Biglycan Has a Major Role in Maintenance of Mature Tendon Mechanics

Decorin and biglycan are two small leucine-rich proteoglycans (SLRPs) that regulate collagen fibrillogenesis and extracellular matrix assembly in tendon.

The objective of this study was to determine the individual roles of these molecules in maintaining the structural and mechanical properties of tendon during homeostasis in mature mice. We hypothesized that knockdown of decorin in mature tendons would result in detrimental changes to tendon structure and mechanics while knockdown of biglycan would have a minor effect on these parameters.
To achieve this objective, we created tamoxifen-inducible mouse knockdown models targeting decorin or biglycan inactivation. This enables the evaluation of the roles of these SLRPs in mature tendon without the abnormal tendon development caused by conventional knockout models.
Contrary to our hypothesis, knockdown of decorin resulted in minor alterations to tendon structure and no changes to mechanics while knockdown of biglycan resulted in broad changes to tendon structure and mechanics. Specifically, knockdown of biglycan resulted in reduced insertion modulus, maximum stress, dynamic modulus, stress relaxation, and increased collagen fiber realignment during loading.
Knockdown of decorin and biglycan produced similar changes to tendon microstructure by increasing the collagen fibril diameter relative to wild-type controls. Biglycan knockdown also decreased the cell nuclear aspect ratio, indicating a more spindle-like nuclear shape. Overall, the extensive changes to tendon structure and mechanics after knockout of biglycan, but not decorin, provides evidence that biglycan plays a major role in the maintenance of tendon structure and mechanics in mature mice during homeostasis. This article is protected by copyright. All rights reserved.

Whole genome sequencing has the potential to improve treatment for rifampicin-resistant tuberculosis in high burden settings: a retrospective cohort study

Background Treatment of multidrug-resistant or rifampicin-resistant tuberculosis (MDR/RR-TB), although improved in recent years with shorter, more tolerable regimens, remains largely standardised and based on limited drug susceptibility testing (DST). More individualised treatment with expanded DST access is likely to improve patient outcomes.
Methods To assess the potential of TB drug resistance prediction based on whole genome sequencing (WGS) to provide more effective treatment regimens, we applied current South African treatment recommendations to a retrospective cohort of MDR/RR-TB patients from Khayelitsha, Cape Town.
Routine DST and clinical data were used to retrospectively categorise patients into a recommended regimen, either a standardised short regimen or a longer individualised regimen. Potential regimen changes were then described with the addition of WGS-derived DST.
Findings WGS data were available for 1274 MDR/RR-TB patient treatment episodes across 2008-2017. Among 834 patients initially eligible for the shorter regimen, 385 (46%) may have benefited from reduced drug dosage or removing ineffective drugs when WGS data were considered.
A further 187 (22%) may have benefited from more effective adjusted regimens. Among 440 patients initially eligible for a longer individualised regimen, 153 (35%) could have been switched to the short regimen.
Overall, 305 (24%) patients had MDR/RR-TB with second-line TB drug resistance, where the availability of WGS-derived DST would have allowed more effective treatment individualization. 
Interpretation These data suggest considerable benefits could accrue from routine access to WGS-derived resistance prediction. Advances in culture-free sequencing and expansion of the reference resistance mutation catalogue will increase the utility of WGS resistance prediction.
Funding Swiss National Science Foundation, South African National Research Foundation, and Wellcome Trust.

Working in a care home during the COVID-19 pandemic: How has the pandemic changed working practices? A qualitative study

Background: The pandemic has significantly affected care homes’ residents and families through the national visiting restrictions. However, less is known on the impact these changes have had on the care home workforce. The aim of this research was to explore the impact of COVID-19 on the working practices of care home staff, caring for people living with dementia.
Methods: Remote qualitative, semi-structured interviews were conducted with care home staff caring for people living with dementia (PLWD) in the UK.
Results: Participants were recruited to the larger programme of research via convenience sampling. Interviews were conducted via telephone or online platforms. This research employed inductive thematic analysis. Sixteen care home staff were included in this study.
Three overarching themes were developed from the analysis that conveyed changes to the everyday working practices of the care home workforce and the impact such changes posed to staff wellbeing: (1) Practical implications of working in a care home during the COVID-19 pandemic; (2); Staff values and changes to the staff roles (3): Impact to the care home staff and concerns for the care sector.
Conclusions: The COVID-19 pandemic has significantly disrupted the daily working practices of care home staff, with staff forced to adopt additional roles on top of increased workloads to compensate for the loss of external agencies and support. Support and guidance must be offered urgently to inform care home staff on how to best adapt to their new working practices, ensuring that they are adequately trained.
Keywords: COVID-19; Care homes; Care workforce; Nursing homes; Older people; Pandemics; Working practices.

Has EVAR changed the outcomes of ruptured abdominal aortic aneurysms? A decades worth of experience in an Australian Teaching Hospital

Background: Ruptured abdominal aortic aneurysms (rAAA) are associated with significant mortality, and equipoise remains as to whether patients managed with endovascular stent grafts (rEVAR) demonstrate better outcomes when compared to traditional open repair (OR). This study sought to examine the outcomes of patients presenting with rAAA to our institution and assess the perioperative outcomes and outpatient mortality of patients over the past decade.
Methods: A retrospective analysis was conducted. Patients treated for rAAA between 2010 and 2019 were identified from a search of the hospital database for ACHI and ICD-10 codes for repair of AAA. Demographic, operative and post-operative variables were collected from electronic medical records of identified patients.
Results: Eighty patients were identified, 51 of whom presented with a rAAA. The majority of repairs were rEVARs (59%). Median age was 76 years. Median length of admission to ICU was 3 days, and median length of hospital admission was 10 days. Overall in-patient mortality was 26%, with rates of 39% at 3 years and 47% at 5 years. No significant difference in outpatient mortality was found in patients undergoing rEVAR compared to OR, with rates of 61% at 5 years compared to 65% at 5 years, respectively (p = 0.8).
Conclusion: Perioperative outcomes of our cohort of patients undergoing endovascular repair compared to open repair for ruptured and symptomatic AAAs are comparable over the past decade. Given equipoise remains between repair methods, further observational studies are required to quantify benefits of OR and endovascular repairs for ruptured and symptomatic AAAs.
Keywords: EVAR; aneurysm; open AAA repair; rupture.

A Poultry Value Chain Intervention Promoting Diversified Diets Has Limited Impact on Maternal and Child Diet Adequacy During the Lean Season in a Cluster Randomized Controlled Trial

Background: SELEVER is a nutrition- and gender-sensitive poultry value chain project designed and implemented by international NGO Tanager which consists of poultry market facilitation and behavior change activities aiming at increasing poultry production and improving diets without free inputs transfer.
Objectives: The study aimed at assessing the impact of SELEVER on diets of women and children during the lean season.
Methods: Within a cluster-randomized controlled trial, 45 communes were assigned to one of three arms, including 1) SELEVER interventions; 2) SELEVER with an intensive hygiene and sanitation component (SELEVER + WASH); and 3) a control group without intervention. Two rounds of survey were conducted 2 years apart during the lean season. Primary dietary outcomes were the probability of adequacy (PA) of iron, zinc and vitamin A intakes, mean PA (MPA) of 11 micronutrients and individual dietary diversity score collected through quantitative 24-hour recall in longitudinal samples of women and index children (2-4 years old) in 1,054 households; and minimum acceptable diet in the repeated cross-sectional sample of their younger sibling aged 6-23 months. Impacts were assessed by intention-to-treat analysis of covariance.
Results: Relative to control, SELEVER interventions (groups 1 + 2) increased the PA of iron intakes in women by 1.8 pp (P = 0.030). We found no further impact on primary outcomes, although eggs consumption increased in index children (+0.73 pp, P = 0.010; +0.69 kcal/d, P = 0.036). Across the three groups, we observed negative effects of SELEVER on the PA of zinc intakes in women relative to SELEVER + WASH (-4.1 pp, P = 0.038), and on a variety of secondary dietary outcomes relative to both other groups. The study was registered on the ISCRCTN registry (ISRCTN16686478).

HAT Antibody

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HAT Antibody

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HAT Antibody

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Conclusions: information-only-based value-chain interventions may not have meaningful positive effects on diets of women and children in the lean season in settings with largely inadequate diets. We found suggestive evidence that synergies between intervention components may have introduced heterogeneity in effects on diet.
Keywords: behavior change communication; cluster-randomized controlled trial; dietary diversity; micronutrient intake; nutrition-sensitive poultry value chain.

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