Time Course Change of Muscle Thickness of the Tibialis Anterior Following Blood Flow Restricted Training

Traditional resistance training programs recommend training loads of at least 60% 1-repetition maximum (1RM) to stimulate muscle hypertrophy within 3 weeks. Low-load blood flow restricted (BFR) resistance training (RT) has implications in rehabilitation since this modality has shown comparable muscle hypertrophy to high-load RT at intensities as low as 30% 1RM. However, the recommended effects of BFR on muscle size in various musculature throughout an intervention has not been thoroughly examined. PURPOSE: Therefore, the purpose of this investigation is to measure temporal changes in muscle thickness (MT) on the tibialis anterior (TA) throughout 4 weeks of BFR training. METHODS: Thirteen untrained participants were randomized into two groups: (BFR; n=8) (177.6 ± 4.1 cm, 84.8 ± 15.1 kg, 21.3 ± 1 years) or control non-BFR (n=5) (172.6 ± 8.2 cm, 76.7 ± 11.1 kg, 23.4 ± 2.7 years) who were matched for training sessions, sets, and reps. During the 4-week period (8 sessions), participants underwent twice-weekly sessions of unilateral isokinetic dorsiflexion training at 30% of their daily peak torque at a velocity of 60°/s with or without BFR. Ultrasound-derived measures of muscle thickness were captured at one-third the distance from the fibular head to the medial malleolus prior to the pre- and post-intervention testing sessions. Two separate linear regression analyses were used to examine group slope differences in MT across all training sessions. RESULTS: Linear regression analyses indicated that the control (i.e., non-BFR) exhibited a significant, positive (b = 0.023, SE = 0.01, r2=0.626, p=0.006) increase in MT from pre- to post testing. However, there was no significant change (b=0.021, SE = 0.01, r2=0.324, p=0.086) in MT across Time for the BFR group. CONCLUSION: Low-load RT without BFR induces temporal changes in muscle size following a short 4-week intervention. This exemplifies the efficacy of low-load training in inducing detectible changes in muscle thickness of the TA, and does not indicate BFR has an additive effect on temporal changes in muscle size of novice males following a 4-week intervention

Elevated CO2 did not stimulate stem growth in 11 provenances of a globally important hardwood plantation species

Elevated atmospheric carbon dioxide (eCO2) often enhances rates of photosynthesis leading to increased productivity in trees. In their native habitats in Australia, eucalypts display considerable phenotypic plasticity in response to changes in environmental conditions. Little is known whether this plasticity can be harnessed effectively under future atmospheric eCO2 conditions and be used to identify provenances with superior growth. Here, we report two experiments that assessed the physiological and growth responses of Eucalyptus grandis—one of the world's most important hardwood plantation species—to eCO2. We used 11 provenances from contrasting climates. Our selection was based on site-specific information of long-term temperature and water availability. In Experiment 1, four provenances exhibited significant variation in light-saturated photosynthetic rates (Asat), stomatal conductance (gs), and concentrations of non-structural carbohydrates in leaves, stems and roots when grown under ambient CO2 (aCO2). Biomass of leaves, stems and roots varied significantly and were negatively correlated with mean annual temperature (MAT) at seed origin, indicating that provenances from cooler, wetter climates generally produced greater biomass. Yet, stem growth of these provenances was not stimulated by eCO2. Given the vast environmental gradient covered by provenances of E. grandis, we expanded the selection from four to nine provenances in Experiment 2. This allowed us to validate results from Experiment 1 with its small selection and detailed measurements of various physiological parameters by focusing on growth responses to eCO2 across a wider environmental gradient in Experiment 2. In Experiment 2, nine provenances also exhibited intraspecific differences in growth, but these were not related to climate of origin, and eCO2 had little effect on growth traits. Growth responses under eCO2 varied widely across provenances in both experiments, confirming phenotypic plasticity in E. grandis, though responses were not systematically correlated with climate of origin. These results indicate that selection of provenances for improved stem growth of E. grandis under future eCO2 cannot be based solely on climate of origin, as is common practice for other planted tree species

High-Content Flow Cytometry and Temporal Data Analysis for Defining a Cellular Signature of Graft-Versus-Host Disease

AbstractAcute graft-versus-host disease (GVHD) is diagnosed by clinical and histologic criteria that are often nonspecific and typically apparent only after the disease is well established. Because GvHD is mediated by donor T cells and other immune effector cells, we sought to determine whether changes within a wide array of peripheral blood lymphocyte populations could predict the development of GvHD. Peripheral blood samples from 31 patients undergoing allogeneic blood and marrow transplant were analyzed for the proportion of 121 different subpopulations defined by 4-color combinations of lymphocyte phenotypic and activation markers at progressive time points posttransplant. Samples were processed using a newly developed high content flow cytometry technique and subjected to a spline- and functional linear discriminant analysis (FLDA)-based temporal analysis technique. This strategy identified a consistent posttransplant increase in the proportion and extent of fluctuation of CD3+CD4+CD8β+ cells in patients who developed GVHD compared to those that did not. Although larger prospective clinical studies will be necessary to validate these results, this study demonstrates that high-content flow cytometry coupled with temporal analysis is a powerful approach for developing new diagnostic tools, and may be useful for developing a sensitive and specific predictive test for GVHD

Psychometric characteristics of the Brunel Mood Scale in a Singaporean context

Mood profiling serves several functions in the sporting domain, including monitoring of athlete mindset, early problem identification, performance prediction, and screening for pathogenic behaviours. The 24-item Brunel Mood Scale (BRUMS; Terry, Lane, Lane, & Keohane, 1999) is yet to be validated or researched extensively in a Singaporean context, and hence the current investigation provided a cross-cultural re-validation of the BRUMS. The six-factor measurement model was tested on a sample of 1,444 English-speaking Singaporean participants (age range = 18– 56+ yr., median = 22–25 yr.; male = 991, female = 440, unspecified = 13), including 954 involved in sport and 490 non-sport participants. In addition, a subgroup of 243 participants completed the BRUMS and concurrent measures of affect and psychological distress. A subgroup of 141 participants completed the BRUMS on two occasions to assess test-retest reliability. Structural equation modelling showed a good fit of the data to the measurement model (CFI = .937, TLI = .927, RMSEA = .062). Multi-sample modelling (sport vs non-sport, ≤ 25 yr. vs 26+ yr.) further supported the factorial validity of the measure. Relationships between BRUMS subscales and concurrent measures were consistent with theoretical predictions. Internal consistency and test-retest reliability coefficients were acceptable. Findings supported the psychometric integrity of the BRUMS for use in a Singaporean context, providing opportunities for further investigation of the antecedents, correlates and behavioural consequences of mood responses among Singaporean sport and non-sport participants

Microbial composition analyses by 16S rRNA sequencing: A proof of concept approach to provenance determination of archaeological ochre

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Many archaeological science studies use the concept of “provenance”, where the origins of cultural material can be determined through physical or chemical properties that relate back to the origins of the material. Recent studies using DNA profiling of bacteria have been used for the forensic determination of soils, towards determination of geographic origin. This manuscript presents a novel approach to the provenance of archaeological minerals and related materials through the use of 16S rRNA sequencing analysis of microbial DNA. Through the microbial DNA characterization from ochre and multivariate statistics, we have demonstrated the clear discrimination between four distinct Australian cultural ochre sites

Care team and practice-level implementation strategies to optimize pediatric collaborative care: Study protocol for a cluster-randomized hybrid type III trial

BACKGROUND: Implementation facilitation is an effective strategy to support the implementation of evidence-based practices (EBPs), but our understanding of multilevel strategies and the mechanisms of change within the black box of implementation facilitation is limited. This implementation trial seeks to disentangle and evaluate the effects of facilitation strategies that separately target the care team and leadership levels on implementation of a collaborative care model in pediatric primary care. Strategies targeting the provider care team (TEAM) should engage team-level mechanisms, and strategies targeting leaders (LEAD) should engage organizational mechanisms. METHODS: We will conduct a hybrid type 3 effectiveness-implementation trial in a 2 × 2 factorial design to evaluate the main and interactive effects of TEAM and LEAD and test for mediation and moderation of effects. Twenty-four pediatric primary care practices will receive standard REP training to implement Doctor-Office Collaborative Care (DOCC) and then be randomized to (1) Standard REP only, (2) TEAM, (3) LEAD, or (4) TEAM + LEAD. Implementation outcomes are DOCC service delivery and change in practice-level care management competencies. Clinical outcomes are child symptom severity and quality of life. DISCUSSION: This statewide trial is one of the first to test the unique and synergistic effects of implementation strategies targeting care teams and practice leadership. It will advance our knowledge of effective care team and practice-level implementation strategies and mechanisms of change. Findings will support efforts to improve common child behavioral health conditions by optimizing scale-up and sustainment of CCMs in a pediatric patient-centered medical home. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04946253 . Registered June 30, 2021

Substrate Type Determines Metagenomic Profiles from Diverse Chemical Habitats

Environmental parameters drive phenotypic and genotypic frequency variations in microbial communities and thus control the extent and structure of microbial diversity. We tested the extent to which microbial community composition changes are controlled by shifting physiochemical properties within a hypersaline lagoon. We sequenced four sediment metagenomes from the Coorong, South Australia from samples which varied in salinity by 99 Practical Salinity Units (PSU), an order of magnitude in ammonia concentration and two orders of magnitude in microbial abundance. Despite the marked divergence in environmental parameters observed between samples, hierarchical clustering of taxonomic and metabolic profiles of these metagenomes showed striking similarity between the samples (>89%). Comparison of these profiles to those derived from a wide variety of publically available datasets demonstrated that the Coorong sediment metagenomes were similar to other sediment, soil, biofilm and microbial mat samples regardless of salinity (>85% similarity). Overall, clustering of solid substrate and water metagenomes into discrete similarity groups based on functional potential indicated that the dichotomy between water and solid matrices is a fundamental determinant of community microbial metabolism that is not masked by salinity, nutrient concentration or microbial abundance.</p

Modeling C3 glomerulopathies: C3 convertase regulation on an extracellular matrix surface

IntroductionC3 glomerulopathies (C3G) are ultra-rare complement-mediated diseases that lead to end-stage renal disease (ESRD) within 10 years of diagnosis in ~50% of patients. Overactivation of the alternative pathway (AP) of complement in the fluid phase and on the surface of the glomerular endothelial glycomatrix is the underlying cause of C3G. Although there are animal models for C3G that focus on genetic drivers of disease, in vivo studies of the impact of acquired drivers are not yet possible.MethodsHere we present an in vitro model of AP activation and regulation on a glycomatrix surface. We use an extracellular matrix substitute (MaxGel) as a base upon which we reconstitute AP C3 convertase. We validated this method using properdin and Factor H (FH) and then assessed the effects of genetic and acquired drivers of C3G on C3 convertase.ResultsWe show that C3 convertase readily forms on MaxGel and that this formation was positively regulated by properdin and negatively regulated by FH. Additionally, Factor B (FB) and FH mutants impaired complement regulation when compared to wild type counterparts. We also show the effects of C3 nephritic factors (C3Nefs) on convertase stability over time and provide evidence for a novel mechanism of C3Nef-mediated C3G pathogenesis.DiscussionWe conclude that this ECM-based model of C3G offers a replicable method by which to evaluate the variable activity of the complement system in C3G, thereby offering an improved understanding of the different factors driving this disease process

Identification of alsterpaullone as a novel small molecule inhibitor to target group 3 medulloblastoma

© Impact Journals, LLC. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Advances in the molecular biology of medulloblastoma revealed four genetically and clinically distinct subgroups. Group 3 medulloblastomas are characterized by frequent amplifications of the oncogene MYC, a high incidence of metastasis, and poor prognosis despite aggressive therapy. We investigated several potential small molecule inhibitors to target Group 3 medulloblastomas based on gene expression data using an in silico drug screen. The Connectivity Map (C-MAP) analysis identified piperlongumine as the top candidate drug for non-WNT medulloblastomas and the cyclin-dependent kinase (CDK) inhibitor alsterpaullone as the compound predicted to have specific antitumor activity against Group 3 medulloblastomas. To validate our findings we used these inhibitors against established Group 3 medulloblastoma cell lines. The C-MAP predicted drugs reduced cell proliferation in vitro and increased survival in Group 3 medulloblastoma xenografts. Alsterpaullone had the highest efficacy in Group 3 medulloblastoma cells. Genomic profiling of Group 3 medulloblastoma cells treated with alsterpaullone confirmed inhibition of cell cycle-related genes, and down-regulation of MYC. Our results demonstrate the preclinical efficacy of using a targeted therapy approach for Group 3 medulloblastomas. Specifically, we provide rationale for advancing alsterpaullone as a targeted therapy in Group 3 medulloblastoma.This study was supported by the Canadian Cancer Society (Grant #2011-70051), the Pediatric Brain Tumor Foundation of the United States, the Brain Tumour Foundation of Canada, Meagan’s Walk, b.r.a.i.n.child and the Wiley Fund at the Hospital for Sick Children.info:eu-repo/semantics/publishedVersio