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2,335,400 |
Breaking sitting with light activities vs structured exercise: a randomised crossover study demonstrating benefits for glycaemic control and insulin sensitivity in type 2 diabetes.
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<AbstractText Label="AIMS/HYPOTHESIS">We aimed to examine the effects of breaking sitting with standing and light-intensity walking vs an energy-matched bout of structured exercise on 24 h glucose levels and insulin resistance in patients with type 2 diabetes.</AbstractText>In a randomised crossover study, 19 patients with type 2 diabetes (13 men/6 women, 63 ± 9 years old) who were not using insulin each followed three regimens under free-living conditions, each lasting 4 days: (1) Sitting: 4415 steps/day with 14 h sitting/day; (2) Exercise: 4823 steps/day with 1.1 h/day of sitting replaced by moderate- to vigorous-intensity cycling (at an intensity of 5.9 metabolic equivalents [METs]); and (3) Sit Less: 17,502 steps/day with 4.7 h/day of sitting replaced by standing and light-intensity walking (an additional 2.5 h and 2.2 h, respectively, compared with the hours spent doing these activities in the Sitting regimen). Blocked randomisation was performed using a block size of six regimen orders using sealed, non-translucent envelopes. Individuals who assessed the outcomes were blinded to group assignment. Meals were standardised during each intervention. Physical activity and glucose levels were assessed for 24 h/day by accelerometry (activPAL) and a glucose monitor (iPro2), respectively. The incremental AUC (iAUC) for 24 h glucose (primary outcome) and insulin resistance (HOMA2-IR) were assessed on days 4 and 5, respectively.</AbstractText>The iAUC for 24 h glucose (mean ± SEM) was significantly lower during the Sit Less intervention than in Sitting (1263 ± 189 min × mmol/l vs 1974 ± 324 min × mmol/l; p = 0.002), and was similar between Sit Less and Exercise (Exercise: 1383 ± 194 min × mmol/l; p = 0.499). Exercise failed to improve HOMA2-IR compared with Sitting (2.06 ± 0.28 vs 2.16 ± 0.26; p = 0.177). In contrast, Sit Less (1.89 ± 0.26) significantly reduced HOMA2-IR compared with Exercise (p = 0.015) as well as Sitting (p = 0.001).</AbstractText><AbstractText Label="CONCLUSIONS/INTERPRETATION">Breaking sitting with standing and light-intensity walking effectively improved 24 h glucose levels and improved insulin sensitivity in individuals with type 2 diabetes to a greater extent than structured exercise. Thus, our results suggest that breaking sitting with standing and light-intensity walking may be an alternative to structured exercise to promote glycaemic control in patients type 2 diabetes.</AbstractText>Clinicaltrials.gov NCT02371239 FUNDING: : The study was supported by a Kootstra grant from Maastricht University Medical Centre+</sup>, and the Dutch Heart Foundation. Financial support was also provided by Novo Nordisk BV, and Medtronic and Roche made the equipment available for continuous glucose monitoring.</AbstractText>
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2,335,401 |
Ad-HGF improves the cardiac remodeling of rat following myocardial infarction by upregulating autophagy and necroptosis and inhibiting apoptosis.
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Cell death in MI is the most critical determinant of subsequent left ventricular remodeling and heart failure. Besides apoptosis, autophagy and necroptosis have been recently found to be another two regulated cell death styles. HGF has been reported to have a protective role in MI, but its impact on the three death styles remains unclear. Thus, our study was performed to investigate the distribution of autophagy, apoptosis and necroptosis in cardiac tissues after MI and explore the role and mechanism of Ad-HGF on cardiac remodeling by regulating the three death styles. We firstly showed the distribution of autophagy, apoptosis and necroptosis differs in temporal and spatial context after MI using immunofluorescence. Notably, Ad-HGF treatment improves the cardiac remodeling of SD rats following MI by preserving the heart function, reducing the scar size and aggresomes. Further mechanism study reveals Ad-HGF promotes autophagy and necroptosis and inhibits apoptosis <i>in vivo</i> and <i>in vitro</i>. Co-immunoprecipitation assays showed Ad-HGF treatment significantly decreased the binding of Bcl-2 to Beclin1 but enhanced Bcl-2 binding to Bax in H9c2 cells under hypoxia. Moreover, HGF-induced sequestration of Bax by Bcl-2 allows Bax to become inactive, thereby inhibiting apoptosis. In addition, Ad-HGF markedly increased the formation of Beclin1-Vps34-Atg14L complex, which accounted for promoting autophagy. Both the western blot and activity assay showed Ad-HGF significantly decreased the caspase 8 protein and activity levels, which obligated the cell to undergo necroptosis under hypoxia and block apoptosis. Thus, our findings offer new evidence and strategies for the treatment of MI and post-MI cardiac remodeling.
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2,335,402 |
[The clinical application of lumbar plexus-the first posterior sacral foramina block for hip arthroplasty in elderly patients].
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<b>Objective:</b> To evaluate the clinical efficacy of lumbar plexus-the first posterior sacral foramina block as an anesthesia technique for hip arthroplasty in elderly patients. <b>Methods:</b> Forty-four patients, aged 60-91 years, weighing 37-100 kg, American Society of Anesthesiologists (ASA) Ⅰ-Ⅲ, underwent elective hip arthroplasty in Tongji Hospital from February 2015 to January 2016.All patients received lumbar plexus and the first posterior sacral foramina block.The first posterior sacral foramina puncture point of 23 cases were located by traditional positioning method, the others were orientated via ultrasonic method.Measurements included effect of sensory blockade after 30 min of completed injection, hemodynamic parameters, quality of surgery blockade, and postoperative adverse reactions related to nerve block. <b>Results:</b> The success rates of the sensory blockade of pinprick for the dermatomes L1-S3 were from 73% to 100%, with 93% success rates of surgical analgesia.Compared with baseline (T<sub>0</sub>) , the systolic blood pressure (SBP) decreased at 10 min after incision (T<sub>5</sub>) and 20 min after incision (T<sub>6</sub>) [T<sub>0</sub> vs T<sub>5</sub>: (137±23) mmHg vs (119±20) mmHg, <i>t</i>=3.825, <i>P</i><0.05; T<sub>0</sub> vs T<sub>6</sub>: (137±23) mmHg vs (118±18) mmHg, <i>t</i>=4.403, <i>P</i><0.05]. Heart rate (HR) and diastolic blood pressure (DBP) had no significant changes at different time points (<i>F</i>=0.877, 1.439, <i>P</i>>0.05). One patient suffered urinary incontinence. <b>Conclusion:</b> Lumbar plexus-the first posterior sacral foramina block is one of safe and effective anesthetic techniques for hip arthroplasty in aged patients.
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2,335,403 |
Defective lymphatic valve development and chylothorax in mice with a lymphatic-specific deletion of Connexin43.
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Lymphatic valves (LVs) are cusped luminal structures that permit the movement of lymph in only one direction and are therefore critical for proper lymphatic vessel function. Congenital valve aplasia or agenesis can, in some cases, be a direct cause of lymphatic disease. Knowledge about the molecular mechanisms operating during the development and maintenance of LVs may thus aid in the establishment of novel therapeutic approaches to treat lymphatic disorders. In this study, we examined the role of Connexin43 (Cx43), a gap junction protein expressed in lymphatic endothelial cells (LECs), during valve development. Mouse embryos with a null mutation in Cx43 (Gja1) were previously shown to completely lack mesenteric LVs at embryonic day 18. However, interpreting the phenotype of Cx43<sup>-/-</sup> mice was complicated by the fact that global deletion of Cx43 causes perinatal death due to heart defects during embryogenesis. We have now generated a mouse model (Cx43<sup>∆LEC</sup>) with a lymphatic-specific ablation of Cx43 and show that the absence of Cx43 in LECs causes a delay (rather than a complete block) in LV initiation, an increase in immature valves with incomplete leaflet elongation, a reduction in the total number of valves, and altered lymphatic capillary patterning. The physiological consequences of these lymphatic changes were leaky valves, insufficient lymph transport and reflux, and a high incidence of lethal chylothorax. These results demonstrate that the expression of Cx43 is specifically required in LECs for normal development of LVs.
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2,335,404 |
The Effect of Reverse Trendelenburg Position on Incidence of Hypotension after Spinal Anesthesia.
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To prove if 10-degree head-up tilt position during conduction of spinal anesthesia and continue through the operation will reduce the incidence of hypotension comparing to horizontal position in elective cesarean section parturient.</AbstractText>In this randomized double-blind controlled trial. Forty-four parturient were equally allocated into 10-degree head-up tilt and horizontal position during conduction of spinal anesthesia and continue during the operation. Blood pressure, heart rate, incidence of hypotension, ephedrine consumption, and anesthesia level were compared.</AbstractText>Incidence of hypotension and percentage of parturient that required ephedrine were comparable in control and study groups (72.73% vs. 45.45%, p = 0.066) but lower before cord clamping in the study group (68.18% vs. 36.36%, p = 0.03). The sensory block levels were identical but more parturient in the study group required reposition in order to gain the required anesthetic level.</AbstractText>Ten-degree head-up tilt position during conduction and maintenance of spinal anesthesia for cesarean section reduced incidence of hypotension and ephedrine consumption without any adverse effect in both parturient and newly-born babies.</AbstractText>
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2,335,405 |
Biological variability of lipoprotein-associated phospholipase A<sub>2</sub> activity in healthy individuals.
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Measuring lipoprotein-associated phospholipase A2</sub> (Lp-PLA2</sub>) activity can aid in identifying individuals at higher risk of coronary heart disease. However, the biological variation of Lp-PLA2</sub> activity and corresponding reference change value (RCV) is unknown which limits interpretation of results. In this study we aim to define the intra- and inter-individual variability of Lp-PLA2</sub> activity in a healthy reference population.</AbstractText>A total of 24 healthy individuals (22-47years of age) were prospectively collected at several time points: daily for five days (after overnight fast), daily for three days (while non-fasting), weekly for four weeks (after overnight fast), and monthly for 6months (after overnight fast). Intra-individual and inter-individual variability was determined. The index of individuality (IoI) and reference change value (RCV) were calculated for each time period.</AbstractText>Variability in Lp-PLA2</sub> activity was not different in fasting versus non-fasting states and also did not change in daily versus monthly testing. The RCV for monthly Lp-PLA2</sub> activity was found to be 17%. More than 90% of the variability was attributable to between person differences while analytic variability comprised <9% of the variability and within-person variability was low at <0.7%. The index of individuality for monthly testing was 0.30 CONCLUSIONS: In a healthy population, Lp-PLA2</sub> activity displays low analytical and within-person variability and higher inter-individual variability. The change required to differentiate a true change in patient status was determined to be 17% for monthly measurements. The between individual variability and corresponding RCV for the activity assay are lower than previously reported results for the Lp-PLA2</sub> mass assay.</AbstractText>Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.</CopyrightInformation>
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2,335,406 |
Complete Heart Block in Pregnancy: A Report of Emergency Caesarean Section in a Parturient without Pacemaker.
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Management of women with Complete Heart Block (CHB) presenting without pacing, during pregnancy and labour is debatable. Temporary pacemakers have been routinely inserted for labour and birth probably to withstand any haemodynamic variations. However, due to lack of large scale prospective studies, the necessity of this procedure has not been objectively assessed. Also, the most appropriate anaesthetic technique for caesarean section in women with CHB is yet to be clarified. We report herein the case of a pregnant woman with CHB who had uneventful emergency caesarean delivery under spinal anaesthesia without temporary pacing. She was an unbooked case detected with congenital CHB first time during active labour; echocardiography showed no structural cardiac disease and her heart rate increased with atropine. We suggest further research so that guidelines could be established to prevent unnecessary morbidity and expense of temporary pacemaker insertion. Newly diagnosed cases of asymptomatic CHB in late pregnancy should be worked up for chronotropic responsiveness using atropine and responsive cases may be managed without pacemaker.
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2,335,407 |
Alcohol Exposure Causes Overexpression of Heart Development-Related Genes by Affecting the Histone H3 Acetylation via BMP Signaling Pathway in Cardiomyoblast Cells.
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Abusive alcohol utilization of pregnant woman may cause congenital heart disease (CHD) of fetus, where alcohol ignites histone H3 hyperacetylation leading to abnormal development of heart morphogenesis and associated genes. Knowledge about the regularized upstream genes is little, but bone morphogenetic protein (BMP) signaling may actively and prominently take part in alteration in acetylation of histone H3. The supreme objective of this study was to unearth the involvement of BMP signaling pathway in alcohol-driven hyperacetylation of histone H3 in cardiomyoblast cells.</AbstractText>Cardiomyoblast cells (H9c2 cells) were addicted with alcohol (100 mM) for 24 hours. Dorsomorphin (5 μM) was used for the inhibition of BMP signaling pathway. We detected the phosphorylation activity of SMAD1/5/8, mRNA expression, histone acetyltransferases (HAT)/histone deacetylase (HDAC) activity, and acetylation of histone H3.</AbstractText>Following alcohol exposure, phosphorylation of SMAD1/5/8 and HAT activities was increased to a significant extent, while histone H3 acetylation and expression of heart development-related genes were also increased. The said phenomenon influenced by alcohol was reverted upon dorsomorphin treatment to the cells without effecting HDAC activity.</AbstractText>The data clearly identified that BMP-mediated histone H3 acetylation of heart development-related genes might be one of the possible cellular mechanisms to control alcohol-induced expression of heart development-related genes. Dorsomorphin, on the other hand, may modulate alcohol-induced hyperacetylation of histone H3 through BMP targeting, which could be a potential way to block CHD.</AbstractText>Copyright © 2016 by the Research Society on Alcoholism.</CopyrightInformation>
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2,335,408 |
Treatment of Postoperative Pain in Pediatric Operations: Comparing the Efficiency of Bupivacaine, Bupivacaine-Dexmedetomidine and Bupivacaine-Fentanyl for Caudal Block.
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Caudal analgesia is a common method for postoperative pain management in pediatric patients. Additive agents such as opioids and α2</sub> agonists have been used to enhance the analgesic effects of local anesthetics for caudal block.</AbstractText>The aim of this study was to compare the additive effects of dexmedetomidine and fentanyl on bupivacaine-induced caudal analgesia in pediatric patients who had undergone elective inguinal hernia repair.</AbstractText>This randomized, double-blind clinical trial included children aged 1 - 5 years who were divided into three groups: the bupivacaine group (Group B) received 0.25% bupivacaine (1 ml/kg), the bupivacaine-dexmedetomidine group (Group BD) received 0.25% bupivacaine (1 mL/kg) plus 2 µg/kg dexmedetomidine, and the bupivacaine-fentanyl group (Group BF) received 0.25% bupivacaine (1 mL/kg) plus 2 µg/kg fentanyl. The hemodynamic variables (heart rate, systolic blood pressure, respiratory rate, and peripheral arterial oxygen saturation) were measured perioperatively. Pain, sedation and motor block scores and adverse events (nausea and vomiting, pruritis, hypotension, bradycardia, urinary retention and respiratory depression) were documented at 30 and 60 minutes, and the 1st, 2nd, 4th, 6th, 12th and 24th hours after the operation. The other recordings include the duration of surgery and analgesic requirement.</AbstractText>A total of 61 patients were analyzed. The lowest pain scores were found in the BD group at all time points (P < 0.001). The sedation scores were higher in the BD group than in the other two groups at all time points (P < 0.001). No motor block was observed after the operation. Only three patients required analgesic administration 2 to 6 hours after the operation in group B. No side effects were observed in any of the groups, and there was no significant difference in the duration of surgery among the three groups.</AbstractText>The results show that the analgesic and sedative effects were better when dexmedetomidine was added to bupivacaine than when fentanyl was added or bupivacaine alone was administered in the pediatric population studied here that underwent elective inguinal hernia repair.</AbstractText>
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2,335,409 |
Dexmedetomidine use in the ED for control of methamphetamine-induced agitation.
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Chemical restraint is often required to control agitation induced by methamphetamine. Dexmedetomidine is an α-2 adrenergic receptor agonist with sedative, analgesic, and sympatholytic properties. Its use in the emergency department (ED) to control methamphetamine-induced agitation has not been reported.</AbstractText>To report two cases of methamphetamine-induced agitation successfully sedated with dexmedetomidine in the ED.</AbstractText>The first case was a 42-year-old man with unstable emotion and violent behaviours after smoking methamphetamine. His agitation did not respond to a large cumulative dose of benzodiazepines (10mg of diazepam and 332mg of midazolam) administered over 48h and sedation was achieved with dexmedetomidine. The second case was a 38-year-old methamphetamine user with unstable emotion and recurrent episodes of agitation despite repeated doses of benzodiazepines, whose agitation was controlled with dexmedetomidine infusion.</AbstractText>In both cases, dexmedetomidine apparently reduced the dose of benzodiazepines needed to achieve adequate sedation. Transient falls in blood pressure and slowing of the heart rate were noted, which resolved either spontaneously or after reducing the infusion rate without requiring drug treatment.</AbstractText>Dexmedetomidine can be considered as an adjunct for chemical restraint when standard treatment fails to control the agitation induced by methamphetamine, but patient's hemodynamic state should be monitored closely during administration. Its efficacy and safety in the ED warrant further evaluation with prospective controlled trials.</AbstractText>Copyright © 2016 Elsevier Inc. All rights reserved.</CopyrightInformation>
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2,335,410 |
Cytokine-Like 1 Regulates Cardiac Fibrosis via Modulation of TGF-β Signaling.
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Cytokine-like 1 (Cytl1) is a secreted protein that is involved in diverse biological processes. A comparative modeling study indicated that Cytl1 is structurally and functionally similar to monocyte chemoattractant protein 1 (MCP-1). As MCP-1 plays an important role in cardiac fibrosis (CF) and heart failure (HF), we investigated the role of Cytl1 in a mouse model of CF and HF. Cytl1 was upregulated in the failing mouse heart. Pressure overload-induced CF was significantly attenuated in cytl1 knock-out (KO) mice compared to that from wild-type (WT) mice. By contrast, adeno-associated virus (AAV)-mediated overexpression of cytl1 alone led to the development of CF in vivo. The endothelial-mesenchymal transition (EndMT) and the transdifferentiation of fibroblasts (FBs) to myofibroblasts (MFBs) have been suggested to contribute considerably to CF. Adenovirus-mediated overexpression of cytl1 was sufficient to induce these two critical CF-related processes in vitro, which were completely abrogated by co-treatment with SB-431542, an antagonist of TGF-β receptor 1. Cytl1 induced the expression of TGF-β2 both in vivo and in vitro. Antagonizing the receptor for MCP-1, C-C chemokine receptor type 2 (CCR2), with CAS 445479-97-0 did not block the pro-fibrotic activity of Cytl1 in vitro. Collectively, our data suggest that Cytl1 plays an essential role in CF likely through activating the TGF-β-SMAD signaling pathway. Although the receptor for Cyt1l remains to be identified, Cytl1 provides a novel platform for the development of anti-CF therapies.
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2,335,411 |
Design of the MEMS Piezoresistive Electronic Heart Sound Sensor.
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This paper proposes the electronic heart sound sensor, based on the piezoresistive principle and MEMS (Micro-Electro-Mechanical System) technology. Firstly, according to the characteristics of heart sound detection, the double-beam-block microstructure has been proposed, and the theoretical analysis and finite element method (FEM) simulation have been carried out. Combined with the natural frequency response of the heart sound (20~600 Hz), its structure sizes have been determined. Secondly, the processing technology of the microstructure with the stress concentration grooves has been developed. The material and sizes of the package have been determined by the three-layer medium transmission principle. Lastly, the MEMS piezoresistive electronic heart sound sensor has been tested compared with the 3200-type electronic stethoscope from 3M (São Paulo, MN, USA). The test results show that the heart sound waveform tested by the MEMS electronic heart sound sensor are almost the same as that tested by the 3200-type electronic stethoscope. Moreover, its signal-to-noise ratio is significantly higher. Compared with the traditional stethoscope, the MEMS heart sound sensor can provide the first and second heart sounds containing more abundant information about the lesion. Compared with the 3200-type electronic stethoscope from 3M, it has better performance and lower cost.
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2,335,412 |
Structure and mechanism of the ATP synthase membrane motor inferred from quantitative integrative modeling.
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Two subunits within the transmembrane domain of the ATP synthase-the c-ring and subunit a-energize the production of 90% of cellular ATP by transducing an electrochemical gradient of H<sup>+</sup> or Na<sup>+</sup> into rotational motion. The nature of this turbine-like energy conversion mechanism has been elusive for decades, owing to the lack of definitive structural information on subunit a or its c-ring interface. In a recent breakthrough, several structures of this complex were resolved by cryo-electron microscopy (cryo-EM), but the modest resolution of the data has led to divergent interpretations. Moreover, the unexpected architecture of the complex has cast doubts on a wealth of earlier biochemical analyses conducted to probe this structure. Here, we use quantitative molecular-modeling methods to derive a structure of the a-c complex that is not only objectively consistent with the cryo-EM data, but also with correlated mutation analyses of both subunits and with prior cross-linking and cysteine accessibility measurements. This systematic, integrative approach reveals unambiguously the topology of subunit a and its relationship with the c-ring. Mapping of known Cd<sup>2+</sup> block sites and conserved protonatable residues onto the structure delineates two noncontiguous pathways across the complex, connecting two adjacent proton-binding sites in the c-ring to the space on either side of the membrane. The location of these binding sites and of a strictly conserved arginine on subunit a, which serves to prevent protons from hopping between them, explains the directionality of the rotary mechanism and its strict coupling to the proton-motive force. Additionally, mapping of mutations conferring resistance to oligomycin unexpectedly reveals that this prototypical inhibitor may bind to two distinct sites at the a-c interface, explaining its ability to block the mechanism of the enzyme irrespective of the direction of rotation of the c-ring. In summary, this study is a stepping stone toward establishing the mechanism of the ATP synthase at the atomic level.
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2,335,413 |
Assessment of the accuracy of common clinical thresholds for cardiac morphology and function by transthoracic echocardiography.
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We evaluated the ability of transthoracic echocardiography (TTE) to correctly identify abnormal left ventricular (LV) size, function, and mass when compared to cardiac magnetic resonance (CMR). Whilst numerous studies have compared TTE and CMR with respect to correlation between measurements and study reproducibility, few have employed categorical analysis relevant to clinical practice.</AbstractText>Two hundred and fifteen consecutive patients who underwent both TTE and CMR were evaluated for the presence of abnormal LV size, systolic function, and mass. Abnormal LV systolic function was further categorized into grades (mild, moderate, and severe). Quantification of LV morphology and function was performed on TTE and CMR according to published guidelines. The level of agreement between TTE and CMR was compared across binary and categorical variables using Cohen's kappa.</AbstractText>Compared to CMR, TTE demonstrated excellent agreement in identification of abnormal versus normal function (κ = 0.87). However, agreement across grades of LV function was less strong (κ = 0.63). Whilst agreement for identification of severe LV dysfunction was good (κ = 0.68), this would still lead to misclassification of severe dysfunction in approximately one in seven cases. Agreement between TTE and CMR was moderate to good for identification of LV dilation (κ = 0.43-0.63), but poor for identification of increased mass (κ = 0.04).</AbstractText>Whilst in clinical practice TTE performs well in identification of normal versus abnormal systolic function, it has substantial limitations across grades of dysfunction and in the assessment of LV size and mass. These limitations have important implications when considering management decisions for patients based on thresholds of LV morphology or function.</AbstractText>
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2,335,414 |
RIG-I-like receptor-induced IRF3 mediated pathway of apoptosis (RIPA): a new antiviral pathway.
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The innate immune response is the first line of host defense to eliminate viral infection. Pattern recognition receptors in the cytosol, such as RIG-I-like receptors (RLR) and Nod-like receptors (NLR), and membrane bound Toll like receptors (TLR) detect viral infection and initiate transcription of a cohort of antiviral genes, including interferon (IFN) and interferon stimulated genes (ISGs), which ultimately block viral replication. Another mechanism to reduce viral spread is through RIPA, the RLR-induced IRF3-mediated pathway of apoptosis, which causes infected cells to undergo premature death. The transcription factor IRF3 can mediate cellular antiviral responses by both inducing antiviral genes and triggering apoptosis through the activation of RIPA. The mechanism of IRF3 activation in RIPA is distinct from that of transcriptional activation; it requires linear polyubiquitination of specific lysine residues of IRF3. Using RIPA-active, but transcriptionally inactive, IRF3 mutants, it was shown that RIPA can prevent viral replication and pathogenesis in mice.
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2,335,415 |
Efficacy and Safety of Dexmedetomidine as an Adjuvant in Epidural Analgesia and Anesthesia: A Systematic Review and Meta-analysis of Randomized Controlled Trials.
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Several clinical trials have examined and indicated the usefulness of epidural dexmedetomidine therapy. However, there has been no systematic analysis of the findings of these trials to date. We undertook this systematic review and meta-analysis to investigate the efficacy and safety of epidural dexmedetomidine adjunctive therapy in different surgical procedures.</AbstractText>We searched EMBASE, PubMed, the Cochrane Library, and the Clinical Trials.gov database to identify randomized controlled trials investigating the effects of epidural dexmedetomidine adjunctive therapy. The article search was conducted without language or date restrictions. The date of the last search was 27 July 2016. The mean differences (MD) or standardized mean differences (SMD) with 95% confidence intervals (CIs) were calculated for continuous variables, and risk ratios (RRs) were presented for dichotomous outcomes. Heterogeneity was assessed using τ 2</sup>, χ 2</sup> and I 2</sup> analyses.</AbstractText>Twelve randomized controlled trials were included in the final analysis. Compared with the control treatment, epidural dexmedetomidine administration prolonged the duration of analgesia (P < 0.0001), reduced the time to sensory block (P = 0.002), decreased the requirement for rescue analgesia (P < 0.00001) and achieved a significantly higher sedation score (P < 0.0001). Although dexmedetomidine adjunctive therapy did not affect mean arterial pressure (P = 0.33), systolic blood pressure (P = 0.32) or diastolic blood pressure (P = 0.28), it significantly lowered heart rate (P = 0.0009). Symptoms indicative of hypotension and bradycardia events were more common in the dexmedetomidine group, but the difference in the overall risk of hypotension and bradycardia was statistically insignificant (P > 0.05) in comparison with that reported for the control therapies. Furthermore, dexmedetomidine effectively reduced post-operative pain (P = 0.03), whilst the occurrence of other side effects, such as pruritus, dizziness, dry mouth, nausea and vomiting did not differ significantly from that reported for the control therapies, except the risk of shivering was significantly higher with control therapies (P = 0.03).</AbstractText>This systematic review and meta-analysis demonstrates that dexmedetomidine as an adjuvant in epidural procedures is generally safe and well tolerated. Furthermore, dexmedetomidine acted synergistically and provided an improved sedation and analgesic profile.</AbstractText>
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2,335,416 |
Effects of prenatal bisphenol-A exposure and postnatal overfeeding on cardiovascular function in female sheep.
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Bisphenol-A (BPA) is a widely used endocrine-disrupting chemical. Prenatal exposure to BPA is known to affect birth weight, but its impact on the cardiovascular system has not been studied in detail. In this study, we investigated the effects of prenatal BPA treatment and its interaction with postnatal overfeeding on the cardiovascular system. Pregnant sheep were given daily subcutaneous injections of corn oil (control) or BPA (0.5 mg/kg/day in corn oil) from day 30 to day 90 of gestation. A subset of female offspring of these dams were overfed to increase body weight to ~30% over that of normal fed controls. Cardiovascular function was assessed using non-invasive echocardiography and cuff blood pressure (BP) monitoring at 21 months of age. Ventricular tissue was analyzed for gene expression of cardiac markers of hypertrophy and collagen at the end of the observation period. Prenatal BPA exposure had no significant effect on BP or morphometric measures. However, it increased atrial natriuretic peptide gene expression in the ventricles and reduced collagen expression in the right ventricle. Overfeeding produced a marked increase in body weight and BP. There were compensatory increases in left ventricular area and internal diameter. Prenatal BPA treatment produced a significant increase in interventricular septal thickness when animals were overfed. However, it appeared to block the increase in BP and left ventricular area caused by overfeeding. Taken together, these results suggest that prenatal BPA produces intrinsic changes in the heart that are capable of modulating morphological and functional parameters when animals become obese in later life.
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2,335,417 |
Possible complication of bee stings and a review of the cardiac effects of bee stings.
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We report the case of a patient who, ∼3 weeks after multiple bee stings, developed a prolonged heart block, syncope and cardiac arrest. This required a temporary pacemaker to be implanted, which was later replaced with a permanent pacemaker. An ECG taken following surgery for a fractured humerus 6 years earlier was reportedly normal. The patient had been a rubber tapper who walked ∼1.5 km/day, but after the bee attack he was no longer able to walk or get up from the bed without experiencing syncope. We presume that the bee venom caused these signs, as well as the resulting heart block, which persisted long after the bee sting had subsided. Since his coronary angiogram was normal we believe he had a Kounis type involvement of the cardiovascular system, namely profound coronary spasm that caused complete heart block that did not recover. Another probable reason for the complete heart block could have been that the bees had consumed the pollen of a rhododendron flower, causing 'grayanotoxin' poisoning and severe heart block. The other effects of bee sting are discussed briefly.
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2,335,418 |
I.V. paracetamol as an adjunct to patient-controlled epidural analgesia with levobupivacaine and fentanyl in labour: a randomized controlled study.
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Use of i.v. paracetamol for postoperative pain is well documented, but it is unclear if it can reduce the consumption of opioids during patient-controlled epidural analgesia (PCEA) in labouring parturients.</AbstractText>In this randomized, double-blind, placebo-controlled clinical trial conducted in a tertiary care hospital, 80</sup>parturients were randomly assigned to two groups of 40 each, to receive either 1000 mg (100 ml) i.v. paracetamol or 100 ml normal saline as placebo, 30 min before the procedure. After insertion of the epidural catheter, all patients received 10 ml of levobupivacaine 0.1% with 2 μg ml-1 fentanyl, followed by continuous background epidural infusion of 6 ml h-1 with a provision of patient-controlled bolus 5 ml of same drug with a lock-out interval of 12 min.The primary outcome was hourly mean consumption of levobupivacaine and fentanyl mixture (ml.h-1). Secondary outcomes included pain score ,: sensory and motor block, haemodynamic parameters of mother, duration of second stage of labour, mode of delivery, Apgar scores, foetal heart rate and adverse effects.</AbstractText>The hourly mean drug consumption in the Paracetamol group was significantly lower as compared with the Placebo group (7.03 ml.h-1, SD 0.83 vs. 8.12 ml.h-1, SD 1.34; p < 0.001). The mean number of boluses taken were also significantly less in the paracetamol group (1.00, SD 0.93 vs. 1.43, SD 0.90; p = 0.036). Pain scores decreased in both the groups without significant inter-group differences.</AbstractText>Use of 1000 mg i.v. paracetamol decreases the mean hourly drug consumption through epidural route. Thus i.v. paracetamol is a safe and effective adjunct to PCEA in labour analgesia.</AbstractText>Clinical Trials Registry-India (http://ctri.nic.in/Clinicaltrials/login.php), trial registration number 2013/09/003968.</AbstractText>© The Author 2016. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: [email protected].</CopyrightInformation>
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2,335,419 |
15<sup>th</sup> Sukaman Memorial Lecture: ST Segment Elevation: New Electrocardiographic Insights in 2014.
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Of all the non-arrhythmic electrocardiographic (ECG) abnormalities, ST segment elevation (ST elevation) is the most important with regard to diagnosis, prognosis and management.
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2,335,420 |
Postoperative analgesia in children when using clonidine in addition to fentanyl with bupivacaine given caudally.
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The aim of the study was to evaluate the efficacy of clonidine in association with fentanyl as an additive to bupivacaine 0.25% given via single shot caudal epidural in pediatric patients for postoperative pain relief. In the present prospective randomized double blind study, 40 children of ASA-I-II aged 1-5 years scheduled for infraumblical surgical procedures were randomly allocated to two groups to receive either bupivacaine 0.25% (1 ml/kg) with fentanyl 1 μg/kg and clonidine 1μg/kg (group I) or bupivacaine 0.25% (1 ml/kg) with fentanyl 1 μg/kg (group II). Caudal block was performed after the induction of general anesthesia. Postoperatively patients were observed for analgesia, sedation, hemodynamic parameters, and side effects or complications. Both the groups were similar with respect to patient and various block characteristics. Heart rate and blood pressure were not different in 2 groups. Significantly prolonged duration of post-operative analgesia was observed in group I (P<0.05). Side effects such as respiratory depression, vomiting and bradycardia were similar in both groups. The adjunction of clonidine to fentanyl as additives to bupivacaine in single shot caudal epidural in children may provide better and longer analgesia after infraumblical surgical procedures.
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2,335,421 |
Genistein attenuates monocrotaline-induced pulmonary arterial hypertension in rats by activating PI3K/Akt/eNOS signaling.
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Phytoestrogen genistein may be useful to treat pulmonary arterial hypertension (PAH). However, its mechanism is still not clear. The aim of the present study was to confirm the therapeutic effects of phytoestrogen genistein on PAH in monocrotaline-induced rat model and to explore its mechanism.</AbstractText>Sprague-Dawley male rats were randomly divided into 4 groups: control group (n=8), PAH group (n=8), genistein treament group with three different doses (n=8 in each dose group) and group of PI3K inhibitor LY294002. The rat model of PAH was induced by monocrotaline (MCT). The situation of survival of rats was observed. Pathological studies of lung and heart tissues were performed. Western-blot detection of P-Akt and P-eNOS expression levels in lung tissue was carried out. Nitrate reductase analysis was used to measure nitric oxide (NO) in lung tissue.</AbstractText>Genistein treatment resulted in significant improvement in the speed of tricuspid regurgitation, diameter of pulmonary artery, mean pulmonary artery pressure and right ventricular hypertrophy index. Genistein treatment also resulted in significant improvement in the stenosis of pulmonary artery, proliferation of smooth muscle, right ventricular hypertrophy and myocardial hypertrophy. These therapeutic effects were more obvious with increasing dose of genistein. After genistein treatment, amelioration in survival rates of PAH rats was observed. PI3K inhibitor LY294002 could block these therapeutic effects. In rat lung tissue, P-Akt, P-eNOS and NO expressions were increased significantly in genistein treatment group when compared with PAH group (p<0.05, respectively). The increase in expression level of P-Akt, P-eNOS and NO was correlated with genistein dose. P-Akt, P-eNOS and NO expressions in lung tissue increased slightly in the PI3K inhibitor LY294002 group when compared with PAH group, but the difference was not statistically significant (p>0.05).</AbstractText>We confirmed that genistein could relax pulmonary vascular resistance, reduce pulmonary artery pressure, improve right heart function and ameliorate survival rate in the rat model of PAH. Our study suggested that its mechanism was related with PI3K/Akt/eNOS signal pathway. Phytoestrogen genistein may become a new and effective drug for patients with PAH.</AbstractText>
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2,335,422 |
Nontoxic Formulations of Scintillation Nanocrystals for Use as X-ray Computed Tomography Contrast Agents.
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X-ray computed tomography (CT) is currently one of the most powerful, noninvasive, clinical in vivo imaging techniques, which has resulted from advances in both X-ray device and contrast enhancement technologies. The present study demonstrates, for the first time, that metal tungstates (such as CaWO<sub>4</sub>) are promising contrast agents for X-ray, radiation, and CT imaging, because of the high X-ray mass attenuation of tungsten (W). We have developed a method of formulation, in which CaWO<sub>4</sub> (CWO) nanoparticles (NPs) are encapsulated within a biocompatible poly(ethylene glycol-b-d,l-lactic acid) (PEG-PLA) block copolymer (BCP) capsule. We show that these PEG-PLA-encapsulated CWO NPs (170 ± 10 nm hydrodynamic diameter) produce a higher CT contrast (by a factor of about 2) than commercial iodine-based radiocontrast agents (e.g., Iohexol) at identical molar concentrations of W or I atoms. PEG-PLA-coated CWO NPs are chemically stable and completely nontoxic. It was confirmed that the maximum tolerated dose (MTD) of this material in mice is significantly higher (250 ± 50 mg per kg body weight following a single intravenous (IV) administration) than, for instance, commercially available dextran-coated iron oxide nanoparticles that are currently used clinically as MRI contrast agents (MTD in mice ≈ 168 mg/kg per dose IV). IV-injected PEG-PLA/CWO NPs caused no histopathologic damage in major excretory organs (heart, liver, lungs, spleen, and kidney). When an IV dose of 100 mg/kg was given to mice, the blood circulation half-life was measured to be about 4 h, and more than 90% of the NPs were cleared from the mice within 24 h via the renal and hepatobiliary systems. When intratumorally administered, PEG-PLA-coated CWO NPs showed complete retention in a tumor-bearing mouse model (measurements were made up to 1 week). These results suggest that PEG-PLA-coated CWO NPs are promising materials for use in CT contrast.
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2,335,423 |
Efficacy and Safety of Clonidine as an Adjuvant to Bupivacaine for Caudal Analgesia in Paediatric Infra-Umbilical Surgeries.
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Caudal analgesia, has gained popularity in paediatric intraoperative and postoperative pain management, more so with the use of adjuvants to prolong its duration, each of them having various results. Clonidine, an alpha2-adrenergic agonist is being used for its analgesic effects in various doses with 0.25% Bupivacaine.</AbstractText>The study was conducted to compare the analgesic efficacy, haemodynamic safety and side effects of 1 μg/kg Clonidine added to 1 ml/kg of 0.125% Bupivacaine solution for caudal analgesia.</AbstractText>A prospective, randomised, double-blind, controlled study was carried out in 60 children of ASA Physical Status I, aged 1-10 years, scheduled for infraumbilical operations in a tertiary care centre. They were randomly assigned for caudal analgesia, to either group B: 1ml/kg of 0.125% Bupivacaine solution or group BC: 1ml/kg of 0.125% Bupivacaine and preservative free Clonidine 1μ/kg. All were premedicated with midazolam 0.75 mg/kg orally 30 minutes prior to induction of anaesthesia. Heart rate (HR), Mean Arterial blood Pressure (MAP) and oxygen saturation (SpO2</sub>) were monitored. General anaesthesia was induced with thiopentone (1.25%) 5mg/kg and inhalation of oxygen, nitrous oxide and sevoflurane. Postoperative pain, sedation and motor block was assessed by the various scores and patients were monitored for adverse effects.</AbstractText>The mean duration of postoperative analgesia was 3 times longer in group BC. Group B received significantly more doses of rescue analgesic than group BC (p-value of 0.004). There was no significant bradycardia, hypotension, sedation or urinary retention in either of the groups. There was no residual motor blockade at 6 hours. Incidence of vomiting was similar in both the groups.</AbstractText>Caudal Clonidine in the dose of 1 μg/kg in children is a satisfactory and efficacious adjuvant to caudal Bupivacaine for producing prolonged postoperative analgesia with minimum side effects.</AbstractText>
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2,335,424 |
Comparison between Thoracic Epidural Block and Thoracic Paravertebral Block for Post Thoracotomy Pain Relief.
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Postoperative pain after thoracotomy is being considered one of the most severe pain and if not treated well, can result in various respiratory and other complications.</AbstractText>Present study was conducted with the aim to compare continuous thoracic epidural infusion with continuous paravertebral infusion for postoperative pain using Visual Analogue Scale (VAS) score and four point observer ranking. The secondary outcomes measured were pulmonary functions and any complication like hypotension, bradycardia, nausea, vomiting, urinary retention and neurological complications if any.</AbstractText>Sixty patients of age group 18-60 years posted for anterolateral thoracotomy surgery for lung resection were randomised either to epidural or paravertebral group in this randomised prospective double blind study. In Epidural group 7.5ml bolus of 0.125% Bupivacaine with 50μg Fentanyl and in Paravertebral group 15ml bolus of 0.125% Bupivacaine with 50μg Fentanyl was given 30 minutes before the anticipated end of surgery. Bolus dose was followed by infusion of 0.125% Bupivacaine with 2μg/ml Fentanyl at the rate of 5 ml/hr in both groups. Parameters noted were Mean Arterial Pressure (MAP), Heart Rate (HR), Oxygen Saturation (SpO2</sub>), Arterial Blood Gas (PaCO2</sub>, P/F ratio), Visual Analogue Scale (VAS) and Four Point Observer Ranking Scale (FPORS) for pain, number of sensory segments blocked (by checking for pinprick sensation), requirement of infusion top ups and rescue analgesia (Tramadol), pre and postoperative pulmonary function test {(Forced Expiratory Volume (FEV)1</sub>, Forced Vital Capacity (FVC), FEV1</sub>/FVC, Peak Expiratory Flow Rate (PEFR)} and complications from start of infusion till 24 hours in the postoperative period.</AbstractText>Both the techniques were effective in relieving pain but pain relief was significantly better with epidural. Postoperatively, HR, SpO2</sub>, P/F ratio and PaCO2</sub> were comparable between group E and P. There was significant decline in FeV1</sub>, FVC, FeV1</sub>/FVC and PEFR in postoperative period as compared to preoperative value in both the groups. Hypotension and bradycardia were more in group E.</AbstractText>Both the techniques, continuous thoracic epidural block and continuous thoracic paravertebral block were effective for post-thoracotomy pain relief; however, epidural block provides better pain relief. The incidence of sympatholytic complications was more in epidural group. The effect on respiratory mechanics was equivalent. Hence, paravertebral block can be used in post thoracotomy pain relief in those patients where thoracic epidural is contraindicated.</AbstractText>
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2,335,425 |
Pharmacological analysis of the cardiac sympatho-inhibitory actions of moxonidine and agmatine in pithed spontaneously hypertensive rats.
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This study shows that in spontaneously hypertensive rats (SHR) of 14-weeks-old, the sympathetically-induced, but not noradrenaline-induced tachycardic response are higher than age-matched Wistar normotensive rats. Furthermore, in SHR the sympathetically-induced tachycardic response was: (1) unaffected by moxonidine (3μg/kgmin); (2) partially inhibited by B-HT 933 (30μg/kgmin), both at the lowest doses; and (3) completely inhibited by the highest doses of B-HT 933 (100μg/kgmin), moxonidine (10μg/kgmin) or agmatine (1000 and 3000μg/kgmin) while the noradrenaline-induced tachycardic responses remained unaffected by the above compounds, except by 3000μg/kgmin agmatine. In SHR, 300μg/kg rauwolscine failed to block the sympatho-inhibition to 100μg/kgmin B-HT 933 or 10μg/kgmin moxonidine, but 1000μg/kg rauwolscine abolished, partially antagonized, and did not modify the sympatho-inhibition to the highest doses of B-HT 933, moxonidine, and agmatine, respectively, 3000μg/kg AGN 192403 or 300μg/kg BU224 given alone had no effect in the moxonidine- or agmatine-induced sympatho-inhibition, and the combination rauwolscine plus AGN 192403 but not plus BU224, abolished the sympatho-inhibition to the highest doses of moxonidine and agmatine. In conclusion, the sympathetically-induced tachycardic responses in SHR are inhibited by moxonidine and agmatine. The inhibition of moxonidine is mainly mediated by prejunctional α<sub>2</sub>-adrenoceptors and to a lesser extent by I<sub>1</sub>-imidazoline receptors, while the inhibition of agmatine is mediated by prejunctional α<sub>2</sub>-adrenoceptors and I<sub>1</sub>-imidazoline receptors at the same extent. Notwithstanding, the inhibitory function of α<sub>2</sub>-adrenoceptors seems to be altered in SHR compared with Wistar normotensive rats.
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2,335,426 |
Development of a PET/OMRI combined system for simultaneous imaging of positron and free radical probes for small animals.
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Positron emission tomography (PET) has high sensitivity for imaging radioactive tracer distributions in subjects. However, it is not possible to image free radical distribution in a subject by PET. Since free radicals are quite reactive, they are related to many diseases, including but not limited to cancer, inflammation, strokes, and heart disease. The Overhauser enhanced magnetic resonance imaging (OMRI) is so far the only method that images free radical distribution in vivo. By combining PET and OMRI, a new hybrid imaging modality might be developed that can simultaneously image the radioactive tracer and free radical distributions. For this purpose, the authors developed a PET/OMRI combined system for small animals.</AbstractText>The developed PET/OMRI system used an optical fiber-based PET system combined with a permanent magnet-based OMRI system. The optical fiber-based PET system uses flexible optical fiber bundles. Eight optical fiber-based block detectors were arranged in a 56 mm diameter ring to form a PET system. The LGSO blocks were located inside the field-of-view (FOV) of the OMRI, and the position sensitive photomultiplier tubes were positioned behind the OMRI to minimize the interference between the PET and the OMRI. The OMRI system used a 0.0165 T permanent magnet. The system has an electron spin resonance coil to enhance the MRI signal using the Overhauser effect to image the free radical in the FOV of the PET/OMRI system.</AbstractText>The spatial resolution and sensitivity of the optical fiber-based PET system were 1.2 mm FWHM and 1.2% at the central FOV, respectively. The OMRI system imaged the distribution of a nitroxyl radical (NXR) solution. The interference between PET and OMRI was small. Simultaneous imaging of the positron radiotracer and the NXR solution was successfully conducted with the developed PET/OMRI system for phantom and small animal studies.</AbstractText>The authors developed a PET/OMRI combined system with the potential to provide interesting new results in molecular imaging research, such as in vivo molecular and free radical distributions.</AbstractText>
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2,335,427 |
Early Fluid Resuscitation by Lactated Ringer's Solution Alleviate the Cardiac Apoptosis in Rats with Trauma-Hemorrhagic Shock.
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Cardiac trauma has been recognized as a complication associated with blunt chest trauma involving coronary artery injury, myocardium contusion and myocardial rupture. Secondary cardiac injuries after trauma supposed to be a critical factor in trauma patients, but the mechanism is not fully explored. Overproduction of TNF-alpha had been reported in multiple trauma animals, this induces oxidative stress resulting in cardiac apoptosis. Apoptosis gradually increases after trauma and reaches to a maximum level in 12 h time. TNF-alpha increases the expression of NFkB, and induces the expression of caspase-3 and resulted in cell apoptosis. The effect can be attenuated by non-selective caspase inhibitor and IL10. Fas induced cardiac apoptosis and hypertrophy in ischemic heart disease. In this study, we demonstrated a trauma-hemorrhagic shock (THS) model in rats and resuscitated rats by lactated Ringer's (L/R) solution after shock in different hours (0 hour, 4 hours, 8 hours). NFkB gradually increased after the first 8 hours of shock, and can be reduced by fluid resuscitation. NFkB is known as a downstream pathway of Fas related apoptosis, we found Fas ligand, caspase-8 levels elevate after shock, and can be reduced by resuscitation. In addition, resuscitation can activate insulin-like growth factor (IGF-1)/Akt pathway, at the same time. It can block mitochondrial damage by decrease the effect of tBid. In conclusion, THS can induce secondary cardiac injury. Fas showed to be an important element in caspase cascade induced myocardium apoptosis. By L/R fluid resuscitation, the suppression of caspase cascade and activation of IGF-I/Akt pathway showed antiapoptotic effects in traumatic heart of rats.
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2,335,428 |
Balance between sodium and calcium currents underlying chronic atrial fibrillation termination: An in silico intersubject variability study.
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Atrial remodeling as a result of long-standing persistent atrial fibrillation (AF) induces substrate modifications that lead to different perpetuation mechanisms than in paroxysmal AF and a reduction in the efficacy of antiarrhythmic treatments.</AbstractText>The purpose of this study was to identify the ionic current modifications that could destabilize reentries during chronic AF and serve to personalize antiarrhythmic strategies.</AbstractText>A population of 173 mathematical models of remodeled human atrial tissue with realistic intersubject variability was developed based on action potential recordings of 149 patients diagnosed with AF. The relationship of each ionic current with AF maintenance and the dynamics of functional reentries (rotor meandering, dominant frequency) were evaluated by means of 3-dimensional simulations.</AbstractText>Self-sustained reentries were maintained in 126 (73%) of the simulations. AF perpetuation was associated with higher expressions of INa</sub> and ICaL</sub> (P <.01), with no significant differences in the remaining currents. ICaL</sub> blockade promoted AF extinction in 30% of these 126 models. The mechanism of AF termination was related with collisions between rotors because of an increase in rotor meandering (1.71 ± 2.01cm2</sup>) and presented an increased efficacy in models with a depressed INa</sub> (P <.01).</AbstractText>Mathematical simulations based on a population of models representing intersubject variability allow the identification of ionic mechanisms underlying rotor dynamics and the definition of new personalized pharmacologic strategies. Our results suggest that the underlying mechanism of the diverging success of ICaL</sub> block as an antiarrhythmic strategy is dependent on the basal availability of sodium and calcium ion channel conductivities.</AbstractText>Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.</CopyrightInformation>
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2,335,429 |
The Impact of Central and Peripheral Cyclooxygenase Enzyme Inhibition on Exercise-Induced Elevations in Core Body Temperature.
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Exercise increases core body temperature (TC</sub>) due to metabolic heat production. However, the exercise-induced release of inflammatory cytokines including interleukin-6 (IL-6) may also contribute to the rise in TC</sub> by increasing the hypothalamic temperature set point. This study investigated whether the exercise-induced increase in TC</sub> is partly caused by an altered hypothalamic temperature set point.</AbstractText>Fifteen healthy, active men age 36 ± 14 y were recruited. Subjects performed submaximal treadmill exercise in 3 randomized test conditions: (1) 400 mg ibuprofen and 1000 mg acetaminophen (IBU/APAP), (2) 1000 mg acetaminophen (APAP), and (3) a control condition (CTRL). Acetaminophen and ibuprofen were used to block the effect of IL-6 at a central and peripheral level, respectively. TC</sub>, skin temperature, and heart rate were measured continuously during the submaximal exercise tests.</AbstractText>Baseline values of TC</sub>, skin temperature, and heart rate did not differ across conditions. Serum IL-6 concentrations increased in all 3 conditions. A significantly lower peak TC</sub> was observed in IBU/APAP (38.8°C ± 0.4°C) vs CTRL (39.2°C ± 0.5°C, P = .02) but not in APAP (38.9°C ± 0.4°C) vs CTRL. Similarly, a lower ΔTC</sub> was observed in IBU/APAP (1.7°C ± 0.3°C) vs CTRL (2.0°C ± 0.5°C, P < .02) but not in APAP (1.7°C ± 0.5°C) vs CTRL. No differences were observed in skin temperature and heart-rate responses across conditions.</AbstractText>The combined administration of acetaminophen and ibuprofen resulted in an attenuated increase in TC</sub> during exercise compared with a CTRL. This observation suggests that a prostaglandin-E2-induced elevated hypothalamic temperature set point may contribute to the exercise-induced rise in TC</sub>.</AbstractText>
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2,335,430 |
Preemptive Oral Clonidine Provides Better Sedation Than Intravenous Midazolam in Brachial Plexus Nerve Blocks.
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Preemptive analgesia is the blocking of pain perception afferent pathways before noxious painful stimuli. Clonidine is an alpha agonist drug that is partially selective for α-2 adrenoreceptors. Clonidine is used as anti-anxiety medication and an, analgesic, and it prolongs the duration of the block in the brachial plexus block.</AbstractText>To compare the effect of preemptive clonidine with midazolam on intraoperative sedation, duration of block, and postoperative pain scores.</b></AbstractText>In a randomized clinical trial, 80 patients with orthopedic fractures of an upper extremity who underwent supraclavicular nerve block were randomly assigned to receive 0.2 mg oral clonidine or 2 mg oral midazolam. Intraoperative sedation was measured at one hour after the start of urgery and again in the PACU (Post-Anesthesia Care Unit) using the Ramsay scale. The duration of sensory blockade was measured. Postoperative pain scores were measured using the VAS (Visual Analogue Scale) after entrance to recovery up to 2 hours.</AbstractText>The percentages of patients in the calm and sedated scale were significantly higher in clonidine group (35 and 42.5%, respectively), compared to the midazolam group (17.5 and 17.5%, respectively) (P = 0.042, 0.029; respectively). Those administered fentanyl in the clonidine group 105 ± 30.8 was significantly lower than that for the midazolam group 165 ± 34.5 (P = 0.0018). The percentages of patients in the calm scale were significantly higher in the clonidine group (52.5), compared to the midazolam group (17.5) (P = 0.001) in the post-operative period. VAS scores were significantly lower at one (P = 0.01) and two hours (P = 0.001) after operation in the clonidine group, compared to the midazolam group.</AbstractText>Preemptive clonidine has many marvelous advantages over midazolam, including better sedation inside the operating room and then in the post-operative care unit, lower fentanyl doses are required during surgery, more stable heart rate and blood pressure are observed during the procedure, and patients report lower post-operative pain scores.</AbstractText>
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2,335,431 |
Contribution of tactile dysfunction to manual motor dysfunction in type II diabetes.
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Changes in sensory and motor functions of the hand in type II diabetes (T2D) patients have been reported; there is speculation that these changes are driven by tactile dysfunction. The purpose of this study was to evaluate the effects of tactile feedback on manual function in T2D patients.</AbstractText>T2D patients and healthy controls underwent median nerve blocks at the wrist and elbow. All participants underwent traditional timed motor evaluations, force dynamometry, laboratory-based kinetic evaluations, and sensory evaluation.</AbstractText>Tactile sensation in the T2D group at baseline was found to be equivalent to tactile function of the control group after median nerve block. Traditional timed evaluation results were negatively impacted by anesthesia, but more sensitive kinetic measures were not impacted.</AbstractText>These data suggest that mechanisms outside of tactile dysfunction play a significant role in motor dysfunction in T2D. Muscle Nerve 54: 895-902, 2016.</AbstractText>© 2016 Wiley Periodicals, Inc.</CopyrightInformation>
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2,335,432 |
Pathophysiology of cardiotoxicity from target therapy and angiogenesis inhibitors.
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The progress in cancer therapy and the increase in number of long-term survivors reveal the issue of cardiovascular side-effects of anticancer drugs. Cardiotoxicity has become a significant problem, and the risks of adverse cardiac events induced by systemic drugs need to be seriously considered. Potential cardiovascular toxicities linked to anticancer agents include arrhythmias, myocardial ischemia and infarction, hypertension, thromboembolism, left ventricular dysfunction, and heart failure. It has been shown that several anticancer drugs seriously affect the cardiovascular system, such as ErbB2 inhibitors, vascular endothelial growth factor (VEGF) inhibitors, multitargeted kinase inhibitors, Abelson murine leukemia viral oncogene homolog inhibitors, and others. Each of these agents has a different mechanism through which it affects the cardiovascular system. ErbB2 inhibitors block the ErbB4/ErbB2 heterodimerization pathway triggered by Neuregulin-1, which is essential for cardiomyocyte survival. VEGF signaling is crucial for vascular growth, but it also has a major impact on myocardial function, and the VEGF pathway is also essential for maintenance of cardiovascular homeostasis. Drugs that inhibit the VEGF signaling pathway lead to a net reduction in capillary density and loss of contractile function. Here, we review the mechanisms and pathophysiology of the most significant cardiotoxic effects of ErbB2 inhibitors and antiangiogenic drugs. Moreover, we highlight the role of cardioncology in recognizing these toxicities, developing strategies to prevent or minimize cardiovascular toxicity, and reducing long-term cardiotoxic effects.
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2,335,433 |
A Parsimonious Model of the Rabbit Action Potential Elucidates the Minimal Physiological Requirements for Alternans and Spiral Wave Breakup.
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Elucidating the underlying mechanisms of fatal cardiac arrhythmias requires a tight integration of electrophysiological experiments, models, and theory. Existing models of transmembrane action potential (AP) are complex (resulting in over parameterization) and varied (leading to dissimilar predictions). Thus, simpler models are needed to elucidate the "minimal physiological requirements" to reproduce significant observable phenomena using as few parameters as possible. Moreover, models have been derived from experimental studies from a variety of species under a range of environmental conditions (for example, all existing rabbit AP models incorporate a formulation of the rapid sodium current, INa, based on 30 year old data from chick embryo cell aggregates). Here we develop a simple "parsimonious" rabbit AP model that is mathematically identifiable (i.e., not over parameterized) by combining a novel Hodgkin-Huxley formulation of INa with a phenomenological model of repolarization similar to the voltage dependent, time-independent rectifying outward potassium current (IK). The model was calibrated using the following experimental data sets measured from the same species (rabbit) under physiological conditions: dynamic current-voltage (I-V) relationships during the AP upstroke; rapid recovery of AP excitability during the relative refractory period; and steady-state INa inactivation via voltage clamp. Simulations reproduced several important "emergent" phenomena including cellular alternans at rates > 250 bpm as observed in rabbit myocytes, reentrant spiral waves as observed on the surface of the rabbit heart, and spiral wave breakup. Model variants were studied which elucidated the minimal requirements for alternans and spiral wave break up, namely the kinetics of INa inactivation and the non-linear rectification of IK.The simplicity of the model, and the fact that its parameters have physiological meaning, make it ideal for engendering generalizable mechanistic insight and should provide a solid "building-block" to generate more detailed ionic models to represent complex rabbit electrophysiology.
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2,335,434 |
Dose-response and Cardiopulmonary Side Effects of the Novel Neuromuscular-blocking Drug CW002 in Man.
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CW002 is a benzylisoquinolinium nondepolarizing neuromuscular-blocking drug found to be inactivated by cysteine in preclinical studies. The current study represents a dose escalation clinical trial designed to describe CW002 potency, duration, cardiopulmonary side effects, and histamine release.</AbstractText>Healthy subjects anesthetized with sevoflurane/nitrous oxide were divided into five groups (n = 6), each receiving a fixed CW002 dose (0.02, 0.04, 0.06, 0.08, or 0.10 mg/kg), and one group (n = 4) receiving 0.14 mg/kg. Blood pressure and heart rate were continuously recorded along with airway dynamic compliance. Neuromuscular blockade was assessed with mechanomyography at the adductor pollicis. Arterial blood was obtained before and after CW002 injection for analysis of plasma histamine concentration. Potency was estimated from a baseline sigmoid Emax model.</AbstractText>ED50 was found to be 0.036 mg/kg (95% CI, 0.020 to 0.053 mg/kg) and ED95 0.077 mg/kg (95% CI, 0.044 to 0.114 mg/kg). At 0.14 mg/kg (1.8 × ED95), 80% twitch depression occurred in 94 ± 18 s with complete block in 200 ± 87 s. Clinical recovery (25% of maximum twitch) occurred in 34 ± 3.4 min, with a 5 to 95% recovery interval of 35.0 ± 2.7 min. The time to a train-of-four ratio greater than 0.9 ranged from 59 to 86 min. CW002 did not elicit histamine release or significant (greater than 10%) changes in blood pressure, heart rate, or dynamic airway compliance.</AbstractText>In healthy subjects receiving sevoflurane/nitrous oxide, CW002 at 1.8 × estimated ED95 produces a clinical duration less than 40 min, elicits no histamine release, and has minimal cardiopulmonary side effects.</AbstractText>
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2,335,435 |
Cold bupivacaine versus magnesium sulfate added to room temperature bupivacaine in sonar-guided femoral and sciatic nerve block in arthroscopic anterior cruciate ligament reconstruction surgery.
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Cooling of local anesthetic potentiates its action and increases its duration. Magnesium sulfate (MgSo4</sub>) added to local anesthetic prolongs the duration of anesthesia and postoperative analgesia with minimal side effects.</AbstractText>The aim of this prospective, randomized, double-blind study was to compare the effect of cold to 4°C bupivacaine 0.5% and Mg added to normal temperature (20-25°C) bupivacaine 0.5% during sonar-guided combined femoral and sciatic nerve blocks on the onset of sensory and motor block, intraoperative anesthesia, duration of sensory and motor block, and postoperative analgesia in arthroscopic anterior cruciate ligament (ACL) reconstruction surgery.</AbstractText>A total of 90 American Society of Anesthesiologists classes I and II patients who were scheduled to undergo elective ACL reconstruction were enrolled in the study. The patients were randomly allocated to 3 equal groups to receive sonar-guided femoral and sciatic nerve blocks. In Group I, 17 ml of room temperature (20-25°C) 0.5% bupivacaine and 3 ml of room temperature saline were injected for each nerve block whereas in Group II, 17 ml of cold (4°C) 0.5% bupivacaine and 3 ml of cold saline were injected for each nerve block. In Group III, 17 ml of room temperature 0.5% bupivacaine and 3 ml of MgSo4</sub> 5% were injected for each nerve block. The onset of sensory and motor block was evaluated every 3 min for 30 min. Surgery was started after complete sensory and motor block were achieved. Intraoperatively, the patients were evaluated for heart rate and mean arterial pressure, rescue analgesic and sedative requirements plus patient and surgeon satisfaction. Postoperatively, hemodynamics, duration of analgesia, resolution of motor block, time to first analgesic, total analgesic consumption, and the incidence of side effects were recorded.</AbstractText>There was no statistically significant difference in demographic data, mean arterial pressure, heart rate, and duration of surgery. Onset of both sensory and motor block was significantly shorter in both Groups II and III compared to Group I. Intraoperative anesthetic quality was comparable between groups with good patient and surgeon satisfaction. The time to first analgesia was significantly longer in Groups II and III compared to Group I with nonsignificant difference between each other. Moreover, the total opioid consumption was significantly lower in Groups II and III and duration of analgesia and motor block were significantly longer in Groups II and III compared to Group I. There was no difference in the incidence of side effects.</AbstractText>The use of cold 0.5% bupivacaine or the addition of Mg to normal temperature 0.5% bupivacaine prolongs the sensory and motor block duration without increasing side effects and enhances the quality of intra- and post-operative analgesia with better patient satisfaction in sonar-guided femoral and sciatic nerve block for arthroscopic ACL reconstruction surgery.</AbstractText>
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2,335,436 |
Comparisons of single-injection thoracic paravertebral block with ropivacaine and bupivacaine in breast cancer surgery: A prospective, randomized, double-blinded study.
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Regional anesthesia using paravertebral block has been suggested as an ideal adjunct to general anesthesia for modified radical mastectomy. Paravertebral block is an effective management of peri-operative pain for Modified radical mastectomy, however, there are no established guidelines regarding what is the most suitable strategy when varying drugs and dosages between different groups.</AbstractText>To evaluate the effectiveness of paravertebral block comparing the most frequently employed drugs in this procedure (bupivacaine vs ropivacaine).</AbstractText>Prospective randomized double blind study.</AbstractText>A total 70 ASA I and II adult female patients undergoing Modified radical mastectomy under paravertebral block followed by general anesthesia were randomly divided into two groups. The first group was administered 0.375% Ropivacaine in a dose 0.25 ml /kg in paravertebral block. The second group was administered bupivacaine 0.375% in dose 0.25 ml /kg in paravertebral block. Standard induction technique followed. Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), were recorded pre block, post block 5 min, post block 10 min, at skin incision, post skin incision initially at 5 interval for first 15 min till one hour, and every 30 min till end of surgery. Post-operative visual analogue score for pain was recorded at 1 hr, 6 hr and 24 hr.</AbstractText>Chi-square test (Fisher's exact test) for qualitative variables. Independent sample t</i>-test for quantitative data.</AbstractText>Ropivacaine and Bupivacaine had no difference in intraoperative analgesia as shown by intraoperative hemodynamic parameters. Bupivacaine got better post-operative VAS scores (P</i> < 0.05) in mean and after first, 6 h and 24 h.</AbstractText>
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2,335,437 |
A comparative study on effect of addition of clonidine and fentanyl as adjuvants to local anaesthetics for subarachnoid block in patients undergoing lumbar laminectomies.
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The synergism between local anesthetic agents such as bupivacaine with intrathecal adjuvants such as opioids and clonidine is well established.</AbstractText>This study evaluates the clinical efficacy of clonidine75 μg versus fentanyl 25 μg as adjuvants to bupivacaine for spinal anesthesia.</AbstractText>A prospective, randomized, parallel arm study was conducted over a period of 12 months in a tertiary care hospital.</AbstractText>Sixty patients were divided randomly into two groups, Group C and Group F. Patients in Group C received 2.5 ml of 0.5% bupivacaine heavy mixed with 0.5 ml (75 μg) clonidine intrathecally, and patients in Group F received 2.5 ml of 0.5% bupivacaine heavy mixed with 0.5 ml (25 μg) fentanyl intrathecally.</AbstractText>Data were analyzed using statistical tests for comparison of means.</AbstractText>The mean durations of sensory block was 253.3 and 249.6 minutes in group C and group F respectively, which was statistically not significant (P</i> = 0.76). The mean durations of motor block were 302.3 and 293.6 min, respectively, in Group C and Group F, which were also statistically not significant (P</i> = 0.53). The mean durations of postoperative analgesia were 653.4 and 611.2 min, respectively, in Group C and Group F, which were statistically not significant (P</i> = 0.09). Mean heart rate after 10 min was 82.5 in Group C and 87.2 in Group F, which was statistically not significant (P</i> = 0.29), and mean arterial pressure in mmHg after 10 min was 96.3 in Group C and 97.3 in Group F, which was also statistically not significant (P</i> = 0.86).</AbstractText>Both clonidine 75 μg and fentanyl 25 μg when used as adjuvants to bupivacaine in the subarachnoid block have comparable beneficial results in terms of duration of analgesia, duration of motor blocks, and hemodynamic stability and also have a comparable incidence of complications.</AbstractText>
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2,335,438 |
A comparison of dexamethasone and clonidine as an adjuvant for caudal blocks in pediatric urogenital surgeries.
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Caudal block is a reliable regional analgesic technique for pediatric urogenital surgeries. Various adjuvants have been tried to enhance the duration of action of bupivicaine. Though clonidine is extensively used as an adjuvant in caudal anaesthesia, it can have troublesome adverse effects like bradycardia, hypotension and sedation. Lately dexamethasone has become popular as an adjuvant in paediatric caudals due to its safety profile.</AbstractText>The aim of this study was to compare dexamethasone and clonidine coadministered with bupivicaine caudally in paediatric patients undergoing urogenital surgeries in terms of analgesia and adverse effects.</AbstractText>Prospective, double blinded randomised study.</AbstractText>Sixty American Society of Anesthesiologists physical status I and II children, aged 1-6 years undergoing urogenital surgeries were allocated in 2 groups: Group I: 0.5 mL.kg-1</sup> of 0.25% bupivicaine with dexamethasone 0.1 mg.kg-1</sup> in 1 ml normal saline (NS) Group II: 0.5 mL.kg-1</sup> of 0.25% bupivicaine with clonidine 1 μg.kg-1</sup> diluted in 1 ml normal saline. The parameters studied included duration of analgesia, intraoperative and postoperative hemodynamics, sedation scores and incidence of adverse effects like wound dehiscence, bleeding, vomiting and respiratory depression.</AbstractText>Statistical analysis was carried out using Stata Version 10. After checking for the normality assumption, t</i>-test for comparing means of two independent samples was used for comparing baseline continuous variables. P</i> values <0.05 were considered significant.</AbstractText>Patients in Group II had longer duration of analgesia postoperatively. Patients in this group also had lower heart rate and more sedation scores.</AbstractText>Our study shows that caudal dexamethasone is a good alternative to clonidine with more stable hemodynamics and lesser sedation scores in the immediate postoperative period. Both the drugs offer good analgesia postoperatively with the duration of analgesia more in clonidine.</AbstractText>
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2,335,439 |
Prevention of hypotension induced by combined spinal epidural anesthesia using continuous infusion of vasopressin: A randomized trial.
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Central neuraxial blockade (CNB) is an established technique of providing anesthesia for surgeries of the lower limb and abdomen. Hypotension is the most common side effect of CNB. It was hypothesized that by supplementing the initial burst of vasopressin following hypovolemia, hypotension following combined spinal epidural anesthesia (CSEA) could be avoided.</AbstractText>A total of 122 patients undergoing lower limb and abdomen surgeries were included in the study, with 61 patients randomized into two groups - I and II. Patients in Group I received infusion of normal saline as soon as CSEA was applied. When systolic blood pressure (SBP) decreased to <90 mmHg, they received a 6 mg bolus of mephentermine to counteract hypotension. Patients in Group II received a continuous infusion of vasopressin as soon as CSEA was applied. If despite maximum dose of vasopressin, SBP dropped to < 90 mmHg, then intravenous mephentermine was administered to counteract hypotension. Hemodynamic parameters and side effects were noted.</AbstractText>Level of block attained in both groups was comparable in terms of dermatomal height. The mean SBP and mean arterial pressure values of Group I were significantly lower than in Group II in the initial 14 min. Diastolic BP was also significantly lower in Group I. Heart rate was found to be lower in Group II, especially after 30 min (P</i> < 0.05).</AbstractText>Maintaining plasma levels of the physiological burst of vasopressin helps to avoid hypotension following neuraxial blockade. Continuous infusion of vasopressin at 1-3 U/h can prevent hypotension following neuraxial blockade.</AbstractText>
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2,335,440 |
Effect of adding clonidine to intrathecal bupivacaine on the quality of subarachnoid block: A prospective randomized double-blind study.
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The purpose of adding an adjuvant to local anesthetic in a central neuraxial blockade is to augment the desirable pharmacological actions of the agent and/or to minimize its undesirable pharmacological effects. Clonidine is an alfa-2 receptor agonist which has gained popularity in recent times as an adjuvant in spinal anesthesia.</AbstractText>To evaluate the influence of clonidine on the hemodynamic stability and the duration of anesthesia when added to intrathecal hyperbaric bupivacaine.</AbstractText>Prospective randomized double blind study.</AbstractText>Fifty patients scheduled for spinal anesthesia were randomized into two Groups A and B with 25 in each. Group A patients received 3 ml 0.5% heavy bupivacaine + 30 μg (0.2 ml) clonidine and Group B patients received 3 ml 0.5% heavy bupivacaine + 0.2 ml normal saline in the subarachnoid space. The blood pressure and heart rate were closely monitored. The time for attaining peak sensory block, time for two segment regression, decrease in the heart rate, total requirement of mephentermine to counter the hypotension, and the number of patients requiring mephentermine in each group was tabulated and analyzed.</AbstractText>Descriptive and inferential statistical methods were used to analyse the data. The power of the study was calculated using online power calculator for two independent sample study.</AbstractText>The time for attaining peak sensory block was similar in both the groups. The time for two segment regression in Group A was 62.6 min and in Group B was 38.08 min. Twelve percent of patients in Group A and 52% of patients in Group B required mephentermine with the mean consumption being 0.72 mg in Group A and 5.65 mg in Group B.</AbstractText>Addition of low-dose clonidine to intrathecal bupivacaine not only prolonged the duration of spinal anesthesia but also provided a stable intraoperative hemodynamic profile.</AbstractText>
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2,335,441 |
Exome-chip association analysis reveals an Asian-specific missense variant in PAX4 associated with type 2 diabetes in Chinese individuals.
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<AbstractText Label="AIMS/HYPOTHESIS">Genome-wide association studies (GWASs) have identified many common type 2 diabetes-associated variants, mostly at the intronic or intergenic regions. Recent advancements of exome-array genotyping platforms have opened up a novel means for detecting the associations of low-frequency or rare coding variants with type 2 diabetes. We conducted an exomechip association analysis to identify additional type 2 diabetes susceptibility variants in the Chinese population.</AbstractText>An exome-chip association study was conducted by genotyping 5640 Chinese individuals from Hong Kong, using a custom designed exome array, the Asian Exomechip. Single variant association analysis was conducted on 77,468 single nucleotide polymorphisms (SNPs). Fifteen SNPs were subsequently genotyped for replication analysis in an independent Chinese cohort comprising 12,362 individuals from Guangzhou. A combined analysis involving 7189 cases and 10,813 controls was performed.</AbstractText>In the discovery stage, an Asian-specific coding variant rs2233580 (p.Arg192His) in PAX4, and two variants at the known loci, CDKN2B-AS1 and KCNQ1, were significantly associated with type 2 diabetes with exome-wide significance (p discovery</sub> < 6.45 × 10-7</sup>). The risk allele (T) of PAX4 rs2233580 was associated with a younger age at diabetes diagnosis. This variant was replicated in an independent cohort and demonstrated a stronger association that reached genome-wide significance (p meta-analysis</sub> [p meta</sub>] = 3.74 × 10-15</sup>) in the combined analysis.</AbstractText><AbstractText Label="CONCLUSIONS/INTERPRETATION">We identified the association of a PAX4 Asian-specific missense variant rs2233580 with type 2 diabetes in an exome-chip association analysis, supporting the involvement of PAX4 in the pathogenesis of type 2 diabetes. Our findings suggest PAX4 is a possible effector gene of the 7q32 locus, previously identified from GWAS in Asians.</AbstractText>
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2,335,442 |
Epidermal Growth Factor Receptor Silencing Blunts the Slow Force Response to Myocardial Stretch.
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Myocardial stretch increases force biphasically: the Frank-Starling mechanism followed by the slow force response (SFR). Based on pharmacological strategies, we proposed that epidermal growth factor (EGF) receptor (EGFR or ErbB1) activation is crucial for SFR development. Pharmacological inhibitors could block ErbB4, a member of the ErbB family present in the adult heart. We aimed to specifically test the role of EGFR activation after stretch, with an interference RNA incorporated into a lentiviral vector (small hairpin RNA [shRNA]-EGFR).</AbstractText>Silencing capability of p-shEGFR was assessed in EGFR-GFP transiently transfected HEK293T cells. Four weeks after lentivirus injection into the left ventricular wall of Wistar rats, shRNA-EGFR-injected hearts showed ≈60% reduction of EGFR protein expression compared with shRNA-SCR-injected hearts. ErbB2 and ErbB4 expression did not change. The SFR to stretch evaluated in isolated papillary muscles was ≈130% of initial rapid phase in the shRNA-SCR group, while it was blunted in shRNA-EGFR-expressing muscles. Angiotensin II (Ang II)-dependent Na+/H+ exchanger 1 activation was indirectly evaluated by intracellular pH measurements in bicarbonate-free medium, demonstrating an increase in shRNA-SCR-injected myocardium, an effect not observed in the silenced group. Ang II- or EGF-triggered reactive oxygen species production was significantly reduced in shRNA-EGFR-injected hearts compared with that in the shRNA-SCR group. Chronic lentivirus treatment affected neither the myocardial basal redox state (thiobarbituric acid reactive substances) nor NADPH oxidase activity or expression. Finally, Ang II or EGF triggered a redox-sensitive pathway, leading to p90RSK activation in shRNA-SCR-injected myocardium, an effect that was absent in the shRNA-EGFR group.</AbstractText>Our results provide evidence that specific EGFR activation after myocardial stretch is a key factor in promoting the redox-sensitive kinase activation pathway, leading to SFR development.</AbstractText>© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.</CopyrightInformation>
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Peptide screen identifies a new NADPH oxidase inhibitor: impact on cell migration and invasion.
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The NADPH oxidase proteins catalyse the formation of superoxide anion which act as signalling molecules in physiological and pathological processes. Nox1-dependent NADPH oxidase is expressed in heart, lung, colon, blood vessels and brain. Different strategies involving Nox1 inhibition based on diphenylene iodonium derivatives are currently tested for colorectal cancer therapy. Here, after peptides screening on Nox1-dependent NADPH oxidase assay in HT-29 cells, we identify a peptide (referred to as NF02), cell-active, that potently block Nox1-dependent reactive oxygen species generation. Study of DEPMPO adduct formation by electron paramagnetic resonance showed that NF02 has no superoxide scavenging activity and no impact on cellular reactive oxygen species-producing enzymes such xanthine oxidase. NF02 was not cytotoxic, inhibited reactive oxygen species production of reconstituted Nox1/Noxo1/Noxa1 complex in HEK293 and did not decrease Nox2 dependent cellular NADPH oxidase reactive oxygen species production. Finally, NF02 inhibited cell migration and invasion of colorectal cancer cells which is consistent with the described impact of Nox1 inhibitors on cell migration. NF02 peptide is a new NADPH oxidase inhibitor specific for Nox1 over Nox2 and xanthine oxidase which might represent a useful Nox1 tool with potential therapeutic insights.
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2,335,444 |
Sunscreen Use and Sweat Production in Men and Women.
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Sunscreen lotions are important to protect the skin during outdoor exercise, but they may interfere with sweating.</AbstractText>To measure the effect of 2 water-resistant sunscreens on local sweat production in men and women exercising in the heat and to compare those effects with the expected inhibition resulting from the use of an antiperspirant.</AbstractText>Randomized crossover study.</AbstractText>Exercise in the heat (ambient temperature = 30.2°C ± 0.4°C dry bulb and 58% ± 4.3% relative humidity) in a controlled-environment laboratory.</AbstractText>Twenty physically active, apparently healthy college students, 10 men (age = 22.5 ± 2.8 years, height = 1.771 ± 0.069 m, mass = 70.2 ± 11.0 kg) and 10 women (age = 22.2 ± 3.2 years, height = 1.625 ± 0.075 m, mass = 57.7 ± 7.9 kg).</AbstractText><AbstractText Label="INTERVENTION(S)" NlmCategory="METHODS">With sweat-collection patches applied to their right and left scapular regions, the participants performed 2 exercise sessions on consecutive days. We assigned skin treatments (antiperspirant; organic chemical sun filter, sunscreen A; inorganic physical sun block, sunscreen B; no lotion) randomly to side and session. Participants pedaled at 79% ± 1% of maximum heart rate for 20 minutes in the heat.</AbstractText><AbstractText Label="MAIN OUTCOME MEASURE(S)" NlmCategory="METHODS">Scapular localized sweat rate.</AbstractText>No baseline, environmental, or exercise condition was different among skin treatments. Scapular localized sweat rate was lower for the antiperspirant treatment (88.3 μL/min·dm 2</sup> ; 95% confidence interval [CI] = 82.0, 94.7 μL/min·dm2</sup>) and the inorganic physical sun block (sunscreen B) treatment (99.3 μL/min·dm 2</sup> ; 95% CI = 93.1, 105.5 μL/min·dm2</sup>) than for the organic chemical sun filter (sunscreen A) treatment (114.8 μL/min·dm 2</sup> ; 95% CI = 108.8, 120.6 μL/min·dm2</sup>) or the no-lotion treatment (122.6 μL/min·dm 2</sup> ; 95% CI = 116.2, 129.0 μL/min·dm2</sup>; P < .01).</AbstractText>The inorganic physical sun block, sunscreen B, hindered effective sweating to the same extent as the antiperspirant, whereas the treatment with the organic chemical sun filter, sunscreen A, was not different from the control treatment. At this stage, it is not possible to identify the specific ingredient responsible for the effect.</AbstractText>
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2,335,445 |
Ranolazine for Congenital Long-QT Syndrome Type III: Experimental and Long-Term Clinical Data.
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The basic defect in long-QT syndrome type III (LQT3) is an excessive inflow of sodium current during phase 3 of the action potential caused by mutations in the SCN5A gene. Most sodium channel blockers reduce the early (peak) and late components of the sodium current (INa</sub> and INaL</sub>), but ranolazine preferentially reduces INaL</sub>. We, therefore, evaluated the effects of ranolazine in LQT3 caused by the D1790G mutation in SCN5A.</AbstractText>We performed an experimental study of ranolazine in TSA201 cells expressing the D1790G mutation. We then performed a long-term clinical evaluation of ranolazine in LQT3 patients carrying the D1790G mutation. In the experimental study, INaL</sub> was significantly higher in D1790G than in wild-type channels expressed in the TSA201 cells. Ranolazine exerted a concentration-dependent block of INaL</sub> of the SCN5A-D1790G channel without reducing peak INa</sub> significantly. In the clinical study, among 8 patients with LQT3 and confirmed D1790G mutation, ranolazine had no effects on the sinus rate or QRS width but shortened the QTc from 509±41 to 451±26 ms, a mean decrease of 56±52 ms (10.6%; P=0.012). The QT-shortening effect of ranolazine remained effective throughout the entire study period of 22.8±12.8 months. Ranolazine reduced the QTc at all heart rates but less so during extreme nocturnal bradycardia. A type I Brugada ECG was never noticed.</AbstractText>Ranolazine blocks INaL</sub> in experimental models of LQT3 harboring the SCN5A-D1790G mutation and shortened the QT interval of LQT3 patients.</AbstractText>URL: https://clinicaltrials.gov; Unique identifier: NCT01728025.</AbstractText>© 2016 American Heart Association, Inc.</CopyrightInformation>
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2,335,446 |
Comparison of cardiovascular responses after injection of lidocaine with either clonidine or adrenaline: a two-year comparative analysis.
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Our aim was to evaluate the efficacy of clonidine with lidocaine as a local anaesthetic agent for inferior alveolar mandibular nerve blocks for dental extraction. We studied 200 patients who required extraction of mandibular teeth and divided them into two groups of 100 each, the first of which was given lidocaine and adrenaline (12.5μg/ml) and the second lidocaine and clonidine (15μg/ml). Cardiovascular vascular variables (blood pressure, heart rate, and mean arterial pressure) were assessed before, during, and after extraction, and postoperative pain was measured on a visual analogue scale. There was a significant reduction in systolic blood pressure (p=0.0001) and heart rate (p=0.000) after injection of clonidine. However, they both increased after injections of lidocaine plus adrenaline, and there was a significant reduction in pain at four hours postoperatively with clonidine (p=0.000). Our results showed that anaesthesia with lidocaine and clonidine decreases systolic blood pressure and heart rate 10minutes after injection for extraction of lower mandibular teeth. We suggest that patients who have local anaesthetic with lidocaine and clonidine are at minimal cardiovascular risk and there is no difference in the onset of anaesthesia.
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2,335,447 |
Construction of Asymmetrical Hexameric Biomimetic Motors with Continuous Single-Directional Motion by Sequential Coordination.
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The significance of bionanomotors in nanotechnology is analogous to mechanical motors in daily life. Here the principle and approach for designing and constructing biomimetic nanomotors with continuous single-directional motion are reported. This bionanomotor is composed of a dodecameric protein channel, a six-pRNA ring, and an ATPase hexamer. Based on recent elucidations of the one-way revolving mechanisms of the phi29 double-stranded DNA (dsDNA) motor, various RNA and protein elements are designed and tested by single-molecule imaging and biochemical assays, with which the motor with active components has been constructed. The motor motion direction is controlled by three operation elements: (1) Asymmetrical ATPase with ATP-interacting domains for alternative DNA binding/pushing regulated by an arginine finger in a sequential action manner. The arginine finger bridges two adjacent ATPase subunits into a non-covalent dimer, resulting in an asymmetrical hexameric complex containing one dimer and four monomers. (2) The dsDNA translocation channel as a one-way valve. (3) The hexameric pRNA ring geared with left-/right-handed loops. Assessments of these constructs reveal that one inactive subunit of pRNA/ATPase is sufficient to completely block motor function (defined as K = 1), implying that these components work sequentially based on the principle of binomial distribution and Yang Hui's triangle.
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2,335,448 |
Quality of Life Changes Following Surgery for Hyperhidrosis.
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The best way to evaluate the impact of primary hyperhidrosis on quality of life (QL) is through specific questionnaires, avoiding generic models that do not appropriately evaluate individuals. QL improves significantly in the short term after sympathectomy. In the longer term, a sustained and stable improvement is seen, although there is a small decline in the numbers; after 5 and even at 10 years of follow-up it shows virtually the same numerical distribution. Compensatory hyperhidrosis is a major side effect and the main aggravating factor in postoperative QL, requiring attention to its management and prevention.
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2,335,449 |
Angiotensin type 2-receptor (AT2R) activation induces hypotension in apolipoprotein E-deficient mice by activating peroxisome proliferator-activated receptor-γ.
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Angiotensin II (Ang II) modulates blood pressure and atherosclerosis development through its vascular type-1 (AT1R) and type-2 (AT2R) receptors, which have opposing effects. AT2R activation produces hypotension, and is anti-atherogenic. Targeted overexpression of AT2Rs in vascular smooth muscle cells (VSMCs) indicates that these effects are due to increased nitric oxide (NO) generation. However, the role of endogenous VSMC AT2Rs in these events is unknown. Effect of 7-day low-dose Ang II-infusion (12 µg/kg/hr) on blood pressure was tested in 9-week-old apoE((-/-)) mice fed a low or high cholesterol diet (LCD or HCD, respectively). Cardiac output was measured by echocardiography. Immunohistochemistry was performed to localize and quantify AT2Rs and p-Ser(1177)-endothelial nitric oxide synthase (eNOS) levels in the aortic arch. PD123319 and GW-9662 were used to selectively block the AT2R and peroxisome proliferator-activated receptor-γ (PPAR-γ), respectively. Ang II infusion decreased blood pressure by 12 mmHg (P < 0.001) in LCD/apoE((-/-)) mice without altering cardiac output; a response blocked by PD123319. Although, AT2R stimulation neither activated eNOS (p-Ser(1177)-eNOS) nor changed plasma NO metabolites, it caused an ~6-fold increase in VSMC PPAR-γ levels (P < 0.001) and the AT2R-mediated hypotension was abolished by GW-9662. AT2R-mediated hypotension was also inhibited by HCD, which selectively decreased VSMC AT2R expression by ~6-fold (P < 0.01). These findings suggest a novel pathway for the Ang II/AT2R-mediated hypotensive response that involves PPAR-γ, and is down regulated by a HCD.
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2,335,450 |
At the cross-point of connexins, calcium, and ATP: blocking hemichannels inhibits vasoconstriction of rat small mesenteric arteries.
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Connexins form gap-junctions (GJs) that directly connect cells, thereby coordinating vascular cell function and controlling vessel diameter and blood flow. GJs are composed of two hemichannels contributed by each of the connecting cells. Hemichannels also exist as non-junctional channels that, when open, lead to the entry/loss of ions and the escape of ATP. Here we investigated cross-talk between hemichannels and Ca2+</sup>/purinergic signalling in controlling blood vessel contraction. We hypothesized that hemichannel Ca2+ </sup>entry and ATP release contributes to smooth muscle cell (SMC) Ca2+ </sup>dynamics, thereby influencing vessel contractility. We applied several peptide modulators of hemichannel function and inhibitors of Ca2+ </sup>and ATP signalling to investigate their influence on SMC Ca2+ </sup>dynamics and vessel contractility.</AbstractText>Confocal Ca2+ </sup>imaging studies on small mesenteric arteries (SMAs) from rat demonstrated that norepinephrine-induced SMC Ca2+ </sup> oscillations were inhibited by blocking IP3</sub> receptors with xestospongin-C and by interfering with hemichannel function, most notably by the specific Cx43 hemichannel blocking peptide TAT-L2 and by TAT-CT9 that promotes Cx43 hemichannel opening. Evidence for hemichannel involvement in SMC function was supported by the fact that TAT-CT9 significantly increased SMC resting cytoplasmic Ca2+ </sup>concentration, indicating it facilitated Ca2+ </sup>entry, and by the observation that norepinephrine-triggered vessel ATP release was blocked by TAT-L2. Myograph tension measurements on isolated SMAs showed significant inhibition of norepinephrine-triggered contractility by the ATP receptor antagonist suramin, but the strongest effect was observed with TAT-L2 that gave ∼80% inhibition at 37 °C. TAT-L2 inhibition of vessel contraction was significantly reduced in conditional Cx43 knockout animals, indicating the effect was Cx43 hemichannel-dependent. Computational modelling suggested these results could be explained by the opening of a single hemichannel per SMC.</AbstractText>These results indicate that Cx43 hemichannels contribute to SMC Ca2+ </sup>dynamics and contractility, by facilitating Ca2+ </sup>entry, ATP release, and purinergic signalling.</AbstractText>Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For Permissions, please email: [email protected].</CopyrightInformation>
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2,335,451 |
Adenosine Receptor Activation in the "Trigger" Limb of Remote Pre-Conditioning Mediates Human Endothelial Conditioning and Release of Circulating Cardioprotective Factor(s).
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Remote ischemic pre-conditioning (rIPC) has emerged as a potential mechanism to reduce ischemia-reperfusion injury. Clinical data, however, have been mixed, and its physiological basis remains unclear, although it appears to involve release of circulating factor(s) and/or neural pathways. Here, the authors demonstrate that adenosine receptor activation is an important step in initiating human pre-conditioning; that pre-conditioning liberates circulating cardioprotective factor(s); and that exogenous adenosine infusion is able to recapitulate release of this factor. However, blockade of adenosine receptors in ischemic tissue does not block the protection afforded by pre-conditioning. These data have important implications for defining the physiology of human pre-conditioning and its translation to future clinical trials.
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2,335,452 |
[Comparison of ultrasound guided femoral and sciatic nerve block versus epidural anaesthesia for orthopaedic surgery in dogs].
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Comparison of ultrasound-guided femoral and sciatic nerve block versus epidural anaesthesia with bupivacaine and morphine for orthopaedic surgery of the pelvic limb in dogs with respect to analgesic effectiveness, clinical utility and side effects.</AbstractText>The study included 22 dogs (American Society of Anesthesiologists, ASA grades I and II) undergoing orthopaedic surgery distal to the mid-femoral bone. The study was designed as a randomized, prospective, blinded clinical trial. All dogs were randomly assigned to receive 0.5 mg/kg bupivacaine (0.5%) and 0.1 mg/kg morphine sulphate (1%) either as epidural anaesthesia (group EPI) or by ultrasound-guided femoral and sciatic nerve block (group LA). During surgery, the heart rate, respiratory rate, mean arterial pressure (MAP), end-tidal isoflurane concentrations and dose of rescue analgesia (fentanyl boluses of 5 µg/kg i. v.) were measured. Pain severity was scored (short form of the Glasgow Composite Measure Pain Scale, GCMPS) before surgery and postoperatively at 2, 4, 6, 12 and 24 hours after extubation. Post-operative rescue analgesia consisted of methadone (0.2 mg/kg i. v.), and was applied when the GCMPS > 6. For statistical analysis, the Chi-square, Fisher, and Wilcoxon tests and one- and two-way ANOVA were applied. Differences were considered statistically significant at p < 0.05.</AbstractText>Only the MAP was significantly different between the two treatment groups. Intra- and postoperative MAP of group LA (111.2 ± 11.2 mmHg and 119.3 ± 18.2 mmHg, respectively) was higher than in group EPI (86.6 ± 8.7 mmHg and 95.2 ± 13.1 mmHg, respectively). None of the dogs developed urinary retention or ambulatory deficits when completely recovered from anaesthesia. No other side effects were noted.</AbstractText>In conclusion, femoral and sciatic nerve blocks and epidural anaesthesia ensure comparable analgesic effects in canine patients undergoing orthopaedic surgery of the pelvic limb. The lower mean arterial blood pressure of group EPI was not of clinical relevance.</AbstractText>
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2,335,453 |
On Being Fired: When Patients or Their Parents Fire Their Physician.
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Wait, what? I've been fired?" I repeated, in the middle of morning rounds in the neonatal intensive care unit. Finally, the nurse who was taking care of our patient, Angela, responded, "Her parents fired you last night. They've already called Patient Relations. They want a new doctor." My heart sank. Only days into my block of service time as the attending physician in the NICU and I was fired, axed, canned, rejected by a family. How could this have happened? On my first day of service, I had introduced myself to Angela's parents, and I had then met with them daily to review results and the plan and to answer their questions. I thought we had connected well. I thought I had done everything right. I thought they trusted me to care for their daughter.
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2,335,454 |
Comparing the Hemodynamic Effects of Spinal Anesthesia in Preeclamptic and Healthy Parturients During Cesarean Section.
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Despite controversies about the safest anesthetic technique for cesarean delivery in severely preeclamptic women, there is evidence that supports the use of spinal anesthesia in this group of patients.</AbstractText>This prospective randomized clinical trial was designed to determine the hemodynamic effects of low-dose spinal bupivacaine and the incidence of spinal anesthesia-associated hypotension in severely preeclamptic and healthy parturients undergoing cesarean sections.</AbstractText>Spinal anesthesia was performed with 10 mg (= 2 mL) hyperbaric 0.5% bupivacaine plus 2.5 µg sufentanil in two groups of patients after they received 500 mL of IV lactated Ringer's solution. Heart rate and blood pressure were recorded before spinal anesthesia and at two minutes intervals for 15 minutes after the block, and then every five minutes until the end of the surgery. Hypotension was defined as more than 25% of decline in the mean arterial blood pressure compared to the baseline in both groups (or systolic blood pressure < 100 mmHg in healthy parturients) and was treated with 5 mg IV ephedrine. The total amounts of intravenous administered fluid and the total doses of ephedrine were recorded for each patient as well.</AbstractText>The incidence rate of hypotension among the preeclamptic patients was lower than that of the healthy parturients, despite the former group receiving smaller volumes of intravenous fluids (P < 0.05). The total doses of IV ephedrine for treating hypotension were significantly lower among the preeclamptic patients (3.2 mg in preeclamptic patients versus 7.6 mg in normotensive patients) (P = 0.02). The one-minute Apgar score was significantly lower for the preeclamptic parturients (8.4 ± 0.7 versus 7.2 ± 1.5) (P = 0.001), but there was no significant difference in the five-minute Apgar scores between the two groups.</AbstractText>Our results confirm that low-dose bupivacaine spinal anesthesia is associated with a lower risk of hypotension than previously believed, and it can therefore be safely used in severe preeclamptic women undergoing cesarean delivery.</AbstractText>
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2,335,455 |
Outcome of pregnancy in patients with systemic lupus erythematosis at Korle-bu Teaching Hospital.
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To study maternal and fetal outcomes in Ghanaian women with systemic lupus erythematosus (SLE).</AbstractText>Retrospective study of pregnancies in women with SLE in a single centre in Ghana.</AbstractText>The mean age was 30.1 years and all were nulliparous. Two out of the seven pregnancies were in disease remission at the time of booking. Nephritis without renal impairment was present in 7 pregnancies (6 women). One woman developed intrapartum eclampsia. Two women had secondary antiphospholipid syndrome (APS). Two suffered early fetal losses and one late fetal loss at 32 weeks. All three who lost their fetus had uncontrolled hypertension. Six had mild flares mainly joint pains during pregnancy. There was no maternal mortality. The median gestational age at delivery was 38 weeks (range, 16 to 40 weeks) and the mean birth weight was 3017 g; the median Apgar scores were 8 and 9 at 1 and 5 minutes of life, respectively. There were no cases of intrauterine growth restriction (IUGR). There were no cases of congenital heart block or neonatal lupus.</AbstractText>Good pregnancy outcomes are possible in women with SLE even in resource poor settings. . All pregnancies should still be considered high risk and be managed jointly between the obstetricians, the perinatologists and the rheumatologists, in particular, those with renal involvement and hypertension. Long term follow up of a larger cohort is needed.</AbstractText>None declared.</AbstractText>
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2,335,456 |
Myxedema Coma Secondary to Central Hypothyroidism: A Rare but Real Cause of Altered Mental Status in Pediatrics.
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Myxedema coma (MC), a medical emergency defined as severe hypothyroidism leading to altered mental status, is more common in older women with hypothyroidism.</AbstractText><AbstractText Label="METHODS/RESULTS" NlmCategory="RESULTS">A 7-year-old Caucasian male with chromosome 1q deletion presented with altered mental status preceded by milestone regression. His presenting labs results were: thyroid-stimulating hormone (TSH) 0.501 μIU/ml and free thyroxine (T4) <0.5 ng/dl. His morning cortisol level was 8.1 μg/dl with repeat testing, while TSH was 1.119 μIU/ml and free T4 was 0.5 ng/dl. Low-dose cosyntropin test showed baseline and peak cortisol levels of 1.9 and 16 μg/dl, respectively. Aside from altered mental status, heart block was present in addition to hypothermia and hypercarbia. Diffuse cerebral cortical and corpus callosum atrophy were seen on MRI. An intravenous (i.v.) stress dose of hydrocortisone was administered for 24 h prior to an i.v. loading dose of levothyroxine. His activity level subsequently returned to baseline within 48 h after treatment had been initiated.</AbstractText>Though MC is rare, occurring mainly with noncompliance in primary hypothyroidism, it may occur at the diagnosis of secondary hypothyroidism. Based on features like hypothermia, hypoventilation, and cardiovascular instability occurring in the setting of central hypothyroidism, it should be suspected and managed urgently in order to avert the associated high mortality resulting from treatment delays.</AbstractText>© 2016 S. Karger AG, Basel.</CopyrightInformation>
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2,335,457 |
[Interest of scopolamine as a treatment of major depressive disorder].
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The number of patients with depression in the world is 350 millions according to estimates. The search for new treatments, particularly in forms of resistant depression, is necessary given the growing number of patients experiencing treatment failure and resistance. Scopolamine, an anticholinergic antimuscarinic molecule, is one of the treatments under evaluation. It falls within the assumptions of cholinergic disruption of the pathophysiology of depression, at different levels (genetic, receptorial [muscarinic and glutamate receptors], hormonal, synaptic…). In 2006, a pilot study made to evaluate the role of the cholinergic system in cognitive symptoms of depression found unexpected results regarding the antidepressant effect of scopolamine in depressive patients. Since that time other studies have been conducted to evaluate the benefits of treatment with intravenous injections of scopolamine.</AbstractText>Our main objective was to evaluate the interest of scopolamine as an antidepressant treatment in depressed populations.</AbstractText>We conducted a literature review with the aim of assessing the effectiveness of treatment with scopolamine in uni- and bipolar patients with depressive symptoms. The protocol consisted of two injection blocks (each block consisting of three injections spaced fifteen minutes apart within three to five days) of active ingredient or placebo crossover. The selected patients were between 18 and 45years and had the DSM-IV major depressive disorder or bipolar disorder criteria. Regarding the methods of measurement, the primary endpoint was the reduction in scores of the Montgomery Asberg Depression Rating Scale (MADRS) with a total response defined by a decrease of more than 50 % of the score and remission corresponding to a MADRS score<10. Seven sessions of evaluations were performed.</AbstractText>The published results are promising in terms of efficiency with rapid antidepressant effect, a total response rate ranging from 59-64% and a remission rate of between 37 and 55% in uni- and bipolar patients, which persists at least 15days. The treatment was well tolerated by patients with relatively mild and transient side effects the most common being the sensation of sleepiness that was also found in the placebo group. There were no serious side effects such as heart failure or confusion. In terms of mood, there was no becoming manic or hypomanic even for bipolar patients.</AbstractText>The results are encouraging, but there is concern for the moment because of the few studies, so to date there is little data on the subject including medium and long term.</AbstractText>Copyright © 2016 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.</CopyrightInformation>
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2,335,458 |
HCN2 ion channels: basic science opens up possibilities for therapeutic intervention in neuropathic pain.
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Nociception - the ability to detect painful stimuli - is an invaluable sense that warns against present or imminent damage. In patients with chronic pain, however, this warning signal persists in the absence of any genuine threat and affects all aspects of everyday life. Neuropathic pain, a form of chronic pain caused by damage to sensory nerves themselves, is dishearteningly refractory to drugs that may work in other types of pain and is a major unmet medical need begging for novel analgesics. Hyperpolarisation-activated cyclic nucleotide (HCN)-modulated ion channels are best known for their fundamental pacemaker role in the heart; here, we review data demonstrating that the HCN2 isoform acts in an analogous way as a 'pacemaker for pain', in that its activity in nociceptive neurons is critical for the maintenance of electrical activity and for the sensation of chronic pain in pathological pain states. Pharmacological block or genetic deletion of HCN2 in sensory neurons provides robust pain relief in a variety of animal models of inflammatory and neuropathic pain, without any effect on normal sensation of acute pain. We discuss the implications of these findings for our understanding of neuropathic pain pathogenesis, and we outline possible future opportunities for the development of efficacious and safe pharmacotherapies in a range of chronic pain syndromes.
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2,335,459 |
Postoperative analgesia with dexmedetomidine in interscalene block. Comparative study.
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Dexmedetomidine prolongs sensory block of ropivacaine. Our objective was to study whether this extension would produce better postoperative pain control compared to that produced by clonidine in patients undergoing arthroscopic shoulder.</AbstractText>Study comparative, longitudinal, controlled, randomized into 3 groups. Control group I: ropivacaine 0.75% clonidine group II: 0.75% ropivacaine plus clonidine 1mg/kg group iiidexmedetomidine: 0.75% ropivacaine more dexmedetomidine 1mg/kg. Interscalene block single dose ultrasound-guided. Sensory and motor blockade, pain intensity, sedation level, heart rate, respiratory rate, blood pressure at 6, 12 and 24hours was measured.</AbstractText>Pain intensity at 6hours in groups I and II moderate to severe pain, mild pain group iii. At 12hours the groups IIand II showed moderate to severe pain by more than 60% of patients, and in group iiionly 10%. At 24hours I and II group 20% of patients they continued to moderate pain.</AbstractText>The prolonged interscalene block produced by dexmedetomidine provided better postoperative pain control during the first 24hours.</AbstractText>Copyright © 2016 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.</CopyrightInformation>
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2,335,460 |
The Mg2+-containing Water Cluster of Mammalian Cytochrome c Oxidase Collects Four Pumping Proton Equivalents in Each Catalytic Cycle.
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Bovine heart cytochrome c oxidase (CcO) pumps four proton equivalents per catalytic cycle through the H-pathway, a proton-conducting pathway, which includes a hydrogen bond network and a water channel operating in tandem. Protons are transferred by H<sub>3</sub>O<sup>+</sup> through the water channel from the N-side into the hydrogen bond network, where they are pumped to the P-side by electrostatic repulsion between protons and net positive charges created at heme a as a result of electron donation to O<sub>2</sub> bound to heme a<sub>3</sub> To block backward proton movement, the water channel remains closed after O<sub>2</sub> binding until the sequential four-proton pumping process is complete. Thus, the hydrogen bond network must collect four proton equivalents before O<sub>2</sub> binding. However, a region with the capacity to accept four proton equivalents was not discernable in the x-ray structures of the hydrogen bond network. The present x-ray structures of oxidized/reduced bovine CcO are improved from 1.8/1.9 to 1.5/1.6 Å resolution, increasing the structural information by 1.7/1.6 times and revealing that a large water cluster, which includes a Mg<sup>2+</sup> ion, is linked to the H-pathway. The cluster contains enough proton acceptor groups to retain four proton equivalents. The redox-coupled x-ray structural changes in Glu<sup>198</sup>, which bridges the Mg<sup>2+</sup> and Cu<sub>A</sub> (the initial electron acceptor from cytochrome c) sites, suggest that the Cu<sub>A</sub>-Glu<sup>198</sup>-Mg<sup>2+</sup> system drives redox-coupled transfer of protons pooled in the water cluster to the H-pathway. Thus, these x-ray structures indicate that the Mg<sup>2+</sup>-containing water cluster is the crucial structural element providing the effective proton pumping in bovine CcO.
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2,335,461 |
Usefulness of a Combination of Interatrial Block and a High CHADS2 Score to Predict New Onset Atrial Fibrillation.
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Interatrial block (IAB) is associated with an increased risk of atrial fibrillation (AF). The aim of this retrospective study was to investigate the association of a combination of IAB and the CHADS2 score, an AF-related risk score for ischemic stroke, with new onset AF in patients in sinus rhythm. A total of 1,571 patients (803 males, 768 females; mean age: 58 ± 16 years) were included in this study. IAB was defined as a P-wave duration > 120 ms in the 12-lead electrocardiogram, and a high CHADS2 score as ≥ 2 points. During the mean follow-up period of 4.8 ± 0.7 years, new onset AF occurred in 122 patients (16.1 per 1,000 patient-years). The incidence of new onset AF was 4.0 per 1,000 patient-years in patients with no IAB and a low CHADS2 score, and 44.0 per 1,000 patient-years in patients with IAB and a high CHADS2 score. In multivariate Cox regression analysis, the hazard ratio for IAB and a high CHADS2 score compared with no IAB and a low CHADS2 score was 12.18 (95% confidence interval: 6.22-23.87, P < 0.001), after adjustment for age, sex, coronary artery disease, valvular heart disease, smoking, medications, and echocardiographic parameters. In conclusion, IAB and a high CHADS2 score independently and synergistically predict new onset AF in patients in sinus rhythm, indicating an approximately 12-fold higher risk in patients with both IAB and a high CHADS2 score. Patients meeting these criteria should have more aggressive early intervention to prevent AF.
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2,335,462 |
Damus-Kaye-Stansel Procedure with Extracardiac Fontan: Successful Recruitment of Previously Ligated Pulmonary Valve.<Pagination><StartPage>E206</StartPage><EndPage>E207</EndPage><MedlinePgn>E206-7</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1532/hsf.1580</ELocationID><Abstract><AbstractText>We present a case of a 2.5-year-old-girl with complex congenital heart disease: tricuspid atresia (TA), bulboventricular septal defect (VSD), hypoplastic right ventricle, d-transposition of the great arteries (d-TGA) with aortic outflow from redundant RV. Due to II/III degree atrioventricular block induced after diagnostic cardiac catheterization, an epicardial pacemaker was implanted during the Glenn procedure. Because of severe left ventricle outflow tract obstruction, she was finally referred for extracardiac TCPC (extracardiac Fontan type) with recruitment of PV and Damus-Kaye-Stansel anastomosis. Intraoperatively, the pulmonary trunk stump was opened and a competent pulmonary valve with flaccid leaflets was found. Simple ligation of the pulmonary trunk with a preserved pulmonary valve enabled an effective aorto-pulmonary bridging of systemic outflow tract with the use of natural fully competent ventricle-arterial valves. The relief of single ventricle outflow tract obstruction led to final stabilization of spontaneous sinus rhythm recovery after 2 years of pacemaker stimulation.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Paczkowski</LastName><ForeName>Konrad</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Department of Pediatric Cardiac Surgery, Mikolaj Kopernik Hospital in Gdańsk, Poland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Haponiuk</LastName><ForeName>Ireneusz</ForeName><Initials>I</Initials><AffiliationInfo><Affiliation>Department of Physiotherapy, Faculty of Rehabilitation and Kinesiology, Gdańsk University of Physical Education and Sport, Gdańsk, Poland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chojnicki</LastName><ForeName>Maciej</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Pediatric Cardiac Surgery, Mikolaj Kopernik Hospital in Gdańsk, Poland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jaworski</LastName><ForeName>Radosław</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Department of Pediatric Cardiac Surgery, Mikolaj Kopernik Hospital in Gdańsk, Poland.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D002363">Case Reports</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2016</Year><Month>08</Month><Day>23</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Heart Surg Forum</MedlineTA><NlmUniqueID>100891112</NlmUniqueID><ISSNLinking>1098-3511</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000015" MajorTopicYN="Y">Abnormalities, Multiple</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006328" MajorTopicYN="N">Cardiac Catheterization</DescriptorName><QualifierName UI="Q000379" MajorTopicYN="Y">methods</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002675" MajorTopicYN="N">Child, Preschool</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004452" MajorTopicYN="N">Echocardiography</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D018729" MajorTopicYN="N">Fontan Procedure</DescriptorName><QualifierName UI="Q000379" MajorTopicYN="Y">methods</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006330" MajorTopicYN="N">Heart Defects, Congenital</DescriptorName><QualifierName UI="Q000175" MajorTopicYN="N">diagnosis</QualifierName><QualifierName UI="Q000601" MajorTopicYN="Y">surgery</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008026" MajorTopicYN="N">Ligation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011664" MajorTopicYN="N">Pulmonary Valve</DescriptorName><QualifierName UI="Q000601" MajorTopicYN="Y">surgery</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2016</Year><Month>4</Month><Day>10</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2016</Year><Month>5</Month><Day>25</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2016</Year><Month>9</Month><Day>2</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2016</Year><Month>9</Month><Day>2</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2017</Year><Month>5</Month><Day>18</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">27585204</ArticleId><ArticleId IdType="doi">10.1532/hsf.1580</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM" IndexingMethod="Curated"><PMID Version="1">27584550</PMID><DateCompleted><Year>2017</Year><Month>08</Month><Day>14</Day></DateCompleted><DateRevised><Year>2019</Year><Month>12</Month><Day>18</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">1940-087X</ISSN><JournalIssue CitedMedium="Internet"><Issue>114</Issue><PubDate><Year>2016</Year><Month>Aug</Month><Day>16</Day></PubDate></JournalIssue><Title>Journal of visualized experiments : JoVE</Title><ISOAbbreviation>J Vis Exp</ISOAbbreviation></Journal>Rodent Working Heart Model for the Study of Myocardial Performance and Oxygen Consumption.
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We present a case of a 2.5-year-old-girl with complex congenital heart disease: tricuspid atresia (TA), bulboventricular septal defect (VSD), hypoplastic right ventricle, d-transposition of the great arteries (d-TGA) with aortic outflow from redundant RV. Due to II/III degree atrioventricular block induced after diagnostic cardiac catheterization, an epicardial pacemaker was implanted during the Glenn procedure. Because of severe left ventricle outflow tract obstruction, she was finally referred for extracardiac TCPC (extracardiac Fontan type) with recruitment of PV and Damus-Kaye-Stansel anastomosis. Intraoperatively, the pulmonary trunk stump was opened and a competent pulmonary valve with flaccid leaflets was found. Simple ligation of the pulmonary trunk with a preserved pulmonary valve enabled an effective aorto-pulmonary bridging of systemic outflow tract with the use of natural fully competent ventricle-arterial valves. The relief of single ventricle outflow tract obstruction led to final stabilization of spontaneous sinus rhythm recovery after 2 years of pacemaker stimulation.</Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Paczkowski</LastName><ForeName>Konrad</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Department of Pediatric Cardiac Surgery, Mikolaj Kopernik Hospital in Gdańsk, Poland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Haponiuk</LastName><ForeName>Ireneusz</ForeName><Initials>I</Initials><AffiliationInfo><Affiliation>Department of Physiotherapy, Faculty of Rehabilitation and Kinesiology, Gdańsk University of Physical Education and Sport, Gdańsk, Poland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chojnicki</LastName><ForeName>Maciej</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Pediatric Cardiac Surgery, Mikolaj Kopernik Hospital in Gdańsk, Poland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jaworski</LastName><ForeName>Radosław</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Department of Pediatric Cardiac Surgery, Mikolaj Kopernik Hospital in Gdańsk, Poland.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D002363">Case Reports</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2016</Year><Month>08</Month><Day>23</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Heart Surg Forum</MedlineTA><NlmUniqueID>100891112</NlmUniqueID><ISSNLinking>1098-3511</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000015" MajorTopicYN="Y">Abnormalities, Multiple</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006328" MajorTopicYN="N">Cardiac Catheterization</DescriptorName><QualifierName UI="Q000379" MajorTopicYN="Y">methods</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002675" MajorTopicYN="N">Child, Preschool</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004452" MajorTopicYN="N">Echocardiography</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D018729" MajorTopicYN="N">Fontan Procedure</DescriptorName><QualifierName UI="Q000379" MajorTopicYN="Y">methods</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006330" MajorTopicYN="N">Heart Defects, Congenital</DescriptorName><QualifierName UI="Q000175" MajorTopicYN="N">diagnosis</QualifierName><QualifierName UI="Q000601" MajorTopicYN="Y">surgery</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008026" MajorTopicYN="N">Ligation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011664" MajorTopicYN="N">Pulmonary Valve</DescriptorName><QualifierName UI="Q000601" MajorTopicYN="Y">surgery</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2016</Year><Month>4</Month><Day>10</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2016</Year><Month>5</Month><Day>25</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2016</Year><Month>9</Month><Day>2</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2016</Year><Month>9</Month><Day>2</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2017</Year><Month>5</Month><Day>18</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">27585204</ArticleId><ArticleId IdType="doi">10.1532/hsf.1580</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM" IndexingMethod="Curated"><PMID Version="1">27584550</PMID><DateCompleted><Year>2017</Year><Month>08</Month><Day>14</Day></DateCompleted><DateRevised><Year>2019</Year><Month>12</Month><Day>18</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">1940-087X</ISSN><JournalIssue CitedMedium="Internet"><Issue>114</Issue><PubDate><Year>2016</Year><Month>Aug</Month><Day>16</Day></PubDate></JournalIssue><Title>Journal of visualized experiments : JoVE</Title><ISOAbbreviation>J Vis Exp</ISOAbbreviation></Journal><ArticleTitle>Rodent Working Heart Model for the Study of Myocardial Performance and Oxygen Consumption.</ArticleTitle><ELocationID EIdType="pii" ValidYN="Y">54149</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.3791/54149</ELocationID><Abstract>Isolated working heart models have been used to understand the effects of loading conditions, heart rate and medications on myocardial performance in ways that cannot be accomplished in vivo. For example, inotropic medications commonly also affect preload and afterload, precluding load-independent assessments of their myocardial effects in vivo. Additionally, this model allows for sampling of coronary sinus effluent without contamination from systemic venous return, permitting assessment of myocardial oxygen consumption. Further, the advent of miniaturized pressure-volume catheters has allowed for the precise quantification of markers of both systolic and diastolic performance. We describe a model in which the left ventricle can be studied while performing both volume and pressure work under controlled conditions. In this technique, the heart and lungs of a Sprague-Dawley rat (weight 300-500 g) are removed en bloc under general anesthesia. The aorta is dissected free and cannulated for retrograde perfusion with oxygenated Krebs buffer. The pulmonary arteries and veins are ligated and the lungs removed from the preparation. The left atrium is then incised and cannulated using a separate venous cannula, attached to a preload block. Once this is determined to be leak-free, the left heart is loaded and retrograde perfusion stopped, creating the working heart model. The pulmonary artery is incised and cannulated for collection of coronary effluent and determination of myocardial oxygen consumption. A pressure-volume catheter is placed into the left ventricle either retrograde or through apical puncture. If desired, atrial pacing wires can be placed for more precise control of heart rate. This model allows for precise control of preload (using a left atrial pressure block), afterload (using an afterload block), heart rate (using pacing wires) and oxygen tension (using oxygen mixtures within the perfusate).
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2,335,463 |
Quadratus lumborum block for femoral-femoral bypass graft placement: A case report.
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Atherosclerosis has a complex etiology that leads to arterial obstruction and often results in inadequate perfusion of the distal limbs. Patients with atherosclerosis can have severe complications of this condition, with widespread systemic manifestations, and the operations undertaken are often challenging for anesthesiologists.</AbstractText>A 79-year-old woman with chronic heart failure and respiratory dysfunction presented with bilateral gangrene of the distal lower extremities with obstruction of the left common iliac artery due to atherosclerosis. Femoral-femoral bypass graft and bilateral foot amputations were planned. Spinal anesthesia failed due to severe scoliosis and deformed vertebrae. General anesthesia was induced after performing multiple nerve blocks including quadratus lumborum, sciatic nerve, femoral nerve, lateral femoral cutaneous nerve, and obturator nerve blocks. However, general anesthesia was abandoned because of deterioration in systemic perfusion. The surgery was completed; the patient remained comfortable and awake without the need for further analgesics.</AbstractText>Quadratus lumborum block may be a useful anesthetic technique to perform femoral-femoral bypass.</AbstractText>
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2,335,464 |
Intraoperative multiple intercostal nerve blocks exert anesthetic-sparing effect: A retrospective study on the effect-site concentration of propofol infusion in nonintubated thoracoscopic surgery.
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<AbstractText Label="OBJECTIVE(S)" NlmCategory="OBJECTIVE">Less general anesthetic is required in patients with regional blocks than in those without, as assessed through commonly used anesthesia monitoring parameters such as blood pressure, heart rate, and bispectral index (BIS). Although intraoperative regional anesthesia has become more widely adopted, few studies have confirmed or monitored its anesthetic-sparing effects. Using recent reports of nonintubated video-assisted thoracoscopic surgery (VATS) by BIS-targeted propofol infusion and intraoperative multilevel thoracoscopic intercostal nerve blocks (TINBs), this retrospective study investigated whether the anesthetic-sparing effect can be realized by reducing the effect-site concentration (Ce) to the targeted BIS level or by reducing the blood pressure at the onset of regional blocks.</AbstractText>A retrospective study of a prospectively collected case series of non-intubated VATS.</AbstractText>Data on 56 adult patients who underwent nonintubated VATS were collected and analyzed. The mean operative time was 121 ± 32 minutes. BIS levels before and after one-lung ventilation/TINBs and surgery were 48% ± 11% and 47% ± 12%, respectively. The Ce of propofol infusion decreased significantly from 3.4 ± 0.8 μg/mL to 3.0 ± 0.7 μg/mL (p < 0.01) after surgery with TINBs. Blood pressure did not change significantly, whereas the heart rate increased moderately but significantly (77 ± 14 beats/minute to 82 ± 15 beats/minute, p < 0.01).</AbstractText>With comparable BIS and blood pressure in the subsequent surgical procedure, the adequacy of anesthesia and the anesthetic component provided by intraoperative TINBs and vagal nerve could be monitored adequately. The anesthetic-sparing effect of intraoperative nerve blocks can be realized when the Ce of propofol infusion was reduced to the target BIS level.</AbstractText>Copyright © 2016. Published by Elsevier B.V.</CopyrightInformation>
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2,335,465 |
Processed Meat, but Not Unprocessed Red Meat, Is Inversely Associated with Leukocyte Telomere Length in the Strong Heart Family Study.
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Telomeres are repetitive nucleotide sequences (TTAGGG) and their associated proteins at the end of eukaryote chromosomes. Telomere length shortens throughout the lifespan with each cell division, and leukocyte telomere length (LTL) is often used as a biomarker of cellular aging. LTL is related to many chronic diseases, including cardiovascular disease and diabetes. However, to our knowledge, the relation between LTL and risk factors for cardiovascular disease and diabetes, such as dietary intake of processed meat and unprocessed red meat, is largely unknown.</AbstractText>We examined the associations of processed meat intake and unprocessed red meat intake with LTL.</AbstractText>This cross-sectional study comprised 2846 American Indians from the Strong Heart Family Study who participated in the 2001-2003 examination. Dietary factors, including past-year consumption of processed meat and unprocessed red meat, were assessed with the use of a 119-item Block Food-Frequency Questionnaire. LTL was measured with the use of quantitative polymerase chain reaction. Generalized estimating equations were used to examine the associations of intake of processed meat and unprocessed red meat with LTL.</AbstractText>Consumption of processed meat was negatively associated with LTL after adjustment for age, sex, site, education, smoking, alcohol use, physical activity, and other dietary factors. For every additional daily serving of processed meat, LTL was 0.021 units (telomeric product-to-single-copy gene ratio) shorter (β ± SE = -0.021 ± 0.008, P = 0.009). No association was observed between the intake of unprocessed red meat and LTL (β ± SE = 0.008 ± 0.011, P = 0.46).</AbstractText>In the Strong Heart Family Study, consumption of processed meat, but not unprocessed red meat, was associated with shorter LTL, a potential mediator for several age-related diseases. Further studies are needed to better understand the biological mechanism by which processed meat intake influences cellular aging.</AbstractText>© 2016 American Society for Nutrition.</CopyrightInformation>
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2,335,466 |
Regulation of Vegf signaling by natural and synthetic ligands.
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The mechanisms that allow cells to bypass anti-vascular endothelial growth factor A (VEGFA) therapy remain poorly understood. Here we use zebrafish to investigate this question and first show that <i>vegfaa</i> mutants display a severe vascular phenotype that can surprisingly be rescued to viability by <i>vegfaa</i> messenger RNA injections at the 1-cell stage. Using <i>vegfaa</i> mutants as an in vivo test tube, we found that zebrafish Vegfbb, Vegfd, and Pgfb can also rescue these animals to viability. Taking advantage of a new <i>vegfr1</i> tyrosine kinase-deficient mutant, we determined that Pgfb rescues <i>vegfaa</i> mutants via Vegfr1. Altogether, these data reveal potential resistance routes against current anti-VEGFA therapies. In order to circumvent this resistance, we engineered and validated new dominant negative Vegfa molecules that by trapping Vegf family members can block vascular development. Thus, our results show that Vegfbb, Vegfd, and Pgfb can sustain vascular development in the absence of VegfA, and our newly engineered Vegf molecules expand the toolbox for basic research and antiangiogenic therapy.
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2,335,467 |
The effects of caudal or intravenous dexmedetomidine on postoperative analgesia produced by caudal bupivacaine in children: a randomized controlled double-blinded study.
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The aim of this study was to compare the effects of caudal and intravenous (IV) dexmedetomidine (1 μg/kg) on postoperative analgesia after caudal bupivacaine in pediatric patients undergoing lower abdominal and perineal surgeries.</AbstractText>A randomized controlled double-blind study.</AbstractText>University-affiliated teaching hospital.</AbstractText>Seventy-five American Society of Anesthesiologists I children, aged 1 to 6 years.</AbstractText>Patients were randomly allocated to 3 groups. All patients received 1 mL/kg caudal 0.25% bupivacaine. In addition, those in group B (n=25) received 10-mL IV saline, those in group B-Dcau (n=25) received 1 μg/kg caudal dexmedetomidine and 10-mL IV saline, and those in group B-DIV (n=25) received 1 μg/kg IV dexmedetomidine in 10-mL saline.</AbstractText>Intraoperative mean blood pressure, heart rate, peripheral oxygen saturation, end-tidal sevoflurane, and bispectral index as well as postoperative pain and behavior scores and time to first analgesia were assessed.</AbstractText>Group B-Dcau had a significantly longer time to first rescue analgesia than groups B-DIV and B, with mean (SD) values of 14.4 (7.5), 9.18 (2.7), and 6.6 (2.5) hours, respectively (P<.05). Fewer patients in group B-Dcau (n=16) required rescue analgesia during the first 24 hours postoperatively compared to group B (n=24) and group B-DIV (n=20) (P<.05). Groups B-Dcau and B-DIV had lower pain and behavior scores than Group B. Eight patients Group B had agitation compared to 2 in Group B-DIV and 0 in Group B-Dcau. Four patients in Group B-DIV developed bradycardia and hypotension during surgery.</AbstractText>Compared to IV administration, caudal administration of dexmedetomidine during caudal bupivacaine anesthesia provided prolonged postoperative analgesia and a greater analgesic sparing effect without significant side effects. This suggests a greater role of neuraxial compared to that of peripheral α-2 adrenoceptors in pain processing.</AbstractText>Copyright © 2016 Elsevier Inc. All rights reserved.</CopyrightInformation>
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2,335,468 |
Transversus abdominis plane block for laparoscopic inguinal hernia repair: a randomized trial.
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Pain after laparoscopic inguinal hernia surgery can be moderate to severe, interfering with return to normal activity. The study aimed to assess the efficacy of bilateral ultrasound-guided (USG) transversus abdominis plane (TAP) block for relieving acute pain after laparoscopic hernia repair as T10-L1 nerve endings are anesthetized with this block.</AbstractText>Seventy-one American Society of Anesthesiologists I to II patients, aged 18 to 65 years, undergoing unilateral/bilateral laparoscopic hernia repair were randomized to port site infiltration (control, 36) and TAP block groups (35). All patients received general anesthesia (fentanyl 2 μg/kg intravenously at induction, 0.5 μg/kg on 20% increase in heart rate or mean blood pressure) and paracetamol 6 hourly. Postintubation, TAP group received bilateral USG TAP block (15-20 mL 0.5% ropivacaine, maximum 3 mg/kg) with 18-G Tuohy needle. Control group had 20 to 30 mL 0.5% ropivacaine infiltrated preincision, at port sites from skin to peritoneum. Postoperative patient-controlled analgesia fentanyl was provided for 6 hours; pain was assessed using 0- to 100-mm visual analog scale (VAS) at 0, 1, 2, 4, 6, and 24 hours and telephonically at 1 week and 3 months.</AbstractText>Demographic profile of the 2 groups was comparable. Significantly more number of patients required intraoperative fentanyl in the control group (24/36) than in the TAP group (13/35); VAS at rest was lower in TAP than control patients in postanesthesia care unit at 0, 2, 6, and 24 hours (median VAS TAP group: 0, 0, 0, and 0; control: 10, 20, 10, and 10; P= .002, P= .001, P= .001, and P= .006, respectively); P< .01 was considered statistically significant. TAP group had significantly lower VAS on deep breathing at 6 hours and on knee bending and walking at 24 hours and lesser patient-controlled analgesia fentanyl requirement. No significant difference in pain scores was observed at 1 week and 3 months.</AbstractText>TAP block reduced postoperative pain up to 24 hours after laparoscopic hernia repair.</AbstractText>Copyright © 2016 Elsevier Inc. All rights reserved.</CopyrightInformation>
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2,335,469 |
Comparison of caudal epidural block and ultrasonography-guided transversus abdominis plane block for pain relief in children undergoing lower abdominal surgery.
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We conducted this study to compare the efficacy of caudal epidural block (CEB) vs ultrasonography-guided transversus abdominis plane (TAP) block for providing postoperative pain relief in children scheduled for lower abdominal surgery. Whereas the primary objective was to compare the duration of postoperative analgesia, the secondary objectives included comparative assessment (TAP vs CEB) of quality of pain relief in the first 24hours postoperatively and rescue analgesia requirements.</AbstractText>Randomized-control, prospective, observer-blinded, 2-arm, single-center comparison.</AbstractText>Operating room, postoperative recovery area.</AbstractText>Eighty-children, aged 2-6years, of American Society of Anesthesiologists physical status I/II scheduled to undergo unilateral lower abdominal surgery under general anesthesia.</AbstractText>The recruited children were randomly allocated to receive under general anesthesia either CEB (group C, 0.75 mL/kg of 0.25% bupivacaine) or ultrasonography-guided administration of TAP block (group T, 0.5 mL/kg of 0.25% bupivacaine).</AbstractText>Intraoperative: heart rate and noninvasive blood pressure; postoperative: pain profile, including duration of postoperative analgesia, quality of pain relief, and rescue analgesia requirements.</AbstractText>The median duration of postoperative analgesia was significantly greater in children who received CEB than those who were administered TAP block (group C: 362.5 minutes [172.5-693.75] vs group T: 210 minutes [108.75-362.5]; P<.05). No difference was found in the incidence of postoperative pain up to 6 hours from the point of initiation of assessment (group C: 47.2% vs group T: 55.9%; P>.05). The children who received CEB experienced greater incidence of pain in the 6- to 24-hour postoperative interval than those administered TAP block (group C: 75% vs group T: 44.1%; P<.05). Although there was no difference in the rescue analgesia requirements, the number of children not requiring any rescue analgesia in the first 24 hours postoperatively was significantly higher in the TAP group (group C: n=2 vs group T: n=8; P<.05).</AbstractText>In children undergoing lower abdominal surgery, CEB provides a significantly prolonged duration of postoperative analgesia when compared with ultrasonography-guided TAP block.</AbstractText>Copyright © 2016 Elsevier Inc. All rights reserved.</CopyrightInformation>
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2,335,470 |
A computational model predicts adjunctive pharmacotherapy for cardiac safety via selective inhibition of the late cardiac Na current.
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The QT interval is a phase of the cardiac cycle that corresponds to action potential duration (APD) including cellular repolarization (T-wave). In both clinical and experimental settings, prolongation of the QT interval of the electrocardiogram (ECG) and related proarrhythmia have been so strongly associated that a prolonged QT interval is largely accepted as surrogate marker for proarrhythmia. Accordingly, drugs that prolong the QT interval are not considered for further preclinical development resulting in removal of many promising drugs from development. While reduction of drug interactions with hERG is an important goal, there are promising means to mitigate hERG block. Here, we examine one possibility and test the hypothesis that selective inhibition of the cardiac late Na current (INaL</sub>) by the novel compound GS-458967 can suppress proarrhythmic markers.</AbstractText>New experimental data has been used to calibrate INaL</sub> in the Soltis-Saucerman computationally based model of the rabbit ventricular action potential to study effects of GS-458967 on INaL</sub> during the rabbit ventricular AP. We have also carried out systematic in silico tests to determine if targeted block of INaL</sub> would suppress proarrhythmia markers in ventricular myocytes described by TRIaD: Triangulation, Reverse use dependence, beat-to-beat Instability of action potential duration, and temporal and spatial action potential duration Dispersion.</AbstractText>Our computer modeling approach based on experimental data, yields results that suggest that selective inhibition of INaL</sub> modifies all TRIaD related parameters arising from acquired Long-QT Syndrome, and thereby reduced arrhythmia risk. This study reveals the potential for adjunctive pharmacotherapy via targeted block of INaL</sub> to mitigate proarrhythmia risk for drugs with significant but unintended off-target hERG blocking effects.</AbstractText>Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.</CopyrightInformation>
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2,335,471 |
Lupus high-density lipoprotein induces proinflammatory responses in macrophages by binding lectin-like oxidised low-density lipoprotein receptor 1 and failing to promote activating transcription factor 3 activity.
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Recent evidence indicates that high-density lipoprotein (HDL) exerts vasculoprotective activities by promoting activating transcription factor 3 (ATF3), leading to downregulation of toll-like receptor (TLR)-induced inflammatory responses. Systemic lupus erythematosus (SLE) is associated with increased cardiovascular disease risk not explained by the Framingham risk score. Recent studies have indicated oxidised HDL as a possible contributor. We investigated the potential mechanisms by which lupus HDL may lose its anti-inflammatory effects and promote immune dysregulation.</AbstractText>Control macrophages were challenged with control and SLE HDL in vitro and examined for inflammatory markers by real-time qRT-PCR, confocal microscopy, ELISA and flow cytometry. Lupus-prone mice were treated with an HDL mimetic (ETC-642) in vivo and inflammatory cytokine levels measured by real-time qRT-PCR and ELISA.</AbstractText>Compared with control HDL, SLE HDL activates NFκB, promotes inflammatory cytokine production and fails to block TLR-induced inflammation in control macrophages. This failure of lupus HDL to block inflammatory responses is due to an impaired ability to promote ATF3 synthesis and nuclear translocation. This inflammation is dependent on lectin-like oxidised low-density lipoprotein receptor 1 (LOX1R) binding and rho-associated, coiled-coil containing protein kinase 1 and 2 (ROCK1/2) kinase activity. HDL mimetic-treated lupus mice showed significant ATF3 induction and proinflammatory cytokine abrogation.</AbstractText>Lupus HDL promotes proinflammatory responses through NFκB activation and decreased ATF3 synthesis and activity in an LOX1R-dependent and ROCK1/2-dependent manner. HDL mimetics should be explored as potential therapies for inflammation and SLE cardiovascular risk.</AbstractText>Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.</CopyrightInformation>
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2,335,472 |
Blocking transport resonances via Kondo many-body entanglement in quantum dots.
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Many-body entanglement is at the heart of the Kondo effect, which has its hallmark in quantum dots as a zero-bias conductance peak at low temperatures. It signals the emergence of a conducting singlet state formed by a localized dot degree of freedom and conduction electrons. Carbon nanotubes offer the possibility to study the emergence of the Kondo entanglement by tuning many-body correlations with a gate voltage. Here we show another side of Kondo correlations, which counterintuitively tend to block conduction channels: inelastic co-tunnelling lines in the magnetospectrum of a carbon nanotube strikingly disappear when tuning the gate voltage. Considering the global SU(2) ⊗ SU(2) symmetry of a nanotube coupled to leads, we find that only resonances involving flips of the Kramers pseudospins, associated to this symmetry, are observed at temperatures and voltages below the corresponding Kondo scale. Our results demonstrate the robust formation of entangled many-body states with no net pseudospin.
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2,335,473 |
The cardiac effects of carbon nanotubes in rat.
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Carbon nanotubes (CNTs) are novel candidates in nanotechnology with a variety of increasing applications in medicine and biology. Therefore the investigation of nanomaterials' biocompatibility can be an important topic. The aim of present study was to investigate the CNTs impact on cardiac heart rate among rats.</AbstractText>Electrocardiogram (ECG) signals were recorded before and after injection of CNTs on a group with six rats. The heart rate variability (HRV) analysis was used for signals analysis. The rhythm-to-rhythm (RR) intervals in HRV method were computed and features of signals in time and frequency domains were extracted before and after injection.</AbstractText>RESULTS of the HRV analysis showed that CNTs increased the heart rate but generally these nanomaterials did not cause serious problem in autonomic nervous system (ANS) normal activities.</AbstractText>Injection of CNTs in rats resulted in increase of heart rate. The reason of phenomenon is that multiwall CNTs may block potassium channels. The suppressed and inhibited IK and potassium channels lead to increase of heart rate.</AbstractText>
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2,335,474 |
A clinical study to determine the efficacy of 7ppm dexmedetomidine as an adjuvant to 2% lignocaine in infraorbital nerve block.
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Dexmedetomidine is a selective alpha-2-adrenoceptor agonist used as an adjuvant for regional anaesthesia. We studied its efficacy as an adjuvant to lidocaine in infraorbital nerve block in 90 patients divided equally into three groups. The first group (control) was given 2% lidocaine 2ml only, the second, 2% lidocaine 2ml with dexmedetomidine 14μg peripherally (peripheral group), and the third, 2% lidocaine 2ml peripherally with dexmedetomidine 14μg systemically (systemic group). Onset of anaesthesia, duration of action, blood pressure, oxygen saturation, and heart rate were evaluated. The mean (SD) onset of action was faster in the peripheral group (185 (39.02) seconds) than in the others (control: 261.67 (67.02); systemic: 217.37 (34.86) seconds). The duration of action was longer in the peripheral group (124.87 (19.75) minutes) than in the others (control: 70.43 (13.62); systemic: 88.83 (20.63) minutes). Differences in blood pressure, oxygen saturation, and heart rate measured at different intervals were not significant. The addition of 7mg/L dexmedetomidine to lidocaine perineurally speeds up the onset of action and prolongs the duration of anaesthesia.
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2,335,475 |
Combined intra- and post-cardiac arrest hypothermic-targeted temperature management in a rat model of asphyxial cardiac arrest improves survival and neurologic outcome compared to either strategy alone.
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Post-cardiac arrest hypothermic-targeted temperature management (HTTM) improves outcomes in preclinical cardiac arrest studies. However, inadequate understanding of the mechanisms and therapeutic windows remains a barrier to optimization. We tested the hypothesis that combined intra- and post-cardiac arrest HTTM provides a synergistic outcome benefit compared to either strategy alone.</AbstractText>Rats subjected to 8-min asphyxial cardiac arrest were block randomized to 4 treatment groups (n=12/group): NTTM) normothermic-targeted temperature management; 1-24 HTTM) HTTM initiated 1h post-ROSC and maintained for 24h; Intra-1 HTTM) HTTM initiated at CPR onset and maintained for 1h; and Intra-24 HTTM) HTTM initiated at CPR onset and maintained for 24h. HTTM was induced by nasopharyngeal cooling and maintained using an automated temperature regulation system. Target temperature range was 36.5-37.5°C for NTTM and 32.0-34.0°C for HTTM. Post-arrest neurologic function score (NFS) was measured daily, and rats surviving 72h were euthanized for histological analysis of neurodegeneration.</AbstractText>Target brain temperature was achieved 7.8±3.3min after initiating intra-arrest cooling. The survival rate was 42%, 50%, 50%, and 92% in the NTTM, 1-24 HTTM, Intra-1 HTTM, and Intra-24 HTTM groups, respectively (p<0.05, Intra-24 group vs. all other groups). The rate of survival with good neurologic function (NFS≥450) was 33% in the Intra-24 HTTM group vs. 0% in all other groups (mid p<0.05). Hippocampal CA1 sector neurodegeneration was significantly reduced in the Intra-24 HTTM group compared to all other groups (p<0.05).</AbstractText>Combined intra- and post-cardiac arrest HTTM has greater outcome benefits than either strategy alone.</AbstractText>Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.</CopyrightInformation>
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2,335,476 |
The Relationship of Fertility, Lifestyle, and Longevity Among Women.
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Longevity in women has been found to be associated with several reproductive factors; the age of women when they give birth, their total number of children, and the age at which they experience menopause. In the context of expectations from the evolutionary theory of aging, the focus of this study examined relationships between lifetime reproduction, age at menopause and longevity, while accounting for various lifestyle factors. The purpose of this study was to assess fertility and age at onset of menopause in 197 women of the Georgia Centenarian Study. It was hypothesized that greater lifetime reproduction would predict earlier menopause and subsequently an earlier death. An independent t test was computed to assess ethnic differences between Caucasian and African American participants. Two block-wise multiple regression analyses were computed to evaluate the impact of low socioeconomic status in childhood, the age at the time of the first childbirth, the total number of children, smoking and alcohol use, incidence of heart disease and stroke, and the age at onset of menopause on longevity. Results from this study suggest a positive association between the total number of children to the age at onset of menopause and longevity. However, when considering the lifestyle factor of smoking, the association of the total number of children to longevity is diminished.
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2,335,477 |
Factors associated with self-rated health status in Southwestern Iran: a population-based study.
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This study aimed to reveal the relationship between self-rated health (SRH) and objective health status in the general population in the Southwest of Iran.</AbstractText>A cross-sectional study.</AbstractText>Data were collected by face-to-face interview with 3554 residents, aged ≥18 years, who were selected by multistage sampling procedure. Collected data included sociodemographic, SRH status, and medical conditions; chronic diseases and mental symptoms. SRH was indicated by a single question in five scales of very good, good, fair, poor and very poor. An ordinal logistic regression analysis was used. Independent variables were organized into four blocks: block 1, age, gender, marital status, education level, employment status, size of household and monthly household income; block 2, chronic or long-term illness (coronary heart disease, hypertension and diabetes mellitus); block 3, psychological disorders (anxiety, impatience and sleep disorders); and block 4 (visual, skin, hearing and oral disorders).</AbstractText>SRH status in most subjects reported to be positive, indicating 47.3% as very good, 30.8% good, 16.2% fair, 3.3% bad and 2.4% very bad. In studied subjects, poorer SRH was significantly related to older age (odds ratio [OR], 1.01), low-education level (OR, 1.09), single status (OR, 1.25), monthly household income (OR, 1.21), more chronic or long-term illness (OR, 1.61), greater psychological health disorders (OR, 1.69), more dermatologic disorders (OR, 1.30), and hearing problems (OR, 1.47).</AbstractText>Results of this study revealed that subjects with worse SRH were older with low-education level, lower household monthly income, more chronic illness, greater psychological health disorders, and more visual, skin, hearing and oral disorders. So, SRH, as indicated globally, can be used as a population screening tool to identify subjects who are most in need of public health services.</AbstractText>Copyright © 2016 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.</CopyrightInformation>
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2,335,478 |
Patient, Caregiver, and Physician Work in Heart Failure Disease Management: A Qualitative Study of Issues That Undermine Wellness.
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To identify factors underlying heart failure hospitalization.</AbstractText>Between January 1, 2012, and May 31, 2012, we combined medical record reviews and cross-sectional qualitative interviews of multiple patients with heart failure, their clinicians, and their caregivers from a large academic medical center in the Midwestern United States. The interview data were analyzed using a 3-step grounded theory-informed process and constant comparative methods. Qualitative data were compared and contrasted with results from the medical record review.</AbstractText>Patient nonadherence to the care plan was the most important contributor to hospital admission; however, reasons for nonadherence were complex and multifactorial. The data highlight the importance of patient education for the purposes of condition management, timeliness of care, and effective communication between providers and patients.</AbstractText>To improve the consistency and quality of care for patients with heart failure, more effective relationships among patients, providers, and caregivers are needed. Providers must be pragmatic when educating patients and their caregivers about heart failure, its treatment, and its prognosis.</AbstractText>Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.</CopyrightInformation>
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2,335,479 |
Beneficial Effects of New Zealand Blackcurrant Extract on Maximal Sprint Speed during the Loughborough Intermittent Shuttle Test.
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New Zealand blackcurrant (NZBC) extract has been shown to enhance high-intensity intermittent treadmill running. We examined the effects of NZBC extract during the Loughborough Intermittent Shuttle Test (LIST) which involves 5 × 15 min blocks with intermittent 15-m maximal sprints, interspersed by moderate and high-intensity running to simulate team sport activity, and a subsequent run to exhaustion. Thirteen males (age: 22 ± 1 year, V ˙ O 2 max : 50 ± 5 mL·kg<sup>-1</sup>·min<sup>-1</sup>) participated in three indoor sessions (T: 24 ± 3 °C, humidity: 52% ± 9%). In the first session, a multistage fitness test was completed to determine peak running speed and estimate V ˙ O 2 max . Participants consumed NZBC extract in capsules (300 mg·day<sup>-1</sup> CurraNZ™) or placebo (PL) (300 mg·day<sup>-1</sup> microcrystalline cellulose M102) for seven days in a double-blind, randomized, cross-over design (wash-out at least seven days). NZBC extract did not affect average 15-m sprint times in each block. NZBC reduced slowing of the fastest sprint between block 1 and 5 (PL: 0.12 ± 0.07 s; NZBC: 0.06 ± 0.12 s; <i>p</i> < 0.05). NZBC extract had no effect on heart rate, vertical jump power, lactate and time to exhaustion (PL: 13.44 ± 8.09 min, NZBC: 15.78 ± 9.40 min, <i>p</i> > 0.05). However, eight participants had higher running times to exhaustion when consuming NZBC extract. New Zealand blackcurrant extract may enhance performance in team sports with repeated maximal sprints.
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2,335,480 |
Modulation of cardiac autonomic tone in non-hypotensive hypovolemia during blood donation.
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Non-hypotensive hypovolemia, observed during mild haemorrhage or blood donation leads to reflex readjustment of the cardiac autonomic tone. In the present study, the cardiac autonomic tone was quantified using heart rate and blood pressure variability during and after non-hypotensive hypovolemia of blood donation. 86 voluntary healthy male blood donors were recruited for the study (age 35 ± 9 years; weight 78 ± 12 kg; height 174 ± 6 cms). Continuous lead II ECG and beat-to-beat blood pressure was recorded before, during and after blood donation followed by offline time and frequency domain analysis of HRV and BPV. The overall heart rate variability (SDNN and total power) did not change during or after blood donation. However, there was a decrease in indices that represent the parasympathetic component (pNN50 %, SDSD and HF) while an increase was observed in sympathetic component (LF) along with an increase in sympathovagal balance (LF:HF ratio) during blood donation. These changes were sustained for the period immediately following blood donation. No fall of blood pressure was observed during the period of study. The blood pressure variability showed an increase in the SDNN, CoV and RMSSD time domain measures in the post donation period. These results suggest that mild hypovolemia produced by blood donation is non-hypotensive but is associated with significant changes in the autonomic tone. The increased blood pressure variability and heart rate changes that are seen only in the later part of donation period could be because of the progressive hypovolemia associated parasympathetic withdrawal and sympathetic activation that manifest during the course of blood donation.
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2,335,481 |
[Ultrasound-guided Rectus Sheath Block vs Transversus Abdominis Plane Block in Children Undergoing Umbilical Hernia Repair].
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Although many reports describe the usefulness of the rectus sheath block (RSB) in the umbilical hernia repair, the efficacy of the transversus abdominis plane block (TAPB) is rarely reported. The purpose of this study was to compare the efficacy and technique of ultrasound-guided RSB and TAPB in children undergoing umbilical hernia repair.</AbstractText>Thirty-four children younger than 12 years of age scheduled for umbilical hernia repair were enrolled in this prospective observer-blinded randomized clinical trial. They were randomly assigned either to RSB group (median age, 3.7 years) or TAPB group (median age, 3.8 years). After the induction of general anesthesia with sevoflurane, nitrous oxide, and oxygen children in both groups received regional anesthesia with 0.3 ml x kg(-1) of 0.25% ropivacaine on each side under ultrasound guidance. Hemodynamic changes at the skin incision, postoperative pain scores and parental satisfaction were recorded. Anesthesiologists rated the quality of ultrasound images and easiness of the block performance.</AbstractText>The patients' demographics of the two groups were similar. There were no significant differences in the time needed for the block procedure, quality of ultrasound images and the change of the heart rate and blood pressure at the skin incision between the two groups. Postoperative pain score (immediately, 2 and 4 hours after the operation), need for rescue analgesia and satisfaction of the parents also did not differ. There were no major complications in the patients.</AbstractText>TAPB provided comparable perioperative analgesia and easiness of block performance to RSB in the pediatric umbilical hernia repair.</AbstractText>
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2,335,482 |
Common Variants in the TBX5 Gene Associated with Atrial Fibrillation in a Chinese Han Population.
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PR interval variations have recently been associated with an increased risk of long-term atrial fibrillation (AF), heart block and all-cause mortality. Genome-wide association studies have linked the PR interval with several common variants in the TBX5 gene. Several variants in the TBX5 gene, including rs7312625 and rs883079, have been associated with AF. The purpose of this study was to determine the association of single-nucleotide polymorphisms (SNPs) in the TBX5 gene, rs7312625 and rs883079, with AF in Chinese Han patients.</AbstractText><AbstractText Label="METHODOLOGY/PRINCIPAL FINDINGS" NlmCategory="RESULTS">In this case-control association study, large cohorts of AF patients (n = 1132) and controls (n = 1206) were recruited from different hospitals. The genotyping was performed using a Rotor-Gene TM 6000 high-resolution melt system. Rs7312625, rs3825214 and rs883079 were analyzed. We found that SNP 3825214 was significantly associated with AF (P-obs = 0.002, odds ratio [OR] = 0.82), and lone AF (P-obs = 6.77x10-5, odds ratio [OR] = 0.71). SNP rs7312625 was significantly associated with lone AF (P-obs = 0.015, odds ratio [OR] = 1.27), although its association with AF was not significant. No significant association of SNP rs883079 with AF or lone AF was observed. Thus, we analyzed the interaction among these three loci. We demonstrated significant interaction among rs3825214, rs7312625 and rs883079. Four-locus risk alleles showed the highest odds ratio in combined rs3825214 and rs7312625 (P-obs<0.0001, odds ratio [OR] = 2.21). Six-locus risk alleles showed the highest odds ratio in combined rs3825214, rs7312625 and rs 883079(P-obs<0.0001, odds ratio [OR] = 2.35). Significance was established with the trend test (P<0.0001).</AbstractText>For the first time, we report the strong association of SNP rs3825214 in the TBX5 gene with AF and lone AF in a Chinese Han population. Rs7312625 was significantly associated with lone AF, and snp-snp interaction increased the risk of atrial fibrillation. Our data might provide new insights into understanding AF pathogenesis and designing novel genetic therapies for AF patients.</AbstractText>
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2,335,483 |
Interaction Between HIV-1 Nef and Calnexin: From Modeling to Small Molecule Inhibitors Reversing HIV-Induced Lipid Accumulation.
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HIV-infected patients are at an increased risk of developing atherosclerosis, in part because of downmodulation and functional impairment of ATP-binding cassette A1 (ABCA1) cholesterol transporter by the HIV-1 protein Nef. The mechanism of this effect involves Nef interacting with an ER chaperone calnexin and disrupting calnexin binding to ABCA1, leading to ABCA1 retention in ER, its degradation and resulting suppression of cholesterol efflux. However, molecular details of Nef-calnexin interaction remained unknown, limiting the translational impact of this finding.</AbstractText>Here, we used molecular modeling and mutagenesis to characterize Nef-calnexin interaction and to identify small molecule compounds that could block it. We demonstrated that the interaction between Nef and calnexin is direct and can be reconstituted using recombinant proteins in vitro with a binding affinity of 89.1 nmol/L measured by surface plasmon resonance. The cytoplasmic tail of calnexin is essential and sufficient for interaction with Nef, and binds Nef with an affinity of 9.4 nmol/L. Replacing lysine residues in positions 4 and 7 of Nef with alanines abrogates Nef-calnexin interaction, prevents ABCA1 downregulation by Nef, and preserves cholesterol efflux from HIV-infected cells. Through virtual screening of the National Cancer Institute library of compounds, we identified a compound, 1[(7-oxo-7H-benz[de]anthracene-3-yl)amino]anthraquinone, which blocked Nef-calnexin interaction, partially restored ABCA1 activity in HIV-infected cells, and reduced foam cell formation in a culture of HIV-infected macrophages.</AbstractText>This study identifies potential targets that can be exploited to block the pathogenic effect of HIV infection on cholesterol metabolism and prevent atherosclerosis in HIV-infected subjects.</AbstractText>© 2016 American Heart Association, Inc.</CopyrightInformation>
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2,335,484 |
Preclinical Pharmacology of CW002: A Nondepolarizing Neuromuscular Blocking Drug of Intermediate Duration, Degraded and Antagonized by l-cysteine-Additional Studies of Safety and Efficacy in the Anesthetized Rhesus Monkey and Cat.
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CW002, a novel nondepolarizing neuromuscular blocking agent of intermediate duration, is degraded in vitro by L-cysteine; CW002-induced neuromuscular blockade (NMB) is antagonized in vivo by exogenous L-cysteine. Further, Institutional Animal Care and Use Committee-approved studies of safety and efficacy in eight anesthetized monkeys and six cats are described.</AbstractText>Mean arterial pressure, heart rate, twitch, and train-of-four were recorded; estimated dose producing 95% twitch inhibition (ED95) for NMB and twitch recovery intervals from 5 to 95% of baseline were derived. Antagonism of 99 to 100% block in monkeys by L-cysteine (50 mg/kg) was tested after bolus doses of approximately 3.75 to 20 × ED95 and after infusions. Vagal and sympathetic autonomic responses were recorded in cats. Dose ratios for [circulatory (ED20) or autonomic (ED50) changes/ED95 (NMB)] were calculated.</AbstractText>ED95s of CW002 in monkeys and cats were 0.040 and 0.035 mg/kg; L-cysteine readily antagonized block in monkeys: 5 to 95% twitch recovery intervals were shortened to 1.8 to 3.6 min after 3.75 to 10 × ED95 or infusions versus 11.5 to 13.5 min during spontaneous recovery. ED for 20% decrease of mean arterial pressure (n = 27) was 1.06 mg/kg in monkeys; ED for 20% increase of HR (n = 27) was 2.16 mg/kg. ED50s for vagal and sympathetic inhibition in cats were 0.59 and >>0.80 mg/kg (n = 14 and 15). Dose ratios for [circulatory or autonomic changes/ED95 (NMB)] were all more than 15 × ED95.</AbstractText>The data further verify the neuromuscular blocking properties of CW002, including rapid reversal by L-cysteine of 100% NMB under several circumstances. A notable lack of autonomic or circulatory effects provided added proof of safety and efficacy.</AbstractText>
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2,335,485 |
The Effects of Shoulder Rotation on the Acoustic Window for Thoracic Paramedian Epidural Approach in the Lateral Decubitus Position.
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The aim of this study was to examine whether shoulder rotation increases the length of the posterior longitudinal ligament (PLL) in the lateral decubitus position.</AbstractText>Thirty-four adult male volunteers were placed in the right or left lateral decubitus and flexion position on a horizontal operating table. Thoracic spinal ultrasonography was performed using the paramedian oblique sagittal plane to obtain the optimal ultrasound view for the PLL on the dependent side. The lengths of the PLL were measured at the T6/7 and T9/10 interspaces before and after ipsilateral 30-degree shoulder rotation.</AbstractText>In the right lateral decubitus position, the ipsilateral shoulder rotation increased the mean (SD) of the PLL from 7.4 (2.8) to 8.4 (2.6) mm (P = 0.006) at the T6/7 level and from 8.4 (2.9) to 10.6 (2.8) mm (P < 0.0001) at the T9/10 level. Similarly, in the left lateral decubitus position, the ipsilateral shoulder rotation increased the mean (SD) of the PLL from 8.0 (2.6) to 9.1 (2.6) mm (P = 0.001) at the T6/7 level and from 9.3 (2.8) to 11.8 (3.1) mm (P < 0.0001) at the T9/10 level.</AbstractText>Shoulder rotation significantly increased the dimension of the acoustic target window for paramedian thoracic epidural access in the lateral decubitus position at both T6/7 and T9/10 levels. Further clinical studies are needed to investigate the effect of shoulder rotation on thoracic epidural access.</AbstractText>
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2,335,486 |
Independent predictors of physical health in community-dwelling patients with coronary heart disease in Singapore.
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Patients with coronary heart disease (CHD) experienced poor physical health which was found to be associated with higher hospital readmission rates and increased mortality. The study aimed to identify the independent predictors of physical health in Singaporean patients with CHD.</AbstractText>A consecutive sample of 129 patients with CHD was recruited from the medical heart clinic of a tertiary public hospital in Singapore. A set of questionnaires including the Short Form 12-item health survey version 2, Perceived Stress Scale, Hospital Anxiety and Depression Scale, and Cardiac Self-Efficacy Scale were used to measure the study outcomes. The patients' socio-demographic and clinical data were also collected.</AbstractText>A multivariate linear regression analysis indicated that depression (B = -0.766, p < 0.05) and self-efficacy for maintaining function (B = 2.351, p < 0.05) remained significant while the other variables were adjusted and identified as the independent predictors of physical health in Singaporean patients with CHD.</AbstractText>This study has shed some light on the key factors influencing the physical health of Singaporean patients with CHD. The finding suggests tailored interventions that target mitigating a patient's depression and promote self-efficacy for maintaining function may be helpful in improving patients' physical health and quality of life.</AbstractText>
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2,335,487 |
Alterations in autonomic cardiac modulation in response to normobaric hypoxia.
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The present study aimed to determine if autonomic cardiac modulation was influenced by acute exposure to normobaric hypoxia.</AbstractText>Ten healthy male lowland dwellers completed five block-randomised single-blinded, crossed-over acute exposures to a normobaric hypoxic environment, each separated by 24 hours' recovery (20.3%, 17.4%, 14.5%, 12.0% and 9.8% FIO2). Supine recordings were made of arterial oxygen saturation and electrocardiogram (ECG). RR intervals from the ECG trace were analysed for time (SDNN, lnrMSSD), frequency (lnVLF, lnLF, lnHF, lnTP, LFnu, and HFnu), and nonlinear (DFA-α1 and SampEn) heart rate variability components.</AbstractText>A significant reduction in arterial SaO2 occurred with reduced FIO2, along with a rise in heart rate (Cohen's d = 1.16, 95% Confidence Interval [2.64-6.46]), significant at 9.8% FIO2. A decrease in autonomic cardiac modulation was also found as shown by a statistically significant (at 9.8% FIO2) decrease in lnTP (d = 1.84 [1.74-1.94]), and SampEn (d = 0.98 [0.83-1.12]) and an increase in DFA-α1 (d = 0.72 [0.60-0.84]) from normoxia at 9.8% FIO2.</AbstractText>The decrease in variability indicated a reduction in autonomic cardiac modulation. There appears to be a threshold ∼9.8% FIO2 (∼6000 m equiv.), below which significant alterations in autonomic control occur.</AbstractText>
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2,335,488 |
Comparison of Transcutaneous Electrical Nerve Stimulation and Parasternal Block for Postoperative Pain Management after Cardiac Surgery.
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Background. Parasternal block and transcutaneous electrical nerve stimulation (TENS) have been demonstrated to produce effective analgesia and reduce postoperative opioid requirements in patients undergoing cardiac surgery. Objectives. To compare the effectiveness of TENS and parasternal block on early postoperative pain after cardiac surgery. Methods. One hundred twenty patients undergoing cardiac surgery were enrolled in the present randomized, controlled prospective study. Patients were assigned to three treatment groups: parasternal block, intermittent TENS application, or a control group. Results. Pain scores recorded 4 h, 5 h, 6 h, 7 h, and 8 h postoperatively were lower in the parasternal block group than in the TENS and control groups. Total morphine consumption was also lower in the parasternal block group than in the TENS and control groups. It was also significantly lower in the TENS group than in the control group. There were no statistical differences among the groups regarding the extubation time, rescue analgesic medication, length of intensive care unit stay, or length of hospital stay. Conclusions. Parasternal block was more effective than TENS in the management of early postoperative pain and the reduction of opioid requirements in patients who underwent cardiac surgery through median sternotomy. This trial is registered with Clinicaltrials.gov number NCT02725229.
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2,335,489 |
Coenzyme Q10 in the Treatment of Corneal Edema in Kearns-Sayre: Is There an Application in Fuchs Endothelial Corneal Dystrophy?
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Corneal involvement in mitochondrial disease is seldom described. Kearns-Sayre syndrome (KSS) is a mitochondrial disorder characterized by retinitis pigmentosa, external ophthalmoplegia, and heart block. We report 2 patients with KSS with corneal lesions involving the endothelium, which improved with Coenzyme Q10 (CoQ10). Based on recent research regarding the role of dysfunctional oxidative metabolism in Fuchs Endothelial Corneal Dystrophy (FECD), we propose that mitochondrial diseases and FECD share a final pathway.</AbstractText>A chart review was performed and a review of the literature was completed with a PubMed search using the terms "Kearns-Sayre Syndrome", "mitochondria", "endothelium", "Fuchs endothelial corneal dystrophy", and "cornea".</AbstractText>There are 19 reports of corneal involvement in clinical phenotypes of mitochondrial disease. Nine of these 19 cases had findings consistent with KSS. Our patients with KSS had microcystic changes throughout the cornea and excrescences on the endothelial surface seen with ultrasound biomicroscopy, similar to the clinical findings in FECD. CoQ10 improved corneal disease in both children. CoQ10 deficiency has been reported in a variety of mitochondrial diseases, and efficacy of supplementation has been demonstrated. It may be beneficial in these patients because of its antioxidant properties and role in oxidative phosphorylation.</AbstractText>The common deletion found in patients with KSS has recently been implicated in FECD, which has recently been shown to be a disease related to dysfunctional oxidative metabolism. Future research should explore the use of antioxidants, such as CoQ10 in patients with FECD.</AbstractText>
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2,335,490 |
Autoantibodies in Sjögren's Syndrome.
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We compiled information on antibodies in Sjögren syndrome, focusing more on clinical manifestations associated with anti-Ro/SSA and anti-La/SSB antibodies and studies regarding novel antibodies. We reviewed previous as well as most recent studies with the subject heading Sjogren in combination with antibodies and congenital heart block (CHB). Almost half of asymptomatic mothers giving birth to children with CHB ultimately develop Sjögren. We discussed studies concerning the presence of antibodies predating clinical manifestations of disease. Studies in the future are required to ascertain the pathogenic mechanisms associated with these antibodies and the specific clinical manifestation related to new autoantibodies.
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2,335,491 |
A randomised controlled trial of calcium channel blockade (CCB) with Amlodipine For the treatment oF subcortical ischaEmic vasCular demenTia (AFFECT): study protocol.
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Vascular dementia is the second most common cause of dementia affecting over seven million people worldwide, yet there are no licensed treatments. There is an urgent need for a clinical trial in this patient group. Subcortical ischaemic vascular dementia is the most common variant of vascular dementia. This randomised trial will investigate whether use of calcium channel blockade with amlodipine, a commonly used agent, can provide the first evidence-based pharmacological treatment for subcortical ischaemic vascular dementia.</AbstractText><AbstractText Label="METHODS/DESIGN">This is a randomised controlled trial of calcium channel blockade with Amlodipine For the treatment oF subcortical ischaEmic vasCular demenTia (AFFECT) to test the hypothesis that treatment with amlodipine can improve outcomes for these patients in a phase IIb, multi-centre, double-blind, placebo-controlled randomised trial. The primary outcome is the change from baseline to 12 months in the Vascular Dementia Assessment Scale cognitive subscale (VADAS-cog). Secondary outcomes include cognitive function, executive function, clinical global impression of change, change in blood pressure, quantitative evaluation of lesion accrual based on magnetic resonance imaging (MRI), health-related quality of life, activities of daily living, non-cognitive dementia symptoms, care-giver burden and care-giver health-related quality of life, cost-effectiveness and institutionalisation. A total of 588 patients will be randomised in a 1:1 ratio to either amlodipine or placebo, recruited from sites across the UK and enrolled in the trial for 104 weeks.</AbstractText>There are no treatments licensed for vascular dementia. The most common subtype is subcortical ischaemic vascular dementia (SIVD). This study is designed to investigate whether amlodipine can produce benefits compared to placebo in established SIVD. It is estimated that the numbers of people with VaD and SIVD will increase globally in the future and the results of this study should inform important treatment decisions.</AbstractText>Current Controlled Trials ISRCTN31208535 . Registered on 7 March 2014.</AbstractText>
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2,335,492 |
Using social and mobile tools for weight loss in overweight and obese young adults (Project SMART): a 2 year, parallel-group, randomised, controlled trial.
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Few weight loss interventions are evaluated for longer than a year, and even fewer employ social and mobile technologies commonly used among young adults. We assessed the efficacy of a 2 year, theory-based, weight loss intervention that was remotely and adaptively delivered via integrated user experiences with Facebook, mobile apps, text messaging, emails, a website, and technology-mediated communication with a health coach (the SMART intervention).</AbstractText>In this parallel-group, randomised, controlled trial, we enrolled overweight or obese college students (aged 18-35 years) from three universities in San Diego, CA, USA. Participants were randomly assigned (1:1) to receive either the intervention (SMART intervention group) or general information about health and wellness (control group). We used computer-based permuted-block randomisation with block sizes of four, stratified by sex, ethnicity, and college. Participants, study staff, and investigators were masked until the intervention was assigned. The primary outcome was objectively measured weight in kg at 24 months. Differences between groups were evaluated using linear mixed-effects regression within an intention-to-treat framework. Objectively measured weight at 6, 12, and 18 months was included as a secondary outcome. The trial is registered with ClinicalTrials.gov, number NCT01200459.</AbstractText>Between May 18, 2011, and May 17, 2012, 404 individuals were randomly assigned to the intervention (n=202) or control (n=202). Participants' mean (SD) age was 22·7 (3·8) years. 284 (70%) participants were female and 125 (31%) were Hispanic. Mean (SD) body-mass index at baseline was 29·0 (2·8) kg/m(2). At 24 months, weight was assessed in 341 (84%) participants, but all 404 were included in analyses. Weight, adjusted for sex, ethnicity, and college, was not significantly different between the groups at 24 months (-0·79 kg [95% CI -2·02 to 0·43], p=0·204). However, weight was significantly less in the intervention group compared with the control group at 6 months (-1·33 kg [95% CI -2·36 to -0·30], p=0·011) and 12 months (-1·33 kg [-2·30 to -0·35], p=0·008), but not 18 months (-0·67 kg [95% CI -1·69 to 0·35], p=0·200). One serious adverse event in the intervention group (gallstones) could be attributable to rapid and excessive weight loss.</AbstractText>Social and mobile technologies did not facilitate sustained reductions in weight among young adults, although these approaches might facilitate limited short-term weight loss.</AbstractText>The National Heart, Lung, and Blood Institute of the National Institutes of Health (U01 HL096715).</AbstractText>Copyright © 2016 Elsevier Ltd. All rights reserved.</CopyrightInformation>
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2,335,493 |
Mapping the Pairwise Choices Leading from Pluripotency to Human Bone, Heart, and Other Mesoderm Cell Types.
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Stem-cell differentiation to desired lineages requires navigating alternating developmental paths that often lead to unwanted cell types. Hence, comprehensive developmental roadmaps are crucial to channel stem-cell differentiation toward desired fates. To this end, here, we map bifurcating lineage choices leading from pluripotency to 12 human mesodermal lineages, including bone, muscle, and heart. We defined the extrinsic signals controlling each binary lineage decision, enabling us to logically block differentiation toward unwanted fates and rapidly steer pluripotent stem cells toward 80%-99% pure human mesodermal lineages at most branchpoints. This strategy enabled the generation of human bone and heart progenitors that could engraft in respective in vivo models. Mapping stepwise chromatin and single-cell gene expression changes in mesoderm development uncovered somite segmentation, a previously unobservable human embryonic event transiently marked by HOPX expression. Collectively, this roadmap enables navigation of mesodermal development to produce transplantable human tissue progenitors and uncover developmental processes. VIDEO ABSTRACT.
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2,335,494 |
Block-based association tests for rare variants using Kullback-Leibler divergence.
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Although genome-wide association studies have successfully detected numerous associations between common variants and complex diseases, these variants typically can only explain a small part of the heritable component of a disease. With the advent of next-generation sequencing, attention has turned to rare variants. Recently, a variety of approaches for detecting associations of rare variants have been proposed, including the Kullback-Leibler divergence-based tests (KLTs) for detecting genotypic differences between cases and controls. However, few of these approaches consider linkage disequilibrium (LD) structure among rare variants and common variants. In this study, we propose two block-based association tests for testing the effects of rare variants on a disease. The main idea for this approach comes from the hypothesis that a region of interest may consist of two or more LD blocks such that single-nucleotide variants (SNVs) within each block are correlated, whereas SNVs in different blocks are independent or weakly correlated. Under this hypothesis, we propose two tests that are generalizations of the KLTs by taking the block structure into account. A simulation study under various scenarios shows that the proposed methods have well-controlled type I error rates and outperform some leading methods in the literature. Moreover, application to the Dallas Heart Study data demonstrates the feasibility and performance of the two proposed methods in a realistic setting.
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2,335,495 |
Update on Pathogenesis of Sjogren's Syndrome.
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Sjogren's syndrome is a common autoimmune disease that presents with sicca symptoms and extraglandular features. Sjogren's syndrome is presumably as common as RA; yet it is poorly understood, underdiagnosed and undertreated. From the usual identity as an autoimmune exocrinopathy to its most recent designate as an autoimmune epithelitis - the journey of SS is complex. We herein review some of the most important milestones that have shed light on different aspects of pathogenesis of this enigmatic disease. This includes role of salivary gland epithelial cells, and their interaction with cells of the innate and adaptive immune system. Non-immune factors acting in concert or in parallel with immune factors may also be important. The risk genes identified so far have only weak association, nevertheless advances in genetics have enhanced understanding of disease mechanisms. Role of epigenetic and environmental role factors is also being explored. SS has also some unique features such as congenital heart block and high incidence of lymphoma; disease mechanisms accounting for these manifestations are also reviewed.
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2,335,496 |
Zwitterionic chitosan for the systemic treatment of sepsis.
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Severe sepsis and septic shock are life-threatening conditions, with Gram-negative organisms responsible for most sepsis mortality. Systemic administration of compounds that block the action of lipopolysaccharide (LPS), a constituent of the Gram-negative outer cell membrane, is hampered by their hydrophobicity and cationic charge, the very properties responsible for their interactions with LPS. We hypothesize that a chitosan derivative zwitterionic chitosan (ZWC), previously shown to suppress the production of pro-inflammatory cellular mediators in LPS-challenged macrophages, will have protective effects in an animal model of sepsis induced by systemic injection of LPS. In this study, we evaluate whether ZWC attenuates the fatal effect of LPS in C57BL/6 mice and investigate the mechanism by which ZWC counteracts the LPS effect using a PMJ2-PC peritoneal macrophage cell line. Unlike its parent compound with low water solubility, intraperitoneally administered ZWC is readily absorbed with no local residue or adverse tissue reaction at the injection site. Whether administered at or prior to the LPS challenge, ZWC more than doubles the animals' median survival time. ZWC appears to protect the LPS-challenged organisms by forming a complex with LPS and thus attenuating pro-inflammatory signaling pathways. These findings suggest that ZWC have utility as a systemic anti-LPS agent.
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2,335,497 |
Sequence effects of combined resistance exercises with step choreography in the same session in women's oxygen uptake during and postexercise.
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The combination of step choreography (SC) with resistance training exercises (RE) in the same session is common in class fitness rooms populated mainly by women to increase energy expenditure. The aim of this study was to evaluate the differences in the exercise oxygen uptake and postexercise between two different combinations of resistance training exercises and step choreography, regarding the order of execution. Thirteen active women (30·31 ± 4·42 years, 62·02 ± 5·37 kg, 162·65 ± 4·40 cm, 19·14 ± 3·29% body fat) performed two combinations: step choreography before resistance training, where resistance training was divided into two blocks of analysis (10 min each); and step choreography divided into three equal blocks (10 min for each block), before, in the middle and after resistance exercise. There were significant differences (P<0·05) between the two sessions in oxygen uptake postexercise in the period of 0-5 min. A significant increase (P<0·0001) in the oxygen uptake absolute and relative in the heart rate between blocks 1 and 2 of resistance exercise in the two sessions was observed. In the step choreography in blocks, a significant (P = 0·001) decrease between blocks 2 and 3 in the step choreography before resistance exercise and a significant (P<0·05) increase in the heart rate in both sessions between blocks were observed. The combination of step choreography and resistance exercises during the same exercise session is a good strategy to promote an elevation of women's oxygen uptake during and after an exercise session, independent of the sequence used.
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2,335,498 |
Occurrence of idiopathic pulmonary fibrosis during immunosuppressive treatment: a case report.
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Immunosuppressive therapy has been-until the recent release of new guidelines on diagnosis and management-the recommended treatment for idiopathic pulmonary fibrosis. However, its efficacy in patients with idiopathic pulmonary fibrosis has always been a matter of debate.</AbstractText>We report the occurrence of idiopathic pulmonary fibrosis in a white man receiving chronic immunosuppressive treatment following a heart transplant.</AbstractText>This case report suggests that the immune mechanisms targeted by azathioprine and cyclosporine do not play a role in the pathogenesis of idiopathic pulmonary fibrosis.</AbstractText>
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2,335,499 |
Assessment of operators' mental workload using physiological and subjective measures in cement, city traffic and power plant control centers.
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The present study aimed to evaluate the operators' mental workload (MW) of cement, city traffic control and power plant control centers using subjective and objective measures during system vital parameters monitoring.</AbstractText>This cross-sectional study was conducted from June 2014 to February 2015 at the cement, city traffic control and power plant control centers. Electrocardiography and electroencephalography data were recorded from forty males during performing their daily working in resting, low mental workload (LMW), high mental workload (HMW) and recovery conditions (each block 5 minutes). The NASA-Task Load Index (TLX) was used to evaluate the subjective workload of the operators.</AbstractText>The results showed that increasing MW had a significant effect on the operators subjective responses in two conditions ([1,53] = 216.303, P < 0.001, η2 = 0.803). Also,the Task-MW interaction effect on operators subjective responses was significant (F [3, 53] = 12.628,P < 0.001, η2 = 0.417). Analysis of repeated measures analysis of variance (ANOVA) indicated that increasing mental demands had a significant effect on heart rate, low frequency/high frequency ratio, theta and alpha band activity.</AbstractText>The results suggested that when operators' mental demands especially in traffic control and power plant tasks increased, their mental fatigue and stress level increased and their mental health deteriorated. Therefore, it may be necessary to implement an ergonomic program or administrative control to manage mental probably health in these control centers. Furthermore, by evaluating MW, the control center director can organize the human resources for each MW condition to sustain the appropriate performance as well as improve system functions.</AbstractText>
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