Skeletal muscle mitochondrial dysfunction in contemporary antiretroviral therapy: a single cell analysis

OBJECTIVE: To quantify mitochondrial function in skeletal muscle of people treated with contemporary antiretroviral therapy. DESIGN: Cross-sectional observational study. METHODS: Quantitative multiplex immunofluorescence was performed to determine mitochondrial mass and respiratory chain complex abundance in individual myofibres from tibialis anterior biopsies. Individual myofibres were captured by laser microdissection and mitochondrial DNA (mtDNA) content and large-scale deletions were measured by real-time PCR. RESULTS: Forty five antiretroviral therapy (ART) treated people with HIV (PWH, mean age 58 years, mean duration of ART 125 months) were compared with 15 HIV negative age-matched controls. Mitochondrial complex I (CI) deficiency was observed at higher proportional levels in PWH than negative controls (P = 0.008). Myofibre mitochondrial mass did not differ by HIV status.No ART class was significantly associated with mitochondrial deficiency, including prior exposure to historical NRTIs (nucleoside analogue reverse transcriptase inhibitors) associated with systemic mitochondrial toxicity.To exclude an effect of untreated HIV, we also studied skeletal muscle from 13 ART-naïve PWH (mean age 37). These showed negligible CI defects, as well as comparable myofibre mitochondrial mass to ART-treated PWH.Most CI-deficient myofibres contained mtDNA deletions. No mtDNA depletion was detected. CONCLUSION: Here, we show that PWH treated with contemporary ART have mitochondrial dysfunction in skeletal muscle, exceeding that expected due to age alone. Surprisingly, this was not mediated by prior exposure to mitochondrially toxic NRTIs, suggesting novel mechanisms of mitochondrial dysfunction in contemporary ART-treated PWH. These findings are relevant for better understanding successful ageing in PWH

Academics' Experiences in Veterinary Educational Research : Results of an International Survey

Research conducted by the veterinary education community is critical to continual improvement of educational outcomes. Additionally, research productivity is one metric in promotion and tenure decisions. We sought to identify challenges encountered or anticipated when undertaking or planning veterinary educational research (VER), to learn how these challenges might be overcome, and to synthesize tips for success from those who have performed VER. A branching survey was developed and deployed along the authors' worldwide veterinary education contacts in a cascading manner. The survey collected quantitative and qualitative information from participants who had performed VER and those who planned to perform VER in the future. The 258 participants represented 41 countries. Of the participants, 204 had performed VER (79%) and 54 planned to in the future (21%). The median time spent teaching was 14 years, and median time performing VER was 5 years. The most commonly reported challenges in performing VER were lack of funding, lack of time, and difficulties encountered when undertaking a study, including data collection, analysis, and publishing. When asked about overcoming the challenges, a major theme emerged around people, who provided expertise and mentoring. The most commonly reported tip for success was collaboration; 73% of experienced researchers reported people as most helpful upon beginning VER. Collaborators provided diverse help with ideas, study design, statistics, and other aspects. These results suggest that institutions can offer support to academics in the form of small grants, protected research time, writing workshops, and mentorship to assist with the production of meaningful VER.Peer reviewe

Educational Brochures Influence Beliefs and Knowledge Regarding Exercise during Pregnancy: A Pilot Study

International Journal of Exercise Science 12(3): 581-589, 2019. Women who are pregnant report receiving little or no advice about physical activity during pregnancy from their obstetric provider. The purpose of this study was to assess the effectiveness of an evidence-based educational brochure on both immediate and two-week retention of knowledge about exercise during pregnancy. Thirty-two women of childbearing age (age: 25.0 ± 4.0 years, body mass index: 29.5 ± 6.5 kg/m2, 93.7% Caucasian, 83.4% had at least some college) completed a survey before exposure to an evidence-based educational brochure regarding exercise during pregnancy. Post surveys were taken immediately after viewing the educational brochure and again 2-weeks later. After exposure to educational brochures, survey scores on both surveys were significantly higher immediately-post and two-weeks post compared to baseline survey scores (Survey 1 (assessing beliefs) – pre: 79.2 ± 8.9%, post: 92.6 ± 7.4%, 2-weeks post: 92.0 ± 6.5%, p \u3c 0.001; Survey 2 (assessing knowledge) – pre: 65.3 ± 16.4%, post: 81.3 ± 14.9%, 2-weeks post: 78.8 ± 12.4%, p \u3c 0.001). No significant differences detected between immediate post and 2-weeks post for either Survey 1 (p = 0.72) or Survey 2 (p = 0.52); suggesting the information was retained. An evidence-based educational brochure is effective for improving and retaining information 2-weeks later regarding exercise during pregnancy. However, replication studies in more diverse populations are needed to confirm the results of this pilot study. The long-term goal for this line of research is to urge health care providers to consider providing patients with educational information in order to improve knowledge and patient-provider communication on this topic

Peripheral blood-derived mesenchymal stem cells demonstrate immunomodulatory potential for therapeutic use in horses

Previously, we showed that mesenchymal stem cells (MSC) can be mobilized into peripheral blood using electroacupuncture (EA) at acupoints, LI-4, LI-11, GV-14, and GV-20. The purpose of this study was to determine whether EA-mobilized MSC could be harvested and expanded in vitro to be used as an autologous cell therapy in horses. Peripheral blood mononuclear cells (PBMC) isolated from young and aged lame horses (n = 29) showed a marked enrichment for MSCs. MSC were expanded in vitro (n = 25) and administered intravenously at a dose of 50 x 106 (n = 24). Treatment resulted in significant improvement in lameness as assessed by the American Association of Equine Practitioners (AAEP) lameness scale (n = 23). MSCs exhibited immunomodulatory function by inhibition of lymphocyte proliferation and induction of IL-10. Intradermal testing showed no immediate or delayed immune reactions to MSC (1 x 106 to 1 x 104). In this study, we demonstrated an efficient, safe and reproducible method to mobilize and expand, in vitro, MSCs in sufficiently high concentrations for therapeutic administration. We confirm the immunomodulatory function of these cells in vitro. This non-pharmacological and non-surgical strategy for stem cell harvest has a broad range of biomedical applications and represents an improved clinically translatable and economical cell source for humans

Disarming Pseudomonas aeruginosa Virulence by the Inhibitory Action of 1,10-Phenanthroline-5,6-Dione- Based Compounds: Elastase B (LasB) as a Chemotherapeutic Target

negative pathogen Pseudomonas aeruginosa, and this enzyme orchestrates several physiopathological events during bacteria-host interplays. LasB is considered to be a potential target for the development of an innovative chemotherapeutic approach, especially against multidrug-resistant strains. Recently, our group showed that 1,10-phenanthroline-5,6-dione (phendione), [Ag(phendione)2]ClO4 (Ag-phendione) and [Cu(phendione)3](ClO4)2.4H2O (Cu-phendione) had anti-P. aeruginosa action against both planktonic- and biofilm-growing cells. In the present work, we have evaluated the effects of these compounds on the (i) interaction with the lasB active site using in silico approaches, (ii) lasB proteolytic activity by using a specific fluorogenic peptide substrate, (iii) lasB gene expression by real time-polymerase chain reaction, (iv) lasB protein secretion by immunoblotting, (v) ability to block the damages induced by lasB on a monolayer of lung epithelial cells, and (vi) survivability of Galleria mellonella larvae after being challenged with purified lasB and lasB-rich bacterial secretions. Molecular docking analyses revealed that phendione and its Ag+ and Cu2+ complexes were able to interact with the amino acids forming the active site of lasB, particularly Cu-phendione which exhibited the most favorable interaction energy parameters. Additionally, the test compounds were effective inhibitors of lasB activity, blocking the in vitro cleavage of the peptide substrate, aminobenzyl-Ala-Gly-Leu-Ala-p-nitrobenzylamide, with Cu- phendione having the best inhibitory action (Ki = 90 nM). Treating living bacteria with a sub-inhibitory concentration (1/2 × MIC value) of the test compounds caused a significant reduction in the expression of the lasB gene as well as its mature protein production/secretion. Further, Ag-phendione and Cu-phendione offered protective rg 1 August 2019 | Volume 10 | Article 1701 1,10-Phenanthroline-5,6-Dione-Based Compounds: As Anti-Virulence Drugs action for lung epithelial cells, reducing the A549 monolayer damage by approximately 32 and 42%, respectively. Interestingly, Cu-phendione mitigated the toxic effect of both purified lasB molecules and lasB-containing bacterial secretions in the in vivo model, increasing the survival time of G. mellonella larvae. Collectively, these data reinforce the concept of lasB being a veritable therapeutic target and phendione-based compounds (mainly Cu-phendione) being prospective anti-virulence drugs against P. aeruginosa

The prevalence of child sexual abuse perpetrated by leaders or other adults in religious organizations in Australia

Background Numerous national public inquiries have highlighted the problem of child sexual abuse in religious organizations. Despite this, evidence of population-wide prevalence is scarce. Objective To provide the first nationally representative prevalence estimates of child sexual abuse perpetrated by adults in religious organizations in Australia. Methods The Australian Child Maltreatment Study (ACMS) surveyed 8503 people aged 16 and over about their experiences of child maltreatment. Weighted prevalence estimates were calculated based on responses to the child sexual abuse questions from the Juvenile Victimization Questionnaire-R2: Adapted Version (ACMS). Results One in 250 people reported being sexually abused as a child by an adult in a religious organization (0.4 %, 95 % CI, 0.3–0.6 %). Men reported significantly higher rates of child sexual abuse by these perpetrators (0.8 %, 95 % CI, 0.5–1.2 %), compared to women (0.1 %, 95 % CI, 0–0.3 %). This type of sexual abuse was overwhelmingly perpetrated by men (0.4 %, 95 % CI, 0.3–0.6 %), compared to women (0 %, 95 % CI, 0–0.1 %), and was substantially more often experienced in Catholic organizations (71.9 %) than other Christian denominations or other religions. Prevalence of child sexual abuse in religious organizations has declined over time (2.2 % of men 65 years and older, compared with 0.2 % of 16–24-year-old men). Conclusions Child sexual abuse has been widespread in religious organizations in Australia. A decline over time indicates progress has been made in preventing sexual abuse of children. Religious organizations must take all reasonable measures to prevent child sexual abuse, with a particular need for interventions targeting male leaders, and organizational cultures

The prevalence of peer sexual harassment during childhood in Australia

Sexual harassment inflicted by adolescents on their peers is a major public health issue, but its prevalence across childhood is not known. We provide the first nationally representative data on the prevalence of peer sexual harassment across childhood, using cross-sectional data from the Australian Child Maltreatment Study (ACMS). The ACMS surveyed 8,503 people aged 16 and over about their experiences of child maltreatment and associated health outcomes. The prevalence of peer sexual harassment was assessed using the Juvenile Victimization Questionnaire (JVQ)-R2 Adapted Version (ACMS), with survey data weighted to reflect characteristics of the Australian population. Overall, 1 in 10 (10.4% (95% Confidence Intervals (CI) [9.7, 11.3])) Australians experienced peer sexual harassment during childhood. Peer sexual harassment is an issue disproportionately affecting gender-diverse individuals (24.0%, 95% CI [15.5, 35.2]) and women (15.3%, 95% CI [14.0, 16.7%]), compared to men (5.0%, 95% CI [4.3, 5.9]). Rates of peer sexual harassment were also very high among sexuality diverse participants (prevalence estimates ranging between 14.2% and 29.8%). Peer sexual harassment was predominately inflicted by male peers (9.6%, 95% CI [8.9, 10.4]), compared to 1.8% (95% CI [1.5, 2.2]) reporting harassment from female peers. These findings have implications for understanding and reducing attitudes supporting peer sexual harassment in childhood, particularly against girls and gender and sexuality diverse youth, and associations with other gendered violence both in childhood and later life

Sexual Display and Mate Choice in an Energetically Costly Environment

Sexual displays and mate choice often take place under the same set of environmental conditions and, as a consequence, may be exposed to the same set of environmental constraints. Surprisingly, however, very few studies consider the effects of environmental costs on sexual displays and mate choice simultaneously. We conducted an experiment, manipulating water flow in large flume tanks, to examine how an energetically costly environment might affect the sexual display and mate choice behavior of male and female guppies, Poecilia reticulata. We found that male guppies performed fewer sexual displays and became less choosy, with respect to female size, in the presence of a water current compared to those tested in still water. In contrast to males, female responsive to male displays did not differ between the water current treatments and females exhibited no mate preferences with respect to male size or coloration in either treatment. The results of our study underscore the importance of considering the simultaneous effects of environmental costs on the sexual behaviors of both sexes

PDK1 and HR46 Gene Homologs Tie Social Behavior to Ovary Signals

The genetic basis of division of labor in social insects is a central question in evolutionary and behavioral biology. The honey bee is a model for studying evolutionary behavioral genetics because of its well characterized age-correlated division of labor. After an initial period of within-nest tasks, 2–3 week-old worker bees begin foraging outside the nest. Individuals often specialize by biasing their foraging efforts toward collecting pollen or nectar. Efforts to explain the origins of foraging specialization suggest that division of labor between nectar and pollen foraging specialists is influenced by genes with effects on reproductive physiology. Quantitative trait loci (QTL) mapping of foraging behavior also reveals candidate genes for reproductive traits. Here, we address the linkage of reproductive anatomy to behavior, using backcross QTL analysis, behavioral and anatomical phenotyping, candidate gene expression studies, and backcross confirmation of gene-to-anatomical trait associations. Our data show for the first time that the activity of two positional candidate genes for behavior, PDK1 and HR46, have direct genetic relationships to ovary size, a central reproductive trait that correlates with the nectar and pollen foraging bias of workers. These findings implicate two genes that were not known previously to influence complex social behavior. Also, they outline how selection may have acted on gene networks that affect reproductive resource allocation and behavior to facilitate the evolution of social foraging in honey bees