Effects of a multi-component exercise program and calcium–vitamin-D3-fortified milk on bone mineral density in older men : a randomised controlled trial

Summary We examined the independent and combined effects of a multi-component exercise program and calcium&ndash;vitamin-D3-fortified milk on bone mineral density (BMD) in older men. Exercise resulted in a 1.8% net gain in femoral neck BMD, but additional calcium&ndash;vitamin D3 did not enhance the response in this group of older well-nourished men.Introduction This 12-month randomised controlled trial assessed whether calcium&ndash;vitamin-D3-fortified milk could enhance the effects of a multi-component exercise program on BMD in older men.Methods Men (n&thinsp; =&thinsp;180) aged 50&ndash;79 years were randomised into: (1) exercise + fortified milk; (2) exercise; (3) fortified milk; or (4) controls. Exercise consisted of high intensity progressive resistance training with weight-bearing impact exercise. Men assigned to fortified milk consumed 400 mL/day of low fat milk providing an additional 1,000 mg/day calcium and 800 IU/day vitamin D3. Femoral neck (FN), total hip, lumbar spine and trochanter BMD and body composition (DXA), muscle strength 25-hydroxyvitamin D and parathyroid hormone (PTH) were assessed.Results There were no exercise-by-fortified milk interactions at any skeletal site. Exercise resulted in a 1.8% net gain in FN BMD relative to no-exercise (p&thinsp;&lt;&thinsp;0.001); lean mass (0.6 kg, p&thinsp;&lt;&thinsp;0.05) and muscle strength (20&ndash;52%, p&thinsp;&lt;&thinsp;0.001) also increased in response to exercise. For lumbar spine BMD, there was a net 1.4&ndash;1.5% increase in all treatment groups relative to controls (all p&thinsp;&lt;&thinsp;0.01). There were no main effects of fortified milk at any skeletal site.Conclusion A multi-component community-based exercise program was effective for increasing FN BMD in older men, but additional calcium&ndash;vitamin D3 did not enhance the osteogenic response.<br /

Energy deficiency, menstrual disturbances, and low bone mass : what do exercising Australian women know about the female athlete triad?

Purpose: Prevention of the female athlete triad is essential to protect female athletes&rsquo; health. The aim of this study was to investigate the knowledge, attitudes, and behaviors of regularly exercising adult women in Australia toward eating patterns, menstrual cycles, and bone health. Methods: A total of 191 female exercisers, age 18&ndash;40 yr, engaging in &ge;2 hr/wk of strenuous activity, completed a survey. After 11 surveys were excluded (due to incomplete answers), the 180 participants were categorized into lean-build sports (n = 82; running/ athletics, triathlon, swimming, cycling, dancing, rowing), non-lean-build sports (n = 94; basketball, netball, soccer, hockey, volleyball, tennis, trampoline, squash, Australian football), or gym/fitness activities (n = 4). Results: Mean (&plusmn; SD) training volume was 9.0 &plusmn; 5.5 hr/wk, with participants competing from local up to international level. Only 10% of respondents could name the 3 components of the female athlete triad. Regardless of reported history of stress fracture, 45% of the respondents did not think that amenorrhea (absence of menses for &ge;3 months) could affect bone health, and 22% of those involved in lean-build sports would do nothing if experiencing amenorrhea (vs. 3.2% in non-lean-build sports, p = .005). Lean-build sports, history of amenorrhea, and history of stress fracture were all significantly associated with not taking action in the presence of amenorrhea (all p &lt; .005). Conclusions: Few active Australian women are aware of the detrimental effects of menstrual dysfunction on bone health. Education programs are needed to prevent the female athlete triad and ensure that appropriate actions are taken by athletes when experiencing amenorrhea.<br /

DLGS97/SAP97 is developmentally upregulated and is required for complex adult behaviors and synapse morphology and function

The synaptic membrane-associated guanylate kinase (MAGUK) scaffolding protein family is thought to play key roles in synapse assembly and synaptic plasticity. Evidence supporting these roles in vivo is scarce, as a consequence of gene redundancy in mammals. The genome of Drosophila contains only one MAGUK gene, discs large (dlg), from which two major proteins originate: DLGA [PSD95 (postsynaptic density 95)-like] and DLGS97 [SAP97 (synapse-associated protein)-like]. These differ only by the inclusion in DLGS97 of an L27 domain, important for the formation of supramolecular assemblies. Known dlg mutations affect both forms and are lethal at larval stages attributable to tumoral overgrowth of epithelia. We generated independent null mutations for each, dlgA and dlgS97. These allowed unveiling of a shift in expression during the development of the nervous system: predominant expression of DLGA in the embryo, balanced expression of both during larval stages, and almost exclusive DLGS97 expression in the adult brain. Loss of embryonic DLGS97 does not alter the development of the nervous system. At larval stages, DLGA and DLGS97 fulfill both unique and partially redundant functions in the neuromuscular junction. Contrary to dlg and dlgA mutants, dlgS97 mutants are viable to adulthood, but they exhibit marked alterations in complex behaviors such as phototaxis, circadian activity, and courtship, whereas simpler behaviors like locomotion and odor and light perception are spared. We propose that the increased repertoire of associations of a synaptic scaffold protein given by an additional domain of protein-protein interaction underlies its ability to integrate molecular networks required for complex functions in adult synapses

Dietary cows\u27 milk protein A1 beta-casein increases the incidence of T1D in NOD mice

The contribution of cows\u27 milk containing beta-casein protein A1 variant to the development of type 1 diabetes (T1D) has been controversial for decades. Despite epidemiological data demonstrating a relationship between A1 beta-casein consumption and T1D incidence, direct evidence is limited. We demonstrate that early life exposure to A1 beta-casein through the diet can modify progression to diabetes in non-obese diabetic (NOD) mice, with the effect apparent in later generations. Adult NOD mice from the F0 generation and all subsequent generations (F1 to F4) were fed either A1 or A2 beta-casein supplemented diets. Diabetes incidence in F0⁻F2 generations was similar in both cohorts of mice. However, diabetes incidence doubled in the F3 generation NOD mice fed an A1 beta-casein supplemented diet. In F4 NOD mice, subclinical insulitis and altered glucose handling was evident as early as 10 weeks of age in A1 fed mice only. A significant decrease in the proportion of non-conventional regulatory T cell subset defined as CD4⁺CD25-FoxP3⁺ was evident in the F4 generation of A1 fed mice. This feeding intervention study demonstrates that dietary A1 beta-casein may affect glucose homeostasis and T1D progression, although this effect takes generations to manifest

A1 beta-casein milk protein and other environmental pre-disposing factors for type 1 diabetes

Globally type 1 diabetes incidence is increasing. It is widely accepted that the pathophysiology of type 1 diabetes is influenced by environmental factors in people with specific human leukocyte antigen haplotypes. We propose that a complex interplay between dietary triggers, permissive gut factors and potentially other influencing factors underpins disease progression. We present evidence that A1 &beta;-casein cows\u27 milk protein is a primary causal trigger of type 1 diabetes in individuals with genetic risk factors. Permissive gut factors (for example, aberrant mucosal immunity), intervene by impacting the gut\u27s environment and the mucosal barrier. Various influencing factors (for example, breastfeeding duration, exposure to other dietary triggers and vitamin D) modify the impact of triggers and permissive gut factors on disease. The power of the dominant trigger and permissive gut factors on disease is influenced by timing, magnitude and/or duration of exposure. Within this framework, removal of a dominant dietary trigger may profoundly affect type 1 diabetes incidence. We present epidemiological, animal-based, in vitro and theoretical evidence for A1 &beta;-casein and its &beta;-casomorphin-7 derivative as dominant causal triggers of type 1 diabetes. The effects of ordinary milk containing A1 and A2 &beta;-casein and milk containing only the A2 &beta;-casein warrant comparison in prospective trials

Osteo-cise: Strong Bones for Life: protocol for a community-based randomised controlled trial of a multi-modal exercise and osteoporosis education program for older adults at risk of falls and fractures

Background : Osteoporosis affects over 220 million people worldwide, and currently there is no \u27cure\u27 for the disease. Thus, there is a need to develop evidence-based, safe and acceptable prevention strategies at the population level that target multiple risk factors for fragility fractures to reduce the health and economic burden of the condition. Methods : The \u27Osteo-cise: Strong Bones for Life\u27 study will investigate the effectiveness and feasibility of a multi-component targeted exercise, osteoporosis education/awareness and behavioural change program for improving bone health and muscle function, and reducing falls risk in community-dwelling older adults at an increased risk of fracture. Men and women aged 60 years or above will participate in an 18-month randomised controlled trial comprising a 12-month structured and supervised community-based program and a 6-month \u27research to practise\u27 translational phase. Participants will be randomly assigned to either the \u27Osteo-cise\u27 intervention or a self-management control group. The intervention will comprise a multi-modal exercise program incorporating high velocity progressive resistance training, moderate impact weight-bearing exercise and high challenging balance exercises performed three times weekly at local community-based fitness centres. A behavioural change program will be used to enhance exercise adoption and adherence to the program. Community-based osteoporosis education seminars will be conducted to improve participant knowledge and understanding of the risk factors and preventative measures for osteoporosis, falls and fractures. The primary outcomes measures, to be collected at baseline, 6, 12, and 18 months, will include DXA-derived hip and spine bone mineral density measurements and functional muscle power (timed stair-climb test). Secondary outcomes measures include: MRI-assessed distal femur and proximal tibia trabecular bone micro-architecture, lower limb and back maximal muscle strength, balance and function (four square step test, functional reach test, timed up-and-go test and 30-second sit-to-stand), falls incidence and health-related quality of life. Cost-effectiveness will also be assessed. Discussion : The findings from the Osteo-cise: Strong Bones for Life study will provide new information on the efficacy of a targeted multi-modal community-based exercise program incorporating high velocity resistance training, together with an osteoporosis education and behavioural change program for improving multiple risk factors for falls and fracture in older adults at risk of fragility fracture.<br /

COVLIAS 3.0: cloud-based quantized hybrid UNet3+ deep learning for COVID-19 lesion detection in lung computed tomography

Background and noveltyWhen RT-PCR is ineffective in early diagnosis and understanding of COVID-19 severity, Computed Tomography (CT) scans are needed for COVID diagnosis, especially in patients having high ground-glass opacities, consolidations, and crazy paving. Radiologists find the manual method for lesion detection in CT very challenging and tedious. Previously solo deep learning (SDL) was tried but they had low to moderate-level performance. This study presents two new cloud-based quantized deep learning UNet3+ hybrid (HDL) models, which incorporated full-scale skip connections to enhance and improve the detections.MethodologyAnnotations from expert radiologists were used to train one SDL (UNet3+), and two HDL models, namely, VGG-UNet3+ and ResNet-UNet3+. For accuracy, 5-fold cross-validation protocols, training on 3,500 CT scans, and testing on unseen 500 CT scans were adopted in the cloud framework. Two kinds of loss functions were used: Dice Similarity (DS) and binary cross-entropy (BCE). Performance was evaluated using (i) Area error, (ii) DS, (iii) Jaccard Index, (iii) Bland–Altman, and (iv) Correlation plots.ResultsAmong the two HDL models, ResNet-UNet3+ was superior to UNet3+ by 17 and 10% for Dice and BCE loss. The models were further compressed using quantization showing a percentage size reduction of 66.76, 36.64, and 46.23%, respectively, for UNet3+, VGG-UNet3+, and ResNet-UNet3+. Its stability and reliability were proved by statistical tests such as the Mann–Whitney, Paired t-Test, Wilcoxon test, and Friedman test all of which had a p &lt; 0.001.ConclusionFull-scale skip connections of UNet3+ with VGG and ResNet in HDL framework proved the hypothesis showing powerful results improving the detection accuracy of COVID-19