Search

Background: This study aims to investigate age- and gender-specific effects of household solid fuels for heating on major depression and buffering effects of outdoor time in a high-income country., Methods: Data were obtained from the UK Biobank. Participants with complete information on our studied variables and no prior diagnosis of major depression at baseline were included. Cox proportional hazards regression models were used to examine the effects of household solid fuels for heating on major depression. Subgroup analyses were conducted to investigate the buffering effects of outdoor time in summer and winter. Sensitivity analyses were performed to test the robustness of the main findings., Results: Of 255,505 participants (50.2 % women), the 12-year cumulative incidence of major depression was 4.4 %. Household solid fuels for heating increased the risk of major depression only in women aged <45 years (HR (95%CI) = 1.30 (1.04, 1.63)). In this group, the solid fuel effect was moderated by outdoor time spending both in summer (HR (95%CI), ≤2 h/day: 1.61 (1.13, 2.28); >2 h/day: 1.13 (0.84, 1.52)) and winter (≤1 h/day: 1.35 (1.01, 1.08); >1 h/day: 1.24 (0.86, 1.77))., Limitations: Self-reported measures might lead to recall bias and some potential confounders, such as ventilation efficiency, were not measured and controlled in data analyses., Conclusions: Younger women are more vulnerable to the impact of domestic air pollution on major depression. Promoting outdoor activities is a cost-effective and efficient approach to mitigating the risk of major depression caused by household solid fuels., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)

Phototransduction in vertebrate photoreceptor cells is controlled by Ca 2+ -dependent feedback loops involving the membrane-bound guanylate cyclase GC-E that synthesizes the second messenger guanosine-3',5'-cyclic monophosphate. Intracellular Ca 2+ -sensor proteins named guanylate cyclase-activating proteins (GCAPs) regulate the activity of GC-E by switching from a Ca 2+ -bound inhibiting state to a Ca 2+ -free/Mg 2+ -bound activating state. The gene GUCY2D encodes for human GC-E, and mutations in GUCY2D are often associated with an imbalance of Ca 2+ and cGMP homeostasis causing retinal disorders. Here, we investigate the Ca 2+ -dependent inhibition of the constitutively active GC-E mutant V902L. The inhibition is not mediated by GCAP variants but by Ca 2+ replacing Mg 2+ in the catalytic center. Distant from the cyclase catalytic domain is an α-helical domain containing a highly conserved helix-turn-helix motif. Mutating the critical amino acid position 804 from leucine to proline left the principal activation mechanism intact but resulted in a lower level of catalytic efficiency. Our experimental analysis of amino acid positions in two distant GC-E domains implied an allosteric communication pathway connecting the α-helical and the cyclase catalytic domains. A computational connectivity analysis unveiled critical differences between wildtype GC-E and the mutant V902L in the allosteric network of critical amino acid positions.

Purpose: Osteoporosis is an important public health challenge given its high prevalence in western populations and the prevalence has shown an upward trend in recent decades in Asia. However, epidemiological evidence on the association between bone mineral density (BMD) and mortality risk in the Asian population is sparse., Methods: The Cox proportional hazards model and cause-specific hazard models were used to investigate the association of BMD with the risk of all-cause mortality and cause-specific mortality., Results: The present study comprised of 3,332,207 person-years with a median follow-up of 14.6 years. 27,508 participants (15,967 men and 11,541 women) died among 233,397 participants (112,348 men and 121,049 women) during the follow-up period. Compared to those with normal BMD level, both men and women with low BMD had a significantly higher risk of all-cause, cardiovascular disease (CVD), and cancer mortality after adjusting for the covariates. [For men with osteoporosis: all-cause: 1.37 (1.27-1.49); CVD: 1.28 (1.08-1.52); cancer: 1.29 (1.12-1.49); For women with osteoporosis: all-cause: 1.72 (1.63-1.82); CVD: 1.85 (1.64-2.08); cancer: 1.47 (1.35-1.61)]. The P for interactions for BMD with sex were significant for all-cause and CVD mortality. The adverse effects of BMD on the risk of all-cause and CVD were higher in women than in men [men vs. women: all-cause: 1.37 (1.27-1.49) vs. 1.72 (1.63-1.82); CVD: 1.28 (1.08-1.52) vs. 1.85 (1.64-2.08)]. In the nonlinear dose-response analyses, the association between BMD increments and all-cause mortality risk shows an L-shaped pattern in men and a similar U-shaped trend in women (P for non-linear association: <0.001). Likewise, a similar L-shaped association was observed between BMD levels and cancer mortality risk in men., Conclusions: Low BMD had an increased risk of all-cause, CVD, and cancer mortality in both men and women. Women had a stronger positive association between low BMD and an increased risk of all-cause and CVD mortality compared to men., Competing Interests: Declaration of competing interest We declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Complete chloroplast genomes of 17 samples from six species of Colocasia (Araceae) were sequenced, assembled, and aligned together with two previously reported complete genome sequences from taro ( Colocasia esculenta ). Analysis provides a well-supported phylogenetic tree for taro and closely-related wild Colocasia species in Southeast Asia. Two chloroplast lineages (CI and CII) form a well-defined haplotype group and are found in cultivated taros known as var. esculenta (dasheen, CI), var. antiquorum (eddoe, CII), and in a widespread, commensal wild form known as var. aquatilis (CI). A third lineage (CIII) is also found in wild taros known as var. aquatilis and in the wild species C. lihengiae , C. formosana , and C. spongifolia . We suggest three different scenarios to explain the grouping of CIII wild taros ( C. esculenta ) with other wild Colocasia species. Chloroplast lineages CI and CIII in C. esculenta and an unknown parent species may be involved in an as yet undated history of hybridization, chloroplast capture, and range extension. Substantial taxonomic revision may be needed for C. esculenta after further studies of morphological and genetic diversity within the crop, in wild populations, and in closely related wild species. The results also point to the Bengal delta as a region of key interest for future research on the origins of tropical wetland taros., Competing Interests: The authors have no conflicts of interest to declare., (© 2024 The Author(s). Ecology and Evolution published by John Wiley & Sons Ltd.)

Background: Virtual reality (VR) in different immersive conditions has been increasingly used as a nonpharmacological method for managing chronic musculoskeletal pain., Objective: We aimed to assess the effectiveness of VR-assisted active training versus conventional exercise or physiotherapy in chronic musculoskeletal pain and to analyze the effects of immersive versus nonimmersive VR on pain outcomes., Methods: This systematic review of randomized control trials (RCTs) searched PubMed, Scopus, and Web of Science databases from inception to June 9, 2024. RCTs comparing adults with chronic musculoskeletal pain receiving VR-assisted training were included. The primary outcome was pain intensity; secondary outcomes included functional disability and kinesiophobia. Available data were pooled in a meta-analysis. Studies were graded using the Cochrane Risk-of-Bias Tool version 2., Results: In total, 28 RCTs including 1114 participants with some concerns for a high risk of bias were identified, and 25 RCTs were included in the meta-analysis. In low back pain, short-term outcomes measured post intervention showed that nonimmersive VR is effective in reducing pain (standardized mean difference [SMD] -1.79, 95% CI -2.72 to -0.87; P<.001), improving disability (SMD -0.44, 95% CI -0.72 to -0.16; P=.002), and kinesiophobia (SMD -2.94, 95% CI -5.20 to -0.68; P=.01). Intermediate-term outcomes measured at 6 months also showed that nonimmersive VR is effective in reducing pain (SMD -8.15, 95% CI -15.29 to -1.01; P=.03), and kinesiophobia (SMD -4.28, 95% CI -8.12 to -0.44; P=.03) compared to conventional active training. For neck pain, immersive VR reduced pain intensity (SMD -0.55, 95% CI -1.02 to -0.08; P=.02) but not disability and kinesiophobia in the short term. No statistical significances were detected for knee pain or other pain regions at all time points. In addition, 2 (8%) studies had a high risk of bias., Conclusions: Both nonimmersive and immersive VR-assisted active training is effective in reducing back and neck pain symptoms. Our study findings suggest that VR is effective in alleviating chronic musculoskeletal pain., Trial Registration: PROSPERO CRD42022302912; https://www.crd.york.ac.uk/prospero/display&#95;record.php?RecordID=302912., (©Hermione Hin Man Lo, Mengting Zhu, Zihui Zou, Cho Lee Wong, Suzanne Hoi Shan Lo, Vincent Chi-Ho Chung, Samuel Yeung-Shan Wong, Regina Wing Shan Sit. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 19.08.2024.)

High-sugar intake is a risk factor for chronic diseases such as cardiovascular disease and type 2 diabetes, but less is known about its role in anxiety disorders. This systematic review aimed to systematically synthesise and assess the existing evidence regarding the association between dietary sugars intake and anxiety disorders. Following PRISMA guidelines, a systematic search of PubMed, MEDLINE, Embase, APA PsycArticles and APA PsycINFO was conducted up to 19th August 2022. Study quality was assessed by the Newcastle-Ottawa scale (NOS) and the Cochrane risk of bias tool. Eleven studies (10 cross-sectional and 1 randomised controlled trial [RCT]) were included. Seven cross-sectional studies had very good quality or good quality, and the quality of the RCT was at low risk of bias. These studies examined sugar-sweetened beverages (n = 7), sugar-sweetened foods (n = 4) and/or added sugar (n = 5). The findings suggest a possible positive relationship of added sugar consumption with anxiety disorders, with age as a potential moderator in such association. No conclusions can be drawn on the associations between sugar-sweetened beverages, sugar-sweetened foods consumption and anxiety disorders. Due to the included studies being mostly cross-sectional, the conclusions drawn from the existing evidence should be interpreted with caution. The longitudinal design is warranted to investigate any causal relationship and the potential mechanisms underlying these heterogeneous results. The potential difference in effect at different ages observed in this review should be further examined., (© 2024 The Author(s). Nutrition Bulletin published by John Wiley & Sons Ltd on behalf of British Nutrition Foundation.)

Background & Aims: Perianal fistulation is a challenging phenotype of Crohn's disease, with significant impact on quality of life. Historically, fistulae have been classified anatomically in relation to the sphincter complex, and management guidelines have been generalized, with lack of attention to the clinical heterogenicity seen. The recent 'TOpClass classification system' for perianal fistulizing Crohn's disease (PFCD) addresses this issue, and classifies patients into defined groups, which provide a focus for fistula management that aligns with disease characteristics and patient goals. In this article, we discuss the clinical applicability of the TOpClass model and provide direction on its use in clinical practice., Methods: An international group of perianal clinicians participated in an expert consensus to define how the TOpClass system can be incorporated into real-life practice. This included gastroenterologists, inflammatory bowel disease surgeons, and radiologists specialized in PFCD. The process was informed by the multi-disciplinary team management of 8 high-volume fistula centres in North America, Europe, and Australia., Results: The process produced position statements to accompany the classification system and guide PFCD management. The statements range from the management of patients with quiescent perianal disease to those with severe PFCD requiring diverting-ostomy and/or proctectomy. The optimization of medical therapies, as well as the use of surgery, in fistula closure and symptom management is explored across each classification group., Conclusion: This article provides an overview of the system's use in clinical practice. It aims to enable clinicians to have a pragmatic and patient goal-centered approach to medical and surgical management options for individual patients with PFCD., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background and Aims: We aimed to assess the relationship between smoking status and carotid atherosclerosis (CA) with different manifestations and to explore the underlying mechanisms., Methods and Results: A total of 60,655 middle-aged and elderly participants were recruited. Logistic regression models were used to examine the association of smoking, various blood indexes [i.e., blood pressure, blood lipid, glycated hemoglobin (HbA1c) and homocysteine (Hcy)] with CA in different manifestations including carotid intima-media thickness (cIMT), plaques, and stenosis. Compared with nonsmokers, current smokers were associated with a higher prevalence of CA (OR = 3.48, 95%CI: 3.21-3.77) and its specific manifestations including cIMT (OR = 2.66, 95%CI: 2.42-2.93), plaques (OR = 3.67, 95%CI: 3.35-4.02) and stenosis (OR = 2.04, 95%CI: 1.64-2.54), after adjusting for potential confounders. Former smokers were also associated with an increased prevalence of CA (OR = 1.82, 95%CI: 1.54-2.14), cIMT (OR = 1.39, 95%CI: 1.14-1.69), plaques (OR = 2.04, 95%CI: 1.71-2.44) and stenosis (OR = 1.72, 95%CI: 1.18-2.51), but the associations were consistently weaker than that of the current smokers. The prevalence of CA, cIMT, plaques and stenosis among current smokers was positively associated with pack-years of cigarette smoking, partially mediated by SBP, HbA1c, TG, HDL-C and Hcy with a mediated proportion of 1.12%, 3.28%, 6.33%, 6.01% and 12.7%, respectively. Stratified analysis by sex showed a significantly higher CA among the current male smokers than females., Conclusions: Current and former smoking was associated with increased carotid atherosclerosis, predominantly by current male smokers. A positive gradient between pack-years and carotid atherosclerosis among current smokers is partially mediated by SBP, HbA1c, TG, HDL-C and Hcy., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Overgeneralization and a lack of baseline data for microorganisms in high-latitude environments have restricted the understanding of the microbial response to climate change, which is needed to establish Antarctic conservation frameworks. To bridge this gap, we examined over 17,000 sequence variants of bacteria and microeukarya across the hyperarid Vestfold Hills and Windmill Islands regions of eastern Antarctica. Using an extended gradient forest model, we quantified multispecies response to variations along 79 edaphic gradients to explore the effects of change and wind-driven dispersal on community dynamics under projected warming trends. We also analyzed a second set of soil community data from the Windmill Islands to test our predictions of major environmental tipping points. Soil moisture was the most robust predictor for shaping the regional soil microbiome; the highest rates of compositional turnover occurred at 10-12% soil moisture threshold for photoautotrophs, such as Cyanobacteria, Chlorophyta, and Ochrophyta. Dust profiles revealed a high dispersal propensity for Chlamydomonas, a microalga, and higher biomass was detected at trafficked research stations. This could signal the potential for algal blooms and increased nonendemic species dispersal as human activities increase in the region. Predicted increases in moisture availability on the Windmill Islands were accompanied by high photoautotroph abundances. Abundances of rare oligotrophic taxa, such as Eremiobacterota and Candidatus Dormibacterota, which play a crucial role in atmospheric chemosynthesis, declined over time. That photosynthetic taxa increased as soil moisture increased under a warming scenario suggests the potential for competition between primary production strategies and thus a more biotically driven ecosystem should the climate become milder. Better understanding of environmental triggers will aid conservation efforts, and it is crucial that long-term monitoring of our study sites be established for the protection of Antarctic desert ecosystems. Furthermore, the successful implementation of an improved gradient forest model presents an exciting opportunity to broaden its use on microbial systems globally., (© 2024 The Authors. Conservation Biology published by Wiley Periodicals LLC on behalf of Society for Conservation Biology.)

Surgical site infection (SSI) caused by pathogenic bacteria leads to delayed wound healing and extended hospitalization. Inappropriate uses of antibiotics have caused a surge in SSI and common antibiotics are proving to be ineffective against SSI. Antimicrobial peptides (AMPs) can be a potential solution to prevent SSI because of their broad spectrum of antimicrobial activities. In this study, naturally sourced AMPs were studied along with microfibers, fabricated by a novel wet-spinning method using sodium alginate and polycaprolactone. Afterward, fibers were functionalized by the catechol groups of dopamine immobilizing nucleophilic AMPs on the surface. Conjugation between PCL and alginate resulted in fibers with smooth surfaces improving their mechanical strength via hydrogen bonds. Having an average diameter of 220 μm, the mechanical properties of the fiber complied with USP standards for suture size 3-0. Engineered microfibers were able to hinder the growth of Proteus spp., a pathogenic bacterium for at least 60 hours whereas antibiotic ceftazidime failed. When subjected to a linear incisional wound model study, accelerated healing was observed when the wound was closed using the engineered fiber compared to Vicryl. The microfibers promoted faster re-epithelialization compared to Vicryl proving their higher wound healing capacity.

Background: Previous literature lacks summative information on the mental health benefits achieved from different forms of walking., Objective: The aim of this study was to assess the effectiveness of different forms of walking in reducing symptoms of depression and anxiety., Methods: This was a systematic review and meta-analysis of randomized controlled trials (RCTs) assessing the effects of walking on depressive and anxiety symptoms. MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), Embase, PsycINFO, Allied and Complementary Medicine Database (AMED), CINAHL, and Web of Science were searched on April 5, 2022. Two authors independently screened the studies and extracted the data. Random-effects meta-analysis was used to synthesize the data. Results were summarized as standardized mean differences (SMDs) with 95% CIs in forest plots. The risk of bias was assessed by using the Cochrane Risk of Bias tool., Results: This review included 75 RCTs with 8636 participants; 68 studies reported depressive symptoms, 39 reported anxiety symptoms, and 32 reported both as the outcomes. One study reported the results for adolescents and was not included in the meta-analysis. The pooled results for adults indicated that walking could significantly reduce depressive symptoms (RCTs: n=44; SMD -0.591, 95% CI -0.778 to -0.403; I2=84.8%; τ2=0.3008; P<.001) and anxiety symptoms (RCTs: n=26; SMD -0.446, 95% CI -0.628 to -0.265; I2=81.1%; τ2=0.1530; P<.001) when compared with the inactive controls. Walking could significantly reduce depressive or anxiety symptoms in most subgroups, including different walking frequency, duration, location (indoor or outdoor), and format (group or individual) subgroups (all P values were <.05). Adult participants who were depressed (RCTs: n=5; SMD -1.863, 95% CI -2.764 to -0.962; I2=86.4%; τ2=0.8929) and those who were not depressed (RCTs: n=39; SMD -0.442, 95% CI -0.604 to -0.280; I2=77.5%; τ2=0.1742) could benefit from walking effects on their depressive symptoms, and participants who were depressed could benefit more (P=.002). In addition, there was no significant difference between walking and active controls in reducing depressive symptoms (RCTs: n=17; SMD -0.126, 95% CI -0.343 to 0.092; I2=58%; τ2=0.1058; P=.26) and anxiety symptoms (14 RCTs, SMD -0.053, 95% CI -0.311 to 0.206, I2=67.7%, τ2=0.1421; P=.69)., Conclusions: Various forms of walking can be effective in reducing symptoms of depression and anxiety, and the effects of walking are comparable to active controls. Walking can be adopted as an evidence-based intervention for reducing depression and anxiety. More evidence on the effect of low-intensity walking is needed in the future., (© Zijun Xu, Xiaoxiang Zheng, Hanyue Ding, Dexing Zhang, Peter Man-Hin Cheung, Zuyao Yang, King Wa Tam, Weiju Zhou, Dicken Cheong-Chun Chan, Wenyue Wang, Samuel Yeung-Shan Wong. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org).)

Our skin provides a protective barrier that shields us from our environment. Barrier function is typically associated with the interfollicular epidermis; however, whether hair follicles influence this process remains unclear. Here, we utilize a potent genetic tool to probe barrier function by conditionally ablating a quintessential epidermal barrier gene, Abca12, which is mutated in the most severe skin barrier disease, harlequin ichthyosis. With this tool, we deduced 4 ways by which hair follicles modulate skin barrier function. First, the upper hair follicle (uHF) forms a functioning barrier. Second, barrier disruption in the uHF elicits non-cell-autonomous responses in the epidermis. Third, deleting Abca12 in the uHF impairs desquamation and blocks sebum release. Finally, barrier perturbation causes uHF cells to move into the epidermis. Neutralizing IL-17a, whose expression is enriched in the uHF, partially alleviated some disease phenotypes. Altogether, our findings implicate hair follicles as multi-faceted regulators of skin barrier function., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The development of a rapid hemostat through a facile method with co-existing antibacterial activity and minimum erythrocyte lysis property stands as a major requirement in the field of hemostasis. Herein, a series of novel microparticle hemostats were synthesized using chitosan, different hydrothermally-treated starches, and cross-linked with tannic acid (TA) simultaneously in an unoxidized environment via ionotropic gelation method. Hemostats' comparative functional properties, such as adjustable antibacterial and erythrocyte compatibility upon various starch additions were evaluated. The in vivo hemostatic study revealed that the developed hemostats for mouse liver laceration and rat tail amputation had clotting times (13 s and 38 s, respectively) and blood loss (51 mg and 62 mg, respectively) similar to those of Celox™. The erythrocyte adhesion test suggested that erythrocyte distortion can be lowered by modifying the antibacterial hemostats with different starches. The broad-spectrum antibacterial efficacy of the hemostats remained intact against S. aureus (>90 %), E. coli (>80 %), and P. mirabilis bacteria upon starch modification. They also demonstrated high hemocompatibility (<3 % hemolysis ratio), moderate cell viability (>81 %), in vivo biodegradation, and angiogenesis indicating adequate biocompatibility and wound healing. The developed hemostats hold significant promise to be employed as rapid hemostatic agents for preventing major bleeding and bacterial infection in emergencies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Both artificial intelligence (AI) and distal attachment devices have been shown to improve adenoma detection rate and reduce miss rate during colonoscopy. We studied the combined effect of Endocuff and AI on enhancing detection rates of various colonic lesions., Methods: This was a 3-arm prospective randomized colonoscopy study involving patients aged 40 years or older. Participants were randomly assigned in a 1:1:1 ratio to undergo Endocuff with AI, AI alone, or standard high-definition (HD) colonoscopy. The primary outcome was adenoma detection rate (ADR) between the Endocuff-AI and AI groups while secondary outcomes included detection rates of polyp (PDR), sessile serrated lesion (sessile detection rate [SDR]), and advanced adenoma (advanced adenoma detection rate) between the 2 groups., Results: A total of 682 patients were included (mean age 65.4 years, 52.3% male), with 53.7% undergoing diagnostic colonoscopy. The ADR for the Endocuff-AI, AI, and HD groups was 58.7%, 53.8%, and 46.3%, respectively, while the corresponding PDR was 77.0%, 74.0%, and 61.2%. A significant increase in ADR, PDR, and SDR was observed between the Endocuff-AI and AI groups (ADR difference: 4.9%, 95% CI: 1.4%-8.2%, P = 0.03; PDR difference: 3.0%, 95% CI: 0.4%-5.8%, P = 0.04; SDR difference: 6.4%, 95% CI: 3.4%-9.7%, P < 0.01). Both Endocuff-AI and AI groups had a higher ADR, PDR, SDR, and advanced adenoma detection rate than the HD group (all P < 0.01)., Discussion: Endocuff in combination with AI further improves various colonic lesion detection rates when compared with AI alone., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Background: Although the general seroprevalence of hepatitis C virus (HCV) infection in Hong Kong is <0.5 %, Hong Kong is still striving for HCV elimination owing to barriers in care cascade encompassing linkage-to-care (LTC), treatment initiation and adherence. We aimed to evaluate the feasibility of a pilot model of micro-elimination to strengthen the HCV care cascade for high-risk groups in Hong Kong., Methods: We initiated the pilot Conquering Hepatitis vIa Micro-Elimination (CHIME) program which adopts an integrated care approach involving outreach visits to halfway house or drug rehabilitation centers run by non-governmental organizations. Participants with history of injection drug use (PWID), recreational drug use, or imprisonment were included. We performed point-of-care test for anti-HCV with reflex HCV RNA testing. LTC with government-subsidized direct acting antiviral was provided to viremic participants. We compared the impact on the care cascade with a cohort of HCV patients (17.8 % PWID) under usual care., Results: 396 participants (62.9 % PWID) were screened and 187 (47.2 %) were viremic, of which 29.8 % had cirrhosis. Proportion with LTC, treatment initiation and adherence were 76.5 % and 63.7 %, 90.9 % and 85.8 %, and 90.0 % and 92.2 %, for the CHIME program and usual care, respectively. The CHIME program was significantly associated with higher odds of LTC (OR 1.797, 95 % CI 1.221-2.644). Non-engagement in care (affecting 37.9 % participants with HCV viremia) was associated with unemployment (OR 2.165, 95 % CI 1.118-4.190)., Conclusion: The pilot CHIME program demonstrated feasibility of an integrated approach to consolidate the HCV care cascade in high-risk populations in Hong Kong., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: LY Mak is an advisory board member of Gilead Sciences and received speaker's fees from AbbVie. WK Seto received speaker's fees from AstraZeneca, is an advisory board member and received speaker's fees from Abbott, received research funding from Alexion Pharmaceuticals, Boehringer Ingelheim, Pfizer and Ribo Life Science, and is an advisory board member, received speaker's fees and researching funding from Gilead Sciences. MFY is an advisor/consultant for and/or received grant/research support from AbbVie, Aligos Therapeutics, AiCuris, Antios Therapeutics, Arbutus Biopharma, Arrowhead Pharmaceuticals, Assembly Biosciences, Bristol-Myers Squibb, Clear B Therapeutics, Dicerna Pharmaceuticals, Finch Therapeutics, Fujirebio Incorporation, GlaxoSmithKline, Gilead Sciences, Immunocore, Janssen, Roche, Silverback Therapeutics, Sysmex Corporation, Tune Therapeutics, Vir Biotechnology and Visirna Therapeutics. The other authors have nothing to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: We designed and implemented a patient-centered, data-driven, holistic care model with evaluation of its impacts on clinical outcomes in patients with young-onset type 2 diabetes (T2D) for which there is a lack of evidence-based practice guidelines., Research Design and Methods: In this 3-year Precision Medicine to Redefine Insulin Secretion and Monogenic Diabetes-Randomized Controlled Trial, we evaluate the effects of a multicomponent care model integrating use of information and communication technology (Joint Asia Diabetes Evaluation (JADE) platform), biogenetic markers and patient-reported outcome measures in patients with T2D diagnosed at ≤40 years of age and aged ≤50 years. The JADE-PRISM group received 1 year of specialist-led team-based management using treatment algorithms guided by biogenetic markers (genome-wide single-nucleotide polymorphism arrays, exome-sequencing of 34 monogenic diabetes genes, C-peptide, autoantibodies) to achieve multiple treatment goals (glycated hemoglobin (HbA1c) <6.2%, blood pressure <120/75 mm Hg, low-density lipoprotein-cholesterol <1.2 mmol/L, waist circumference <80 cm (women) or <85 cm (men)) in a diabetes center setting versus usual care (JADE-only). The primary outcome is incidence of all diabetes-related complications., Results: In 2020-2021, 884 patients (56.6% men, median (IQR) diabetes duration: 7 (3-12) years, current/ex-smokers: 32.5%, body mass index: 28.40±5.77 kg/m 2 , HbA1c: 7.52%±1.66%, insulin-treated: 27.7%) were assigned to JADE-only (n=443) or JADE-PRISM group (n=441). The profiles of the whole group included positive family history (74.7%), general obesity (51.4%), central obesity (79.2%), hypertension (66.7%), dyslipidemia (76.4%), albuminuria (35.4%), estimated glomerular filtration rate <60 mL/min/1.73 m 2 (4.0%), retinopathy (13.8%), atherosclerotic cardiovascular disease (5.2%), cancer (3.1%), emotional distress (26%-38%) and suboptimal adherence (54%) with 5-item EuroQol for Quality of Life index of 0.88 (0.87-0.96). Overall, 13.7% attained ≥3 metabolic targets defined in secondary outcomes. In the JADE-PRISM group, 4.5% had pathogenic/likely pathogenic variants of monogenic diabetes genes; 5% had autoantibodies and 8.4% had fasting C-peptide <0.2 nmol/L. Other significant events included low/large birth weight (33.4%), childhood obesity (50.7%), mental illness (10.3%) and previous suicide attempts (3.6%). Among the women, 17.3% had polycystic ovary syndrome, 44.8% required insulin treatment during pregnancy and 17.3% experienced adverse pregnancy outcomes., Conclusions: Young-onset diabetes is characterized by complex etiologies with comorbidities including mental illness and lifecourse events., Trial Registration Number: NCT04049149., Competing Interests: Competing interests: JCNC and RCWM hold patents for using genetic markers to predict diabetes and its complications for personalized care. JCNC, RCWM and CL are cofounders of a start-up biotech company partially supported by the Technology Start-up Support Scheme for Universities (TSSSU) of the Hong Kong Government Innovation and Technology Commission., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background & Aims: Perianal fistulizing Crohn's disease (PFCD)-associated anorectal and fistula cancers are rare but often devastating diagnoses. However, given the low incidence and consequent lack of data and clinical trials in the field, there is little to no guidance on screening and management of these cancers. To inform clinical practice, we developed consensus guidelines on PFCD-associated anorectal and fistula cancers by multidisciplinary experts from the international TOpClass consortium., Methods: We conducted a systematic review by standard methodology, using the Newcastle-Ottawa Scale quality assessment tool. We subsequently developed consensus statements using a Delphi consensus approach., Results: Of 561 articles identified, 110 were eligible, and 76 articles were included. The overall quality of evidence was low. The TOpClass consortium reached consensus on 6 structured statements addressing screening, risk assessment, and management of PFCD-associated anorectal and fistula cancers. Patients with long-standing (>10 years) PFCD should be considered at small but increased risk of developing perianal cancer, including squamous cell carcinoma of the anus and anorectal carcinoma. Risk factors for squamous cell carcinoma of the anus, notably human papilloma virus, should be considered. New, refractory, or progressive perianal symptoms should prompt evaluation for fistula cancer. There was no consensus on timing or frequency of screening in patients with asymptomatic perianal fistula. Multiple modalities may be required for diagnosis, including an examination under anesthesia with biopsy. Multidisciplinary team efforts were deemed central to the management of fistula cancers., Conclusions: Inflammatory bowel disease clinicians should be aware of the risk of PFCD-associated anorectal and fistula cancers in all patients with PFCD. The TOpClass consortium consensus statements outlined herein offer guidance in managing this challenging scenario., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

In recent years, frequent and substantial area-wide power outages have underscored the critical need for cities to possess robust backup power sources capable of swift response to prevent prolonged power system disruptions. Electric vehicles can contribute electricity to the power grid using vehicle-to-grid technology. The power delivered by electric vehicles in this context is termed as response capability. However, existing studies have overlooked response capability dynamics during transitions between electric vehicle states-such as the shift from charging or discharging to an idle state, thereby hindering a comprehensive understanding of this aspect. Hence, this paper introduces a multi-timescale response capability prediction model that evaluates the electric vehicle's state of charge to ensure users' requirements are met for upcoming trips. To better assess users' travel demand, the gravity model is employed as a precursor to response capability prediction to further enhance the validity of the prediction outcomes. Three neighborhoods in Los Angeles have been chosen for analysis: Downtown, Lincoln Heights, and Silver Lake. Predictions indicate that neglecting the response capability when electric vehicles undergo state transformation can lead to a differential response capability ranging from 2000 kWh to 4000 kWh, resulting in a loss of prediction accuracy by 20 % to 25 %.•The response capability of EV is non-zero during state transformations•Users' travel demand assessment•Seamless integration of vehicle-to-grid technology into the power grid., (© 2024 The Authors. Published by Elsevier B.V.)

The ability to experience pleasurable sexual activity is important for human health. Receptive anal intercourse (RAI) is a common, though frequently stigmatized, pleasurable sexual activity. Little is known about how diseases of the colon, rectum, and anus and their treatments affect RAI. Engaging in RAI with gastrointestinal disease can be difficult due to the unpredictability of symptoms and treatment-related toxic effects. Patients might experience sphincter hypertonicity, gastrointestinal symptom-specific anxiety, altered pelvic blood flow from structural disorders, decreased sensation from cancer-directed therapies or body image issues from stoma creation. These can result in problematic RAI - encompassing anodyspareunia (painful RAI), arousal dysfunction, orgasm dysfunction and decreased sexual desire. Therapeutic strategies for problematic RAI in patients living with gastrointestinal diseases and/or treatment-related dysfunction include pelvic floor muscle strengthening and stretching, psychological interventions, and restorative devices. Providing health-care professionals with a framework to discuss pleasurable RAI and diagnose problematic RAI can help improve patient outcomes. Normalizing RAI, affirming pleasure from RAI and acknowledging that the gastrointestinal system is involved in sexual pleasure, sexual function and sexual health will help transform the scientific paradigm of sexual health to one that is more just and equitable., (© 2024. Springer Nature Limited.)

Angiosperms are the cornerstone of most terrestrial ecosystems and human livelihoods 1,2 . A robust understanding of angiosperm evolution is required to explain their rise to ecological dominance. So far, the angiosperm tree of life has been determined primarily by means of analyses of the plastid genome 3,4 . Many studies have drawn on this foundational work, such as classification and first insights into angiosperm diversification since their Mesozoic origins 5-7 . However, the limited and biased sampling of both taxa and genomes undermines confidence in the tree and its implications. Here, we build the tree of life for almost 8,000 (about 60%) angiosperm genera using a standardized set of 353 nuclear genes 8 . This 15-fold increase in genus-level sampling relative to comparable nuclear studies 9 provides a critical test of earlier results and brings notable change to key groups, especially in rosids, while substantiating many previously predicted relationships. Scaling this tree to time using 200 fossils, we discovered that early angiosperm evolution was characterized by high gene tree conflict and explosive diversification, giving rise to more than 80% of extant angiosperm orders. Steady diversification ensued through the remaining Mesozoic Era until rates resurged in the Cenozoic Era, concurrent with decreasing global temperatures and tightly linked with gene tree conflict. Taken together, our extensive sampling combined with advanced phylogenomic methods shows the deep history and full complexity in the evolution of a megadiverse clade., (© 2024. The Author(s).)

This study explores the impact of thermal motion on the magnetic compass mechanism in migratory birds, focusing on the radical pair mechanism within cryptochrome photoreceptors. The coherence of radical pairs, crucial for magnetic field inference, is curbed by spin relaxation induced by intra-protein motion. Molecular dynamics simulations, density-functional-theory-based calculations, and spin dynamics calculations were employed, utilizing Bloch-Redfield-Wangsness (BRW) relaxation theory, to investigate compass sensitivity. Previous research hypothesized that European robin's cryptochrome 4a (ErCry4a) optimized intra-protein motion to minimize spin relaxation, enhancing magnetic sensing compared to the plant Arabidopsis thaliana's cryptochrome 1 (AtCry1). Different correlation times of the nuclear hyperfine coupling constants in AtCry1 and ErCry4a were indeed found, leading to distinct radical pair recombination yields in the two species, with ErCry4a showing optimized sensitivity. However, this optimization is likely negligible in realistic spin systems with numerous nuclear spins. Beyond insights in magnetic sensing, the study presents a detailed method employing molecular dynamics simulations to assess for spin relaxation effects on chemical reactions with realistically modelled protein motion, relevant for studying radical pair reactions at finite temperature., (© 2024 The Authors. ChemPhysChem published by Wiley-VCH GmbH.)

Background: Accurate identification of individuals at risk of developing chronic kidney disease (CKD) may improve clinical care. Nelson et al. developed prediction equations to estimate the risk of incident eGFR of less than 60 mL/min/1.73 m2 in diabetic and non-diabetes patients using data from 34 multinational cohorts. We aim to validate the non-diabetes equation in our local multi-ethnic cohort and develop further prediction models., Methods: Demographics, clinical and laboratory data of hypertensive non-diabetes patients with baseline eGFR ≥60 mL/min/1.73 m2 on follow-up with primary care clinics between 2010 and 2015 were collected. Follow-up was 5 years from entry to study. We validated Nelson's equation and developed our own model which we subsequently validated. The developmental cohort included patients between 2010 and 2014 while the validation cohort included patients in 2015. Variables included age, sex, eGFR, history of cardiovascular disease, ever smoker, body mass index, albuminuria, cholesterol, and treatment. Primary outcome was incident eGFR &lt;60/min/1.73 m2 within 5 years. Model performance was evaluated by C-statistics and calibration was assessed., Results: In the developmental cohort of 27,800 patients, 2823 (10.2%) developed the outcome during a mean follow-up of 4.4 years while 638 (12.8%) patients developed the outcome in the validation cohort of 4,994 patients. Applicability of Nelson's equation was limited by missing albuminuria, absence of black race, and exclusion of non-hypertensive patients in our cohort. Nonetheless, the modified Nelson's model demonstrated C-statistic of 0.85 (95% CI: 0.84-0.86). The C-statistic of our bespoke model was 0.85 (0.85-0.86) and 0.87 (0.85-0.88) for the developmental cohort and validation cohort, respectively. Calibration was suboptimal as the predicted risk exceeded the observed risk., Conclusions: The modified Nelson's equation and our locally derived novel model demonstrated high discrimination. Both models may potentially be used in predicting risk of CKD in hypertensive patients who are managed in primary care, allowing for early interventions in high-risk population., (© 2024 S. Karger AG, Basel.)

Purpose: Recent trials suggest glucagon-like peptide-1 receptor agonists (GLP-1RAs) may have a cardioprotective role by reducing major adverse cardiac events, stroke mortality and heart failure-related hospitalisations. We examined whether and how GLP-1RAs affect cardiac function in cardiovascular and metabolic diseases including type 2 diabetes, heart failure and post-myocardial infarction., Methods: In this PRISMA-adherent systematic review and meta-analysis, three databases were searched from inception to July 2021 and registered on PROSPERO (CRD42021259661)., Results: 20 reports of 19 randomized placebo-controlled trials including 2062 participants were meta-analyzed. Among type 2 diabetes patients, GLP-1RA resulted in improved systolic function measured by circumferential strain (mean difference [MD]= -5.48; 95% CI: -10.47 to -0.49; P= 0.03; I 2 = 89%) and diastolic dysfunction measured by E / A (MD= -0.15; 95% CI: -0.25 to -0.05; P= 0.003; I 2 = 0%). For post-myocardial infarction patients, GLP-1RA reduced infarct size (g) (MD= -5.36; 95% CI: -10.68 to -0.04; P= 0.05; I 2 = 78%). Liraglutide, but not exenatide, demonstrated improved systolic function, by increasing left ventricular ejection fraction (MD= 4.89; 95% CI: 3.62 to 6.16; P< 0.00001; I 2 = 0%) and reducing left ventricular end-systolic volume (MD= -4.15; 95% CI: -7.49 to -0.81; P = 0.01; I 2 = 0%). Among heart failure patients, no significant changes were noted., Conclusion: GLP-1RA drugs may improve systolic and diastolic function in type 2 diabetes and reduce infarct size post-acute myocardial infarction with no demonstrable effect on cardiac function in heart failure. Tailored recommendations for the use of GLP-1RAs for cardioprotection should be considered for each patient's condition., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Hypovitaminosis D during infancy is associated with the development of chronic diseases and poor health later in life. While the effect of environmental factors on vitamin D concentration has been extensively explored, this study aimed to explore the effect of genetic factors on vitamin D concentration among Chinese infants. We conducted a multi-centre cross-sectional study in Hong Kong from July 2019 to May 2021. A candidate genetic approach was adopted to study four selected genetic variants of the vitamin D-binding protein (DBP) and vitamin D receptor (VDR) (rs4588, rs7041, rs2282679 and rs2228570) to examine their associations with measured serum 25(OH)D concentration. A total of 378 Chinese infants aged 2-12 months were recruited in this study. Peripheral blood samples were collected from the infants to measure serum 25(OH)D concentration and extract DNA. Results showed that rs7041T and rs2282679C were significantly associated with lower serum 25(OH)D concentration. Further analysis of the DBP variants revealed that the GC1F allele was significantly associated with lower 25(OH)D concentration and identified as the risk DBP isoform in infants. While our results revealed that there is no direct association between VDR-FokI genotype and serum 25(OH)D concentration, a VDR-FokI genotype-specific pattern was observed in the association between DBP isoforms and serum 25(OH)D concentration. Specifically, significant associations were observed in the DBP genotypes GC1F/F, GC1F/2 and GC1S/2 among VDR-FokI TT/TC carriers, but not in VDR-FokI CC carriers. Our findings lay down the basis for the potential of genetic screening to identify high risk of hypovitaminosis D in Chinese infants., (© 2023 The Authors. Nutrition Bulletin published by John Wiley & Sons Ltd on behalf of British Nutrition Foundation.)

Frequent administrations are often needed during the treatment of ocular diseases due to the low bioavailability of the existing eye drops owing to inadequate corneal penetration and rapid drug washout. Herein, sodium alginate polymannuronate (SA) nanocarriers were developed using ionic gelation method that can provide better bioavailability through mucoadhesivity and sustained drug release by binding to the ocular mucus layer. This study disproves the common belief that only the G block of SA participates in the crosslinking reaction during ionic gelation. Self-assembly capability due to the linear flexible structure of the M block, better biocompatibility than G block along with the feasibility of controlling physicochemical characteristics postulate a high potential for designing efficient ocular drug delivery systems. Initially, four crosslinkers of varied concentrations were investigated. Taguchi design of experiment revealed the statistically significant effect of the crosslinker type and concentration on the particle size and stability. The best combination was detected by analyzing the particle size and zeta potential values that showed the desired microstructural properties for ocular barrier penetration. The desired combination was SA-Ca-1 that had particle size within the optimal corneal penetration range, that is 10-200 nm (135 nm). The drug carriers demonstrated excellent entrapment efficiency (∼89 % for Ciprofloxacin and ∼96 % for Dexamethasone) along with a sustained and simultaneous release of dual drug for at least 2 days. The nanoparticles also showed biocompatibility (4 ± 0.6 % hemolysis) and high mucoadhesivity (73 ± 2 % for 0.25 g) which was validated by molecular docking analysis. The prepared formulation was able to reduce the scleral inflammation of the rabbit uveitis models significantly within 3 days. Thus, the eye drop showed remarkable potential for efficient drug delivery leading to faster recovery., Competing Interests: Declaration of competing interest There is no conflict of interest to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Female athletes who endure intense training are at risk of developing the 'female athlete triad,' making energy intake management crucial. However, the fluctuations in estradiol and progesterone levels throughout the menstrual cycle present a challenge in maintaining consistent energy intake. This study aimed to uncover the underlying factors associated with appetite regulation linked to menstrual phases and exercise using proteomic approach. Five female athletes engaged in 60 min of bicycle exercise, followed by 90 min of rest, during both the follicular and luteal phases. Serum samples were collected before, during, and after exercise, and the serum proteome was analyzed using 2D-gel electrophoresis. A total of 511 spots were detected in the subjects' serum profiles, with significant decreases observed in haptoglobin during the luteal phase and complement component 3 during bicycle training. Unsupervised learning with a generalized estimating equation analysis showed that serum peptide YY (PYY), an appetite suppressor, significantly influenced the fluctuations of serum proteins induced by exercise (p < 0.05). Regression analysis demonstrated a positive correlation between PYY and serum IgM (R = 0.87), implying that the intestinal environment and the immune response in female athletes may contribute to appetite regulation., (© 2024. The Author(s).)

We investigate how matrix stiffness regulates chromatin reorganization and cell reprogramming and find that matrix stiffness acts as a biphasic regulator of epigenetic state and fibroblast-to-neuron conversion efficiency, maximized at an intermediate stiffness of 20 kPa. ATAC sequencing analysis shows the same trend of chromatin accessibility to neuronal genes at these stiffness levels. Concurrently, we observe peak levels of histone acetylation and histone acetyltransferase (HAT) activity in the nucleus on 20 kPa matrices, and inhibiting HAT activity abolishes matrix stiffness effects. G-actin and cofilin, the cotransporters shuttling HAT into the nucleus, rises with decreasing matrix stiffness; however, reduced importin-9 on soft matrices limits nuclear transport. These two factors result in a biphasic regulation of HAT transport into nucleus, which is directly demonstrated on matrices with dynamically tunable stiffness. Our findings unravel a mechanism of the mechano-epigenetic regulation that is valuable for cell engineering in disease modeling and regenerative medicine applications.

Introduction: Multiple Cochrane Reviews have demonstrated 'hospital at home' (HaH) as a promising healthcare model to be explored, with benefits such as higher care quality, reduced readmissions, shorter lengths of stay, lower cost and greater patient satisfaction. While there have been many reviews focusing on the quantitative clinical outcomes of HaH, there is generally a lack of collation of qualitative insights from stakeholders and lessons learnt from past HaH implementation., Methods: We performed a systematic literature search on four databases and included 17 papers involving the provision of acute and/or subacute care by healthcare professionals in patients' homes. Review characteristics and relevant outcomes were extracted from the reported findings and tables in the reviews, and these included stakeholder attitudes and factors contributing to the success of HaH implementation., Results: Factors relating to patients and caregivers included home setup, preference for care and death settings, and support for caregiver. Factors involving the healthcare professionals and intervention included a multidisciplinary care team, accessibility to emergency care and support, training of providers and patients, adequate manpower allocation, robust eligibility and referral criteria, sufficient awareness of the HaH referral pathway, communication and medication management., Conclusion: HaH presents a promising alternative care model, and many of the success factors identified, including the strong push for multidisciplinary single care teams, existing frameworks for data sharing and strong community network, are already present today. As such, Singapore appears to be well positioned to adopt a new care model like HaH., (Copyright © 2024 Copyright: © 2024 Singapore Medical Journal.)

Background: ATG16L1 plays a fundamental role in the degradative intracellular pathway known as autophagy, being a mediator of inflammation and microbial homeostasis. The variant rs2241880 can diminish these capabilities, potentially contributing to inflammatory bowel disease (IBD) pathogenesis., Objectives: To perform an updated meta-analysis on the association between ATG16L1 rs2241880 and IBD susceptibility by exploring the impact of age, ethnicity, and geography. Moreover, to investigate the association between rs2241880 and clinical features., Methods: Literature searches up until September 2022 across 7 electronic public databases were performed for all case-control studies on ATG16L1 rs2241880 and IBD. Pooled odds ratios (OR P ) and 95% CI were calculated under the random effects model., Results: Our analyses included a total of 30,606 IBD patients, comprising 21,270 Crohn's disease (CD) and 9336 ulcerative colitis (UC) patients, and 33,329 controls. ATG16L1 rs2241880 was significantly associated with CD susceptibility, where the A allele was protective (OR P : 0.74, 95% CI: 0.72-0.77, p-value: <0.001), while the G allele was a risk factor (OR P : 1.23, 95% CI: 1.09-1.39, p-value: 0.001), depending on the minor allele frequencies observed in this multi-ancestry study sample. rs2241880 was predominantly relevant in Caucasians from North America and Europe, and in Latin American populations. Importantly, CD patients harbouring the G allele were significantly more predisposed to perianal disease (OR P : 1.21, 95% CI: 1.07-1.38, p-value: 0.003)., Conclusions: ATG16L1 rs2241880 (G allele) is a consistent risk factor for IBD in Caucasian cohorts and influences clinical outcomes. As its role in non-Caucasian populations remains ambiguous, further studies in under-reported populations are necessary., (© 2023 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Background: This study aimed to identify the significant physical, psychological, and social determinants associated with EuroQuol-5D (EQ-5D) among Chinese older people with chronic musculoskeletal pain, and to evaluate how these determinants affected the five dimensions of EQ-5D., Method: This is a cross-sectional study. Data were collected through a cohort involving 946 community-dwelling older people aged ≥ 60 with chronic musculoskeletal pain in Hong Kong. Selected independent variables were categorized into physical, psychological, and social domains. Physical variables included age, sex, body mass index (BMI), pain severity score, number of pain regions, the most painful site, and the number of comorbidities. Psychological variables included depression level measured using the 9-question Patient Health Questionnaire (PHQ-9), and anxiety level measured using the Generalized Anxiety Disorder Assessment (GAD-7). Social variables included living, marital, and social welfare recipient's status. The dependent variables comprised the index scores and the five dimensions of the EQ-5D descriptive system. Ordinal least squares (OLS) model and logistic regression model were used for data analysis., Results: The mean age of the participants was 67.1 (SD = 5.1), with 77.6% being female. Higher pain severity scores (beta (β) coefficient =-0.044, P < 0.001), depression scores (β=-0.007, P < 0.001) and higher anxiety scores (β=-0.01, P < 0.001) were associated with lower EQ-5D index scores. Specifically, knee pain (β=-0.061, P < 0.001) was significantly associated with lower EQ-5D index scores. Participants with higher pain severity and depression scores were more likely to report problems in most EQ-5D dimensions. Participants with anxiety primarily faced challenges related to mood, and those with knee pain were more likely to have problems with mobility and daily activities., Conclusion: Among the selected determinants in our study, pain intensity, depression, anxiety, and knee pain were identified as key determinants associated with reduced HRQoL in older Chinese people with chronic musculoskeletal pain. Each of these determinants showed distinct associations with different dimensions of the EQ-5D, potentially informed resource allocation and the development of targeted interventions to improve the overall HRQoL of this specific population., (© 2024. The Author(s).)

Objective: Patients with systemic lupus erythematosus (SLE) have increased risk of premature atherosclerosis but the exact mechanisms remains unclear. Flow-mediated dilatation (FMD) is an established non-invasive assessment of vascular endothelial function. Lipoprotein subfractions may be better predictors of FMD than conventional cholesterol measurements. We tested the hypothesis that lipoprotein subfractions are independently associated with FMD., Methods: Forty-one consecutive adult patients with SLE without known cardiovascular risk factors or disease were recruited in this cross-sectional study. Endothelial function and early atherosclerosis were assessed by brachial FMD and common carotid artery (CCA) intima-media thickness (IMT). High-density lipoprotein (HDL)/low-density lipoprotein (LDL) subfractions were measured. Machine learning models were also constructed to predict FMD and CCA IMT., Results: Median FMD was 4.48% (IQR 5.00%) while median IMT was 0.54 mm (IQR 0.12 mm). Univariate analysis showed lower LDL1 (r=-0.313, p<0.05) and higher HDL2 subfractions (r=0.313, p<0.05) were significantly associated with higher log-transformed FMD. In a multiple linear regression model, HDL2 (β=0.024, SE=0.012, p<0.05) remained an independent predictor of higher FMD after adjusting for age, body mass index, LDL1 and systolic blood pressure. The machine learning model included parameters such as HDL2 (positive association), prednisolone dose, LDL cholesterol and LDL1 for prediction of FMD (r=0.433, p<0.01). Age, LDL cholesterol and systolic blood pressure were independently associated with higher CCA IMT after adjusting for body mass index and HDL2., Conclusions: HDL 2, a large HDL particle, was independently associated with greater FMD and may be a biomarker of vascular health in SLE., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

A stable anode-free lithium metal battery (AFLMB) is accomplished by the adoption of a facile fabricated amorphous antimony (Sb)-coated separator (SbSC). The large specific surface area of the separator elevates lithium (Li)-Sb alloy kinetic, improving Li wetting ability on pristine copper current collector (Cu). When tested with LiNi 0.8 Mn 0.1 Co 0.1 O 2 (NMC811) as cathode, the full cell with SbSC demonstrates low nucleation overpotential with compact, dendrite-free and homogeneous Li plating, and exhibits a notable lithium inventory retention rate (LIRR) of 99.8 % with capacity retention of 93.6 % after 60 cycles at 0.5 C-rate. Conversely, full cells containing pristine separator/Cu (i. e., SC) and pristine separator/Sb-coated current collector (i. e., SSbC) display poor cycling performances with low LIRRs. Density functional theory corroborates the nucleation behaviours observed during in-situ half-cell Li deposition. Functionalizing polymeric separator by metallic coating in AFLMB is a novel approach in improving the cycle life of an AFLMB by promoting homogeneous Li plating behavior. This innovative approach exemplifies a promising applicability for uniform Li-plating behavior to achieve a longer cycle life in AFLMB., (© 2023 Wiley-VCH GmbH.)

While differential antibody responses SARS-CoV-2 in patients with inflammatory bowel disease (IBD) receiving infliximab and vedolizumab are well-characterized, the immune pathways underlying these differences remain unknown. Prior to COVID-19 vaccine development, we screened 235 patients with IBD receiving biological therapy for antibodies to SARS-CoV-2 and measured serum cytokines. In seropositive patients, we prospectively collected clinical data. We found a cytokine signature in patients receiving vedolizumab who are seropositive compared with seronegative for SARS-CoV-2 antibodies that may be linked to repeated SARS-CoV-2 infections. However, there were no differences between seropositive and seronegative patients receiving infliximab. In this single-center cohort of patients with IBD with anti-SARS-CoV-2 antibodies at the onset of the COVID-19 pandemic, and therefore without influence of vaccination, there is a cytokine signature in patients receiving vedolizumab but not infliximab. These findings lay the groundwork for further studies on immune consequences of viral infection in patients with IBD, which is postulated to evolve from aberrant host-microbe responses., (© 2024. The Author(s).)

Telomere repeat binding factor 2 (TRF2) is an essential component of the telomeres and also plays an important role in a number of other non-telomeric processes. Detailed knowledge of the binding and interaction of TRF2 with telomeric nucleosomes is limited. Here, we study the binding of TRF2 to in vitro-reconstituted kilobasepair-long human telomeric chromatin fibres using electron microscopy, single-molecule force spectroscopy and analytical ultracentrifugation sedimentation velocity. Our electron microscopy results revealed that full-length and N-terminally truncated TRF2 promote the formation of a columnar structure of the fibres with an average width and compaction larger than that induced by the addition of Mg 2+ , in agreement with the in vivo observations. Single-molecule force spectroscopy showed that TRF2 increases the mechanical and thermodynamic stability of the telomeric fibres when stretched with magnetic tweezers. This was in contrast to the result for fibres reconstituted on the 'Widom 601' high-affinity nucleosome positioning sequence, where minor effects on fibre stability were observed. Overall, TRF2 binding induces and stabilises columnar fibres, which may play an important role in telomere maintenance., (© 2023. The Author(s).)

In this study, olive oil nanoemulsion modified with xanthan gum and gum acacia was explored as a potential controlled topical delivery vehicle. Oil-in-water nanoemulsion formulated with optimized composition of olive oil, tween 80, and water was used as the drug carrier and further modified with gum. Effect of gum on nanoemulsion different physiochemical characteristics, stability, rheology, drug release and encapsulation efficiency were investigated. Results showed that developed nanoemulsion behaved as low viscosity Newtonian fluid and released 100 % drug within 6 h. Modification with xanthan and gum acacia had significantly improved formulation viscosity, drug encapsulation efficiency (>85 %) and controlled drug release up to 40 % with release pattern following Korsmeyer-Peppas model. Additionally, xanthan gum modified formulation exhibited shear thinning rheology by forming an extended network in the continuous phase, whereas gum acacia modified formulation behaved as Newtonian fluid at high shear rate (>200 s -1 ). Furthermore, xanthan gum modified formulations had improved zeta potential, stability, monodispersity, and hemocompatibility and showed high antibacterial activity against S. aureus than gum acacia modified formulations. These results indicate the higher potential of xanthan gum modified formulation as a topical delivery vehicle. Moreover, skin irritation test demonstrated the safety of developed formulations for topical application., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Beyond systematic reviews and meta-analyses, there have been no direct studies of serological response to COVID-19 in patients with inflammatory bowel disease (IBD) across continents. In particular, there has been limited data from Asia, with no data reported from India. The ICARUS-IBD (International study of COVID-19 Antibody Response Under Sustained immunosuppression in IBD) consortium assessed serological response to SARS-CoV-2 in patients with IBD in North America, Europe, and Asia., Methods: The ICARUS-IBD study is a multicenter observational cohort study spanning sites in 7 countries. We report seroprevalence data from 2303 patients with IBD before COVID-19 vaccination between May 2020 and November 2021. SARS-CoV-2 anti-spike and anti-nucleocapsid antibodies were analyzed., Results: The highest and lowest SARS-CoV-2 anti-spike seropositivity rates were found in Asia (81.2% in Chandigarh and 57.9% in Delhi, India; and 0% in Hong Kong). By multivariable analysis, country (India: odds ratio [OR], 18.01; 95% confidence interval [CI], 12.03-26.95; P < .0001; United Kingdom: OR, 2.43; 95% CI, 1.58-3.72; P < .0001; United States: OR, 2.21; 95% CI, 1.27-3.85; P = .005), male sex (OR, 1.46; 95% CI, 1.07-1.99; P = .016), and diabetes (OR, 2.37; 95% CI, 1.04-5.46; P = .039) conferred higher seropositivity rates. Biological therapies associated with lower seroprevalence (OR, 0.22; 95% CI, 0.15-0.33; P < .0001). Multiple linear regression showed associations between anti-spike and anti-nucleocapsid titers with medications (P < .0001) but not with country (P = .3841)., Conclusions: While the effects of medications on anti-SARS-CoV-2 antibody titers in patients with IBD were consistent across sites, geographical location conferred the highest risk of susceptibility to serologically detectable SARS-CoV-2 infection. Over half of IBD patients in India were seropositive prior to vaccination. These insights can help to inform shielding advice, therapeutic choices, and vaccine strategies in IBD patients for COVID-19 and future viral challenges., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Aims: Blue-light imaging (BLI) is a new image-enhanced endoscopy with a wavelength filter similar to narrow-band imaging (NBI). We compared the 2 with white-light imaging (WLI) on proximal colonic lesion detection and miss rates., Methods: In this 3-arm prospective randomized study with tandem examination of the proximal colon, we enrolled patients aged ≥40 years. Eligible patients were randomized in 1:1:1 ratio to receive BLI, NBI, or WLI during the first withdrawal from the proximal colon. The second withdrawal was performed using WLI in all patients. Primary outcomes were proximal polyp (pPDRs) and adenoma (pADRs) detection rates. Secondary outcomes were miss rates of proximal lesions found on tandem examination., Results: Of 901 patients included (mean age, 64.7 years; 52.9% men), 48.1% underwent colonoscopy for screening or surveillance. The corresponding pPDRs of the BLI, NBI, and WLI groups were 45.8%, 41.6, and 36.6%, whereas the corresponding pADRs were 36.6%, 33.8%, and 28.3%. There was a significant difference in pPDR and pADR between BLI and WLI groups (difference, 9.2% [95% confidence interval {CI}, 3.3-16.9] and 8.3% [95% CI, 2.7-15.9]) and between NBI and WLI groups (difference, 5.0% [95% CI, 1.4-12.9] and 5.6% [95% CI, 2.1-13.3]). Proximal adenoma miss rates were significantly lower with BLI (19.4%) than with WLI (27.4%; difference, -8.0%; 95% CI, -15.8 to -.1) but not between NBI (27.2%) and WLI., Conclusions: Both BLI and NBI were superior to WLI on detecting proximal colonic lesions, but only BLI had lower proximal adenoma miss rates than WLI. (Clinical trial registration number: NCT03696992.)., (Copyright © 2023 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Using prostate-specific antigen (PSA) for prostate cancer (PCa) screening led to overinvestigation and overdiagnosis of indolent PCa. We aimed to investigate the value of prostate health index (PHI) and magnetic resonance imaging (MRI) prostate in an Asian PCa screening program. Men aged 50-75 years were prospectively recruited from a community-based PSA screening program. Men with PSA 4.0-10.0 ng ml -1 had PHI result analyzed. MRI prostate was offered to men with PSA 4.0-50.0 ng ml -1 . A systematic prostate biopsy was offered to men with PSA 4.0-9.9 ng ml -1 and PHI ≥35, or PSA 10.0-50.0 ng ml -1 . Additional targeted prostate biopsy was offered if they had PI-RADS score ≥3. Clinically significant PCa (csPCa) was defined as the International Society of Urological Pathology (ISUP) grade group (GG) ≥2 or ISUP GG 1 with involvement of ≥30% of total systematic cores. In total, 12.8% (196/1536) men had PSA ≥4.0 ng ml -1 . Among 194 men with PSA 4.0-50.0 ng ml -1 , 187 (96.4%) received MRI prostate. Among them, 28.3% (53/187) had PI-RADS ≥3 lesions. Moreover, 7.0% (107/1536) men were indicated for biopsy and 94.4% (101/107) men received biopsy. Among the men received biopsy, PCa, ISUP GG ≥2 PCa, and csPCa was diagnosed in 42 (41.6%), 24 (23.8%), and 34 (33.7%) men, respectively. Compared with PSA/PHI pathway in men with PSA 4.0-50.0 ng ml -1 , additional MRI increased diagnoses of PCa, ISUP GG ≥2 PCa, and csPCa by 21.2% (from 33 to 40), 22.2% (from 18 to 22), and 18.5% (from 27 to 32), respectively. The benefit of additional MRI was only observed in PSA 4.0-10.0 ng ml -1 , and the number of MRI needed to diagnose one additional ISUP GG ≥2 PCa was 20 in PHI ≥35 and 94 in PHI <35. Among them, 45.4% (89/196) men with PSA ≥4.0 ng ml -1 avoided unnecessary biopsy with the use of PHI and MRI. A screening algorithm with PSA, PHI, and MRI could effectively diagnose csPCa while reducing unnecessary biopsies. The benefit of MRI prostate was mainly observed in PSA 4.0-9.9 ng ml -1 and PHI ≥35 group. PHI was an important risk stratification step for PCa screening., (Copyright © 2023 Copyright: © The Author(s)(2023).)

Background: The Traditional Chinese Medicine (TCM) Body Constitution Questionnaire (For Elderly People) (TCMECQ) is a patient-reported outcome questionnaire developed in Mandarin in 2013 to differentiate the body constitutions of the elderly aged 65 and above. Considering the cultural and linguistic differences between Mainland China and Hong Kong (HK) Special Administrative Region, the TCMECQ was translated into Cantonese following "back translation" policy and validated in proper process., Methods: Ten Chinese Medicine Practitioners (CMPs) and 30 senior citizens aged 65 or above were recruited to evaluate the first version of the Traditional Chinese Medicine Body Constitution Questionnaire (For Elderly People) (Cantonese version) (TCMECQ-C). Based on their comments, the second version was developed and discussed in the panel meeting to form the third version, validated the third version on 270 recruited seniors. Based on the validation results, a panel of 5 experts finalized the Questionnaire as the final version. The TCMECQ-C developers finalized the Questionnaire as the validated endorsed third version (i.e. final version)., Results: The item-level content validity index of most items of the TCMECQ-C (First Version) were ranging from 0.80 to 1.00 in terms of clarity, relevance and appropriateness. Factor loadings of Qi-deficiency Constitution ranging from 0.37 to 0.71, Yang-deficiency Constitution ranging from 0.36 to 0.65, Yin-deficiency Constitution ranging from 0.36 to 0.65, and Stagnant Qi Constitution ranging from 0.68 to 0.82. The chi-squared degree-of-freedom ratio was 2.13 (928.63/436), Goodness-of-Fit Index (0.83), Adjusted Goodness-of-Fit Index (0.79), Normed Fit Index (0.66), Comparative Fit Index (0.78), Incremental Fit Index (0.78), Relative Fit Index (0.61) and Tucker-Lewis Index (0.75), and Root Mean Square Error of Approximation (0.07) and Standardized Root Mean Square Residual (0.07), implied acceptable Confirmatory Factor Analysis model fit of the overall scale. A Pearson correlation coefficient (r) showed the sufficient convergent validity for excessive subscales (Phlegm-dampness Constitution and Dampness-heat Constitution with r = 0.35, p < 0.01). Cronbach's alpha coefficient ranged from 0.56 to 0.89, including Qi-deficiency Constitution (0.67), Yang-deficiency Constitution (0.84), Yin-deficiency Constitution (0.59), Stagnant Blood Constitution (0.56), Stagnant Qi Constitution (0.89), Inherited Special Constitution (0.76) and Balanced Constitution (0.73), indicating acceptable internal consistency for subscales. The intra-class correlation coefficients of the TCMECQ-C ranged from 0.70 to 0.87 (p < 0.001), indicating moderate to good test-retest reliability., Conclusion: TCMECQ-C is a valid and reliable questionnaire for assessing the body constitution in Cantonese elderly., (© 2023. International Society for Chinese Medicine and BioMed Central Ltd.)

Background: Adequate calcium intake at an early age is crucial to achieving peak bone mass. Nevertheless, low calcium intake is common in Malaysian children. Aim: This study examined the calcium food sources and factors associated with low calcium intake among 243 children aged 9-11 years in Kuala Lumpur. Methods: Diet histories and bone density were measured. Results: The mean calcium intake was 370 ± 187 mg/day. The main contributors to calcium intake were beverages (19.2%), cereal (18.6%), milk and dairy (13.0%), meat and poultry (12.9%), and fish and seafood (10.1%). Within each food group, calcium-contributing foods tend to be from low bioavailability sources such as rice, cocoa-based and malted drinks, and chicken rather than milk. Children who practised regular meals, ate breakfast and snacks and consumed milk more than one serving daily have a higher calcium intake. Conclusion: In conclusion, public health strategies to improve the status of low calcium intake and poor choices of calcium-rich foods are needed to optimise bone health in this population., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Sebaceous glands (SGs) release oils that protect our skin, but how these glands respond to injury has not been previously examined. Here, we report that SGs are largely self-renewed by dedicated stem cell pools during homeostasis. Using targeted single-cell RNA sequencing, we uncovered both direct and indirect paths by which resident SG progenitors ordinarily differentiate into sebocytes, including transit through a Krt5+PPARγ+ transitional basal cell state. Upon skin injury, however, SG progenitors depart their niche, reepithelialize the wound, and are replaced by hair-follicle-derived stem cells. Furthermore, following targeted genetic ablation of >99% of SGs from dorsal skin, these glands unexpectedly regenerate within weeks. This regenerative process is mediated by alternative stem cells originating from the hair follicle bulge, is dependent upon FGFR2 signaling, and can be accelerated by inducing hair growth. Altogether, our studies demonstrate that stem cell plasticity promotes SG durability following injury., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Despite Hong Kong's world leading longevity, little is known about its associated disability burden and social patterning. Hence, this study assessed the gender-specific secular trends and area-level inequalities in life expectancy (LE) and disability-free life expectancy (DFLE) at age 65 in Hong Kong., Methods: Population structure, death records, and disability data in 2007, 2013, and 2020 were retrieved from the Census and Statistics Department to estimate LE and DFLE using the Sullivan Method. District-based sociodemographic indicators were used to compare LE and DFLE across 18 districts of Hong Kong in 2013., Findings: Between 2007 and 2020, LE at age 65 increased by 3.7 years (from 18.3 to 22.0) in men and by 2.1 years (from 22.7 to 24.8) in women. By contrast, DFLE increased more slowly, by 1.8 years (from 14.6 to 16.3) in men and by only 0.1 year (from 16.4 to 16.5) in women, leading to a substantial increase in proportion of life spent with disability. Results from multiple linear regression using district-based data in 2013 showed a similar extent of associations of education with LE and DFLE (mean year difference: 0.81 [95% CI: 0.14, 1.48] and 0.68 [0.10, 1.27], respectively, per 10% increase in average education level), while female gender was more strongly associated with LE (4.44 [3.56, 5.31]) than with DFLE (2.00 [1.18, 2.82])., Interpretation: Expansion of disability burden and male-female health-survival paradox hold true in Hong Kong. Unlike Western countries with a stronger socioeconomic patterning of DFLE, the extent of area-level socioeconomic inequalities in LE and DFLE appears to be more comparable in Hong Kong., Funding: Health and Medical Research Fund (Ref. no.: 19202031) by the Health Bureau of Hong Kong., Competing Interests: The authors declare that they have no conflict of interest., (© 2023 The Author(s).)

Background: Little is known about how multisystemic childhood exposures predict adult depression. This study aims to examine the effects of multisystemic childhood exposures on the onset and remission of adult depression., Methods: Data were drawn from the China Health and Retirement Longitudinal Survey (CHARLS) (wave 1-4), which is a nationally representative longitudinal survey of people 45 years of age or older in China. Childhood family relationships (CFR), childhood peer friendships (CPF), and childhood neighborhood quality (CNQ) scores were recoded into binary (No = 0, Yes = 1) according to the first quantile value. Participants were divided into four groups based on the total number of poor childhood exposures (group 0-3). The generalized linear mixed model was used to test the longitudinal relationship between combined poor childhood exposures and adult depression., Results: Of the 4696 participants (55.1 % males), 22.5 % suffered from depression at baseline. The incidence of depression increased from group0 to group3 in four waves, reaching the peak in wave 2018 (incidence of group0 to group3: 14.1 %, 18.5 %, 22.8 %, 27.4 %, p < 0.001), with declining remission rates that reached its lowest in wave 2018 (50.8 %, 41.3 %, 34.3 %, 31.7 %, p < 0.001). The persistent depression rate increased from group0 to group3 (2.7 %, 5.0 %, 8.1 %, 13.0 %, p < 0.001). The risk of depression in group1 (AOR = 1.50, 95%CI: 1.27-1.77), group2 (AOR = 2.43, 95%CI: 2.01-2.94) and group3 (AOR = 4.24, 95%CI: 3.25-5.54) were significantly higher than that in group0., Limitations: Childhood histories were collected via self-reported questionnaires, and thus recall bias was inevitable., Conclusions: Multisystem poor childhood exposures jointly increased the onset and persistence of adult depression, as well as reduced the remission rate of depression., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

A partially neutralized polyacrylic acid (Pn-PAA) is used for coating sub-micron-sized α-alumina on a conventional microporous polyolefin separator, fabricating a ceramic-coated separator (CCS). Pn-PAA acts as a dispersant and binder by adsorbing itself on alpha(α)-alumina surfaces under acidic condition through the columbic interaction, providing a repulsive force to disperse fine alumina in aqueous suspension, and binds alumina strongly on plasma-treated separator through hydrogen bonding. This CCS shows favorable wettability in carbonate-based liquid electrolyte and ionic conduction due to the high hydrophilicity of Pn-PAA and alumina. With that, this study found that Pn-PAA-made-CCS yields a substantial adhesion strength of ~106 N/m with enhanced cycle stability, a specific capacity of 145.0 mAh/g after 200 cycles at 1 C at room temperature in half cells (LFP/Li metal)., (© 2023 Wiley-VCH GmbH.)