Characterization of native interaction of hsp110 with hsp25 and hsc70

AbstractThe 110 kDa heat shock protein (HSP) (hsp110) has been shown to be a diverged subgroup of the hsp70 family and is one of the major HSPs in mammalian cells [1,2]. In examining the native interactions of hsp110, we observed that it is found to reside in a large molecular complex. Immunoblot analysis and co-immunoprecipitation studies identified two other HSPs as components of this complex, hsc70 and hsp25. When examined in vitro, purified hsp25, hsp70 and hsp110 were observed to spontaneously form a large complex and to directly interact with one another. When luciferase was added to this in vitro system, it was observed to migrate into this chaperone complex following heat shock. Examination of two deletion mutants of hsp110 demonstrated that its peptide-binding domain is required for interaction with hsp25, but not with hsc70. The potential function of the hsp110-hsc70-hsp25 complex is discussed

Home Program of Hip Abductor Exercises: Effect on Knee Joint Loading, Strength, Function and Pain in Persons with Knee Osteoarthritis

Background Hip abductor muscle weakness may result in impaired frontal-plane pelvic control during gait, leading to greater medial compartment loading in people with knee osteoarthritis (OA). Objective This study investigated the effect of an 8-week home strengthening program for the hip abductor muscles on knee joint loading (measured by the external knee adduction moment during gait), strength (force-generating capacity), and function and pain in individuals with medial knee OA. Design The study design was a nonequivalent, pretest-posttest, control group design. Setting Testing was conducted in a motor performance laboratory. Patients An a priori sample size calculation was performed. Forty participants with knee OA were matched for age and sex with a control group of participants without knee OA. Intervention Participants with knee OA completed a home hip abductor strengthening program. Measurements Three-dimensional gait analysis was performed to obtain peak knee adduction moments in the first 50% of the stance phase. Isokinetic concentric strength of the hip abductor muscles was measured using an isokinetic dynamometer. The Five-Times-Sit-to-Stand Test was used to evaluate functional performance. Knee pain was assessed with the Western Ontario and McMaster Universities Osteoarthritis Index questionnaire. Results Following the intervention, the OA group demonstrated significant improvement in hip abductor strength, but not in the knee adduction moment. Functional performance on the sit-to-stand test improved in the OA group compared with the control group. The OA group reported decreased knee pain after the intervention. Limitations Gait strategies that may have affected the knee adduction moment, including lateral trunk lean, were not evaluated in this study. Conclusions Hip abductor strengthening did not reduce knee joint loading but did improve function and reduce pain in a group with medial knee OA

Do psychological factors predict caesarean delivery in Australia? A cohort study

Background: The proportion of babies delivered by Cesarean Section (CS) in Australia has almost doubled over the last 25 years. Factors known to contribute to CS such as higher maternal age, mothers being overweight or obese, or having had a previous CS do not completely account for the increased rate and it is clear that other influences exist. Our study used nationally-representative data from the Longitudinal Study of Australian Children (LSAC) to identify risk factors associated with CS, with a view to identifying previously unidentified influences. Methods: Data were from the birth cohort of LSAC, a long-term prospective study of approximately 5,000 children that includes richly-detailed data regarding maternal health and exposures during pregnancy. Logistic regression was used to examine the contribution of a wide range of pregnancy, birth and social factors to CS. Results: 28% of 4,862 mothers were delivered by CS. The nal adjusted analyses revealed that use of diabetes medication (OR=3.1, 95% CI=1.7-5.5, p<0.001) and maternal mental health problems during pregnancy (OR=1.3, CI=1.1-1.6, p=0.003) were associated with increased odds of CS. Young maternal age (OR=0.6, CI=0.5-0.7, p<0.001), having two or more children (OR=0.7, CI=0.6-0.9, p<0.001), and fathers having an unskilled occupation (OR=0.7, CI=0.6-1.0, p=0.036) were associated with reduced odds of CS. Conclusion: Our findings raise the prospect that screening and intervention programs for maternal mental health problems, and attention to diabetic control in pregnancy, might be beneficial in reducing CS rates and should be studied in appropriately-constructed prospective trials.This work was supported by a project grant from the Bupa Health Foundation. The paper uses unit record data from Growing Up in Australia, the Longitudinal Study of Australian Children (LSAC). The LSAC study is conducted in partnership between the Australian Government Department of Social Services (DSS, formerly the department of Families, Housing, Community Services and Indigenous Affairs), the Australian Institute of Family Studies (AIFS) and the Australian Bureau of Statistics (ABS

Africa faces difficult choices in responding to COVID-19.

Coronavirus disease 2019 (COVID-19) is now established in Africa, with more than 63 000 cases and 2200 deaths in 53 countries, as of May 11, 2020.1 Fragile health systems leave African countries vulnerable to the anticipated surge in severely ill patients with COVID-19, despite much younger populations

Exploring How We Teach: Lived Experiences, Lessons, and Research about Graduate Instructors by Graduate Instructors

This book combines the knowledge of 30 graduate student instructors sharing about how they teach and how they’ve learned how to teach

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Identification of field caught Anopheles gambiae s.s. and Anopheles arabiensis by TaqMan single nucleotide polymorphism genotyping

BACKGROUND: Identification of Anopheles gambiae s.s. and Anopheles arabiensis from field-collected Anopheles gambiae s.l. is often necessary in basic and applied research, and in operational control programmes. The currently accepted method involves use of standard polymerase chain reaction amplification of ribosomal DNA (rDNA) from the 3' 28S to 5' intergenic spacer region of the genome, and visual confirmation of amplicons of predicted size on agarose gels, after electrophoresis. This report describes development and evaluation of an automated, quantitative PCR method based upon TaqMan™ single nucleotide polymorphism (SNP) genotyping. METHODS: Standard PCR, and TaqMan SNP genotyping with newly designed primers and fluorophore-labeled probes hybridizing to sequences of complementary rDNA specific for either An. gambiae s.s. or An. arabiensis, were conducted in three experiments involving field-collected An. gambiae s.l. from western Kenya, and defined laboratory strains. DNA extraction was from a single leg, sonicated for five minutes in buffer in wells of 96-well PCR plates. RESULTS: TaqMan SNP genotyping showed a reaction success rate, sensitivity, and species specificity comparable to that of standard PCR. In an extensive field study, only 29 of 3,041 (0.95%) were determined to be hybrids by TaqMan (i.e., having rDNA sequences from both species), however, all but one were An. arabiensis by standard PCR, suggesting an acceptably low (ca. 1%) error rate for TaqMan genotyping in mistakenly identifying species hybrids. CONCLUSION: TaqMan SNP genotyping proved to be a sensitive and rapid method for identification of An. gambiae s.l. and An. arabiensis, with a high success rate, specific results, and congruence with the standard PCR method

Cardiac disease in patients with mucopolysaccharidosis: presentation, diagnosis and management

The mucopolysaccharidoses (MPSs) are inherited lysosomal storage disorders caused by the absence of functional enzymes that contribute to the degradation of glycosaminoglycans (GAGs). The progressive systemic deposition of GAGs results in multi-organ system dysfunction that varies with the particular GAG deposited and the specific enzyme mutation(s) present. Cardiac involvement has been reported in all MPS syndromes and is a common and early feature, particularly for those with MPS I, II, and VI. Cardiac valve thickening, dysfunction (more severe for left-sided than for right-sided valves), and hypertrophy are commonly present; conduction abnormalities, coronary artery and other vascular involvement may also occur. Cardiac disease emerges silently and contributes significantly to early mortality