Progressive resistance training for concomitant increases in muscle strength and bone mineral density in older adults: A systematic review and meta-analysis

Background: Older adults experience considerable muscle and bone loss that are closely interconnected. The efficacy of progressive resistance training programs to concurrently reverse/slow the age-related decline in muscle strength and bone mineral density (BMD) in older adults remains unclear. Objectives: We aimed to quantify concomitant changes in lower-body muscle strength and BMD in older adults following a progressive resistance training program and to determine how these changes are influenced by mode (resistance only vs. combined resistance and weight-bearing exercises), frequency, volume, load, and program length. Methods: MEDLINE/PubMed and Embase databases were searched for articles published in English before 1 June, 2021. Randomized controlled trials reporting changes in leg press or knee extension one repetition maximum and femur/hip or lumbar spine BMD following progressive resistance training in men and/or women ≥ 65 years of age were included. A random-effects meta-analysis and meta-regression determined the effects of resistance training and the individual training characteristics on the percent change (∆%) in muscle strength (standardized mean difference) and BMD (mean difference). The quality of the evidence was assessed using the Cochrane risk-of-bias tool (version 2.0) and Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) criteria. Results: Seven hundred and eighty studies were identified and 14 were included. Progressive resistance training increased muscle strength (∆ standardized mean difference = 1.1%; 95% confidence interval 0.73, 1.47; p ≤ 0.001) and femur/hip BMD (∆ mean difference = 2.77%; 95% confidence interval 0.44, 5.10; p = 0.02), but not BMD of the lumbar spine (∆ mean difference = 1.60%; 95% confidence interval − 1.44, 4.63; p = 0.30). The certainty for improvement was greater for muscle strength compared with BMD, evidenced by less heterogeneity (I2 = 78.1% vs 98.6%) and a higher overall quality of evidence. No training characteristic significantly affected both outcomes (p \u3e 0.05), although concomitant increases in strength and BMD were favored by higher training frequencies, increases in strength were favored by resistance only and higher volumes, and increases in BMD were favored by combined resistance plus weight-bearing exercises, lower volumes, and higher loads. Conclusions: Progressive resistance training programs concomitantly increase lower-limb muscle strength and femur/hip bone mineral density in older adults, with greater certainty for strength improvement. Thus, to maximize the efficacy of progressive resistance training programs to concurrently prevent muscle and bone loss in older adults, it is recommended to incorporate training characteristics more likely to improve BMD

Legionella pneumophila strain 130b possesses a unique combination of type IV secretion systems and novel Dot/Icm secretion system effector proteins

Legionella pneumophila is a ubiquitous inhabitant of environmental water reservoirs. The bacteria infect a wide variety of protozoa and, after accidental inhalation, human alveolar macrophages, which can lead to severe pneumonia. The capability to thrive in phagocytic hosts is dependent on the Dot/Icm type IV secretion system (T4SS), which translocates multiple effector proteins into the host cell. In this study, we determined the draft genome sequence of L. pneumophila strain 130b (Wadsworth). We found that the 130b genome encodes a unique set of T4SSs, namely, the Dot/Icm T4SS, a Trb-1-like T4SS, and two Lvh T4SS gene clusters. Sequence analysis substantiated that a core set of 107 Dot/Icm T4SS effectors was conserved among the sequenced L. pneumophila strains Philadelphia-1, Lens, Paris, Corby, Alcoy, and 130b. We also identified new effector candidates and validated the translocation of 10 novel Dot/Icm T4SS effectors that are not present in L. pneumophila strain Philadelphia-1. We examined the prevalence of the new effector genes among 87 environmental and clinical L. pneumophila isolates. Five of the new effectors were identified in 34 to 62% of the isolates, while less than 15% of the strains tested positive for the other five genes. Collectively, our data show that the core set of conserved Dot/Icm T4SS effector proteins is supplemented by a variable repertoire of accessory effectors that may partly account for differences in the virulences and prevalences of particular L. pneumophila strains. Copyright © 2010, American Society for Microbiology. All Rights Reserved

Bilateral volume reduction in posterior hippocampus in psychosis of epilepsy

Objective Psychosis of epilepsy (POE) occurs more frequently in temporal lobe epilepsy, raising the question as to whether abnormalities of the hippocampus are aetiologically important. Despite decades of investigation, it is unclear whether hippocampal volume is reduced in POE, perhaps due to small sample sizes and methodological limitations of past research. Methods In this study, we examined the volume of the total hippocampus, and the hippocampal head, body and tail, in a large cohort of patients with POE and patients with epilepsy without psychosis (EC). One hundred adults participated: 50 with POE and 50 EC. Total and subregional hippocampal volumes were manually traced and compared between (1) POE and EC; (2) POE with temporal lobe epilepsy, extratemporal lobe epilepsy and generalised epilepsy; and (3) patients with POE with postictal psychosis (PIP) and interictal psychosis (IP). Results Compared with EC the POE group had smaller total left hippocampus volume (13.5% decrease, p<0.001), and smaller left hippocampal body (13.3% decrease, p=0.002), and left (41.5% decrease, p<0.001) and right (36.4% decrease, p<0.001) hippocampal tail volumes. Hippocampal head volumes did not differ between groups. Conclusion Posterior hippocampal volumes are bilaterally reduced in POE. Volume loss was observed on a posteroanterior gradient, with severe decreases in the tail and moderate volume decreases in the body, with no difference in the hippocampal head. Posterior hippocampal atrophy is evident to a similar degree in PIP and IP. Our findings converge with those reported for the paradigmatic psychotic disorder, schizophrenia, and suggest that posterior hippocampal atrophy may serve as a biomarker of the risk for psychosis, including in patients with epilepsy.JA is supported by an Australian Postgraduate Award

Effect of 6 months of hybrid closed-loop insulin delivery in adults with type 1 diabetes: a randomised controlled trial protocol

INTRODUCTION: Manual determination of insulin dosing largely fails to optimise glucose control in type 1 diabetes. Automated insulin delivery via closed-loop systems has improved glucose control in short-term studies. The objective of the present study is to determine the effectiveness of 6 months\u27 closed-loop compared with manually determined insulin dosing on time-in-target glucose range in adults with type 1 diabetes. METHODS AND ANALYSIS: This open-label, seven-centre, randomised controlled parallel group clinical trial will compare home-based hybrid closed-loop versus standard diabetes therapy in Australia. Adults aged &ge;25 years with type 1 diabetes using intensive insulin therapy (via multiple daily injections or insulin pump, total enrolment target n=120) will undertake a run-in period including diabetes and carbohydrate-counting education, clinical optimisation and baseline data collection. Participants will then be randomised 1:1 either to 26 weeks of MiniMed 670G hybrid closed-loop system therapy (Medtronic, Northridge, CA, USA) or continuation of their current diabetes therapy. The hybrid closed-loop system delivers insulin automatically to address basal requirements and correct to target glucose level, while bolus doses for meals require user initiation and carbohydrate estimation. Analysis will be intention to treat, with the primary outcome time in continuous glucose monitoring (CGM) target range (3.9-10.0&thinsp;mmol/L) during the final 3 weeks of intervention. Secondary outcomes include: other CGM parameters, HbA1c, severe hypoglycaemia, psychosocial well-being, sleep, cognition, electrocardiography, costs, quality of life, biomarkers of vascular health and hybrid closed-loop system performance. Semistructured interviews will assess the expectations and experiences of a subgroup of hybrid closed-loop users. ETHICS AND DISSEMINATION: The study has Human Research Ethics Committee approval. The study will be conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice. Results will be disseminated at scientific conferences and via peer-reviewed publications

Progressive resistance training for concomitant increases in muscle strength and bone mineral density in older adults: a systematic review and meta-analysis

Background Older adults experience considerable muscle and bone loss that are closely interconnected. The efficacy of progressive resistance training programs to concurrently reverse/slow the age-related decline in muscle strength and bone mineral density (BMD) in older adults remains unclear. Objectives We aimed to quantify concomitant changes in lower-body muscle strength and BMD in older adults following a progressive resistance training program and to determine how these changes are influenced by mode (resistance only vs. combined resistance and weight-bearing exercises), frequency, volume, load, and program length. Methods MEDLINE/PubMed and Embase databases were searched for articles published in English before 1 June, 2021. Randomized controlled trials reporting changes in leg press or knee extension one repetition maximum and femur/hip or lumbar spine BMD following progressive resistance training in men and/or women ≥ 65 years of age were included. A random-effects meta-analysis and meta-regression determined the effects of resistance training and the individual training characteristics on the percent change (∆%) in muscle strength (standardized mean difference) and BMD (mean difference). The quality of the evidence was assessed using the Cochrane risk-of-bias tool (version 2.0) and Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) criteria. Results Seven hundred and eighty studies were identified and 14 were included. Progressive resistance training increased muscle strength (∆ standardized mean difference = 1.1%; 95% confidence interval 0.73, 1.47; p ≤ 0.001) and femur/hip BMD (∆ mean difference = 2.77%; 95% confidence interval 0.44, 5.10; p = 0.02), but not BMD of the lumbar spine (∆ mean difference = 1.60%; 95% confidence interval − 1.44, 4.63; p = 0.30). The certainty for improvement was greater for muscle strength compared with BMD, evidenced by less heterogeneity (I2 = 78.1% vs 98.6%) and a higher overall quality of evidence. No training characteristic significantly affected both outcomes (p > 0.05), although concomitant increases in strength and BMD were favored by higher training frequencies, increases in strength were favored by resistance only and higher volumes, and increases in BMD were favored by combined resistance plus weight-bearing exercises, lower volumes, and higher loads. Conclusions Progressive resistance training programs concomitantly increase lower-limb muscle strength and femur/hip bone mineral density in older adults, with greater certainty for strength improvement. Thus, to maximize the efficacy of progressive resistance training programs to concurrently prevent muscle and bone loss in older adults, it is recommended to incorporate training characteristics more likely to improve BMD

Handheld ultrasound to reduce requests for inappropriate echocardiogram (HURRIE)

Background: Handheld ultrasound could provide sufficient information to satisfy the clinical questions underlying 'rarely appropriate' echo requests, but there are limited data about its use as a gatekeeper to standard echocardiography. We sought to determine whether the use of handheld ultrasound could improve the appropriate use of echocardiography. Method: A prospective study comparing handheld ultrasound strategy to standard echocardiography for studies deemed rarely appropriate, using a questionnaire based on appropriate use criteria was conducted across two hospitals, from October 2017 to April 2018. Results: Groups undergoing Handheld ultrasound (n = 76, 58 (46.5-72.5) years, 53 males, 78% outpatients) and standard echocardiography (n = 72, 61 (49.0-71.5) years, 42 males, 76% outpatients) were comparable. There was a significant decrease in the time to scan from just over 1 month in standard group to a median of 12 days in handheld ultrasound group (P < 0.001). This difference was small for inpatients (from 1 day to a median of 10 min in handheld ultrasound, P = 0.014), but prominent in outpatients (from 1.5 months in the standard group to median of 2 weeks in the handheld ultrasound group, P < 0.001). There was no increase in the need for follow-up scan within 6 months and no significant differences in length of hospital stay for inpatients. Conclusion: Handheld ultrasound can be an effective gatekeeper to standard echocardiography for requests deemed rarely appropriate, reducing time to echocardiography significantly and potentially decreasing the need for standard echocardiography by up to 20%

Evolutionary Differences in the Vegf/Vegfr Code Reveal Organotypic Roles for the Endothelial Cell Receptor Kdr in Developmental Lymphangiogenesis

Lymphatic vascular development establishes embryonic and adult tissue fluid balance and is integral in disease. In diverse vertebrate organs, lymphatic vessels display organotypic function and develop in an organ-specific manner. In all settings, developmental lymphangiogenesis is considered driven by vascular endothelial growth factor (VEGF) receptor-3 (VEGFR3), whereas a role for VEGFR2 remains to be fully explored. Here, we define the zebrafish Vegf/Vegfr code in receptor binding studies. We find that while Vegfd directs craniofacial lymphangiogenesis, it binds Kdr (a VEGFR2 homolog) but surprisingly, unlike in mammals, does not bind Flt4 (VEGFR3). Epistatic analyses and characterization of a kdr mutant confirm receptor-binding analyses, demonstrating that Kdr is indispensible for rostral craniofacial lymphangiogenesis, but not caudal trunk lymphangiogenesis, in which Flt4 is central. We further demonstrate an unexpected yet essential role for Kdr in inducing lymphatic endothelial cell fate. This work reveals evolutionary divergence in the Vegf/Vegfr code that uncovers spatially restricted mechanisms of developmental lymphangiogenesis. Lymphatic vessels display organotypic function and develop in an organ-specific manner. Vogrin et al. find that the zebrafish Kdr receptor is indispensible for craniofacial, but not trunk, lymphangiogenesis whereas Flt4 is essential for the latter. Thus, vascular endothelial growth factor (VEGF) receptor signaling pathways are differentially employed in different tissues to drive developmental lymphangiogenesis