The influence of socioeconomic deprivation on outcomes in transplant patients infected with SARS-CoV-2 in Wales.

INTRODUCTION: SARS-CoV-2 infection has had a significant impact on vulnerable individuals including transplant patients. Socioeconomic deprivation negatively affects outcomes of many health conditions. The aim of this study was to evaluate the effect of socioeconomic deprivation on the incidence and severity of SARS-CoV-2 infection among Welsh transplant patients. METHODS: This study is a retrospective, cross-sectional study on the transplant population of Wales. The Welsh Index of Multiple Deprivation (WIMD) was used to assess the influence of socioeconomic deprivation on outcomes of Welsh transplant patients who developed SARS-CoV-2 infection. Outcome measures were the incidence of SARS-CoV-2 infection, rates of hospital and ICU admission, development of acute kidney injury (AKI) and mortality. A logistic binomial regression analysis was used to correlate the various risk factors with the incidence of SARS-CoV-2 infection. RESULTS: Two hundred and sixty-six (25%) of regular follow up patients had SARS-CoV-2 infection; of these 55 (20.7%) were admitted, 15 (5.6%) to ICU, 37 (13.9%) developed AKI, and 23 (8.6%) died. In a regression analysis, patients of younger age were associated with more (p = .001) and those with SPK (simultaneous pancreas kidney) transplant less chance of infection (p = .038), whereas social deprivation was not associated with the chance of infection (p = .14). In regression analysis increased social deprivation was associated with higher chance of AKI post SARS-CoV-2 (p = .049). CONCLUSIONS: Socioeconomic deprivation did not affect the rates or severity of SARS-CoV-2 infection apart from the degree of AKI in Welsh Transplant patients. Adherence to the preventive measures for this high-risk population must continue to remain a priority.

New Computerized Planning Algorithm and Clinical Testing of Optimized Nuss Bar Design for Patients with Pectus Excavatum.

BACKGROUND Computer-aided design (CAD) has been used in the Nuss procedure to determine the bar length and shape. Despite computer aid, the shape and design remain quite intuitive. We tested a new algorithm to determine the optimal bar shape. MATERIAL AND METHODS The normal sterno-vertebral distance was defined on computed tomography (CT) scans of patients without pectus excavatum (PEx) at the same level where the deepest depression was found on CT scans of 97 patients with PEx. Four points were marked on the CT scan of 60 patients with PEx at the deepest deformity: P1: edge of the vertebra; P2: edge of the deformity; P3: the expected contact point of the bar and the rib; and P4: the expected end of the bar. The algorithm generated 3 circles upon these points, and the fusion of the arcs drew the line of the ideal bar. Corrected and normal sterno-vertebral distance values were compared with the Mann-Whitney U test. Ten bars were bent manually guided by a 1: 1 printout of the designed bar and were implanted in 10 adolescents. RESULTS The shortest sterno-vertebral distance was 3 cm below the intermammillary line in PEx patients. The normal mean sterno-vertebral distance at this level was 10.16±1.35 cm in non-PEx patients. The mean virtually corrected sterno-vertebral distance was 10.28±1.27 cm. No significant difference was found (P=0.44). The bars were seamless and were successfully implanted. No bar needed adjustment, the operation time was shorter, and the patient satisfaction score was 9.4/10. CONCLUSIONS With our new algorithm, an optimal Nuss bar can be designed.

Outcomes of Exeter cemented total hip arthroplasty in a county hospital: survivorship of eight hundred and ninety four hips with a minimum ten-year follow up.

PURPOSE: A total of 894 hips were evaluated to describe the survivorship of Exeter cemented femoral stems and report the outcomes and complications of our 'Exeter- era', and there is no study from Central or Eastern Europe demonstrating similar results. METHODS: Between January 2000 and December 2009, a total of 894 hips were included who underwent Exeter universal and V40 femoral stems with a mean follow up of 13 years. Cemented Exeter low profile polyethylene cups were used in 889 patients (99.4%) cups. Harris hip score (HHS) was used and statistical outcome measures were calculated with revision as an endpoint for aseptic loosening of the stem, aseptic loosening of any component, all-cause revision of the stem, and all-cause revision of the hip. RESULTS: A total of 103 patients died and 129 (14.4%) operated hips were lost to follow-up before ten years. Out of the 662, ten stems (1.5%) were revised for aseptic loosening. Aseptic loosening of any component was the reason for revision in 43 cases (6.5%), consisting of 40 cup revisions and ten stem exchanges. Periprosthetic fracture occurred in 17 cases (1.9%) Periprosthetic joint infection occurred in 18 cases (2.01%). Three cups were exchanged for recurrent dislocation, and two stems had broken. CONCLUSION: Exeter hip system has provided reproducible results across different centres worldwide, as it did in our series. Thorough surgical and cementing technique is of utmost importance for achieving these results. The cup is the weak point of the system and use of a hybrid system is worth considering.

Pharmacological Activation of Piezo1 Channels Enhances Astrocyte-Neuron Communication via NMDA Receptors in the Murine Neocortex.

The Piezo1 mechanosensitive ion channel is abundant on several elements of the central nervous system including astrocytes. It has been already demonstrated that activation of these channels is able to elicit calcium waves on astrocytes, which contributes to the release of gliotransmitters. Astrocyte- and N-methyl-D-aspartate (NMDA) receptor-dependent slow inward currents (SICs) are hallmarks of astrocyte-neuron communication. These currents are triggered by glutamate released as gliotransmitter, which in turn activates neuronal NMDA receptors responsible for this inward current having slower kinetics than any synaptic events. In this project, we aimed to investigate whether Piezo1 activation and inhibition is able to alter spontaneous SIC activity of murine neocortical pyramidal neurons. When the Piezo1 opener Yoda1 was applied, the SIC frequency and the charge transfer by these events in a minute time was significantly increased. These changes were prevented by treating the preparations with the NMDA receptor inhibitor D-AP5. Furthermore, Yoda1 did not alter the spontaneous EPSC frequency and amplitude when SICs were absent. The Piezo1 inhibitor Dooku1 effectively reverted the actions of Yoda1 and decreased the rise time of SICs when applied alone. In conclusion, activation of Piezo1 channels is able to alter astrocyte-neuron communication. Via enhancement of SIC activity, astrocytic Piezo1 channels have the capacity to determine neuronal excitability.

Urine flow acceleration in healthy children: A retrospective cohort study.

AIMS: To establish normal reference values of urine flow acceleration (Qacc ) in healthy children, as there is a lack of nomograms for normative reference values of Qacc by voided volumes in the pediatric population so far. Qacc might be an early indicator of autonomic neuropathy in children and adolescents. METHODS: Data were retrospectively collected from healthy children who underwent uroflowmetry between 1990 and 1992. Exclusion criteria were voided volume less than 20 ml, and postvoid residual more than 15%. Baseline characteristics and uroflowmetry parameters were collected from girls and boys aged between 6 and 18 years. Voided volume, voiding time, time to maximum flow rate, and maximum and average flow rates of urine were measured, and Qacc was calculated. Postvoid bladder diameter was measured by ultrasonography and converted to volume. RESULTS: Uroflowmetry parameters of 208 children (≤18 years old, 45.2% girls, mean age 9.68 ± 3.09 years) who performed 404 micturition were analyzed. Median voided volume, voiding time, time to Qmax , Qave , Qmax , Qacc , and postvoid residual volume were 130 [20-460] ml, 10 [3-56] s, 3 [1-14] s, 11.7 [2.5-36.6] ml/s, 20.5 [5-50] ml/s, 6 [0.81-25] ml/s2 , and 1.83 [0-38.62] ml, respectively. Qacc nomograms were given in centile forms for girls and boys separately, which show an inversely proportional correlation between voided volumes. CONCLUSIONS: These are the first nomograms for normative reference values of Qacc in the pediatric population (girls and boys separately) by voided volumes in centile forms. These may be useful to interpret abnormal Qacc values and diagnose lower urinary tract diseases over a wide range of voided volumes.

The Role of the Piezo1 Mechanosensitive Channel in the Musculoskeletal System.

Since the recent discovery of the mechanosensitive Piezo1 channels, many studies have addressed the role of the channel in various physiological or even pathological processes of different organs. Although the number of studies on their effects on the musculoskeletal system is constantly increasing, we are still far from a precise understanding. In this review, the knowledge available so far regarding the musculoskeletal system is summarized, reviewing the results achieved in the field of skeletal muscles, bones, joints and cartilage, tendons and ligaments, as well as intervertebral discs.

Reduced Expression of Septin7 Hinders Skeletal Muscle Regeneration.

Septins are considered the fourth component of the cytoskeleton with the septin7 isoform playing a critical role in the formation of diffusion barriers in phospholipid bilayers and intra- and extracellular scaffolds. While its importance has already been confirmed in different intracellular processes, very little is known about its role in skeletal muscle. Muscle regeneration was studied in a Sept7 conditional knock-down mouse model to prove the possible role of septin7 in this process. Sterile inflammation in skeletal muscle was induced which was followed by regeneration resulting in the upregulation of septin7 expression. Partial knock-down of Sept7 resulted in an increased number of inflammatory cells and myofibers containing central nuclei. Taken together, our data suggest that partial knock-down of Sept7 hinders the kinetics of muscle regeneration, indicating its crucial role in skeletal muscle functions.

Loss of Uncoupling Protein 1 Expression in the Subcutaneous Adipose Tissue Predicts Childhood Obesity.

Stimulation of thermogenesis by inducing uncoupling protein 1 (UCP1) expression in adipocytes is thought to promote weight loss by increasing energy expenditure, and it is postulated that the human newborn has thermogenic subcutaneous fat depots. However, it remains unclear whether a relevant number of UCP1-expressing (UCP1+) adipocytes exist in the early postnatal life. Here we studied the distribution of UCP1 and the expression of thermogenic genes in the subcutaneous adipose tissues of the human fetus, infant and child. We show that the deep layer of human fetal and neonatal subcutaneous fat, particularly the abdominal wall, is rich in UCP1+ adipocytes. These adipocytes develop in the late third trimester and persist throughout childhood, expressing a panel of genes linked to mitochondrial biogenesis and thermogenesis. During the early childhood adiposity rebound-a critical phase that determines obesity risk later in life-the absence of adipose tissue UCP1 expression in children with normal body mass index (BMI) correlates with an obesity-associated gene expression signature. Finally, UCP1 expression is negatively correlated with BMI z-score and adipocyte size in infants and children. Overall, our results show that the absence of UCP1 expression in adipose tissue is an early indicator of adipose tissue expansion in children.

Characterization of technical skill progress in a standardized rabbit model for training in laparoscopic duodenal atresia repair.

BACKGROUND: Laboratory skills training is an essential step before conducting minimally invasive surgery in clinical practice. Our main aim was to develop an animal model for training in clinically highly challenging laparoscopic duodenal atresia repair that could be useful in establishing a minimum number of repetitions to indicate safe performance of similar interventions on humans. MATERIALS AND METHODS: A rabbit model of laparoscopic duodenum atresia surgery involving a diamond-shaped duodeno-duodenostomy was designed. This approach was tested in two groups of surgeons: in a beginner group without any previous clinical laparoscopic experience (but having undergone previous standardized dry-lab training, n = 8) and in an advanced group comprising pediatric surgery fellows with previous clinical experience of laparoscopy (n = 7). Each participant performed eight interventions. Surgical time, expert assessment using the Global Operative Assessment of Laparoscopic Skills (GOALS) score, anastomosis quality (leakage) and results from participant feedback questionnaires were analyzed. RESULTS: Participants in both groups successfully completed all eight surgeries. The surgical time gradually improved in both groups, but it was typically shorter in the advanced group than in the beginner group. The leakage rate was significantly lower in the advanced group in the first two interventions, and it reached its optimal level after five operations in both groups. The GOALS and participant feedback scores showed gradual increases, evident even after the fifth surgery. CONCLUSIONS: Our data confirm the feasibility of this advanced pediatric laparoscopic model. Surgical time, anastomosis quality, GOALS score and self-assessment parameters adequately quantify technical improvement among the participants. Anastomosis quality reaches its optimal value after the fifth operation even in novice, but uniformly trained surgeons. A minimum number of wet-lab operations can be determined before surgery can be safely conducted in a clinical setting, where the development of further non-technical skills is also required.

Urodynamics in Early Diagnosis of Diabetic Bladder Dysfunction in Women: A Systematic Review and Meta-Analysis.

BACKGROUND Urodynamics can detect subtle voiding changes before cystopathy symptoms manifest. The aim of the present study was to assess urodynamic changes in diabetic women. MATERIAL AND METHODS A systematic search was performed on 04 November 2021 to identify studies reporting urodynamic parameters in diabetic women. Data were analyzed in a single-arm meta-analysis due to lack of sufficient studies with direct comparisons to healthy women. For data synthesis, a random-effects model with restricted maximum-likelihood estimation was applied. The calculated effect sizes were visualized in forest plots. Statistical heterogeneity was assessed using the I² measure and the χ² test. The risk of bias was assessed using the QUIPS tool. PROSPERO ID: CRD42021256275. RESULTS Out of 1750 records, 10 studies were used in the analysis (n=2342 diabetic women). Pooled event rates showed that mean voided volume was 288.21 mL [95% confidence interval (CI): 217.35-359.06, I²=98%], mean postvoid residual volume was 93.67 mL [95% CI: 31.35-155.99, I²=100%], mean Qmax was 18.80 mL/sec [95% CI: 15.27-22.33, I²=99%], mean PdetQmax is 30.13 cmH2O [95% CI: 25.53-34.73, I²=90%], mean first sensation of bladder filling was 178.66 mL [95% CI: 150.59-206.72, I²=97%], and mean cystometric capacity was 480.41 mL [95% CI: 409.32-551.50, I²=98%] in diabetic women. CONCLUSIONS Pooled results indicate that diabetic women tend to have a smaller voided volume, slower Qmax and PdetQmax, larger postvoid residual, and higher first sensation of bladder filling and cystometric capacity compared to the general female population.

Janus Kinase Inhibitors Improve Disease Activity and Patient-Reported Outcomes in Rheumatoid Arthritis: A Systematic Review and Meta-Analysis of 24,135 Patients.

Pain, fatigue, and physical activity are major determinants of life quality in rheumatoid arthritis (RA). Janus kinase (JAK) inhibitors have emerged as effective medications in RA and have been reported to exert direct analgesic effect in addition to reducing joint inflammation. This analysis aims to give an extensive summary of JAK inhibitors especially focusing on pain and patient reported outcomes (PRO). MEDLINE, CENTRAL, Embase, Scopus, and Web of Science databases were searched on the 26 October 2020, and 50 randomized controlled trials including 24,135 adult patients with active RA met the inclusion criteria. JAK inhibitors yielded significantly better results in all 36 outcomes compared to placebo. JAK monotherapy proved to be more effective than methotrexate in 9 out of 11 efficacy outcomes. In comparison to biological disease-modifying antirheumatic drugs, JAK inhibitors show statistical superiority in 13 of the 19 efficacy outcomes. Analgesic effect determined using the visual analogue scale and American College of Rheumatology (ACR) 20/50/70 response rates was significantly greater in the JAK group in all comparisons, and no significant difference regarding safety could be explored. This meta-analysis gives a comprehensive overview of JAK inhibitors and provides evidence for their superiority in improving PROs and disease activity indices in RA.

The Utilization of Physiologically Active Molecular Components of Grape Seeds and Grape Marc.

Nutritional interventions may highly contribute to the maintenance or restoration of human health. Grapes (Vitis vinifera) are one of the oldest known beneficial nutritional components of the human diet. Their high polyphenol content has been proven to enhance human health beyond doubt in statistics-based public health studies, especially in the prevention of cardiovascular disease and cancer. The current review concentrates on presenting and classifying polyphenol bioactive molecules (resveratrol, quercetin, catechin/epicatechin, etc.) available in high quantities in Vitis vinifera grapes or their byproducts. The molecular pathways and cellular signaling cascades involved in the effects of these polyphenol molecules are also presented in this review, which summarizes currently available in vitro and in vivo experimental literature data on their biological activities mostly in easily accessible tabular form. New molecules for different therapeutic purposes can also be synthesized based on existing polyphenol compound classes available in high quantities in grape, wine, and grape marc. Therefore an overview of these molecular structures is provided. Novel possibilities as dendrimer nanobioconjugates are reviewed, too. Currently available in vitro and in vivo experimental literature data on polyphenol biological activities are presented in easily accessible tabular form. The scope of the review details the antidiabetic, anticarcinogenic, antiviral, vasoprotective, and neuroprotective roles of grape-origin flavonoids. The novelty of the study lies in the description of the processing of agricultural by-products (grape seeds and skins) of industrial relevance, and the detailed description of the molecular mechanisms of action. In addition, the review of the clinical therapeutic applications of polyphenols is unique as no summary study has yet been done.

Genetic Manipulation of CB1 Cannabinoid Receptors Reveals a Role in Maintaining Proper Skeletal Muscle Morphology and Function in Mice.

The endocannabinoid system (ECS) refers to a widespread signaling system and its alteration is implicated in a growing number of human diseases. Cannabinoid receptors (CBRs) are highly expressed in the central nervous system and many peripheral tissues. Evidence suggests that CB1Rs are expressed in human and murine skeletal muscle mainly in the cell membrane, but a subpopulation is present also in the mitochondria. However, very little is known about the latter population. To date, the connection between the function of CB1Rs and the regulation of intracellular Ca2+ signaling has not been investigated yet. Tamoxifen-inducible skeletal muscle-specific conditional CB1 knock-down (skmCB1-KD, hereafter referred to as Cre+/-) mice were used in this study for functional and morphological analysis. After confirming CB1R down-regulation on the mRNA and protein level, we performed in vitro muscle force measurements and found that peak twitch, tetanus, and fatigue were decreased significantly in Cre+/- mice. Resting intracellular calcium concentration, voltage dependence of the calcium transients as well as the activity dependent mitochondrial calcium uptake were essentially unaltered by Cnr1 gene manipulation. Nevertheless, we found striking differences in the ultrastructural architecture of the mitochondrial network of muscle tissue from the Cre+/- mice. Our results suggest a role of CB1Rs in maintaining physiological muscle function and morphology. Targeting ECS could be a potential tool in certain diseases, including muscular dystrophies where increased endocannabinoid levels have already been described.

Astaxanthin Exerts Anabolic Effects via Pleiotropic Modulation of the Excitable Tissue.

Astaxanthin is a lipid-soluble carotenoid influencing lipid metabolism, body weight, and insulin sensitivity. We provide a systematic analysis of acute and chronic effects of astaxanthin on different organs. Changes by chronic astaxanthin feeding were analyzed on general metabolism, expression of regulatory proteins in the skeletal muscle, as well as changes of excitation and synaptic activity in the hypothalamic arcuate nucleus of mice. Acute responses were also tested on canine cardiac muscle and different neuronal populations of the hypothalamic arcuate nucleus in mice. Dietary astaxanthin significantly increased food intake. It also increased protein levels affecting glucose metabolism and fatty acid biosynthesis in skeletal muscle. Inhibitory inputs innervating neurons of the arcuate nucleus regulating metabolism and food intake were strengthened by both acute and chronic astaxanthin treatment. Astaxanthin moderately shortened cardiac action potentials, depressed their plateau potential, and reduced the maximal rate of depolarization. Based on its complex actions on metabolism and food intake, our data support the previous findings that astaxanthin is suitable for supplementing the diet of patients with disturbances in energy homeostasis.

A multicenter randomized controlled trial indicates that paclitaxel-coated balloons provide no benefit for arteriovenous fistulas.

The role of paclitaxel-coated balloons has been established in the coronary and peripheral arterial circulations with recent interest in the use of paclitaxel-coated balloons to improve patency rates following angioplasty of arteriovenous fistulas. To assess the efficacy of paclitaxel-coated angioplasty balloons to prolong the survival time of target lesion primary patency in arteriovenous fistulas, we designed an investigator-led multi-center randomized controlled trial with follow up time variable for a minimum of one year. Patients with an arteriovenous fistula who were undergoing an angioplasty for a clinical indication were included but patients with one or more lesions outside the treatment segment were excluded. Following successful treatment with a high-pressure balloon, 212 patients were randomized. In the intervention arm, the second component was insertion of a paclitaxel-coated balloon. In the control arm, an identical procedure was followed, but using a standard balloon. The primary endpoint was time to loss of clinically driven target lesion primary patency. Primary analysis showed no significant evidence for a difference in time to end of target lesion primary patency between groups: hazard ratio 1.18 with a 95% confidence interval of 0.78 to 1.79. There were no significant differences for any secondary outcomes, including patency outcomes and adverse events. Thus, our study demonstrated no evidence that paclitaxel-coated balloons provide benefit, following standard care high-pressure balloon angioplasty, in the treatment of arteriovenous fistulas. Hence, in view of the benefit suggested by other trials, the role of paclitaxel-coated angioplasty balloons remains uncertain.

A drop of self-confidence program about urinary incontinence.

AIM: The aim of our study was to find and map untreated incontinence patients through general practitioner (GP) practices. METHODS: General practitioners and their assistants participated in the program (Group A). GPs of all the country were involved in a representative manner. The process of the program was preparing the education program, praxis involvement, participant education, a population screening, and by questionnaire by medical staff. In Group B urological outpatients clinics participated. RESULTS: A total of 2761 GPs, 3015 nurses, and 110 specialists participated in the program between 2011 and 2019. The population participating in the program was 162,871, 86% women and 14% men. The age range was 18-96. 68% had urinary incontinence (UI), 76% of patients had stress, and 49% had urge incontinence. Incontinence is very high (98%) among bedridden patients. On average, 20% had very little information, 40% had little information, 33% had enough information about incontinence, and 7% thought they knew everything about it. 41% reported diabetes mellitus, 33% had frequent cough and sneezing, 31% obesity as a risk factor. 30% of incontinent patients did not go to the GP and 66% to the specialist. 34% of patients who were at GPs received no information, 34% of the patients received symptomatic, and 30% did not receive treatment from the GP. CONCLUSION: The incidence of UI is similar to that in other countries. Patient recognition care is similar, perhaps worse. The findings of this study clearly indicate that harmful physical and psychosocial effects of UI are significant and require attention of the healthcare system.

Recognizing Early Regulation Disorders in Pediatric Care: The For Healthy Offspring Project.

BACKGROUND Regulation disorders are already apparent in infancy. The For Healthy Offspring Project was the first Hungarian study aimed at building an effective model for screening and examining the prevalence and complex (medical and psychosocial) background of classic behavior regulation disorders (excessive crying, feeding, and sleep problems) in infancy. MATERIAL AND METHODS Data were collected from families of 0- to 3-year-old children in a pediatric hospital and its neighboring areas through questionnaires, medical examinations, and individual and small-group consultations. RESULTS In the questionnaire study about their children's behavior (n=1133), 15% of mothers reported excessive crying, 16% reported feeding problems, and 10% reported sleep problems. In a subsample (n=619) in which medical examinations were also conducted, the prevalence of medical diagnoses was 15.0% for excessive crying, 15.2% for sleep disorders, 10.3% for breastfeeding difficulties, and 14.8% for feeding disorders. Children who were referred to the screening program (n=183) had significantly more behavior regulation disorders than the other children in our study. Regulation disorders were found to be comorbid with other health conditions in some cases. CONCLUSIONS We developed a complex model to screen for regulatory problems in early childhood. This study adds more information about the relationship between regulation problems and other health conditions. The general incidence (5-15%) of early childhood regulation disorders in other countries is likely similar to that found in Hungary. In order to effectively recognize early regulation disorders, diagnostic instruments widely used in the international field should be adapted in general Hungarian pediatric care.

Electrophysiological Effects of the Transient Receptor Potential Melastatin 4 Channel Inhibitor (4-Chloro-2-(2-chlorophenoxy)acetamido) Benzoic Acid (CBA) in Canine Left Ventricular Cardiomyocytes.

Transient receptor potential melastatin 4 (TRPM4) plays an important role in many tissues, including pacemaker and conductive tissues of the heart, but much less is known about its electrophysiological role in ventricular myocytes. Our earlier results showed the lack of selectivity of 9-phenanthrol, so CBA ((4-chloro-2-(2-chlorophenoxy)acetamido) benzoic acid) was chosen as a new, potentially selective inhibitor. Goal: Our aim was to elucidate the effect and selectivity of CBA in canine left ventricular cardiomyocytes and to study the expression of TRPM4 in the canine heart. Experiments were carried out in enzymatically isolated canine left ventricular cardiomyocytes. Ionic currents were recorded with an action potential (AP) voltage-clamp technique in whole-cell configuration at 37 °C. An amount of 10 mM BAPTA was used in the pipette solution to exclude the potential activation of TRPM4 channels. AP was recorded with conventional sharp microelectrodes. CBA was used in 10 µM concentrations. Expression of TRPM4 protein in the heart was studied by Western blot. TRPM4 protein was expressed in the wall of all four chambers of the canine heart as well as in samples prepared from isolated left ventricular cells. CBA induced an approximately 9% reduction in AP duration measured at 75% and 90% of repolarization and decreased the short-term variability of APD90. Moreover, AP amplitude was increased and the maximal rates of phase 0 and 1 were reduced by the drug. In AP clamp measurements, CBA-sensitive current contained a short, early outward and mainly a long, inward current. Transient outward potassium current (Ito) and late sodium current (INa,L) were reduced by approximately 20% and 47%, respectively, in the presence of CBA, while L-type calcium and inward rectifier potassium currents were not affected. These effects of CBA were largely reversible upon washout. Based on our results, the CBA induced reduction of phase-1 slope and the slight increase of AP amplitude could have been due to the inhibition of Ito. The tendency for AP shortening can be explained by the inhibition of inward currents seen in AP-clamp recordings during the plateau phase. This inward current reduced by CBA is possibly INa,L, therefore, CBA is not entirely selective for TRPM4 channels. As a consequence, similarly to 9-phenanthrol, it cannot be used to test the contribution of TRPM4 channels to cardiac electrophysiology in ventricular cells, or at least caution must be applied.

Prophylaxis of Wound Infections-antibiotics in Renal Donation (POWAR): A UK Multicentre Double Blind Placebo Controlled Randomised Trial.

BACKGROUND: Postoperative infection after hand-assisted laparoscopic donor nephrectomy (HALDN) confers significant morbidity to a healthy patient group. Current UK guidelines cite a lack of evidence for routine antibiotic prophylaxis. This trial assessed if a single preoperative antibiotic dose could reduce post HALDN infections. METHODS: Eligible donors were randomly and blindly allocated to preoperative single-dose intravenous co-amoxiclav or saline. The primary composite endpoint was clinical evidence of any postoperative infection at 30 days, including surgical site infection (SSI), urinary tract infection (UTI), and lower respiratory tract infection (LRTI). FINDINGS: In all, 293 participants underwent HALDN (148 antibiotic arm and 145 placebo arm). Among them, 99% (291/293) completed follow-up. The total infection rate was 40.7% (59/145) in the placebo group and 23% (34 of 148) in the antibiotic group (P = 0.001). Superficial SSIs were 20.7% (30/145 patients) in the placebo group versus 10.1% (15/148 patients) in the antibiotic group (P = 0.012). LRTIs were 9% (13/145) in the placebo group and 3.4% (5/148) in the antibiotic group (P = 0.046). UTIs were 4.1% (6/145) in the placebo group and 3.4% (5/148) in the antibiotic group (P = 0.72).Antibiotic prophylaxis conferred a 17.7% (95% confidence interval 7.2%-28.1%), absolute risk reduction in developing postoperative infection, with 6 donors requiring treatment to prevent 1 infection. INTERPRETATION: Single-dose preoperative antibiotic prophylaxis dramatically reduces post-HALDN infection rates, mainly impacting SSIs and LRTIs.

From Mice to Humans: An Overview of the Potentials and Limitations of Current Transgenic Mouse Models of Major Muscular Dystrophies and Congenital Myopathies.

Muscular dystrophies are a group of more than 160 different human neuromuscular disorders characterized by a progressive deterioration of muscle mass and strength. The causes, symptoms, age of onset, severity, and progression vary depending on the exact time point of diagnosis and the entity. Congenital myopathies are rare muscle diseases mostly present at birth that result from genetic defects. There are no known cures for congenital myopathies; however, recent advances in gene therapy are promising tools in providing treatment. This review gives an overview of the mouse models used to investigate the most common muscular dystrophies and congenital myopathies with emphasis on their potentials and limitations in respect to human applications.