Durability of Sutures Used in Partial Nephrectomy: Tested Across Commonly Used Diameters and Materials Stopped with LAPRA-TY® Suture Clips and Hem-o-Lok® Ligation Systems under a Given Tension

The primary healing of soft tissue incision advances in the first fourteen days after surgery. Sutures used to close the incision are terminated with knots to last over this period under tension inside the tissue. However, knots significantly reduce the tensile strength of the sutures, and make the surgery closing time longer and tedious. Suture clips are used to overcome these limitations. It was found in prior researches that sutures slip out of the suture clips, although the manufacturer of the LAPRA-TY® suture clips claims endurance of this product under tension for at least fourteen days. Use of suture clips and ligation systems together to terminate sutures was found to endure more tension than using only knot or only clip. This calls for an investigation on the durability of different types and sizes of sutures stopped with suture clips and ligation systems under a tension used to control bleeding and urine leakage following partial nephrectomy. This research examined the tension durability of synthetic absorbable sutures (smooth and barbed) commonly used in partial nephrectomy, for four weeks under four Newton tension, when stopped with surgeon placed LAPRA-TY® suture clip and Hem-o-Lok® ligation system. The suture samples were prepared with knots and a Hem-o-Lok® at one end, and a Hem-o-Lok® and a LAPRA-TY® at the other end. They were hung vertically (with LAPRA-TY® at the top) in a simulated in vitro environment. Slippage from LAPRA-TY® and Hem-o-Lok® combination at the top was found to be the major mode of failure. Vicryl 0 and Vicryl 2-0 had 100% survival rate over fourteen days, followed by Vicryl 3-0 which had 50% failure before seven days. Vicryl 4-0 and Vicryl 5-0 failed 100% before fourteen days, though manufacturer’s recommendation for the use of LAPRA-TY® includes Vicryl 4-0. Use of more than one LAPRA-TY® or more than one Hem-o-Lok®, tissue closure and suture performance under other tension levels, and durability of other types and sizes of sutures in the same set-up are necessary to be explored

PLATERÍA EN LA COLONIA: LA HISTORIA DE DOS ATRILES

Este texto presenta el estudio de dos piezas de platería neogranadina, cuya realización está datada en la segunda mitad del siglo XVII, en un contexto social multifacético influenciado por manos españolas e indígenas. Se expone cómo el análisis de estos artefactos, desde el punto de vista del diseño industrial, permite ver aspectos que otras disciplinas estudian superficialmente, como la forma y la función de un objeto. El objetivo es entender el contexto histórico de una sociedad a través del uso de sus objetos, su simbología y las dinámicas de su manufactura. Esta investigación se desarrolló en alianza con el Museo Colonial de Bogotá, el cual posibilitó el acceso directo a la pareja de atriles, lo que permitió la verificación de huellas técnicas para establecer su proceso de elaboración; a pesar de la falta de marcajes coloniales reglamentarios en las piezas, se pudo indagar sobre el contexto histórico de la Nueva Granada y las técnicas plateras que se aplicaron en estos artefactos, tanto en las fuentes secundarias de investigadores expertos en el tema, como en la contrastación con la información técnica directa suministrada por un maestro de platería actual. Se concluye que el papel de los plateros en la Nueva Granada era de vital importancia para los propósitos que tenía la Corona española de expandir la religión católica por todo el Imperio, pues por medio de la realización de objetos de culto en metales preciosos, se lograba representar la devoción y a su vez capturar la atención de los feligreses, debido al alto nivel de detalle decorativo influenciado por el movimiento Barroco

STIM1 signalling controls store-operated calcium entry required for development and contractile function in skeletal muscle

It is now well established that stromal interaction molecule 1 (STIM1) is the calcium sensor of endoplasmic reticulum (ER) stores required to activate store-operated calcium entry (SOC) channels at the surface of non-excitable cells. Yet little is known about STIM1 in excitable cells such as striated muscle where the complement of calcium regulatory molecules is rather disparate from that of non-excitable cells. Here, we show that STIM1 is expressed in both myotubes and adult skeletal muscle. Myotubes lacking functional STIM1 fail to exhibit SOC and fatigue rapidly. Moreover, mice lacking functional STIM1 die perinatally from a skeletal myopathy. In addition, STIM1 haploinsufficiency confers a contractile defect only under conditions where rapid refilling of stores would be needed. These findings provide novel insight to the role of STIM1 in skeletal muscle and suggest that STIM1 has a universal role as an ER/SR calcium sensor in both excitable and non-excitable cells

Enhancing Mobility and Exploration in Young Children with Motor Delays

PURPOSE: Young children with severe motor, cognitive, and communication deficits are often dismissed as either too young or too physically involved to use the common power mobility options such as power wheelchair, ride-on-toys for lack of external support necessary to ensure safety and effective access to motion initiators (joystick or switch). Given that self-initiated locomotion is critical in the development of you children’s perceptual and social skills, the Play & Mobility Device affords an opportunity for them to safely explore power mobility while providing sufficient external support to optimize a child’s safety, posture and access to motion initiators. PROCEDURES: The Play & Mobility Device was designed and built following medical device design procedure, which takes customer’s requirements (sponsor’s in our case) as inputs, develops the design and then the device using engineering know-how and skills, and finally validates the performance of the device through test runs by the customer. Safety, power mobility, maneuverability and control components constitute this device. Small size and maneuverability of the device, allows its transportation and storage without any special requirement. OUTCOME: A child can drive and control the device through the joystick or switch as interface. Parent or attendant of the child can set the speed of the device and override child’s control as safe. Because of the use of FDA licensed, crush tested car seat with 5-point harness system, the child’s posture remains secured. Use of a universal arm to hold the joystick or switch ensures any child’s convenient access to these motion initiators. IMPACT: Building the Play & Mobility Device utilized the involved students’ electromechanical and biomedical design know-how. The process got them through the regulator’s manufacturing guidelines, licensing and patenting procedures. Engineering discipline enriched its footprints with the contribution of a performing device to the real field of pediatric physiotherapy

The Case for Using a Behavior Change Model to Design Interventions to Promote Respectful Maternal Care.

Applying a behavior change framework to guide the design of interventions to improve respectful maternity care (RMC) could accelerate and unify the implementation and evaluation of diverse RMC interventions

Resistance to diet-induced obesity and associated metabolic perturbations in haploinsufficient monocarboxylate transporter 1 mice

The monocarboxylate transporter 1 (MCT1 or SLC16A1) is a carrier of short-chain fatty acids, ketone bodies, and lactate in several tissues. Genetically modified C57BL/6J mice were produced by targeted disruption of the mct1 gene in order to understand the role of this transporter in energy homeostasis. Null mutation was embryonically lethal, but MCT1 (+/-) mice developed normally. However, when fed high fat diet (HFD), MCT1 (+/-) mice displayed resistance to development of diet-induced obesity (24.8% lower body weight after 16 weeks of HFD), as well as less insulin resistance and no hepatic steatosis as compared to littermate MCT1 (+/+) mice used as controls. Body composition analysis revealed that reduced weight gain in MCT1 (+/-) mice was due to decreased fat accumulation (50.0% less after 9 months of HFD) notably in liver and white adipose tissue. This phenotype was associated with reduced food intake under HFD (12.3% less over 10 weeks) and decreased intestinal energy absorption (9.6% higher stool energy content). Indirect calorimetry measurements showed ∼ 15% increase in O2 consumption and CO2 production during the resting phase, without any changes in physical activity. Determination of plasma concentrations for various metabolites and hormones did not reveal significant changes in lactate and ketone bodies levels between the two genotypes, but both insulin and leptin levels, which were elevated in MCT1 (+/+) mice when fed HFD, were reduced in MCT1 (+/-) mice under HFD. Interestingly, the enhancement in expression of several genes involved in lipid metabolism in the liver of MCT1 (+/+) mice under high fat diet was prevented in the liver of MCT1 (+/-) mice under the same diet, thus likely contributing to the observed phenotype. These findings uncover the critical role of MCT1 in the regulation of energy balance when animals are exposed to an obesogenic diet

Safety and efficacy of ganaxolone in patients with CDKL5 deficiency disorder: results from the double-blind phase of a randomised, placebo-controlled, phase 3 trial

Background CDKL5 deficiency disorder (CDD) is a rare, X-linked, developmental and epileptic encephalopa thy characterised by severe global developmental impairment and seizures that can begin in the first few months after birth and are often treatment refractory. Ganaxolone, an investigational neuroactive steroid, reduced seizure frequency in an open-label, phase 2 trial that included patients with CDD. We aimed to further assess the efficacy and safety of ganaxolone in patients with CDD-associated refractory epilepsy.Methods In the double-blind phase of this randomised, placebo-controlled, phase 3 trial, done at 39 outpatient clinics in eight countries (Australia, France, Israel, Italy, Poland, Russia, the UK, and the USA), patients were eligible if they were aged 2-21 years with a pathogenic or probably pathogenic CDKL5 variant and at least 16 major motor seizures (defined as bilateral tonic, generalised tonic-clonic, bilateral clonic, atonic, or focal to bilateral tonic-clonic) per 28 days in each 4-week period of an 8-week historical period. After a 6-week prospective baseline period, patients were randomly assigned (1:1) via an interactive web response system to receive either enteral adjunctive ganaxolone or matching enteral adjunctive placebo (maximum dose 63 mg/kg per day for patients weighing <= 28 kg or 1800 mg/day for patients weighing >28 kg) for 17 weeks. Patients, caregivers, investigators (including those analysing data), trial staff, and the sponsor (other than the investigational product manager) were masked to treatment allocation. The primary efficacy endpoint was percentage change in median 28-day major motor seizure frequency from the baseline period to the 17-week double-blind phase and was analysed (using a Wilcoxon-rank sum test) in all patients who received at least one dose of trial treatment and for whom baseline data were available. Safety (compared descriptively across groups) was analysed in all patients who received at least one dose of trial treatment. This study is registered with ClinicalTrials.gov, NCT03572933, and the open-label extension phase is ongoing.Findings Between June 25, 2018, and July 2, 2020, 114 patients were screened for eligibility, of whom 101 (median age 6 years [IQR 3 to 101) were randomly assigned to receive either ganaxolone (n=50) or placebo (n=51). All patients received at least one dose of a study drug, but seizure frequency for one patient in the ganaxolone group was not recorded at baseline and so the primary endpoint was analysed in a population of 100 patients. There was a median percentage change in 28-day major motor seizure frequency of -30.7% (IQR -49.5 to -1.9) in the ganaxolone group and of -6.9% (-24.1 to 39.7) in the placebo group (p=0.0036). The Hodges-Lehmann estimate of median difference in responses to ganaxolone versus placebo was -27.1% (95% CI -47.9 to - 9.6). Treatment-emergent adverse events occurred in 43 (86%) of 50 patients in the ganaxolone group and in 45 (88%) of 51 patients in the placebo group. Somnolence, pyrexia, and upper respiratory tract infections occurred in at least 10% of patients in the ganaxolone group and more frequently than in the placebo group. Serious adverse events occurred in six (12%) patients in the ganaxolone group and in five (10%) patients in the placebo group. Two (4%) patients in the ganaxolone group and four (8%) patients in the placebo group discontinued the trial. There were no deaths in the double-blind phase.Interpretation Ganaxolone significantly reduced the frequency of CDD-associated seizures compared with placebo and was generally well tolerated. Results from what is, to our knowledge, the first controlled trial in CDD suggest a potential treatment benefit for ganaxolone. Long-term treatment is being assessed in the ongoing open-label extension phase of this trial. Copyright (C) 2022 Published by Elsevier Ltd. All rights reserved

Genetic variants are major determinants of CSF antibody levels in multiple sclerosis

Immunological hallmarks of multiple sclerosis include the production of antibodies in the central nervous system, expressed as presence of oligoclonal bands and/or an increased immunoglobulin G index-the level of immunoglobulin G in the cerebrospinal fluid compared to serum. However, the underlying differences between oligoclonal band-positive and -negative patients with multiple sclerosis and reasons for variability in immunoglobulin G index are not known. To identify genetic factors influencing the variation in the antibody levels in the cerebrospinal fluid in multiple sclerosis, we have performed a genome-wide association screen in patients collected from nine countries for two traits, presence or absence of oligoclonal bands (n = 3026) and immunoglobulin G index levels (n = 938), followed by a replication in 3891 additional patients. We replicate previously suggested association signals for oligoclonal band status in the major histocompatibility complex region for the rs9271640*A-rs6457617*G haplotype, correlated with HLA-DRB1*1501, and rs34083746*G, correlated with HLA-DQA1*0301 (P comparing two haplotypes = 8.88 × 10(-16)). Furthermore, we identify a novel association signal of rs9807334, near the ELAC1/SMAD4 genes, for oligoclonal band status (P = 8.45 × 10(-7)). The previously reported association of the immunoglobulin heavy chain locus with immunoglobulin G index reaches strong evidence for association in this data set (P = 3.79 × 10(-37)). We identify two novel associations in the major histocompatibility complex region with immunoglobulin G index: the rs9271640*A-rs6457617*G haplotype (P = 1.59 × 10(-22)), shared with oligoclonal band status, and an additional independent effect of rs6457617*G (P = 3.68 × 10(-6)). Variants identified in this study account for up to 2-fold differences in the odds of being oligoclonal band positive and 7.75% of the variation in immunoglobulin G index. Both traits are associated with clinical features of disease such as female gender, age at onset and severity. This is the largest study population so far investigated for the genetic influence on antibody levels in the cerebrospinal fluid in multiple sclerosis, including 6950 patients. We confirm that genetic factors underlie these antibody levels and identify both the major histocompatibility complex and immunoglobulin heavy chain region as major determinants.status: publishe

NR1H3 p.Arg415Gln Is Not Associated to Multiple Sclerosis Risk

A recent study by Wang et al. (2016a) claims that the low-frequency variant NR1H3 p.Arg415Gln is sufficient to cause multiple sclerosis in certain individuals and determines a patient's likelihood of primary progressive disease. We sought to replicate this finding in the International MS Genetics Consortium (IMSGC) patient collection, which is 13-fold larger than the collection of Wang et al. (2016a), but we find no evidence that this variant is associated with either MS or disease subtype. Wang et al. (2016a) also report a common variant association in the region, which we show captures the association the IMSGC reported in 2013. Therefore, we conclude that the reported low-frequency association is a false positive, likely generated by insufficient sample size. The claim of NR1H3 mutations describing a Mendelian form of MS-of which no examples exist-can therefore not be substantiated by data. This Matters Arising paper is in response to Wang et al. (2016a), published in Neuron. See also the related Matters Arising paper by Minikel and MacArthur (2016) and the response by Wang et al. (2016b), published in this issue