present heterophilic antibodies and to validate this procedure by evaluating the effect on correlations of cytokine levels to clinical response in RA patients treated with adalimumab.</AbstractText>Fourteen patients with active RA were evaluated at baseline and 3 months after starting adalimumab treatment. Cytokines were analysed with a commercial 12-plex bead ELISA. To block interference by RF, a commercial blocker (HeteroBlock) was used. To determine the optimal concentration of HeteroBlock, patient sera were analysed with different concentrations of HeteroBlock. Subsequently, baseline and follow-up sera from the 14 patients were analysed and correlated with clinical outcome.</AbstractText>Measured cytokine levels were reduced in the majority of samples when adding the blocker. The optimal concentration of HeteroBlock was 1600 &#x3bc;g/mL of serum. Sera with high RF levels were more prone to produce false positive values, although some RF-negative sera also demonstrated evidence of interference. HeteroBlock did not interfere with the analysis. In RA patients treated with adalimumab, changes in interleukin (IL)-6 levels between baseline and follow-up correlated with changes in erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) in sera with added HeteroBlock.</AbstractText>When analysing sera from patients with RA with multiplex bead ELISA, the assay should be evaluated for interference by heterophilic antibodies, and if present corrected with, for example, HeteroBlock.</AbstractText>
2,335,549
Cellular mechanisms and consequences of glycation in atherosclerosis and obesity.
Post-translational modification of proteins imparts diversity to protein functions. The process of glycation represents a complex set of pathways that mediates advanced glycation endproduct (AGE) formation, detoxification, intracellular disposition, extracellular release, and induction of signal transduction. These processes modulate the response to hyperglycemia, obesity, aging, inflammation, and renal failure, in which AGE formation and accumulation is facilitated. It has been shown that endogenous anti-AGE protective mechanisms are thwarted in chronic disease, thereby amplifying accumulation and detrimental cellular actions of these species. Atop these considerations, receptor for advanced glycation endproducts (RAGE)-mediated pathways downregulate expression and activity of the key anti-AGE detoxification enzyme, glyoxalase-1 (GLO1), thereby setting in motion an interminable feed-forward loop in which AGE-mediated cellular perturbation is not readily extinguished. In this review, we consider recent work in the field highlighting roles for glycation in obesity and atherosclerosis and discuss emerging strategies to block the adverse consequences of AGEs. This article is part of a Special Issue entitled: The role of post-translational protein modifications on heart and vascular metabolism edited by Jason R.B. Dyck &amp; Jan F.C. Glatz.
2,335,550
Deletion of neurturin impairs development of cholinergic nerves and heart rate control in postnatal mouse hearts.
The neurotrophic factor neurturin is required for normal cholinergic innervation of adult mouse heart and bradycardic responses to vagal stimulation. Our goals were to determine effects of neurturin deletion on development of cardiac chronotropic and dromotropic functions, vagal baroreflex response, and cholinergic nerve density in nodal regions of postnatal mice. Experiments were performed on postnatal C57BL/6 wild-type (WT) and neurturin knockout (KO) mice. Serial electrocardiograms were recorded noninvasively from conscious pups using an ECGenie apparatus. Mice were treated with atenolol to evaluate and block sympathetic effects on heart rate (HR) and phenylephrine (PE) to stimulate the baroreflex. Immunohistochemistry was used to label cholinergic nerves in paraffin sections. WT and KO mice showed similar age-dependent increases in HR and decreases in PR interval between postnatal days (P) 2.5 and 21. Treatment with atenolol reduced HR significantly in WT and KO pups at P7.5. PE caused a reflex bradycardia that was significantly smaller in KO pups. Cholinergic nerve density was significantly less in nodal regions of P7.5 KO mice. We conclude that cholinergic nerves have minimal influence on developmental changes in HR and PR, QRS, and QTc intervals in mouse pups. However, cholinergic nerves mediate reflex bradycardia by 1&#xa0;week postnatally. Deletion of neurturin impairs cholinergic innervation of the heart and the vagal efferent component of the baroreflex early during postnatal development.
2,335,551
Analgesic and Sedative Effects of Dezocine and Midazolam During Vitrectomy.
To evaluate the analgesic and sedative effectiveness of dezocine and midazolam in vitrectomy.</AbstractText>One hundred and sixty patients undergoing vitrectomy were randomized into four groups. The control group was given local anesthetic in retrobulbar nerve block only, while the other three groups received a single dose of 0.1 mg/kg dezocine or/and 0.05 mg/kg midazolam (groups D, M, DM), respectively, at 10 min before retrobulbar block. Mean arterial pressure (MAP), heart rate (HR), and oxygen saturation (SpO2</sub>) were recorded prior to local anesthesia (Tp), at the start of surgery (T0), 5, 15, 30 min during (T1-T3), and at the end of surgery (T4). Pain at T2 and T4 was assessed by Numeric Rating Scale (NRS). Level of sedation at T2 was assessed using the Ramsay scale. Postoperative nausea and vomiting (PONV) events were recorded for 24 h.</AbstractText>Group DM showed a decrease in HR during T0-T4 compared to Tp (p &lt; 0.001). The MAP of all groups decreased significantly at T0 compared to Tp (p &lt; 0.05), but remained unchanged at T1-T4. At T2, all groups have lower pain level than control (p &lt; 0.001), while group DM showed the lowest pain level. At T4, groups D and DM showed a lower pain level than control (p &lt; 0.01). Groups M and DM showed a higher Ramsay score than group C (p &lt; 0.01). Compared with control, group D had a higher PONV rate (p &lt; 0.1). Groups M and DM showed a lower PONV rate than group D (p &lt; 0.0001), and group M had a lower PONV rate than group C (p &lt; 0.01).</AbstractText>Combinatory use of dezocine and midazolam in addition to local anesthetic in retrobulbar nerve block can help relief pain and anxiety during vitrectomy and reduce PONV.</AbstractText>
2,335,552
Effects of interstimulus intervals on behavioral, heart rate, and event-related potential indices of infant engagement and sustained attention.
Maximizing infant attention to stimulus presentation during an EEG or ERP experiment is important for making valid inferences about the neural correlates of infant cognition. The present study examined the effects of stimulus presentation interstimulus interval (ISI) on behavioral and physiological indices of infant attention including infants' fixation to visual presentation, the amount of heart rate (HR) change during sustained attention, and ERP components. This study compared an ISI that is typically used in infant EEG/ERP studies (e.g., 1,500-2,000 ms) with two shorter durations (400-600 ms and 600-1,000 ms). Thirty-six infants were tested cross-sectionally at 3, 4.5, and 6 months. It was found that using the short (400-600 ms) and medium (600-1,000 ms) ISIs resulted in more visually fixated trials and reduced frequency of fixation disengagement per experimental block. We also found larger HR changes during sustained attention to both of the shorter ISIs compared with the long ISI, and larger ERP responses when using the medium ISI compared to using the short and long ISIs. These data suggest that utilizing an optimal ISI (e.g., 600-1,000 ms), which increases the presentation complexity and provides sufficient time for information processing, can promote infant engagement and sustained attention during stimulus presentation.
2,335,553
Physiological and psychological responses in Fire Instructors to heat exposures.
Fire Service Instructors (FSI) are exposed to many repeated periods of high environmental temperatures when training firefighters. Such repeated exposures will impose significant strains on the function of instructors. We aimed to measure the effects of a training programme including repeated exposures to heat, termed "Wears" in the fire service, on the physiological, psychological some immunological markers of Fire Service Instructors.</AbstractText>Six FSI and six physiologically matched controls completed blood and cardiovascular tests pre and post a 4wk heat instruction training block, controls completed the tests only. FSI were given a 7wk period of no heat exposure prior to starting the training. Physiological and perceptual measures were taken pre and post the first and last Wear of the 4wk training protocol.</AbstractText>There were acute effects of a Wear on core temperature and physiological strain index, as well as measures of fatigue. The acute exposure to heat during a Wear led to a consistent decrease in CRP (-10% to -40%), increased IL6 concentrations 33-45%) as well as increased RPE and TSS. Over the training programme significantly lower quantities of white cells, particularly neutrophils, leukocytes and monocytes were found in the FSI group. Between the start and the end of the 4 week training programme the FSI showed a significantly greater physiological strain index (PSI) to the Wears, which nearly doubled from 2.5 to 4.7 (p&lt;0.05).</AbstractText>Physiological and psychological measures indicate that FSI may be experiencing symptoms and changes to their health consistent with an overtraining type condition.</AbstractText>Copyright &#xa9; 2016 Elsevier Ltd. All rights reserved.</CopyrightInformation>
2,335,554
The meaning of being in uncertainty after heart transplantation - an unrevealed source to distress.
As many as 88% of heart transplant recipients (HTRs) suffer from psychological distress. Both psychosocial factors and physical health are associated with increased psychological distress. However, the causes and impacts of psychological distress are unclear. HTRs strive for a sense of control over their health and daily lives in order to improve their psychological well-being. Perceived control was found to be related to the patients' construction of normality, their emotional state, as well as their thoughts and feelings of uncertainty about the future.</AbstractText>An in-depth exploration of the meaning of uncertainty during the first year after a heart transplantation (HTX).</AbstractText>A phenomenological-hermeneutic method was employed. Interviews were conducted with 14 patients, four women and ten men, with a mean age of 51 years (range: 28-67 years).</AbstractText>Being in uncertainty after HTX means losing a sense of coherence, which shatters the HTR's whole worldview. The HTRs search for meaning and strive for coherence, which is no longer achievable. By using a nursing theory, we understand that uncertainty should be seen as a natural state among HTRs. It constitutes the starting point from which the HTRs can reorganise their self-structure and find a new view of life. When striving for normality, certainty and predictability (i.e., the healthcare professional's perspective), we block or prolong this process, thus causing distress among HTRs because they are unable to create a new orientation in life.</AbstractText>This study presents a hypothesis of the primary cause of psychological distress after HTX and provides a useful framework for how to approach this condition.</AbstractText>
2,335,555
Effects on hemodynamic variables and echocardiographic parameters after a stellate ganglion block in 15 healthy volunteers.
The sympathetic nervous system has an important role in generating pain. Various pathomechanisms are involved that respond well to the application of local anesthetics (LA), for example to the stellate ganglion block (SGB).</AbstractText>We wanted to know more about the effects of SGB on cardiovascular parameters.</AbstractText>We included 15 healthy volunteers; another 15 healthy volunteers as a control group (sham injection of LA). In order to produce a more precise SGB, we employed only a small volume of LA (3mL), a LA with a lower permeability (procaine 1%), and a modified injection technique. Systolic and diastolic blood pressure (SBP, DBP), heart rate (HR), and echocardiographic parameters were recorded before and after SGB. We also investigated whether there are side differences (left and right SBG).</AbstractText>At baseline all parameters were within the normal range. After performing right and left SGB DBP significantly increased (on the right side from 68.73&#xb1;8.61 to 73.53&#xb1;11.10, p=0.015; on the left side from 70.66&#xb1;13.01 to 77.93&#xb1;10.40, p=0.003). In the control group no increase in DBP was observed. No side-specific differences were found, except a significant reduction in the maximum velocity of myocardial contraction during the systole with left-sided SGB.</AbstractText>Even with our methods we could not prevent the simultaneous occurrence of a partial parasympatholytic effect. For this reason, the SGB has only minor hemodynamic effects, which is desirable as it enhances the safety of the SGB.</AbstractText>Copyright &#xa9; 2016 The Authors. Published by Elsevier B.V. All rights reserved.</CopyrightInformation>
2,335,556
Lidocaine Enhances Contractile Function of Ischemic Myocardial Regions in Mouse Model of Sustained Myocardial Ischemia.
Perioperative myocardial ischemia is common in high-risk patients. The use of interventional revascularisation or even thrombolysis is limited in this patient subset due to exceedingly high bleeding risks. Blockade of voltage-gated sodium channels (VGSC) with lidocaine had been suggested to reduce infarct size and cardiomyocyte cell death in ischemia/reperfusion models. However, the impact of lidocaine on cardiac function during sustained ischemia still remains unclear.</AbstractText>Sustained myocardial ischemia was induced by ligation of the left anterior descending artery in 12-16 weeks old male BALB/c mice. Subcutaneous lidocaine (30 mg/kg) was used to block VGSC. Cardiac function was quantified at baseline and at 72h by conventional and speckle-tracking based echocardiography to allow high-sensitivity in vivo phenotyping. Infarct size and cardiomyocyte cell death were assessed post mortem histologically and indirectly using troponin measurements.</AbstractText>Ischemia strongly impaired both, global systolic and diastolic function, which were partially rescued in lidocaine treated in mice. No differences regarding infarct size and cardiomyocyte cell death were observed. Mechanistically, and as shown with speckle-tracking analysis, lidocaine specifically improves residual contractility in the ischemic but not in the remote, non-ischemic myocardium.</AbstractText>VGSC blockade with lidocaine rescues function of ischemic myocardium as a potential bridging to revascularisation in the setting of perioperative myocardial ischemia.</AbstractText>
2,335,557
Relevance of HCN2-expressing human mesenchymal stem cells for the generation of biological pacemakers.
The transfection of human mesenchymal stem cells (hMSCs) with the hyperpolarization-activated cyclic nucleotide-gated ion channel 2 (HCN2) gene has been demonstrated to provide biological pacing in dogs with complete heart block. The mechanism appears to be the generation of the ion current (If) by the HCN2-expressing hMSCs. However, it is not clear how the transfection process and/or the HCN2 gene affect the growth functions of the hMSCs. Therefore, we investigated survival, proliferation, cell cycle, and growth on a Kapton&#xae; scaffold of HCN2-expressing hMSCs.</AbstractText>hMSCs were isolated from the bone marrow of healthy volunteers applying a selective cell adhesion procedure and were identified by their expression of specific surface markers. Cells from passages 2-3 were transfected by electroporation using commercial transfection kits and a pIRES2-EGFP vector carrying the pacemaker gene, mouse HCN2 (mHCN2). Transfection efficiency was confirmed by enhanced green fluorescent protein (EGFP) fluorescence, quantitative real-time polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA). After hMSCs were transfected, their viability, proliferation, If generation, apoptosis, cell cycle, and expression of transcription factors were measured and compared with non-transfected cells and cells transfected with pIRES2-EGFP vector alone.</AbstractText>Intracellular mHCN2 expression after transfection increased from 22.14 to 62.66 ng/mg protein (p &lt; 0.05). Transfection efficiency was 45 &#xb1; 5 %. The viability of mHCN2-transfected cells was 82 &#xb1; 5 %; they grew stably for more than 3 weeks and induced If current. mHCN2-transfected cells had low mitotic activity (10.4 &#xb1; 1.24 % in G2/M and 83.6 &#xb1; 2.5 % in G1 phases) as compared with non-transfected cells (52-53 % in G2/M and 31-35 % in G1 phases). Transfected cells showed increased activation of nine cell cycle-regulating transcription factors: the most prominent upregulation was of AMP-dependent transcription factor ATF3 (7.11-fold, p = 0.00056) which regulates the G1 phase. mHCN2-expressing hMSCs were attached and made anchorage-dependent connection with other cells without transmigration through a 12.7-&#x3bc;m thick Kapton&#xae; HN film with micromachined 1-3 &#x3bc;m diameter pores.</AbstractText>mHCN2-expressing hMSCs preserved the major cell functions required for the generation of biological pacemakers: high viability, functional activity, but low proliferation rate through the arrest of cell cycle in the G1 phase. mHCN2-expressing hMSCs attached and grew on a Kapton&#xae; scaffold without transmigration, confirming the relevance of these cells for the generation of biological pacemakers.</AbstractText>
2,335,558
Chemoimmunotherapy with methotrexate, cytarabine, thiotepa, and rituximab (MATRix regimen) in patients with primary CNS lymphoma: results of the first randomisation of the International Extranodal Lymphoma Study Group-32 (IELSG32) phase 2 trial.
Standard treatment for patients with primary CNS lymphoma remains to be defined. Active therapies are often associated with increased risk of haematological or neurological toxicity. In this trial, we addressed the tolerability and efficacy of adding rituximab with or without thiotepa to methotrexate-cytarabine combination therapy (the MATRix regimen), followed by a second randomisation comparing consolidation with whole-brain radiotherapy or autologous stem cell transplantation in patients with primary CNS lymphoma. We report the results of the first randomisation in this Article.</AbstractText>For the international randomised phase 2 International Extranodal Lymphoma Study Group-32 (IELSG32) trial, HIV-negative patients (aged 18-70 years) with newly diagnosed primary CNS lymphoma and measurable disease were enrolled from 53 cancer centres in five European countries (Denmark, Germany, Italy, Switzerland, and the UK) and randomly assigned (1:1:1) to receive four courses of methotrexate 3&#xb7;5 g/m(2) on day 1 plus cytarabine 2 g/m(2) twice daily on days 2 and 3 (group A); or the same combination plus two doses of rituximab 375 mg/m(2) on days -5 and 0 (group B); or the same methotrexate-cytarabine-rituximab combination plus thiotepa 30 mg/m(2) on day 4 (group C), with the three groups repeating treatment every 3 weeks. Patients with responsive or stable disease after the first stage were then randomly allocated between whole-brain radiotherapy and autologous stem cell transplantation. A permuted blocks randomised design (block size four) was used for both randomisations, and a computer-generated randomisation list was used within each stratum to preserve allocation concealment. Randomisation was stratified by IELSG risk score (low vs intermediate vs high). No masking after assignment to intervention was used. The primary endpoint of the first randomisation was the complete remission rate, analysed by modified intention to treat. This study is registered with ClinicalTrials.gov, number NCT01011920.</AbstractText>Between Feb 19, 2010, and Aug 27, 2014, 227 eligible patients were recruited. 219 of these 227 enrolled patients were assessable. At median follow-up of 30 months (IQR 22-38), patients treated with rituximab and thiotepa had a complete remission rate of 49% (95% CI 38-60), compared with 23% (14-31) of those treated with methotrexate-cytarabine alone (hazard ratio 0&#xb7;46, 95% CI 0&#xb7;28-0&#xb7;74) and 30% (21-42) of those treated with methotrexate-cytarabine plus rituximab (0&#xb7;61, 0&#xb7;40-0&#xb7;94). Grade 4 haematological toxicity was more frequent in patients treated with methotrexate-cytarabine plus rituximab and thiotepa, but infective complications were similar in the three groups. The most common grade 3-4 adverse events in all three groups were neutropenia, thrombocytopenia, anaemia, and febrile neutropenia or infections. 13 (6%) patients died of toxicity.</AbstractText>With the limitations of a randomised phase 2 study design, the IELSG32 trial provides a high level of evidence supporting the use of MATRix combination as the new standard chemoimmunotherapy for patients aged up to 70 years with newly diagnosed primary CNS lymphoma and as the control group for future randomised trials.</AbstractText>Associazione Italiana del Farmaco, Cancer Research UK, Oncosuisse, and Swiss National Foundation.</AbstractText>Copyright &#xa9; 2016 Elsevier Ltd. All rights reserved.</CopyrightInformation>
2,335,559
Differential inhibition of cardiac and neuronal Na(+) channels by the selective serotonin-norepinephrine reuptake inhibitors duloxetine and venlafaxine.
Duloxetine and venlafaxine are selective serotonin-norepinephrine-reuptake-inhibitors used as antidepressants and co-analgesics. While venlafaxine rather than duloxetine induce cardiovascular side-effects, neither of the substances are regarded cardiotoxic. Inhibition of cardiac Na(+)-channels can be associated with cardiotoxicity, and duloxetine was demonstrated to block neuronal Na(+)-channels. The aim of this study was to investigate if the non-life threatening cardiotoxicities of duloxetine and venlafaxine correlate with a weak inhibition of cardiac Na(+)-channels. Effects of duloxetine, venlafaxine and amitriptyline were examined on endogenous Na(+)-channels in neuroblastoma ND7/23 cells and on the &#x3b1;-subunits Nav1.5, Nav1.7 and Nav1.8 with whole-cell patch clamp recordings. Tonic block of the cardiac Na(+)-channel Nav1.5 and rat-cardiomyocytes (CM) revealed a higher potency for duloxetine (Nav 1.5 IC50 14&#xb1;1&#xb5;M, CM IC50 27&#xb1;3&#xb5;M) as compared to venlafaxine (Nav 1.5 IC50 671&#xb1;26&#xb5;M, CM IC50 452&#xb1;34&#xb5;M). Duloxetine was as potent as the cardiotoxic antidepressant amitriptyline (IC50 13&#xb1;1&#xb5;M). While venlafaxine almost failed to induce use-dependent block on Nav1.5 and cardiomyocytes, low concentrations of duloxetine (1, 10&#xb5;M) induced prominent use-dependent block similar to amitriptyline. Duloxetine, but not venlafaxine stabilized fast and slow inactivation and delayed recovery from inactivation. Duloxetine induced an unselective inhibition of neuronal Na(+)-channels (IC50 ND7/23 23&#xb1;1&#xb5;M, Nav1.7 19&#xb1;2&#xb5;M, Nav1.8 29&#xb1;2). Duloxetine, but not venlafaxine inhibits cardiac Na(+)-channels with a potency similar to amitriptyline. These data indicate that an inhibition of Na(+)-channels does not predict a clinically relevant cardiotoxicity.
2,335,560
Specific Delivery of MiRNA for High Efficient Inhibition of Prostate Cancer by RNA Nanotechnology.
Both siRNA and miRNA can serve as powerful gene-silencing reagents but their specific delivery to cancer cells in vivo without collateral damage to healthy cells remains challenging. We report here the application of RNA nanotechnology for specific and efficient delivery of anti-miRNA seed-targeting sequence to block the growth of prostate cancer in mouse models. Utilizing the thermodynamically ultra-stable three-way junction of the pRNA of phi29 DNA packaging motor, RNA nanoparticles were constructed by bottom-up self-assembly containing the anti-prostate-specific membrane antigen (PSMA) RNA aptamer as a targeting ligand and anti-miR17 or anti-miR21 as therapeutic modules. The 16&#x2009;nm RNase-resistant and thermodynamically stable RNA nanoparticles remained intact after systemic injection in mice and strongly bound to tumors with little or no accumulation in healthy organs 8 hours postinjection, and subsequently repressed tumor growth at low doses with high efficiency.
2,335,561
Using physiologically based models for clinical translation: predictive modelling, data interpretation or something in-between?
Heart disease continues to be a significant clinical problem in Western society. Predictive models and simulations that integrate physiological understanding with patient information derived from clinical data have huge potential to contribute to improving our understanding of both the progression and treatment of heart disease. In particular they provide the potential to improve patient selection and optimisation of cardiovascular interventions across a range of pathologies. Currently a significant proportion of this potential is still to be realised. In this paper we discuss the opportunities and challenges associated with this realisation. Reviewing the successful elements of model translation for biophysically based models and the emerging supporting technologies, we propose three distinct modes of clinical translation. Finally we outline the challenges ahead that will be fundamental to overcome if the ultimate goal of fully personalised clinical cardiac care is to be achieved.
2,335,562
MR Image Reconstruction Using Block Matching and Adaptive Kernel Methods.
An approach to Magnetic Resonance (MR) image reconstruction from undersampled data is proposed. Undersampling artifacts are removed using an iterative thresholding algorithm applied to nonlinearly transformed image block arrays. Each block array is transformed using kernel principal component analysis where the contribution of each image block to the transform depends in a nonlinear fashion on the distance to other image blocks. Elimination of undersampling artifacts is achieved by conventional principal component analysis in the nonlinear transform domain, projection onto the main components and back-mapping into the image domain. Iterative image reconstruction is performed by interleaving the proposed undersampling artifact removal step and gradient updates enforcing consistency with acquired k-space data. The algorithm is evaluated using retrospectively undersampled MR cardiac cine data and compared to k-t SPARSE-SENSE, block matching with spatial Fourier filtering and k-t &#x2113;1-SPIRiT reconstruction. Evaluation of image quality and root-mean-squared-error (RMSE) reveal improved image reconstruction for up to 8-fold undersampled data with the proposed approach relative to k-t SPARSE-SENSE, block matching with spatial Fourier filtering and k-t &#x2113;1-SPIRiT. In conclusion, block matching and kernel methods can be used for effective removal of undersampling artifacts in MR image reconstruction and outperform methods using standard compressed sensing and &#x2113;1-regularized parallel imaging methods.
2,335,563
Similar molecular determinants on Rem mediate two distinct modes of inhibition of Ca<sub>V</sub>1.2 channels.
Rad/Rem/Rem2/Gem (RGK) proteins are Ras-like GTPases that potently inhibit all high-voltage-gated calcium (Ca<sub>V</sub>1/Ca<sub>V</sub>2) channels and are, thus, well-positioned to tune diverse physiological processes. Understanding how RGK proteins inhibit Ca<sub>V</sub> channels is important for perspectives on their (patho)physiological roles and could advance their development and use as genetically-encoded Ca<sub>V</sub> channel blockers. We previously reported that Rem can block surface Ca<sub>V</sub>1.2 channels in 2 independent ways that engage distinct components of the channel complex: (1) by binding auxiliary &#x3b2; subunits (&#x3b2;-binding-dependent inhibition, or BBD); and (2) by binding the pore-forming &#x3b1;<sub>1C</sub> subunit N-terminus (&#x3b1;<sub>1C</sub>-binding-dependent inhibition, or ABD). By contrast, Gem uses only the BBD mechanism to block Ca<sub>V</sub>1.2. Rem molecular determinants required for BBD Ca<sub>V</sub>1.2 inhibition are the distal C-terminus and the guanine nucleotide binding G-domain which interact with the plasma membrane and Ca<sub>V</sub>&#x3b2;, respectively. However, Rem determinants for ABD Ca<sub>V</sub>1.2 inhibition are unknown. Here, combining fluorescence resonance energy transfer, electrophysiology, systematic truncations, and Rem/Gem chimeras we found that the same Rem distal C-terminus and G-domain also mediate ABD Ca<sub>V</sub>1.2 inhibition, but with different interaction partners. Rem distal C-terminus interacts with &#x3b1;<sub>1C</sub> N-terminus to anchor the G-domain which likely interacts with an as-yet-unidentified site. In contrast to some previous studies, neither the C-terminus of Rem nor Gem was sufficient to inhibit Ca<sub>V</sub>1/Ca<sub>V</sub>2 channels. The results reveal that similar molecular determinants on Rem are repurposed to initiate 2 independent mechanisms of Ca<sub>V</sub>1.2 inhibition.
2,335,564
Unmet need in the hyperlipidaemia population with high risk of cardiovascular disease: a targeted literature review of observational studies.
The aim of this study was to examine recommended target levels of low-density lipoprotein cholesterol (LDL-C) for hyperlipidaemia patients at high risk (i.e., with two or more risk factors or coronary heart disease or its risk equivalents) for cardiovascular disease (CVD); to determine LDL-C targets recommended by guidelines, and to examine the proportions of patients who do not achieve targeted LDL-C levels in real-world studies.</AbstractText>Electronic databases were searched: Medline, Medline In-Process, Embase, BIOSIS, and the Cochrane Library (1 January 2005 to 31 December 2013). Guideline searches were limited to publications in the last 5 years. There were no geographical or language restrictions.</AbstractText>Seventeen guidelines and 42 observational studies that reported on high-risk hyperlipidaemia patients were identified. The National Cholesterol Education Program-Adult Treatment Panel III's LDL-C target levels were the most common guidelines used for patients with very high hyperlipidaemia. However, between 68 and 96 % of patients in the studies did not achieve an LDL-C goal &lt;70 mg/dL, except in one study conducted in China (16.9 %). In high-risk patients, 61.8 to 93.8 % did not achieve a target of &lt;100 mg/dL. Regarding common comorbidities, patients with concomitant CVD or diabetes were least likely to reach their target LDL-C goals.</AbstractText>In patients with high risk for CVD, the majority of patients do not attain recommended LDL-C goals, highlighting worldwide suboptimal hyperlipidaemia management and missed opportunities for reduction of the patients CVD risk. Lipid-modifying management strategies need to be intensified.</AbstractText>
2,335,565
Intrathecal Dexmedetomidine and Fentanyl as Adjuvant to Bupivacaine on Duration of Spinal Block in Addicted Patients.
Addicted patients have innate tolerance to local anesthetics in both neuraxial and peripheral blocks. Dexmedetomidine (Dex) is a highly selective &#x3b1;2 adrenergic receptor agonist used as additive to increase quality and duration of peripheral nerve blocks.</AbstractText>The current study aimed to compare the effect of dexmedetomidine and fentanyl additives on bupivacaine to prolong the duration of block and minimizing side effects.</AbstractText>Patients were candidates for elective surgery less than three hours of lower abdomen or lower extremities surgeries. Patients were randomly allocated to receive dexmedetomidine 5 &#xb5;g added to 12.5 mg (2.5 mL) of 0.5% hyperbaric bupivacaine (DEX group), or 25 &#xb5;g (0.5 mL) fentanyl added to 12.5 mg (2.5 mL) of 0.5% hyperbaric bupivacaine (F group) or only 12.5 mg of 0.5% hyperbaric bupivacaine. Data were recorded based on sensory block. Motor block was tested using modified Bromage scale every 30 minutes until the end of block. Time to return of sensory block to 4 dermatomes below and time to return of Bromage scale to 0 were recorded. All vital measurements (oxygen saturation, heart rate, electrocardiogram, and non-invasive blood pressure) were performed at 0, 30, 60, 90, 120 and 180 minutes in all three groups of the study. Group DEX received dexmedetomidine additive and group F received fentanyl additive and group C (control) received normal saline.</AbstractText>Totally, 84 patients were randomly divided into three groups of 28 patients. Onset of sensory block in DEX group was significantly lower than those of fentanyl (P = 0.012) and control groups (P = 0.001). Duration of sensory block was significantly longer in DEX group compared to Fentanyl (P = 0.043) and control (P = 0.016) groups. Duration of motor block in the DEX group was significantly longer than those of the fentanyl (P = 0.014) and control groups. Heart rate and mean arterial pressure were significantly higher in the DEX group at 30, 60, 90,120, and 180 minutes compared to those of the other two groups (P &lt; 0.05).</AbstractText>Dexmedetomidine added to bupivacaine in spinal anesthesia is more effective to increase duration of block, providing more appropriate sedation and less postoperative pain scale and post-operative nausea and vomiting (PONV) compared to fentanyl additive.</AbstractText>
2,335,566
Influence of daily social stimulation on behavioral and physiological outcomes in an animal model of PTSD.
We have shown in previous work that acute episodes of predator exposure occurring in the context of chronic social instability produced PTSD-like sequelae in rats. Our animal model of PTSD contained two components: (1) acute trauma, immobilization of rats in close proximity to a cat twice in 10&#xa0;days, and (2) chronic social instability, 31&#xa0;days of randomized housing of cage cohorts. Here we tested the hypothesis that daily social stimulation would block the development of the PTSD-like sequelae.</AbstractText>Beginning 24&#xa0;h after the first cat exposure, adult male rats were given our established PTSD model, alone or in conjunction with daily social stimulation, in which all rats within a group interacted in a large apparatus for 2&#xa0;h each day for the final 30&#xa0;days of the PTSD regimen. All behavioral, for example, anxiety, memory, startle testing, and physiological assessments, for example, body growth, organ weights, and corticosterone levels, took place following completion of the psychosocial stress period.</AbstractText>Daily social stimulation blocked the expression of a subset of PTSD-like effects, including predator-based cued fear conditioning, enhanced startle response, heightened anxiety on the elevated plus maze and the stress-induced suppression of growth rate. We also found that social stimulation and psychosocial stress produced equivalent outcomes in some measures, including adrenal and heart hypertrophy, thymus atrophy, and a reduction in poststress corticosterone levels.</AbstractText>Daily exposure of rats to a highly social environment blocked the development of a subset of trauma-induced sequelae, particularly fear-related outcomes. It is notable that daily social stimulation normalized a subset, but not all, of the PTSD-like effects. We discuss our findings in the context of the literature demonstrating that social stimulation can counteract the adverse effects of traumatic stress on behavioral and physiological measures, as well as to produce its own stress-like outcomes.</AbstractText>
2,335,567
The muscarinic antagonists scopolamine and atropine are competitive antagonists at 5-HT3 receptors.
Scopolamine is a high affinity muscarinic antagonist that is used for the prevention of post-operative nausea and vomiting. 5-HT3 receptor antagonists are used for the same purpose and are structurally related to scopolamine. To examine whether 5-HT3 receptors are affected by scopolamine we examined the effects of this drug on the electrophysiological and ligand binding properties of 5-HT3A receptors expressed in Xenopus oocytes and HEK293&#xa0;cells, respectively. 5-HT3 receptor-responses were reversibly inhibited by scopolamine with an IC50 of 2.09&#xa0;&#x3bc;M. Competitive antagonism was shown by Schild plot (pA2&#xa0;=&#xa0;5.02) and by competition with the 5-HT3 receptor antagonists [(3)H]granisetron (Ki&#xa0;=&#xa0;6.76&#xa0;&#x3bc;M) and G-FL (Ki&#xa0;=&#xa0;4.90&#xa0;&#x3bc;M). The related molecule, atropine, similarly inhibited 5-HT evoked responses in oocytes with an IC50 of 1.74&#xa0;&#x3bc;M, and competed with G-FL with a Ki of 7.94&#xa0;&#x3bc;M. The reverse experiment revealed that granisetron also competitively bound to muscarinic receptors (Ki&#xa0;=&#xa0;6.5&#xa0;&#x3bc;M). In behavioural studies scopolamine is used to block muscarinic receptors and induce a cognitive deficit, and centrally administered concentrations can exceed the IC50 values found here. It is therefore possible that 5-HT3 receptors are also inhibited. Studies that utilise higher concentrations of scopolamine should be mindful of these potential off-target effects.
2,335,568
DNA methylation regulates hypothalamic gene expression linking parental diet during pregnancy to the offspring's risk of obesity in Psammomys obesus.
<AbstractText Label="BACKGROUND/OBJECTIVE">The rising incidence of obesity is a major public health issue worldwide. Recent human and animal studies suggest that parental diet can influence fetal development and is implicated with risk of obesity and type 2 diabetes in offspring. The hypothalamus is central to body energy homoeostasis and appetite by controlling endocrine signals. We hypothesise that offspring susceptibility to obesity is programmed in the hypothalamus in utero and mediated by changes to DNA methylation, which persist to adulthood. We investigated hypothalamic genome-wide DNA methylation in Psammomys obesus diet during pregnancy to the offspring's risk of obesity.</AbstractText>Using methyl-CpG binding domain capture and deep sequencing (MBD-seq), we examined the hypothalamus of offspring exposed to a low-fat diet and standard chow diet during the gestation and lactation period.</AbstractText>Offspring exposed to a low-fat parental diet were more obese and had increased circulating insulin and glucose levels. Methylome profiling identified 1447 genomic regions of differential methylation between offspring of parents fed a low-fat diet compared with parents on standard chow diet. Pathway analysis shows novel DNA methylation changes of hypothalamic genes associated with neurological function, nutrient sensing, appetite and energy balance. Differential DNA methylation corresponded to changes in hypothalamic gene expression of Tas1r1 and Abcc8 in the offspring exposed to low-fat parental diet.</AbstractText>Subject to parental low-fat diet, we observe DNA methylation changes of genes associated with obesity in offspring.</AbstractText>
2,335,569
Excess centrosomes perturb dynamic endothelial cell repolarization during blood vessel formation.
Blood vessel formation requires dynamic movements of endothelial cells (ECs) within sprouts. The cytoskeleton regulates migratory polarity, and centrosomes organize the microtubule cytoskeleton. However, it is not well understood how excess centrosomes, commonly found in tumor stromal cells, affect microtubule dynamics and interphase cell polarity. Here we find that ECs dynamically repolarize during sprouting angiogenesis, and excess centrosomes block repolarization and reduce migration and sprouting. ECs with excess centrosomes initially had more centrosome-derived microtubules but, paradoxically, fewer steady-state microtubules. ECs with excess centrosomes had elevated Rac1 activity, and repolarization was rescued by blockade of Rac1 or actomyosin blockers, consistent with Rac1 activity promoting cortical retrograde actin flow and actomyosin contractility, which precludes cortical microtubule engagement necessary for dynamic repolarization. Thus normal centrosome numbers are required for dynamic repolarization and migration of sprouting ECs that contribute to blood vessel formation.
2,335,570
Complete heart block in a Caucasian woman with Beh&#xe7;et's disease: a case report.
Beh&#xe7;et's disease is a progressive diffuse inflammatory vasculitis characterized by recurrent oral and genital ulceration and ocular inflammation. Cardiac involvement is a rare but well-documented manifestation of Beh&#xe7;et's disease. Complete heart block in non-Caucasian populations has been reported previously; however, in this report, we describe a unique case of complete heart block in a Caucasian woman with Beh&#xe7;et's disease.</AbstractText>A 48-year-old Caucasian woman presented to our hospital with symptomatic complete heart block requiring a pacemaker implant on a background of recurrent oral and genital ulcers and oligoarthritis of 10&#xa0;months' duration. She also had a history of recurrent diarrhea with a single episode of ocular inflammation in the recent past. She had no evidence of cardiac ischemia, and her autoimmune antibodies were within normal ranges. She was diagnosed with Beh&#xe7;et's disease according to international study group criteria and was commenced on prednisolone and sulfasalazine, to which she responded very well.</AbstractText>Cardiac complications should be considered when making a diagnosis of Beh&#xe7;et's disease, even in Caucasian patients. While mucocutaneous ulceration is indeed the most common manifestation of Beh&#xe7;et's disease, cardiovascular involvement tends to cause the most morbidity and mortality.</AbstractText>
2,335,571
Cardiovascular effects of combined hyaluronidase and mepivacaine in dental anesthesia: A randomized clinical trial.
To evaluate the effects of combined administration of mepivacaine with epinephrine and the diffusion agent hyaluronidase on hemodynamic and electrocardiographic parameters in healthy individuals undergoing dental surgery.</AbstractText>In a double-blind, split-mouth, randomized clinical trial, the cardiovascular effects induced by 2.7 mL of 2% mepivacaine with 1:100,000 epinephrine injected concomitantly with 1 mL of 75 TRU/mL hyaluronidase or placebo for inferior alveolar nerve block was evaluated in systemically healthy subjects that underwent bilateral third molar extraction in two separate sessions. Systolic and diastolic blood pressure and heart rate were monitored using oscillometric and photoplethysmographic methods in 10 clinical stages, while electrocardiographic records of 12 leads were obtained in four stages.</AbstractText>Hyaluronidase injected concomitantly with local anesthetic did not induce changes in blood pressure and heart rate compared to placebo. There were no instances of ST segment depression or elevation, or wide or narrow QRS complex extrasystoles in ECG. The use of mepivacaine injected concomitantly with 75 TRU/mL hyaluronidase was safe, from a cardiovascular standpoint.</AbstractText>
2,335,572
The Association of Folic Acid Deficiency and Diabetic Nephropathy in Patients with Type 2 Diabetes Mellitus.
Diabetic Mellitus is the chronic metabolic illness characterised by hyperglycemia and various complications of heart, eyes, nerves, kidney etc. Diabetic Nephropathy is the leading causes of morbidity and mortality in diabetic patient. We hypothesized that decreased serum folic acid levels are associated with Diabetic Nephropathy.</AbstractText>Our study population consist of 100 subjects out of which 50 cases of Diabetes Mellitus are without Diabetic Nephropathy and 50 cases of Diabetes Mellitus with Diabetic Nephropathy. We measured various routine lab parameters, apart from that, we measured spot urinary albumin to creatinine ratio to assess diabetic nephropathy and we used chemiluminesence based immunoassay to measure serum folic acid.</AbstractText>Serum folic acid in the group with nephropathy was significantly lower than that of the group without nephropathy (4.9 &#xb1; 0.4 ng/dl) vs (6.8 &#xb1; 0.5 ng/dl) p = 0.05. We found that serum folic acid was negatively correlated with spot urinary albumin ratio and on multivariate logistic regression analysis we found that decrease in folic acid significantly (p &lt; 0.05) increases the chances of diabetes with nephropathy by 19.9 %.</AbstractText>Our study tilt toward the deficiency of serum folic acid levels in diabetes mellitus patient with nephropathy. So if we would correct folic acid deficiency in diabetic patient then we could prevent the development of various complication associated with diabetes and help in reducing the morbidity and mortality of diabetic patient.</AbstractText>Copyright&#xa9; Bentham Science Publishers; For any queries, please email at [email protected].</CopyrightInformation>
2,335,573
The density of calcified plaques and the volume of calcium predict mortality in hemodialysis patients.
In the general population lipid-rich plaques are prone to rupture and healing of the plaque involves calcification. Patients undergoing hemodialysis have a severe derangement of mineral metabolism and calcification of the arterial tree may have different implications.</AbstractText>Between 2004 and 2005, 125 hemodialysis patients (60 men) underwent computed tomography imaging for quantification of coronary artery calcium via the Agatston and the Volume methods. Since the Agatston score is derived by multiplying the density by the volume of a calcified lesion, the Agatston/Volume ratio (AVR) is an indication of the density (i.e. calcium accumulation) within the plaque.</AbstractText>Patients were classified as high AVR (&gt;1) or low (&#x2264;1) AVR. Survival analyses tested the association between AVR and all-cause mortality during a median follow-up of 5 years. The mean age was 57.2&#xb1;13.5 years; 75% of the patients had AVR &gt;1. The mortality rate of patients with AVR &gt;1 was significantly higher than in patients with AVR &#x2264;1 (Hazard Ratio(HR): 2.46; 95% Confidence Intervals(CI): 1.16-5.21, p &#x2264;0.018). After adjustment for confounders, AVR &gt;1 remained independently associated with all-cause mortality (HR: 2.24; 95% CI: 1.02-4.88, p &#x2264;0.042). There was a significant interaction of plaque density and calcium volume on mortality.</AbstractText>Increased plaque density is an independent predictor of all-cause mortality in hemodialysis patients. These data suggest that increased calcium content in the coronary arteries of patients in dialysis is an index of high-risk rather than a marker of plaque stabilization.</AbstractText>Copyright &#xa9; 2016 Elsevier Ireland Ltd. All rights reserved.</CopyrightInformation>
2,335,574
Manipulation of exercise to rest ratio within set duration on physical and technical outcomes during small-sided games in elite youth soccer players.
Training practices for elite soccer players should take into account specific technical, tactical and physical components. As a consequence of these demands small-sided games (SSGs) have become a popular conditioning tool that replicate the demands encountered during match play. The aim of this investigation was to examine how the manipulation of exercise to rest ratio, within the same overall duration, affected both physical and technical outcomes during SSGs in elite youth soccer. Twelve elite youth soccer players participated in three variations of eight minute 6v6 SSGs. The three variations included eight minutes continuous, 2&#xd7;4min and 4&#xd7;2min. Players perceived the continuous 8min block as the hardest (4.5&#xb1;1.5AU), followed by the 2&#xd7;4min (3.9&#xb1;1.4AU) and the 4&#xd7;2min (3.3&#xb1;1.4AU), although no difference in mean HR or physical measures via GPS analysis between SSGs was evident. From the technical perspective, only goals scored reached significance, with post hoc analysis identifying the number of goals scored were significantly higher during the 4&#xd7;2min and 2&#xd7;4min SSGs compared to 8min continuous block. These results show that subjective ratings of exertion differed between conditions, but only minor technical manipulations were observed by adjusting work to rest ratios, with no significant effect on physical performance.
2,335,575
Electrocardiographic Advanced Interatrial Block and Atrial Fibrillation Risk in the General Population.
Although advanced interatrial block (aIAB) is an established electrocardiographic phenotype, its prevalence, incidence, and prognostic significance in the general population are unclear. We examined the prevalence, incidence, and prognostic significance of aIAB in 14,625 (mean age&#xa0;= 54 &#xb1; 5.8&#xa0;years; 26% black; 55% female) participants from the Atherosclerosis Risk in Communities (ARIC) study. aIAB was detected from digital electrocardiograms recorded during 4 study visits (1987 to 1989, 1990 to 1992, 1993 to 1995, and 1996 to 1998). Risk factors for the development of aIAB were examined using multivariable Poisson regression models with robust variance estimates. Cox regression was used to compute hazard ratios and 95% CIs for the association between aIAB, as a time-dependent variable, and atrial fibrillation (AF). AF was ascertained from study electrocardiogram data, hospital discharge records, and death certificates thorough 2010. A total of 69 participants (0.5%) had aIAB at baseline, and 193 (1.3%) developed aIAB during follow-up. The incidence for aIAB was 2.27 (95% CI 1.97 to 2.61) per 1,000 person-years. Risk factors for aIAB development included age, male gender, white race, antihypertensive medication use, low-density lipoprotein cholesterol, body mass index, and systolic blood pressure. In a Cox regression analysis adjusted for sociodemographics, cardiovascular risk factors, and potential confounders, aIAB was associated with an increased risk for AF (hazard ratio 3.09, 95% CI 2.51 to 3.79). In conclusion, aIAB is not uncommon in the general population. Risk factors for developing aIAB are similar to those for AF, and the presence of aIAB is associated with an increased risk for AF.
2,335,576
Impact of carprofen administration on stress and nociception responses of calves to cautery dehorning.
The objective of this study was to investigate the effects of carprofen administered immediately before cautery dehorning on nociception and stress. Forty Holstein calves aged approximately 6 to 8 wk old were either placebo treated and sham dehorned ( = 10) or cautery dehorned following administration of carprofen (1.4 mg/kg) subcutaneously ( = 10) or orally ( = 10) or a subcutaneous and oral placebo ( = 10) in a randomized, controlled trial. All animals were given a cornual nerve block using lidocaine before dehorning. Response variables including mechanical nociception threshold, ocular temperature, heart rate, and respiratory rate were measured before and following cautery dehorning for 96 h. Blood samples were also collected over 96 h following dehorning and analyzed for plasma cortisol and substance P concentrations by RIA. Plasma carprofen concentration and ex vivo PGE concentrations were also determined for this time period. Average daily gain was calculated for 7 d after dehorning. Data were analyzed using a linear mixed effects model with repeated measures, controlling for baseline values by their inclusion as a covariate in addition to planned contrasts. Dehorning was associated with decreased nociception thresholds throughout the study and a stress response immediately after dehorning, following the loss of local anesthesia, and 48 h after dehorning compared with sham-dehorned calves. Carprofen was well absorbed after administration and reached concentrations that inhibited ex vivo PGE concentrations for 72 h (subcutaneous) and 96 h (oral) compared with placebo-treated calves ( &lt; 0.05). Carprofen-treated calves tended to be less sensitive ( = 0.097) to nociceptive threshold tests. Overall, at the dosing regimen studied, the effect of carprofen on sensitivity and stress following cautery dehorning was minimal. Consideration of route of administration and dose determination studies may be warranted.
2,335,577
pH-Sensitive and Thermosensitive Hydrogels as Stem-Cell Carriers for Cardiac Therapy.
Stem-cell therapy has the potential to regenerate damaged heart tissue after a heart attack. Injectable hydrogels may be used as stem-cell carriers to improve cell retention in the heart tissue. However, current hydrogels are not ideal to serve as cell carriers because most of them block blood vessels after solidification. In addition, these hydrogels have a relatively slow gelation rate (typically &gt;60 s), which does not allow them to quickly solidify upon injection, so as to efficiently hold cells in the heart tissue. As a result, the hydrogels and cells are squeezed out of the tissue, leading to low cell retention. To address these issues, we have developed hydrogels that can quickly solidify at the pH of an infarcted heart (6-7) at 37 &#xb0;C but cannot solidify at the pH of blood (7.4) at 37 &#xb0;C. These hydrogels are also clinically attractive because they can be injected through catheters commonly used for minimally invasive surgeries. The hydrogels were synthesized by free-radical polymerization of N-isopropylacrylamide, propylacrylic acid, hydroxyethyl methacrylate-co-oligo(trimethylene carbonate), and methacrylate poly(ethylene oxide) methoxy ester. Hydrogel solutions were injectable through 0.2-mm-diameter catheters at pH 8.0 at 37 &#xb0;C, and they can quickly form solid gels under pH 6.5 at 37 &#xb0;C. All of the hydrogels showed pH-dependent degradation and mechanical properties with less mass loss and greater complex shear modulus at pH 6.5 than at pH 7.4. When cardiosphere-derived cells (CDCs) were encapsulated in the hydrogels, the cells were able to survive during a 7-day culture period. The surviving cells were differentiated into cardiac cells, as evidenced by the expression of cardiac markers at both the gene and protein levels, such as cardiac troponin T, myosin heavy chain &#x3b1;, calcium channel CACNA1c, cardiac troponin I, and connexin 43. The gel integrity was found to largely affect CDC cardiac differentiation. These results suggest that the developed dual-sensitive hydrogels may be promising carriers for cardiac cell therapy.
2,335,578
Seborrheic dermatitis treatment with stellate ganglion block: a case report.
Seborrheic dermatitis is a chronic recurrent inflammatory disorder presumed to be caused by increased sebaceous gland secretion, metabolic changes in the cutaneous microflora, and changes in the host immune function. Stellate ganglion block (SGB) is known to increase the blood flow rate without altering the blood pressure, heart rate, or cardiac output, to stabilize hypertonic conditions of the sympathetic nerves, and to affect the endocrine and immune systems. It is used in the differential diagnosis and treatment of autonomic nervous system disorders of the head, neck, and upper limbs. The authors report the first case of successful treatment of a patient with seborrheic dermatitis through repeated SGB trials.
2,335,579
The First Report of Bay&#xe9;s Syndrome in Hemodialysis Patient.
A chronic hemodialysis patient-known to have advanced interatrial block (IAB)-had reported symptoms suggesting arrhythmias, hence she underwent hemodialysis treatment while on the cardiac monitor. This allowed us to recognize the occurrence of paroxysmal atrial fibrillation and, in turn, disclose the first case of Bay&#xe9;s syndrome. Even though atrial fibrillation and IAB are very frequent in hemodialysis patients, Bay&#xe9;s syndrome, that comprehends both, has never been described, likely because the IAB is often overlooked and undiagnosed. This case could improve the awareness of IAB and of the Bay&#xe9;s syndrome in hemodialysis population.
2,335,580
MicroRNA and Heart Failure.
Heart failure (HF) imposes significant economic and public health burdens upon modern society. It is known that disturbances in neurohormonal status play an important role in the pathogenesis of HF. Therapeutics that antagonize selected neurohormonal pathways, specifically the renin-angiotensin-aldosterone and sympathetic nervous systems, have significantly improved patient outcomes in HF. Nevertheless, mortality remains high with about 50% of HF patients dying within five years of diagnosis thus mandating ongoing efforts to improve HF management. The discovery of short noncoding microRNAs (miRNAs) and our increasing understanding of their functions, has presented potential therapeutic applications in complex diseases, including HF. Results from several genome-wide miRNA studies have identified miRNAs differentially expressed in HF cohorts suggesting their possible involvement in the pathogenesis of HF and their potential as both biomarkers and as therapeutic targets. Unravelling the functional relevance of miRNAs within pathogenic pathways is a major challenge in cardiovascular research. In this article, we provide an overview of the role of miRNAs in the cardiovascular system. We highlight several HF-related miRNAs reported from selected cohorts and review their putative roles in neurohormonal signaling.
2,335,581
Mathematical Model for an Effective Management of HIV Infection.
Human immunodeficiency virus infection destroys the body immune system, increases the risk of certain pathologies, damages body organs such as the brain, kidney, and heart, and causes death. Unfortunately, this infectious disease currently has no cure; however, there are effective retroviral drugs for improving the patients' health conditions but excessive use of these drugs is not without harmful side effects. This study presents a mathematical model with two control variables, where the uninfected CD4(+)T cells follow the logistic growth function and the incidence term is saturated with free virions. We use the efficacy of drug therapies to block the infection of new cells and prevent the production of new free virions. Our aim is to apply optimal control approach to maximize the concentration of uninfected CD4(+)T cells in the body by using minimum drug therapies. We establish the existence of an optimal control pair and use Pontryagin's principle to characterize the optimal levels of the two controls. The resulting optimality system is solved numerically to obtain the optimal control pair. Finally, we discuss the numerical simulation results which confirm the effectiveness of the model.
2,335,582
[Comparison of neostigmine induced reversal of rocuronium in different age children].
To compare the effectiveness of neostigmine induced reversal of rocuronium in neonates, infants, young children and children.</AbstractText>One hundred and sixty ASA I or II pediatric patients undergoings elective surgical procedures under total intravenous anesthesia were enrolled during July 2014 to April 2015 in Tianjin Children's Hospital. The patients were divided into four groups according to ages: neonate group, infant group, young children group and children group.Then control subgroup and neostigmine reversal subgroup including twenty patients were randomly selected from every different age groups by the method of random number table. After induction of anesthesia, 0.6 mg/kg rocuronium was administered, and 0.2 mg/kg maintenance doses given as required during period of operation. Neuromuscular block was monitored using acceleromyographic train of four (TOF). When T1/control returned to 15%, 0.03 mg/kg neostigmine and 0.01 mg/kg atropine were given to patients of reversal subgroups, and saline 0.1 ml/kg was given to patients of control subgroups. The recovery time of T25, T75, TR0.7, recovery index, blood pressure, heart rate and adverse reactions were observed and recorded.</AbstractText>In control subgroups, the recovery time of T75 for neonates, infants, young children and children were (27.10&#xb1;8.72), (16.70&#xb1;6.35), (13.05&#xb1;1.96), (14.40&#xb1;3.08) min, respectively (F=25.052, P&lt;0.01). The recovery time of TR0.7 were (27.75&#xb1;8.56), (18.45&#xb1;5.62), (14.95&#xb1;2.64), (15.70&#xb1;3.36) min, respectively (F=22.496, P&lt;0.01). The recovery index were (20.75&#xb1;7.09), (12.40&#xb1;5.04), (10.01&#xb1;2.00), (10.55&#xb1;2.82) min, respectively (F=22.725, P&lt;0.01). There were no significant difference for the every recovery time and recovery index between infants, young children and children (all P&gt;0.05). But the recovery time of T75, TR0.7 and recovery index in neonate group were longer than other age groups (all P&lt;0.01). In reversal subgroups , the recovery time of T75 for neonates, infants, young children and children were (14.05&#xb1;3.54), (8.08&#xb1;3.08), (6.53&#xb1;0.98), (7.10&#xb1;1.54) min, respectively (F=37.947, P&lt;0.01). The recovery time of TR0.7 were (14.95&#xb1;3.19), (9.32&#xb1;3.44), (7.45&#xb1;1.40), (8.12&#xb1;1.67) min, respectively (F=34.744, P&lt;0.01). The recovery index were (11.05&#xb1;3.26), (5.96&#xb1;2.46), (4.99&#xb1;0.95), (5.22&#xb1;1.39) min, respectively (F=33.542, P&lt;0.01). The recovery time of T75, TR0.7 and recovery index were delayed in neonates compared with other age groups (all P&lt;0.01). Haemodynamics were stable in all groups before or after giving antagonist, and no significant adverse reactions were observed.</AbstractText>The spontaneous recovery time after administrating rocuronium are comparable in infant, young children and children. There are obviously reversal effects in all of age groups when neostigmine is given to antagonize rocuronium. Either spontaneous recovery time or reversal recovery time of neostigmine to rocuronium is longer for neonates than other age's children.</AbstractText>
2,335,583
Intraprocedural increase in heart rate during EUS-guided celiac&#xa0;plexus neurolysis: Clinically relevant or just a physiologic&#xa0;change?
Although EUS-guided celiac plexus neurolysis (EUS-CPN) is performed frequently for palliation of pain in pancreatic cancer, response to treatment is variable. Although intraprocedural increases in heart rate during alcohol injection are observed frequently, their significance and relationship to treatment outcome are unknown. The objective of this study was to examine whether a correlation exists between an increase in heart rate and treatment outcomes in patients undergoing EUS-CPN for pain relief in pancreatic cancer.</AbstractText>This is a prospective observational study of patients with abdominal pain caused by inoperable pancreatic cancer who underwent EUS-CPN. Heart rate change was defined as an increase of&#xa0;&#x2265;15 beats per minute (bpm) for&#xa0;&#x2265;30 seconds during alcohol injection. Main outcome measures were to compare pain, quality of life, opioid use, and survival between heart rate change and no-change groups.</AbstractText>Heart rate change was observed in 25 of 51 patients (49.0%) who underwent EUS-CPN over a 12-month period. Although the heart rate change cohort had significantly better adjusted scores for pain (60 vs 73; P&#xa0;= .042) and components of quality of life such as nausea and/or vomiting (65 vs 81; P&#xa0;= .004), financial difficulties (41 vs 57; P&#xa0;= .02), weight loss (45 vs 65; P&#xa0;= .007), and satisfaction with body image (52 vs 62; P&#xa0;= .035), there was no significant difference in postprocedural opioid use or survival between groups.</AbstractText>Because patients with an increase in intraprocedural heart rate experienced significant improvement in pain and quality of life components, this observation must be further explored in order to improve the technique and outcomes of EUS-CPN.</AbstractText>Copyright &#xa9; 2016 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.</CopyrightInformation>
2,335,584
Space maintenance in autogenous fresh demineralized tooth blocks with platelet-rich plasma for maxillary sinus bone formation: a prospective study.
This prospective study evaluated the effectiveness of autogenous fresh demineralized tooth block (Auto-FDT block) with platelet-rich plasma (PRP) for maxillary sinus augmentation with simultaneous implant installation. Auto-FDT block with PRP was used in Group 1 (n&#xa0;=&#xa0;15) and combined graft (allograft and xenograft) powder with PRP was used in Group 2 (n&#xa0;=&#xa0;15). For up to 2&#xa0;years after the final prosthesis was installed, clinical and radiographic examinations were performed to evaluate the amount of graft materials, residual alveolar height (RAH), sinus height (SH) after grafting, augmented graft height (AGH) and resorption height (RH). In ten cases, biopsies were harvested for histological and histomorphometric analyses. A total of 59 implants were placed in a severe atrophic posterior maxilla with less than 5&#xa0;mm of RAH and sinus augmentation. None of the patients developed sinusitis or other complications, such as implant loss. The graft material extracted included one molar (or 2 premolars) in Group 1 and 1.8&#xa0;cc in Group 2. The radiologic examination revealed the following average between-group difference SH (Group 1, 14.12&#xa0;&#xb1;&#xa0;1.63&#xa0;mm vs Group 2, 16.51&#xa0;&#xb1;&#xa0;1.29&#xa0;mm) and AGH (Group 1, 11.62&#xa0;&#xb1;&#xa0;2.22&#xa0;mm vs Group 2, 13.65&#xa0;&#xb1;&#xa0;1.35&#xa0;mm). However, sufficient SH and AGH were observed for the implants in the Auto-FDT block group. Two years after final prosthesis was installed, no between-group difference in the RH was observed (Group 1, 1.23&#xa0;&#xb1;&#xa0;0.73&#xa0;mm vs Group 2, 1.77&#xa0;&#xb1;&#xa0;0.54&#xa0;mm, P&#xa0;=&#xa0;0.021). The histomorphometric analysis revealed no between-group difference in the new bone volume (Group 1, 23.13&#xa0;&#xb1;&#xa0;1.42&#xa0;% vs Group 2, 24.18&#xa0;&#xb1;&#xa0;2.19&#xa0;%, P&#xa0;=&#xa0;0.548). The results showed that Auto-FDT block with PRP can be used in grafted sinuses for implants with only one extracted molar (or two premolars). Auto-FDT block with PRP promotes new bone formation that is comparable with combined grafts. Auto-FDT block with PRP is as an alternative to bone grafting and can be a predictable procedure for sinus augmentation.
2,335,585
Brain-heart interactions: physiology and clinical implications.
The brain controls the heart directly through the sympathetic and parasympathetic branches of the autonomic nervous system, which consists of multi-synaptic pathways from myocardial cells back to peripheral ganglionic neurons and further to central preganglionic and premotor neurons. Cardiac function can be profoundly altered by the reflex activation of cardiac autonomic nerves in response to inputs from baro-, chemo-, nasopharyngeal and other receptors as well as by central autonomic commands, including those associated with stress, physical activity, arousal and sleep. In the clinical setting, slowly progressive autonomic failure frequently results from neurodegenerative disorders, whereas autonomic hyperactivity may result from vascular, inflammatory or traumatic lesions of the autonomic nervous system, adverse effects of drugs and chronic neurological disorders. Both acute and chronic manifestations of an imbalanced brain-heart interaction have a negative impact on health. Simple, widely available and reliable cardiovascular markers of the sympathetic tone and of the sympathetic-parasympathetic balance are lacking. A deeper understanding of the connections between autonomic cardiac control and brain dynamics through advanced signal and neuroimage processing may lead to invaluable tools for the early detection and treatment of pathological changes in the brain-heart interaction.
2,335,586
Prostaglandin-targeting agents and spectral heart rate variability in experimental partial bladder outlet obstruction in rats.
The purpose of this study was to determine the activity of the autonomic nervous system (ANS), using spectral analysis of the heart rate variability (HRV) in the model of partial bladder outlet obstruction (PBOO) in rats treated with selected non-steroidal anti-inflammatory drugs (NSAID): piroxicam (PRX) or meloxicam (MLX), and following administration of PGF2a prostaglandin analogue (Enzaprost F5). Neither the use of PGF2a analogue nor of MLX, caused significant changes in the HRV spectrum (except for HRV spectrum total power reduction with MLX). The use of PRX caused reduction of the total power and powers of all components of the HRV spectrum (except for VLF). Moreover, increased nLF and reduced nHF were observed. The obtained results suggest that the total prostaglandin synthesis block with a non-selective cyclooxygenase inhibitor (PRX) results in reduced ANS total activity, with decreased parasympathetic activity and a relative sympathetic predominance. The preferential cyclooxygenase-2 block (MLX) caused reduction of the total ANS activity as well, however with no clear disproportion of any part of the ANS. Therefore, prostaglandin synthesis inhibition and associated decrease of parasympathetic activity may constitute an additional and favourable feature of NSAID pharmacodynamics in the treatment of BPH.
2,335,587
Alginate for cardiac regeneration: From seaweed to clinical trials.
Heart failure is a growing endemic in the aging Western population with a prevalence of over 20 million people worldwide<sup>1</sup>. Existing heart failure therapies are unable to reverse heart failure and do not address its fundamental cause, the loss of cardiomyocytes<sup>2</sup>. In order to induce myocardial regeneration for the myocardium and the heart valve, facilitate self-repair, improve tissue salvage, reduce or reverse the adverse-remodeling and ultimately achieve long-term functional stabilization and improvement in the heart function, novel strategies for therapeutic regeneration are being developed which are aiming to compensate for the insufficient and low intrinsic regenerative ability of the adult heart<sup>3</sup>. Similarly, valve replacement with mechanical or biological substitutes meets numerous hurdles. New approaches using multicellular approaches and new material are extensively studied. Most of those strategies depend on biomaterials that help to achieve functional integrated vasculogenesis and myogenesis in the heart/tissue. Especially for failed heart valve function a number of therapeutic approaches are common from corrective intervention to complete replacement<sup>4</sup>. However the complexity of the heart valve tissue and its high physical exposure has led to a variety of approaches, however therapeutic regeneration needs to be established. Beside other approaches alginate has been identified as one building block to achieve therapeutic regeneration. Alginate is a versatile and adaptable biomaterial that has found numerous biomedical applications which include wound healing, drug delivery and tissue engineering. Due to its biologically favorable properties including the ease of gelation and its biocompatibility, alginate-based hydrogels have been considered a particularly attractive material for the application in cardiac regeneration and valve replacement techniques. Here, we review current applications of alginate in cardiac regeneration as well as perspectives for the alginate-dependent, cardiac regeneration strategies.
2,335,588
Maternal autoantibody profiles at risk for autoimmune congenital heart block: a prospective study in high-risk patients.
This prospective study aimed to identify antibody profiles characterising mothers with fetuses developing congenital heart block (CHB) by comparing their antibody frequencies and levels with those in unaffected mothers.</AbstractText>Eighty-one consecutive pregnant patients positive to anti-Ro&#xb1;anti-La antibodies, at high risk of developing fetal CHB were prospectively studied. The 16 patients with fetal CHB outcome were considered the study population and the 65 patients with normal pregnancy outcomes were considered the control cohort. Anti-Ro52, anti-Ro60, anti-p200 and anti-La antibodies were assayed using home-made ELISA assays.</AbstractText>The prevalence of anti-p200 antibodies was significantly higher in the fetal CHB affected patients than in the controls (p=0.03). Combinations of anti-p200 with anti-Ro52 and anti-Ro60 antibodies were significantly more frequent in the women with fetuses developing CHB than in the controls (p=0.03 for all combinations). The women with fetal CHB had significantly higher mean anti-Ro52, anti-Ro60 and anti-p200 levels than the controls (p=0.003, p=0.0001 and p=0.04, respectively); mean anti-La/SSB level was not significantly different in the two cohorts (p=0.25).</AbstractText>Since anti-p200, anti-Ro52 and anti-Ro60 antibodies, especially at high level, seem to identify patients at increased risk of developing fetal CHB, their detection could recognise anti-Ro/La positive women at risk for having an infant with this rare, potentially dangerous disorder.</AbstractText>
2,335,589
Minimally invasive implantable fetal micropacemaker: mechanical testing and technical refinements.
This paper discusses the technical and safety requirements for cardiac pacing of a human fetus with heart failure and hydrops fetalis secondary to complete heart block. Engineering strategies to meet specific technical requirements were integrated into a systematic design and implementation consisting of a novel fetal micropacemaker, a percutaneous implantation system, and a sterile package that enables device storage and recharging maintenance in a clinical setting. We further analyzed observed problems on myocardial fixation and pacing lead fatigue previously reported in earlier preclinical trials. This paper describes the technical refinements of the implantable fetal micropacemaker to overcome these challenges. The mechanical performance has been extensively tested to verify the improvement of reliability and safety margins of the implantation system.
2,335,590
A Computational Tool for the Microstructure Optimization of a Polymeric Heart Valve Prosthesis.
Styrene-based block copolymers are promising materials for the development of a polymeric heart valve prosthesis (PHV), and the mechanical properties of these polymers can be tuned via the manufacturing process, orienting the cylindrical domains to achieve material anisotropy. The aim of this work is the development of a computational tool for the optimization of the material microstructure in a new PHV intended for aortic valve replacement to enhance the mechanical performance of the device. An iterative procedure was implemented to orient the cylinders along the maximum principal stress direction of the leaflet. A numerical model of the leaflet was developed, and the polymer mechanical behavior was described by a hyperelastic anisotropic constitutive law. A custom routine was implemented to align the cylinders with the maximum principal stress direction in the leaflet for each iteration. The study was focused on valve closure, since during this phase the fibrous structure of the leaflets must bear the greatest load. The optimal microstructure obtained by our procedure is characterized by mainly circumferential orientation of the cylinders within the valve leaflet. An increase in the radial strain and a decrease in the circumferential strain due to the microstructure optimization were observed. Also, a decrease in the maximum value of the strain energy density was found in the case of optimized orientation; since the strain energy density is a widely used criterion to predict elastomer's lifetime, this result suggests a possible increase of the device durability if the polymer microstructure is optimized. The present method represents a valuable tool for the design of a new anisotropic PHV, allowing the investigation of different designs, materials, and loading conditions.
2,335,591
Dexmedetomidine Dose Dependently Enhances the Local Anesthetic Action of Lidocaine in Inferior Alveolar Nerve Block: A Randomized Double-Blind Study.
Dexmedetomidine (DEX) dose dependently enhances the local anesthetic action of lidocaine in rats. We hypothesized that the effect might also be dose dependent in humans. We evaluated the effect of various concentrations of DEX with a local anesthetic in humans.</AbstractText>Eighteen healthy volunteers were randomly assigned by a computer to receive 1.8 mL of 1 of 4 drug combinations: (1) 1% lidocaine with 2.5 ppm (parts per million) (4.5 &#x3bc;g) DEX, (2) lidocaine with 5.0 ppm (9.0 &#x3bc;g) DEX, (3) lidocaine with 7.5 ppm (13.5&#x3bc;g) DEX, or (4) lidocaine with 1:80,000 (22.5 &#x3bc;g) adrenaline (AD), to produce inferior alveolar nerve block. Pulp latency and lower lip numbness (for assessing onset and duration of anesthesia) were tested, and sedation level, blood pressure, and heart rate were recorded every 5 minutes for 20 minutes, and every 10 minutes from 20 to 60 minutes.</AbstractText>Pulp latency of each tooth increased compared with baseline, from 5 to 15 minutes until 60 minutes. There were no significant intergroup differences at any time point. Anesthesia onset was not different between groups. Anesthesia duration was different between groups (that with DEX 7.5 ppm was significantly longer than that with DEX 2.5 ppm and AD; there was no difference between DEX 2.5 ppm and AD). Blood pressure decreased from baseline in the 5.0 and 7.5 ppm DEX groups at 30 to 60 minutes, although there was no hypotension; moreover, heart rate did not change in any group. Sedation score did not indicate deep sedation in any of the groups.</AbstractText>Dexmedetomidine dose dependently enhances the local anesthetic action of lidocaine in humans. Dexmedetomidine at 2.5 ppm produces similar enhancement of local anesthesia effect as addition of 1:80,000 AD.</AbstractText>
2,335,592
Identifying and Managing a Malpositioned Endotracheal Tube Bite Block in an Orotracheally Intubated Patient: A Case Report.
The universal bite block is increasingly used in orotracheally intubated patients. Here, we report a case of pilot tube dysfunction caused by a malpositioned universal bite block in an orotracheally intubated patient. We summarize the key points on identifying and managing a malpositioned universal bite block from this case and literature review.A 74-year-old woman was emergently intubated during an episode of hyperkalemia-related cardiac arrest. A universal bite block was used for fixing the endotracheal tube. After her condition stabilized, ventilator weaning was attempted; however, a positive cuff-leak test result was observed.The cuff-leak test revealed a lack of elasticity of the pilot balloon, which was completely deflated after 2&#x200a;mL of air was removed. Pilot tube dysfunction was highly suspected. The bite block was slightly pulled out, and 8&#x200a;mL of air was aspirated from the pilot tube. The patient was successfully extubated without stridor and respiratory distress.Our case highlighted that a malpositioned bite block may obstruct the pilot tube, causing unfavorable consequences. While fixing the bite block on an endotracheal tube, it is crucial to ensure that the takeoff point of the pilot tube is located within the C-notch of the bite block.
2,335,593
Relationship between regional cerebral blood volume and oxygenation and blood pressure during spinal anesthesia in women undergoing cesarean section.
During spinal anesthesia for cesarean section, cerebral oxygenation decreases may be related to an abrupt drop in cerebral blood flow due to hypotension. We measured the changes in maternal regional cerebral blood volume (rCBV) and oxygenation (rCBO) using near-infrared spectroscopy (NIRS) to evaluate whether a decrease in arterial blood pressure during spinal anesthesia diminishes rCBV and rCBO.</AbstractText>Forty patients scheduled for elective cesarean section under spinal anesthesia were monitored for mean arterial pressure (MAP), heart rate (HR), respiratory rate (RR), and concentrations of oxy-hemoglobin (Hb), deoxy-Hb, total-Hb, and tissue oxygenation index (TOI), before spinal anesthesia (baseline) and for 20&#xa0;min after intrathecal injection of bupivacaine. We investigated changes in the values from baseline and evaluated whether the maximum changes in total-Hb (&#x394;-total-Hb) and TOI (&#x394;-TOI) correlate with changes in MAP at the same time point.</AbstractText>The mean oxy-Hb, total-Hb, TOI, and MAP significantly decreased from baseline after intrathecal injection of bupivacaine (P&#xa0;&lt;&#xa0;0.01). There were significant positive correlations between both &#x394;-total-Hb and &#x394;-TOI and the decrease in MAP (&#x394;-total-Hb: r&#xa0;=&#xa0;0.53, P&#xa0;&lt;&#xa0;0.01; &#x394;-TOI: r&#xa0;=&#xa0;0.59, P&#xa0;&lt;&#xa0;0.01).</AbstractText>Maternal rCBV and rCBO decrease significantly during spinal anesthesia for cesarean section. Reductions in rCBV and rCBO may be associated with the severity of hypotension induced by subarachnoid sympathetic block with bupivacaine.</AbstractText>
2,335,594
Multi-Modal Treatment Approach to Painful Rib Syndrome: Case Series and Review of the Literature.
Mechanical chest wall pain is a common presenting complaint in the primary care office, emergency room, and specialty clinic. Diagnostic testing is often expensive due to similar presenting symptoms that may involve the heart or lungs. Since the chest wall biomechanics are poorly understood by many clinicians, few effective treatments are offered to patients with rib-related acute pain, which may lead to chronic pain.</AbstractText>This case series and literature review illustrates biomechanics involved in the pathogenesis of rib-related chest wall pain and suggests an effective multi-modal treatment plan using interventional techniques with emphasis on manual manipulative techniques.</AbstractText>Case series and literature review.</AbstractText>Pain clinic in an academic medical center.</AbstractText>This is a case series of 3 patients diagnosed with painful rib syndrome using osteopathic palpatory physical examination techniques. Ultrasound-guided intercostal nerve blocks were followed by manual manipulation of mechanically displaced ribs as a part of our multi-modal treatment plan. A review of the literature was undertaken to clarify nomenclature used in the description of rib-related pain, to describe the biomechanics involved in the pathogenesis of mechanical rib pain, and to illustrate the use of effective manual manipulation techniques.</AbstractText>This review is introductory and not a complete review of all manual or interventional pain management techniques applicable to the treatment of mechanical rib-related pain.</AbstractText>Manual diagnostic and therapeutic skills can be learned by physicians to treat biomechanically complex rib-related chest wall pain in combination with interventional image-guided techniques. Pain physicians should learn certain basic manual manipulation skills both for diagnostic and therapeutic purposes.</AbstractText>
2,335,595
A 10-year retrospective study of neonatal lupus erythematous in China.
Neonatal lupus erythematosus (NLE) is not a common disease. The death rate of complete congenital heart block (CCHB), which is the most severe clinical manifestation, is as high as 20% to 30%, so early recognition of infants at risk is important.</AbstractText>To investigate the clinical features and long-term prognosis of NLE.</AbstractText>Twenty-five cases with NLE were reviewed. The clinical manifestations of patients and their mothers were summarized and analyzed. Autoantibodies were detected, and long-term follow-up was carried out.</AbstractText>There were 25 patients (male:female ratio of 11:14). CCHB was detected in only 3 of the 25 patients (12%). Cutaneous neonatal lupus erythematosus (CNLE) was seen in 22 of the 25 patients (88%). Eight babies were treated with intravenous immunoglobulin (IVIG), five of whom had a prolonged PR interval that reverted to normal sinus rhythm. During the follow-up of the patients, we found only two patients with CCHB without a pacemaker, who both exhibited growth delay. One patient with CCHB without a pacemaker died.</AbstractText>Children with NLE have an excellent outcome when only skin lesions are present. Even the hepatic, hematological and neurological abnormalities are transient, with generally good outcomes. IVIG might have some effectiveness due to enhanced anti-inflammatory activity to treat early diseases that may be reversible (e.g. prolonged PR interval). The long-term prognosis for patients with NLE is still under investigation, and some infants with NLE may progress to other autoimmune diseases later in childhood.</AbstractText>
2,335,596
Addition of low-dose ketamine to midazolam and low-dose bupivacaine improves hemodynamics and postoperative analgesia during spinal anesthesia for cesarean section.
Spinal anesthesia for cesarean section (CS) is associated with an incidence of hypotension of 60-94%. This study hypothesizes that intrathecal combination of low-dose ketamine, midazolam, and low-dose bupivacaine improves hemodynamics and postoperative analgesia compared with fentanyl and low-dose bupivacaine during CS.</AbstractText>Fifty parturients undergoing elective CS were randomized equally to receive ketamine (10 mg), midazolam (2 mg) and 0.5% hyperbaric bupivacaine (8 mg) in group ketamine-midazolam-bupivacaine (KMB) or fentanyl (25 &#x3bc;g) and 0.5% hyperbaric bupivacaine (8 mg) in group fentanyl-bupivacaine (FB). Heart rate (HR), mean arterial blood pressure (MAP), oxygen saturation, sensorimotor block characteristics, pain-free period, side-effects including: hypotension, bradycardia, nausea, vomiting, sedation, pruritus, respiratory depression and dissociative manifestations, Apgar score at 1 and 5 min, and patients' satisfaction visual analog scores (VAS) were recorded. Patients in group KMB were followed for 6 months in order to assess any neurological disorder.</AbstractText>Group KMB showed higher sensory level (P = 0.006), rapid sensory (P = 0.001) and motor (P = 0.005) onsets, prolonged sensory (P = 0.008) and motor (P = 0.002) blocks, and prolonged pain free period (P = 0.002). Ketamine-midazolam stabilized HR and MAP, and significantly reduced incidence of hypotension (P = 0.002), bradycardia (P = 0.013) and vomiting (P = 0.019). Apgar scores at 1 and 5 min were comparable in both groups (P = 0.699 and 0.646 respectively). Patients' satisfaction VAS scores were significantly higher in group KMB (P = 0.001). No patients in KMB group showed dissociative or neurotoxic manifestations.</AbstractText>Intrathecal low-dose ketamine combined with midazolam and low-dose bupivacaine stabilizes hemodynamics and prolongs postoperative analgesia without significant side-effects in parturients undergoing CS.</AbstractText>
2,335,597
Nanoparticle drug delivery systems and their use in cardiac tissue therapy.
Cardiovascular diseases make up one of the main causes of death today, with myocardial infarction and ischemic heart disease contributing a large share of the deaths reported. With mainstream clinical therapy focusing on palliative medicine following myocardial infarction, the structural changes that occur in the diseased heart will eventually lead to end-stage heart failure. Heart transplantation remains the only gold standard of cure but a shortage in donor organs pose a major problem that led to clinicians and researchers looking into alternative strategies for cardiac repair. This review will examine some alternative methods of treatment using chemokines and drugs carried by nanoparticles as drug delivering agents for the purposes of treating myocardial infarction through the promotion of revascularization. We will also provide an overview of existing studies involving such nanoparticulate drug delivery systems, their reported efficacy and the challenges facing their translation into ubiquitous clinical use.
2,335,598
Protocol for a block randomised controlled trial of an intervention to improve heart failure care.
To describe the design of a randomised controlled trial conducted to evaluate a culturally tailored, nurse-led educational intervention.</AbstractText>Self-care strategies are critical to improving health outcomes in heart failure. The family unit is crucial in collectivist cultures, but little is known about involving the family in the self-care of patients with heart failure.</AbstractText>Involving the family in the self-care of heart failure is a novel approach. To the authors' knowledge, no one has evaluated it using a randomised controlled trial.</AbstractText>A valid comparison of outcomes between the control group and the intervention group involved in the study was provided in this trial. The chosen design, randomised controlled trial, enabled the assessment of the intervention.</AbstractText>The application of a family self-care intervention in a collectivist culture was shown to improve clinical and quality outcomes of patients with heart failure. Considering the individual and the community needs is vital in improving these outcomes.</AbstractText>
2,335,599
Medication regimen complexity and readmissions after hospitalization for heart failure, acute myocardial infarction, pneumonia, and chronic obstructive pulmonary disease.
Readmission rate is increasingly being viewed as a key indicator of health system performance. Medication regimen complexity index scores may be predictive of readmissions; however, few studies have examined this potential association. The primary objective of this study was to determine whether medication regimen complexity index is associated with all-cause 30-day readmission after admission for heart failure, acute myocardial infarction, pneumonia, or chronic obstructive pulmonary disease.</AbstractText>This study was an institutional review board-approved, multi-center, case-control study. Patients admitted with a primary diagnosis of heart failure, acute myocardial infarction, pneumonia, or chronic obstructive pulmonary disease were randomly selected for inclusion. Patients were excluded if they discharged against medical advice or expired during their index visit. Block randomization was utilized for equal representation of index diagnosis and site. Discharge medication regimen complexity index scores were compared between subjects with readmission versus those without. Medication regimen complexity index score was then used as a predictor in logistic regression modeling for readmission.</AbstractText>Seven hundred and fifty-six patients were randomly selected for inclusion, and 101 (13.4%) readmitted within 30&#x2009;days. The readmission group had higher medication regimen complexity index scores than the no-readmission group (p&#x2009;&lt;&#x2009;0.01). However, after controlling for demographics, disease state, length of stay, site, and medication count, medication regimen complexity index was no longer a significant predictor of readmission (odds ratio 0.99, 95% confidence interval 0.97-1.01) or revisit (odds ratio 0.99, 95% confidence interval 0.98-1.02).</AbstractText>There is little evidence to support the use of medication regimen complexity index in readmission prediction when other measures are available. Medication regimen complexity index may lack sufficient sensitivity to capture an effect of medication regimen complexity on all-cause readmission.</AbstractText>