Whole-exome sequencing reveals a comprehensive germline mutation landscape and identifies twelve novel predisposition genes in Chinese prostate cancer patients.

Prostate cancer is the most inheritable cancer with approximately 42% of disease risk attributed to inherited factors by studies of twins, indicating the importance of additional genetic screening to identify predisposition variants. However, only DNA damage repair (DDR) genes have been investigated thoroughly in prostate cancer. To determine the comprehensive germline mutation landscape in Chinese prostate cancer patients, we performed whole exome sequencing in 100 Han Chinese patients with prostate cancer in Hong Kong and identified deleterious germline mutations. A total of 36 deleterious germline variants in 25 genes were identified in 29% patients. Variants were found in eight pathways, including DNA methylation, DDR, and tyrosine-protein kinase. These findings were validated in an independent Chinese cohort of 167 patients with prostate cancer in Shanghai. Seven common deleterious-variant-containing genes were found in discovery cohort (7/25, 28%) and validation cohort (7/28, 25%) with three genes not described before (LDLR, MYH7 and SUGCT) and four genes previously reported (FANCI, ITGA6, PABPC1 and RAD54B). When comparing with that of a cohort of East Asian healthy individuals, 12 non-DDR novel potential predisposition genes (ADGRG1, CHD4, DNMT3A, ERBB3, GRHL1, HMBS, LDLR, MYH7, MYO6, NT5C2, NUP98 and SUGCT) were identified using the discovery and validation cohorts, which have not been previously reported in prostate cancer patients in all ethnic groups. Taken together, this study reveals a comprehensive germline mutation landscape in Chinese prostate cancer patients and discovers 12 novel non-DDR predisposition genes to lay the groundwork for the optimization of genetic screening.

Identification of novel single nucleotide variants in the drug resistance mechanism of Mycobacterium tuberculosis isolates by whole-genome analysis.

BACKGROUND: Tuberculosis (TB) represents a major global health challenge. Drug resistance in Mycobacterium tuberculosis (MTB) poses a substantial obstacle to effective TB treatment. Identifying genomic mutations in MTB isolates holds promise for unraveling the underlying mechanisms of drug resistance in this bacterium. METHODS: In this study, we investigated the roles of single nucleotide variants (SNVs) in MTB isolates resistant to four antibiotics (moxifloxacin, ofloxacin, amikacin, and capreomycin) through whole-genome analysis. We identified the drug-resistance-associated SNVs by comparing the genomes of MTB isolates with reference genomes using the MuMmer4 tool. RESULTS: We observed a strikingly high proportion (94.2%) of MTB isolates resistant to ofloxacin, underscoring the current prevalence of drug resistance in MTB. An average of 3529 SNVs were detected in a single ofloxacin-resistant isolate, indicating a mutation rate of approximately 0.08% under the selective pressure of ofloxacin exposure. We identified a set of 60 SNVs associated with extensively drug-resistant tuberculosis (XDR-TB), among which 42 SNVs were non-synonymous mutations located in the coding regions of nine key genes (ctpI, desA3, mce1R, moeB1, ndhA, PE_PGRS4, PPE18, rpsA, secF). Protein structure modeling revealed that SNVs of three genes (PE_PGRS4, desA3, secF) are close to the critical catalytic active sites in the three-dimensional structure of the coding proteins. CONCLUSION: This comprehensive study elucidates novel resistance mechanisms in MTB against antibiotics, paving the way for future design and development of anti-tuberculosis drugs.

Regulatory T cells hamper the efficacy of T-cell-engaging bispecific antibody therapy.

T-cell-engaging bispecific antibodies (T-BsAb) have produced impressive clinical responses in patients with relapsed/refractory B-cell malignancies, although treatment failure remains a major clinical challenge. Growing evidence suggests that a complex interplay between immune cells and tumor cells is implicated in the mechanism of action and therefore, understanding immune regulatory mechanisms might provide a clue for how to improve the efficacy of T-BsAb therapy. Here, we investigated the functional impact of regulatory T (Treg) cells on anti-tumor immunity elicited by T-BsAb therapy. In a preclinical model of myeloma, the activation and expansion of Treg cells in the bone marrow were observed in response to anti-B-cell maturation antigen (BCMA) T-BsAb therapy. T-BsAb triggered the generation of induced Treg cells from human conventional CD4 cells after co-culture with tumor cells. Moreover, T-BsAb directly activated freshly isolated circulating Treg cells, leading to the production of interleukin-10 and inhibition of T-BsAb-mediated CD8 T-cell responses. The activation of Treg cells was also seen in bone marrow samples from myeloma patients after ex vivo treatment with T-BsAb, further supporting that T-BsAb have an impact on Treg homeostasis. Importantly, transient ablation of Treg cells in combination with T-BsAb therapy dramatically improved effector lymphocyte activities and disease control in the preclinical myeloma model, leading to prolonged survival. Together, this information suggests that therapy-induced activation of Treg cells critically regulates anti-tumor immunity elicited by T-BsAb therapy, with important implications for improving the efficacy of such treatment.

Harnessing the cytotoxic granule exocytosis to augment the efficacy of T-cell-engaging bispecific antibody therapy.

T-cell-engaging bispecific antibody (T-BsAb, also known as BiTE) therapy has emerged as a powerful therapeutic modality against multiple myeloma. Given that T-BsAb therapy redirects endogenous T cells to eliminate tumor cells, reinvigorating dysfunctional T cells may be a potential approach to improve the efficacy of T-BsAb. While various immunostimulatory cytokines can potentiate effector T-cell functions, the optimal cytokine treatment for T-BsAb therapy is yet to be established, partly due to a concern of cytokine release syndrome driven by aberrant interferon (IFN)-γ production. Here, we functionally screen immunostimulatory cytokines to determine an ideal combination partner for T-BsAb therapy. This approach reveals interleukin (IL)-21 as a potential immunostimulatory cytokine with the ability to augment T-BsAb-mediated release of granzyme B and perforin, without increasing IFN-γ release. Transcriptome profiling and functional characterization strongly support that IL-21 selectively targets the cytotoxic granule exocytosis pathway, but not pro-inflammatory responses. Notably, IL-21 modulates multiple steps of cytotoxic effector functions including upregulation of co-activating CD226 receptor, increasing cytotoxic granules, and promoting cytotoxic granule delivery at the immunological synapse. Indeed, T-BsAb-mediated myeloma killing is cytotoxic granule-dependent, and IL-21 priming significantly augments cytotoxic activities. Furthermore, in vivo IL-21 treatment induces cytotoxic effector reprogramming in bone marrow T cells, showing synergistic anti-myeloma effects in combination with T-BsAb therapy. Together, harnessing the cytotoxic granule exocytosis pathway by IL-21 may be a potential approach to achieve better responses by T-BsAb therapy.

Use of behavior change techniques in physical activity programs and services for older adults: findings from a rapid review.

BACKGROUND: Understanding behavior change techniques (BCTs) used in randomized controlled trials (RCTs) of physical activity programs/services for older adults can help us to guide their implementation in real-world settings. PURPOSE: This study aims to: (a) identify the number and type of BCTs used in physical activity programs/services for older adults evaluated in large, good quality RCTs and (b) explore the impact of different BCTs on different outcome domains. METHODS: This is a secondary data analysis of a WHO-commissioned rapid review of physical activity programs/services for older adults. Fifty-six trials testing 70 interventions were coded for the type and number of BCTs present using a published BCT taxonomy. The proportion of positive effects found from physical activity interventions using the most common BCTs was calculated for the outcomes of physical activity, intrinsic capacity, functional ability, social domain, cognitive and emotional functioning, and well-being and quality of life. RESULTS: Thirty-nine of the 93 possible BCTs were identified in the included trials and 529 BCTs in total (mean 7.6, range 2-17). The most common BCTs were "action planning" (68/70 interventions), "instructions on how to perform a behavior" (60/70), "graded tasks" (53/70), "demonstration of behavior" (44/70), and "behavioral practice/rehearsal" (43/70). Interventions that used any of the most common BCTs showed overwhelmingly positive impacts on physical activity and social domain outcomes. CONCLUSION: Consideration of which BCTs are included in interventions and their impact on outcomes can improve the effectiveness and implementation of future interventions. To enable this, providers can design, implement, and evaluate interventions using a BCT taxonomy.

Interventions aimed at modifying health-related behaviors, such as physical activity, are often complex, with numerous components. To better understand interventions' "active ingredients," we conducted a secondary analysis of a World Health Organization (WHO)-commissioned rapid review, using a behavior change technique (BCT) taxonomy. We aimed to classify the number and types of BCTs in physical activity programs for older adults, as identified in randomized controlled trials (RCTs), and examine their impact on outcomes, including physical activity, intrinsic capacity, functional ability, social domain, cognitive and emotional functioning, and well-being. Examining 56 trials testing 70 interventions, we identified 39 out of 93 possible BCTs, totaling 529 instances across interventions. Common BCTs included "action planning," "instructions on how to perform a behavior," "graded tasks," "demonstration of behavior," and "behavioral practice/rehearsal." Interventions using the 10 most common BCTs demonstrated overwhelmingly positive impacts on physical activity and social domain outcomes. However, these BCTs were not consistently present in interventions yielding positive outcomes in other domains, with greater variation in effects. Our study highlights the significance of identifying both BCTs and desired outcomes when designing physical activity interventions. We advocate for the use of a taxonomy in designing and implementing future programs to maximize effectiveness.

Effective fall prevention exercise in residential aged care: an intervention component analysis from an updated systematic review.

OBJECTIVE: The effect of fall prevention exercise programmes in residential aged care (RAC) is uncertain. This paper reports on an intervention component analysis (ICA) of randomised controlled trials (RCTs), from an update of a Cochrane review, to develop a theory of features of successful fall prevention exercise in RAC. METHODS: Trial characteristics were extracted from RCTs testing exercise interventions in RAC identified from an update of a Cochrane review to December 2022 (n=32). Eligible trials included RCTs or cluster RCTs in RAC, focusing on participants aged 65 or older, assessing fall outcomes with stand-alone exercise interventions. ICA was conducted on trials with >30 participants per treatment arm compared with control (n=17). Two authors coded trialists' perceptions on intervention features that may have contributed to the observed effect on falls. Inductive thematic analysis was used to identify the key differences between the trials which might account for positive and negative outcomes. RESULTS: 32 RCTs involving 3960 residents including people with cognitive (57%) and mobility (41%) impairments were included. ICA on the 17 eligible RCTs informed the development of a theory that (1) effective fall prevention exercise delivers the right exercise by specifically targeting balance and strength, tailored to the individual and delivered simply at a moderate intensity and (2) successful implementation needs to be sufficiently resourced to deliver structured and supervised exercise at an adequate dose. CONCLUSIONS: This analysis suggests that delivering the right exercise, sufficiently resourced, is important for preventing falls in RAC. This clinical guidance requires confirmation in larger trials.

Effects of sport or physical recreation for adults with physical or intellectual disabilities: a systematic review with meta-analysis.

OBJECTIVES: To evaluate the effects of sport or physical recreation on participation, mobility and quality of life for adults living with disabilities. DESIGN: Systematic review with meta-analysis. DATA SOURCES: Six databases searched from inception to May 2022. ELIGIBILITY CRITERIA: Randomised controlled trials including adults living with a physical or intellectual disability, comparing sport or physical recreation to non-active control. RESULTS: Seventy-four trials (n=2954; mean age 55 years) were included. Most (70) trials included people with physical disabilities, none evaluated sport and the most common physical recreation activities tested were traditional Chinese exercise (35%), yoga (27%) and dance (18%). Mean frequency and duration was 65 min/session, two times per week for 13 weeks. Most (86%) interventions were led by people with experience and/or training in the recreation activity, and only 37% reported leader experience and/or training working with people with disabilities. Participation was measured as attendance (mean 81%, 30 intervention groups). Physical recreation improved mobility (standardised mean difference (SMD) 0.38, 95% CI 0.07 to 0.69, n=469) and walking endurance (mean difference (MD) 40.3 m, 95% CI 19.5 to 61.1, n=801) with low certainty evidence and balance (Berg Balance Scale, range 0-56 points; MD 3.4 points, 95% CI 2.3 to 4.4, n=906) and quality of life (physical health; SMD 0.37, 95% CI 0.02 to 0.72, n=468) with very low certainty evidence, but not walking speed (MD 0.03 m/s, 95% CI -0.05 to 0.11, n=486). CONCLUSION: Physical recreation may confer multiple benefits for people living with disabilities regardless of the activity chosen, thus offering a potentially enjoyable and scalable strategy to increase physical activity. PROSPERO REGISTRATION NUMBER: CRD42018104379.

Exercise Interventions Delivered Through Telehealth to Improve Physical Functioning for Older Adults with Frailty, Cognitive, or Mobility Disability: A Systematic Review and Meta-Analysis.

Introductions: This study assessed the effects of telehealth-delivered exercise interventions on physical functioning for older adults and explored implementation measures related to program delivery. Methods: We conducted a systematic review of studies investigating effects of exercise interventions delivered through telehealth in adults 60+ years of age with frailty, mobility, or cognitive disability on mobility, strength, balance, falls, and quality of life (QoL). Electronic databases (MEDLINE, CINAHL, SPORTSDiscus, and Physiotherapy Evidence Database) were searched from inception until May 2022. Evidence certainty was assessed with Grading of Recommendations, Assessment, Development, and Evaluation and meta-analysis summarized study effects. Results: A total of 11 studies were included, 5 randomized controlled trials, 2 pilot studies, and 4 feasibility studies. The overall certainty of evidence was rated as "low" or "very low." Pooled between-group differences were not statistically significant, but effect sizes suggested that telehealth produced a moderate improvement on mobility (n = 5 studies; standardized mean difference [SMD] = 0.63; 95% confidence interval [CI] = -0.25 to 1.51; p = 0.000, I2 = 86%) and strength (n = 4; SMD = 0.73; 95% CI = -0.10 to 1.56; p = 0.000, I2 = 84%), a small improvement on balance (n = 3; SMD = 0.40; 95% CI = -035 to 1.15; p = 0.012, I2 = 78%), and no effect on QoL. Analysis of implementation measures suggested telehealth to be feasible in this population, given high rates of acceptability and adherence with minimal safety concerns. Discussion: Telehealth may provide small to moderate benefits on a range of physical outcomes and appears to be well received in aged care populations.

Comparative analysis of asian carps parvalbumin reveals the divergence pattern of major fish allergen.

BACKGROUND: Asian carps, a popular freshwater fish globally, are valued for their flavor and serve as a crucial protein source, especially for infants. However, grass carp parvalbumin is highly allergenic, surpassing the allergenicity of fish like salmon and cod. The allergenic potential of parvalbumin in other Asian carps remains unknown, underscoring the need for allergen identification to improve the precision of fish allergy diagnosis and treatment. OBJECTIVE: To identify all parvalbumin homologs in Asian carps and investigate the role of gene divergence in allergenic homolog formation. METHODS: Three annotated genomes of Asian carp, including grass carp, black carp and bighead carp, were constructed using a hybrid assembly approach. Through sequence homology at the genomic level, all the homologs of major fish allergens were identified. Bioinformatics tools were then employed to reveal the gene structures, expression levels, and protein conformations of parvalbumin. RESULTS: Grass carp genome analysis showed nine parvalbumin homologs, with Cid_PV2 most similar to Cten i 1. Bighead and black carp genomes had ten homologs, including potentially allergenic Mpi_PV7 and Hno_PV7. Tissue-specific expression patterns revealed alternative usage of parvalbumin homologs. Gene duplication events expanded parvalbumin copies in bony fish, with two gene clusters identified in Asian carp genomes. CONCLUSION: All the homologs of Asian carps' parvalbumin were accurately identified and gene divergence contributed to the formation of allergenic homologs. Together with a comprehensive gene sequence profile of carps' parvalbumin, those could be applied to achieve a more precise clinical diagnostic test.

Tetradentate C∧C∧N∧N Ligand-Containing Gold(III) Complexes with Orange to Deep-Red Thermally Activated Delayed Fluorescence (TADF) and Their Application in Organic Light-Emitting Devices.

A new class of thermally activated delayed fluorescence (TADF) tetradentate C∧C∧N∧N ligand-containing gold(III) complexes containing acridinyl moieties has been designed and synthesized. These complexes exhibit orange-red to deep-red emission with photoluminescence quantum yields (PLQYs) of up to 0.76 in solid-state thin films. Short excited-state lifetimes of ≤2.0 µs and large radiative decay rate constants (kr) in the order of 105 s-1 have also been found in the complexes. High-performance solution-processed and vacuum-deposited organic light-emitting devices (OLEDs) based on these complexes have been fabricated, demonstrating high maximum external quantum efficiencies (EQEs) of 12.2 and 12.7%, respectively, which are among the best values ever reported for red-emitting gold(III)-based OLEDs. In addition, satisfactory operational half-lifetime (LT50) values of up to 34,058 h have been attained in these red-emitting devices. It is found that the operational stability is strongly dependent on the choice of functional groups on the acridinyl moieties, of which the incorporation of -O- and -S- linkers can effectively prolong the LT50 value by an order of magnitude. The TADF properties of the complexes are substantiated by the hypsochromic shift in emission energies and the remarkable enhancement in the emission intensity upon increasing temperature. The TADF properties have also been supported by temperature-dependent ultrafast transient absorption studies, with the direct observation of reverse intersystem crossing (RISC) and the determination of the activation parameters for the very first time, together with their excited-state dynamics.

Comparative Genomics Reveals Insights into the Divergent Evolution of Astigmatic Mites and Household Pest Adaptations.

Highly diversified astigmatic mites comprise many medically important human household pests such as house dust mites causing ∼1-2% of all allergic diseases globally; however, their evolutionary origin and diverse lifestyles including reversible parasitism have not been illustrated at the genomic level, which hampers allergy prevention and our exploration of these household pests. Using six high-quality assembled and annotated genomes, this study not only refuted the monophyly of mites and ticks, but also thoroughly explored the divergence of Acariformes and the diversification of astigmatic mites. In monophyletic Acariformes, Prostigmata known as notorious plant pests first evolved, and then rapidly evolving Astigmata diverged from soil oribatid mites. Within astigmatic mites, a wide range of gene families rapidly expanded via tandem gene duplications, including ionotropic glutamate receptors, triacylglycerol lipases, serine proteases and UDP glucuronosyltransferases. Gene diversification after tandem duplications provides many genetic resources for adaptation to sensing environmental signals, digestion, and detoxification in rapidly changing household environments. Many gene decay events only occurred in the skin-burrowing parasitic mite Sarcoptes scabiei. Throughout the evolution of Acariformes, massive horizontal gene transfer events occurred in gene families such as UDP glucuronosyltransferases and several important fungal cell wall lytic enzymes, which enable detoxification and digestive functions and provide perfect drug targets for pest control. This comparative study sheds light on the divergent evolution and quick adaptation to human household environments of astigmatic mites and provides insights into the genetic adaptations and even control of human household pests.

meGPS: a multi-omics signature for hepatocellular carcinoma detection integrating methylome and transcriptome data.

MOTIVATION: Hepatocellular carcinoma (HCC) is a primary malignancy with a poor prognosis. Recently, multi-omics molecular-level measurement enables HCC diagnosis and prognosis prediction, which is crucial for early intervention of personalized therapy to diminish mortality. Here, we introduce a novel strategy utilizing DNA methylation and RNA expression data to achieve a multi-omics gene pair signature (GPS) for HCC discrimination. RESULTS: The immune genes with negative correlations between expression and promoter methylation are enriched in the highly connected cancer-related pathway network, which are considered as the candidates for HCC detection. After that, we separately construct a methylation GPS (mGPS) and an expression GPS (eGPS), and then assemble them as a meGPS with five gene pairs, in which the significant methylation and expression changes occur between HCC tumor and non-tumor groups. Reliable performance has been validated by independent tissue (age, gender and etiology) and blood datasets. This study proposes a procedure for multi-omics GPS identification and develops a novel HCC signature using both methylome and transcriptome data, suggesting potential molecular targets for the detection and therapy of HCC. AVAILABILITY AND IMPLEMENTATION: Models are available at https://github.com/bioinformaticStudy/meGPS.git. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Genome assembly and annotation of Periplaneta americana reveal a comprehensive cockroach allergen profile.

BACKGROUND: One of the most common cockroach types in urban areas, the American cockroach (Periplaneta americana), has been reported to impose an increased risk of allergies and asthma. Limited groups of allergens (Per a 1-13) have been identified in this species due to the lack of genome-related information. METHODS: To expand the allergen profile of P. americana, genomic, transcriptomic, and proteomic approaches were applied. With the support of a high-quality genome assembled using nanopore, Illumina, and Hi-C sequencing techniques, potential allergens were identified based on protein homology. Then, using enzyme-linked immunosorbent assay, selected allergens were tested in Thai patients allergic to P. americana. RESULTS: A chromosomal-level genome of P. americana (3.06 Gb) has been assembled with 94.6% BUSCO completeness, and its contiguity has been significantly improved (N50 = 151 Mb). A comprehensive allergen profile has been characterized, with seven novel groups of allergens, including enolase (Per a 14), cytochrome C (Per a 15), cofilin (Per a 16), alpha-tubulin (Per a 17), cyclophilin (Per a 18), porin3 (Per a 19), and peroxiredoxin-6 (Per a 20), showing IgE sensitivity in enzyme-linked immunosorbent assay. A new isoallergen of tropomyosin (Per a 7.02) and multiple potential isoallergens of Per a 5 were revealed using bioinformatics and proteomic approaches. Additionally, comparative analysis of P. americana with the closely related Blattodea species revealed the possibility of cross-reaction. CONCLUSION: The high-quality genome and proteome of P. americana are beneficial in studying cockroach allergens at the molecular level. Seven novel allergen groups and one isoallergen in Per a 7 were identified.

Critical features of multifactorial interventions for effective falls reduction in residential aged care: a systematic review, intervention component analysis and qualitative comparative analysis.

BACKGROUND: Multifactorial fall prevention trials providing interventions based on individual risk factors have variable success in aged care facilities. To determine configurations of trial features that reduce falls, intervention component analysis (ICA) and qualitative comparative analysis (QCA) were undertaken. METHODS: Randomised controlled trials (RCTs) from a Cochrane Collaboration review (Cameron, 2018) with meta-analysis data, plus trials identified in a systematic search update to December 2021 were included. Meta-analyses were updated. A theory developed through ICA of English publications of trialist's perspectives was assessed through QCA and a subgroup meta-analysis. RESULTS: Pooled effectiveness of multifactorial interventions indicated a falls rate ratio of 0.85 (95% confidence interval, CI, 0.65-1.10; I2 = 85%; 11 trials). All tested interventions targeted both environmental and personal risk factors by including assessment of environmental hazards, a medical or medication review and exercise intervention. ICA emphasised the importance of co-design involving facility staff and managers and tailored intervention delivery to resident's intrinsic factors for successful outcomes. QCA of facility engagement plus tailored delivery was consistent with greater reduction in falls, supported by high consistency (0.91) and coverage (0.85). An associated subgroup meta-analysis demonstrated strong falls reduction without heterogeneity (rate ratio 0.61, 95%CI 0.54-0.69, I2 = 0%; 7 trials). CONCLUSION: Multifactorial falls prevention interventions should engage aged care staff and managers to implement strategies which include tailored intervention delivery according to each resident's intrinsic factors. Such approaches are consistently associated with a successful reduction in falls, as demonstrated by QCA and subgroup meta-analyses. Co-design approaches may also enhance intervention success.

Physical activity and injurious falls in older Australian women: adjusted associations and modification by physical function limitation and frailty in the Australian Longitudinal Study on Women's Health.

OBJECTIVES: To investigate associations between leisure-time physical activity (LPA) and injurious falls in older women and explore modification of associations by physical function and frailty. METHODS: Women born during 1946-51 from the Australian Longitudinal Study on Women's Health, injurious falls (self-reported fall with injury and/or medical attention) and self-reported weekly LPA (duration and type). We undertook cross-sectional and prospective analyses using data from 2016 [n = 8,171, mean (SD) age 68 (1)] and 2019 surveys (n = 7,057). Associations were quantified using directed acyclic graph-informed logistic regression and effect modification examined using product terms. RESULTS: Participation in LPA as recommended by World Health Organization (150-300 min/week) was associated with lower odds of injurious falls in cross-sectional (adjusted Odds Ratio (OR) 0.74, 95% CI 0.61-0.90) and prospective analyses (OR 0.75, 95% CI 0.60-0.94). Compared with those who reported no LPA, cross-sectionally, odds of injurious falls were lower in those who reported brisk walking (OR 0.77, 95% CI 0.67-0.89) and vigorous LPA (OR 0.86, 95% CI 0.75-1.00). No significant association was found between different types of LPA and injurious falls prospectively. Only cross-sectionally, physical function limitation and frailty modified the association between LPA and injurious falls, with tendencies for more injurious falls with more activity in those with physical limitation or frailty, and fewer injurious falls with more activity among those without physical function limitation or frailty. CONCLUSION: Participation in recommended levels of LPA was associated with lower odds of injurious falls. Caution is required when promoting general physical activity among people with physical limitation or frailty.

Cost-effectiveness of physical activity programs and services for older adults: a scoping review.

BACKGROUND: Evidence supporting physical activity for older adults is strongly positive. Implementation and scale-up of these interventions need to consider the value for money. This scoping review aimed to assess the volume of (i) systematic review evidence regarding economic evaluations of physical activity interventions, and (ii) of cost utility analysis (CUA) studies (trial- or model-based) of physical activity interventions for older people. METHODS: We searched five databases (January 2010 to February 2022) for systematic reviews of economic evaluations, and two databases (1976 to February 2022) for CUA studies of physical activity interventions for any population of people aged 60+ years. RESULTS: We found 12 potential reviews, two of which were eligible for inclusion. The remaining 10 reviews included eligible individual studies that were included in this review. All individual studies from the 12 reviews (n = 37) investigated the cost-effectiveness of structured exercise and most showed the intervention was more costly but more effective than no intervention. We identified 27 CUA studies: two investigated a physical activity promotion program and the remainder investigated structured exercise. Most interventions (86%) were more costly but more effective, and the remaining were cost-saving compared to no intervention. CONCLUSIONS: There is a scarcity of reviews investigating the value for money of physical activity interventions for older adults. Most studies investigated structured exercise. Physical activity interventions were generally more effective than no intervention but more costly. As such an intervention could be cost-effective and therefore worthy of wider implementation, but there is a need for more frequent economic evaluation in this field.

Exercise for falls prevention in aged care: systematic review and trial endpoint meta-analyses.

BACKGROUND: There is strong evidence that exercise reduces falls in older people living in the community, but its effectiveness in residential aged care is less clear. This systematic review examines the effectiveness of exercise for falls prevention in residential aged care, meta-analysing outcomes measured immediately after exercise or after post-intervention follow-up. METHODS: Systematic review and meta-analysis, including randomised controlled trials from a Cochrane review and additional trials, published to December 2022. Trials of exercise as a single intervention compared to usual care, reporting data suitable for meta-analysis of rate or risk of falls, were included. Meta-analyses were conducted according to Cochrane Collaboration methods and quality of evidence rated using the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS: 12 trials from the Cochrane review plus 7 new trials were included. At the end of the intervention period, exercise probably reduces the number of falls (13 trials, rate ratio [RaR] = 0.68, 95% confidence interval [CI] = 0.49-0.95), but after post-intervention follow-up exercise had little or no effect (8 trials, RaR = 1.01, 95% CI = 0.80-1.28). The effect on the risk of falling was similar (end of intervention risk ratio (RR) = 0.84, 95% CI = 0.72-0.98, 12 trials; post-intervention follow-up RR = 1.05, 95% CI = 0.92-1.20, 8 trials). There were no significant subgroup differences according to cognitive impairment. CONCLUSIONS: Exercise is recommended as a fall prevention strategy for older people living in aged care who are willing and able to participate (moderate certainty evidence), but exercise has little or no lasting effect on falls after the end of a programme (high certainty evidence).

Telomere Length among Chinese Aged 75+ Years.

INTRODUCTION: Telomere length (TL) is generally regarded as a biomarker of aging. TL, which is influenced by sociodemographic factors, has been shown to be inversely associated with morbidity. However, most studies examined the youngest, and whether the findings can be extended to older individuals is less clear. Further, few studies have examined these questions in Chinese older adults. This cross-sectional study examined TL and its associated factors in Chinese aged 75+ years in Hong Kong. METHODS: Participants were from the Mr. and Ms. Osteoporosis cohort. A structured interview on sociodemographic factors and physical measurement was conducted. Frailty and sarcopenia status were respectively determined by Fried's criteria and the Asian Working Group for Sarcopenia definition. TL was measured by a molecular inversion probe-quantitative PCR assay and expressed as a novel telomere/a single copy reference gene (T/S) ratio. Adjusted binary logistic regressions were used to examine the associations between TL and the presence of multimorbidity, age-related diseases, frailty, and sarcopenia. RESULTS: Among 555 participants (mean age 83.6 ± 3.8 years, 41.3% females), the mean T/S ratio was 1.01 ± 0.20. Males had a lower T/S ratio (0.97 ± 0.20) compared with females (1.07 ± 0.18) (p < 0.001). A lower education level was related to a longer TL (p = 0.016). Being a current smoker was related to a shorter TL (p = 0.007). TL was not significantly different across categories of age, subjective socioeconomic status, drinking status, physical activity level, and body mass index (p > 0.05). There were no associations between TL and the presence of multimorbidity, diabetes, stroke, cardiovascular diseases, cognitive impairment, frailty, and sarcopenia. CONCLUSION: Among Chinese aged 75+ years, males had shorter TL compared with females. TL was not associated with age-related diseases, frailty, and sarcopenia in this age group. TL may not be a biological marker of aging among older individuals.

Effect of sport on health in people aged 60 years and older: a systematic review with meta-analysis.

OBJECTIVES: To summarise evidence of benefits of sport for health among people aged 60+. DESIGN: Systematic review with meta-analysis of randomised controlled trials (RCTs). DATA SOURCES: Medline, CINAHL, SPORTDiscus, the Physiotherapy Evidence Database from inception to April 2021. STUDY SELECTION: RCTs investigating the effect of sport on health-related outcomes in people aged 60+ compared with non-active control. DATA SYNTHESIS AND ANALYSIS: Pooled effect sizes were calculated using random-effect models. Standardised mean differences (SMD), and mean difference (MD) were calculated. The Grading of Recommendations Assessment, Development and Evaluation system was used to assess the certainty of the evidence for analyses with ≥3 studies. RESULTS: Nine trials (628 participants) reported in 15 articles were included. Participation in sport improved cardiorespiratory fitness (n=5 trials; SMD=0.43, 95% CI 0.17 to 0.70; low certainty evidence), physical function (n=4; SMD=0.62, 95% CI 0.05 to 1.18; very low certainty evidence), and mental health (n=2; SMD=0.28, 95% CI 0.06 to 0.51) and reduced fat mass (n=6; MD=-0.99 kg, 95% CI -1.75kg to -0.23 kg; low certainty evidence) among older people. We found no significant effects of sport on overall physical activity participation, strength, balance, lean mass and bone mineral density (BMD). One study investigating quality of life reported a positive, but non-significant effect of sport. CONCLUSION: Sport may have a positive impact on health outcomes in people aged 60+. There was uncertainty on the effect of sport on strength, balance, lean mass and BMD. Further research is needed to investigate the optimal type and dose of sport to maximise the long-term benefits among older people.

Unique Gut Microbiome Signatures among Adult Patients with Moderate to Severe Atopic Dermatitis in Southern Chinese.

Imbalance of the immune system caused by alterations of the gut microbiome is considered to be a critical factor in the pathogenesis of infant eczema, but the exact role of the gut microbiome in adult atopic dermatitis (AD) patients remains to be clarified. To investigate the differences of the gut microbiome between adult AD patients and healthy individuals, stool samples of 234 adults, containing 104 AD patients and 130 healthy subjects, were collected for 16S rRNA gene amplicon. Altered structure and metabolic dysfunctions of the gut microbiome were identified in adult AD patients. Our results illustrated that the adult AD patients were more likely to have allergies, particularly non-food allergies. In addition, the gut microbiome composition of the AD and normal groups were considerably different. Moreover, Romboutsia and Clostridi-um_sensu_stricto_1 was enriched in the normal group, whereas Blautia, Butyricicoccus, Lachnoclostridium, Eubacterium_hallii_group, Erysi-pelatoclostridium, Megasphaera, Oscillibacter, and Flavonifractor dominated in the AD group. Additionally, purine nucleotide degradation pathways were significantly enriched in the AD group, and the enrichment of proteinogenic amino acid biosynthesis pathways was found in the normal group. This study provides insights into new therapeutic strategies targeting the gut microbiome for AD and evidence for the involvement of the gut-skin axis in AD patients.