Isometric versus isotonic exercise for greater trochanteric pain syndrome: a randomised controlled pilot study

Objectives: Greater trochanteric pain syndrome (GTPS) is a common cause of lateral hip pain. Limited evidence exists for the effectiveness of exercise for GTPS. This study aimed to compare the effectiveness of isometric and isotonic exercise for individuals with GTPS. Methods: This randomised controlled pilot trial recruited 30 participants with GTPS. Both programmes consisted of daily, progressive home exercise for 12 weeks with 8 individual physiotherapy sessions over the trial period. The primary outcome measure was the Victorian Institute of Sport Assessment-Gluteal (VISA-G) and secondary outcome measures included the Numeric Pain Rating Scale (0–10) and an 11-point Global Rating of Change Scale. Outcome measures were assessed at baseline, 4 and 12 weeks. Results: Twenty-three participants completed the trial. After 12 weeks, mean VISA-G scores improved in both groups; 55–65 in the isometric group and 62–72 in the isotonic group. 55% of the isometric group and 58% of the isotonic group achieved a reduction in pain of at least 2 points (minimally clinically important difference (MCID)) on the Numeric Pain Rating Scale. 64% of the isometric group and 75% of the isotonic group had improved by at least 2 points (MCID) on the Global Rating of Change Scale. Conclusion: Isometric and isotonic exercise programmes appear to be effective for individuals with GTPS and should be considered in the loading management of patients with this condition

Effectiveness of isometric exercise in the management of tendinopathy: a systematic review and meta-analysis of randomised trials

Objective: To systematically review and critically appraise the literature on the effectiveness of isometric exercise in comparison with other treatment strategies or no treatment in tendinopathy. Design: A systematic review and meta-analysis of randomised controlled trials. Data sources: Electronic searches of Medline, Cumulative Index to Nursing and Allied Health Literature, EMBASE and Cochrane were undertaken from inception to May 2020. Methods: Overall quality of each study was determined based on a combined assessment of internal validity, external validity and precision. For each outcome measure, level of evidence was rated based on the system by van Tulder et al. Results: Ten studies were identified and included in the review, including participants with patellar (n=4), rotator cuff (n=2), lateral elbow (n=2), Achilles (n=1) and gluteal (n=1) tendinopathies. Three were of good and seven were of poor overall quality. Based on limited evidence (level 3), isometric exercise was not superior to isotonic exercise for chronic tendinopathy either immediately following treatment or in the short term (≤12 weeks) for any of the investigated outcome measures. Additionally, for acute rotator cuff tendinopathy, isometric exercise appears to be no more effective than ice therapy in the short term (limited evidence; level 3). Summary: Isometric exercise does not appear to be superior to isotonic exercise in the management of chronic tendinopathy. The response to isometric exercise is variable both within and across tendinopathy populations. Isometric exercise can be used as part of a progressive loading programme as it may be beneficial for selected individuals

Evaluation of the utilization of the preanaesthetic clinics in a University teaching hospital

BACKGROUND: Dedicated out-patient preanaesthetic clinics are relatively recent phenomenon and information is sparse from developing world. This study attempted to evaluate the utilization of adult and paediatric preanaesthetic clinics and its impact on the cancellations of surgery in Trinidad. METHODS: All patients scheduled to have elective surgery during the period of twelve weeks were enrolled for prospective collection of data including demographics, the admitting diagnoses, surgical procedure, category of surgery and specialty, and the patients' attendance to preanaesthetic clinics. Cancellations on the day of surgery along with reasons were recorded. The difference between patients who attended and did not attend the clinic was analysed. RESULTS: Of 424 patients scheduled for procedures during the study period, 213 were adults and 211 were children. Overall 39% of adults and 46% of the children scheduled for surgery had previously attended the preanaesthetic clinic. Among adults, general surgery patients were the largest majority to attend the preanaesthetic clinic. The paediatric preanaesthetic clinic was mostly utilized by paediatric general surgery. Overall 30% of procedures in adults and 26% of those in children were cancelled. There was a statistically significant difference in cancellations between patients who attended and did not attend the preanaesthetic clinic (p = 0.004). There was a 52% more chance of the procedure getting cancelled if the patient did not attend the clinic. CONCLUSION: The study highlights the inadequate use of the preanaesthetic clinics and the impact of the clinics on last-minute cancellations

Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity

The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management. © 2021, The Author(s)

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Identification of Genomic Regions Associated with Phenotypic Variation between Dog Breeds using Selection Mapping

Peer reviewe

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

Diversity and function of the lipooligosaccharide biosynthesis genes from Campylobacter jejuni

The enteric pathogen, Campylobacter jejuni, produces a range of LOS structures, however, the precise functions of LOS molecules in infection are largely undetermined. LOS structural diversity is known to arise from variation in LOS biosynthesis gene content and gene sequence. In determining the extent of LOS biosynthesis gene content variation in a group of mainly clinical C. jejuni isolates, in this study two new clusters of LOS biosynthesis genes have been identified. The C. jejuni LOS core can also undergo phase variation due to the presence of GC homopolymeric tracts in the protein coding sequence of biosynthesis genes in the cluster. Therefore, the variation in homopolymeric tract length was investigated in five genes including those in the LOS biosynthesis cluster. Many bacteria are known to vary LPS or LOS structure in response to different environment stimuli. Following the identification of a number of promoters in the LOS core biosynthesis cluster, promoter activity was measured following growth under several different conditions. Although promoter expression did not vary extensively with the different environmental stimuli, less LOS was extracted from cell grown under iron-limitation. The other aim of this work was to investigate LOS biosynthesis gene function. The genes waaF and lpxL are involved in core and lipid A biosynthesis respectively. Mutation of both genes had a substantial effect on LOS core structure and preliminary studies indicate both genes are important for adhesion and invasion of human intestinal cells. The deletion of several genes from the general protein glycosylation pathway also led to the truncation of the LOS core, indicating overlap between the two carbohydrate biosynthesis pathways

Characterization of the Campylobacter jejuni Heptosyltransferase II Gene, waaF, Provides Genetic Evidence that Extracellular Polysaccharide Is Lipid A Core Independent

Campylobacter jejuni produces both lipooligosaccharide (LOS) and a higher-molecular-weight polysaccharide that is believed to form a capsule. The role of these surface polysaccharides in C. jejuni-mediated enteric disease is unclear; however, epitopes associated with the LOS are linked to the development of neurological complications. In Escherichia coli and Salmonella enterica serovar Typhimurium the waaF gene encodes a heptosyltransferase, which catalyzes the transfer of the second l-glycero-d-manno-heptose residue to the core oligosaccharide moiety of lipopolysaccharide (LPS), and mutation of waaF results in a truncated core oligosaccharide. In this report we confirm experimentally that C. jejuni gene Cj1148 encodes the heptosyltransferase II enzyme, WaaF. The Campylobacter waaF gene complements an S. enterica serovar Typhimurium waaF mutation and restores the ability to produce full-sized lipopolysaccharide. To examine the role of WaaF in C. jejuni, waaF mutants were constructed in strains NCTC 11168 and NCTC 11828. Loss of heptosyltransferase activity resulted in the production of a truncated core oligosaccharide, failure to bind specific ligands, and loss of serum reactive GM(1), asialo-GM(1), and GM(2) ganglioside epitopes. The mutation of waaF did not affect the higher-molecular-weight polysaccharide supporting the production of a LOS-independent capsular polysaccharide by C. jejuni. The exact structural basis for the truncation of the core oligosaccharide was verified by comparative chemical analysis. The NCTC 11168 core oligosaccharide differs from that known for HS:2 strain CCUG 10936 in possessing an extra terminal disaccharide of galactose-β(1,3) N-acetylgalactosamine. In comparison, the waaF mutant possessed a truncated molecule consistent with that observed with waaF mutants in other bacterial species