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Effectiveness of an AI-based home exercise app for rehabilitation of rotator cuff-related shoulder pain: A randomized controlled trial.

BACKGROUND: Rotator cuff-related shoulder pain contributes to disability and healthcare use. Although therapeutic exercise is first-line treatment, limited supervision and adherence may reduce its effectiveness; digital rehabilitation with real-time feedback may address these limitations. OBJECTIVES: To evaluate the effectiveness of adding a digital rehabilitation program to standard physiotherapy on pain, function, fear-avoidance beliefs, and healthcare utilization. DESIGN: Single-center, assessor-blinded, randomized controlled trial with two parallel groups. METHOD: Forty-six adults (mean age 59 years) with rotator cuff-related shoulder pain were randomized to 12 weeks of conventional physiotherapy or physiotherapy plus an AI-based digital rehabilitation program using computer vision for real-time feedback and performance monitoring. Outcomes were assessed at baseline and at 2, 4, and 12 weeks. Pain intensity (NPRS) was primary outcome; secondary outcomes included upper limb function (QuickDASH), fear-avoidance beliefs (FABQ), and post-intervention healthcare utilization. Analyses followed an intention-to-treat approach. RESULTS: Pain reduction exceeded the MCID (1.3) at 4 and 12 weeks. Between-group differences favoured the intervention at Weeks 2 and 4 (MD -0.7; 95% CI -1.13 to -0.14 and MD -1.01; 95% CI -1.8 to -0.2, respectively). Upper limb function improved more at Week 4 (MD -7.3; 95% CI -12.3 to -2.2). FABQ scores decreased more at Week 12 (MD -7.6; 95% CI -14 to -0.5). Fewer participants in the experimental group required post-intervention healthcare (3 vs 10; p = 0.02). CONCLUSION: Adding AI-based home exercise app to conventional treatment improve pain and may improve function and reduce healthcare utilization in rotator cuff-related shoulder pain.

Humans

Long-term safety of oral orforglipron in Japanese participants with type 2 diabetes (ACHIEVE-J): a multicentre, randomised, open-label, parallel-group phase 3 trial.

BACKGROUND: Orforglipron, an oral GLP-1 receptor agonist, requires further evaluation in east Asian populations with type 2 diabetes, given this group's distinct pathophysiological characteristics. This study aimed to assess orforglipron as add-on treatment to diet and exercise alone or to oral antihyperglycaemic medications in Japanese participants with type 2 diabetes. METHODS: This multicentre, randomised, open-label phase 3 study was conducted in 40 medical research centres and hospitals in Japan. Adults with type 2 diabetes and elevated glucose levels managing their condition with diet and exercise alone or with one or two oral antihyperglycaemic medications were assigned (1:1:1) via computer-generated random sequence to receive once-daily oral orforglipron (3 mg, 12 mg, or 36 mg). Randomisation was stratified by background therapy, baseline HbA1c (&#x2264;8&#xb7;5% or >8&#xb7;5%), and metformin use (yes vs no; applied only to &#x3b1;-glucosidase inhibitors, thiazolidinedione, and glinides). Investigators, participants, and site staff were not masked to treatment. The primary endpoint was safety for 52 weeks, assessed in all randomly assigned participants who received at least one dose of orforglipron. This study is registered with ClinicalTrials.gov, NCT06010004 (ACHIEVE-J). FINDINGS: Between Sept 28, 2023, and June 5, 2025, 450 participants were screened and 401 were randomly assigned to three groups (3 mg, n=132; 12 mg, n=135; and 36 mg, n=134). 352 (88%) completed study treatment. 339 participants (85%, 95% CI 80&#xb7;7-87&#xb7;8) had at least one treatment-emergent adverse event (TEAE), more frequently in the 36-mg group (118 [88%, 95% CI 81&#xb7;5-92&#xb7;5]) than in the 3-mg (107 [81%, 73&#xb7;5-86&#xb7;8]) and 12-mg (114 [84%, 77&#xb7;4-89&#xb7;6]) groups. Most TEAEs were of mild (267 [67%, 61&#xb7;8-71&#xb7;0]) or moderate (63 [16%, 12&#xb7;5-19&#xb7;6]) severity. Discontinuations due to an adverse event occurred in 19 of 134 participants (14%, 95% CI 9&#xb7;3-21&#xb7;1) in the 36-mg group compared with seven of 132 (5%, 2&#xb7;6-10&#xb7;5) in the 3-mg group and 11 of 135 (8%, 4&#xb7;6-14&#xb7;0) in the 12-mg group. Across treatment groups, gastrointestinal symptoms were the most common TEAEs leading to study treatment discontinuation (3 mg: 5 [3&#xb7;8%, 1&#xb7;6-8&#xb7;6]; 12 mg: 8 [5&#xb7;9%, 3&#xb7;0-11&#xb7;3]; and 36 mg: 11 [8&#xb7;2%, 4&#xb7;7-14&#xb7;1]). Level 2 (blood glucose <54 mg/dL) hypoglycaemia events occurred in three of 135 participants in the 12-mg group (2%, 0&#xb7;8-6&#xb7;3) and in three of 134 in the 36-mg group (2%, 0&#xb7;8-6&#xb7;4) groups. No level 3 (severe) hypoglycaemia events occurred. Outcomes were generally similar across background therapies. INTERPRETATION: Treatment with orforglipron in combination with diet and exercise alone or one or two oral antihyperglycaemic medications for 52 weeks demonstrated an acceptable safety profile in Japanese adults with type 2 diabetes. FUNDING: Eli Lilly. TRANSLATION: For the Japanese translation of the abstract see Supplementary Materials section.

Aged

Genome-wide characterization of heat shock protein genes reveals thermal stress-responsive candidates in Litopenaeus vannamei.

Heat shock proteins (HSPs) are conserved molecular chaperones involved in protein folding, refolding, aggregation prevention, and degradation of damaged proteins. However, the genomic organization and thermal responsiveness of HSP genes in the Pacific white shrimp (Litopenaeus vannamei) remain incompletely understood. Here, we performed a genome-wide analysis of the HSP gene family and examined its phylogenetic relationships, structural features, duplication patterns, sequence variation, interaction networks, and transcriptional responses to acute heat stress. A total of 34 HSP genes were identified and classified into the HSP90, HSP70, HSP40/DNAJ, HSP60, and small HSP families. Phylogenetic, motif, gene structure, synteny, and subcellular localization analyses revealed evolutionary conservation and structural diversification among family members. Three duplicated gene pairs were identified, comprising two segmental duplications and one tandem duplication. All pairs exhibited Ka/Ks ratios below 1, consistent with purifying selection of varying strength. Sequence analysis identified 295 nonsynonymous single-nucleotide polymorphisms, of which 12 were consistently predicted to be deleterious by multiple algorithms. Protein-protein interaction analysis indicated enrichment of protein-folding and cellular stress-response functions. RT-qPCR analysis showed significant induction of HSPA4, HSP90AA1, TRAP1, BiP, and DNAJA1 after 6, 12, and 24&#xa0;h of exposure to 34&#xa0;&#xb0;C, whereas DNAJC3 was significantly induced only at 12&#xa0;h. All six genes reached their highest transcript abundance at 12&#xa0;h. These findings may provide a genomic framework for HSP genes in L. vannamei and identify candidate genes and variants associated with thermal stress responses.

Animals

Effects of aerosol aging on composition and light-absorbance of nitrogen-containing organic compounds: Evidences from ultra-high-resolution mass spectrometry analysis.

Nitrogen-containing organic compounds (NOCs) are key components of particulate matter (PM), but their compositional evolution and light-absorbing properties during atmospheric aging remain poorly understood. In this study, ultra-high-performance liquid chromatography coupled with Orbitrap mass spectrometry was used to semi-quantitatively analyze 59 PM1 samples collected in Shanghai. NOCs accounted for 31 % and 64 % of the detected species in negative (ESI-) and positive (ESI+) ionization modes, respectively. Atmospheric aging significantly reduced the molecular diversity of polar organics, with both the number and mass concentration percentages of CHON- compounds showing significant negative correlations with aging degree. Van Krevelen analysis demonstrated a decrease in the number of carboxylic-rich alicyclic molecules and their CHON- contributions during the aging process (from 37.7 % in fresh samples to 21.2 % in aged samples). CHN+ compounds, a major NOCs group in ESI+ mode, also decreased with aging. Correlation analyses involving the Bep/(Bep+Bap) ratio, relative humidity, and mass absorption efficiency at 365 nm revealed a decline in light absorption capacity with aging, suggesting aqueous-phase oxidation as a dominant aging mechanism. CHON- and CHN+ compounds were identified as the principal light-absorbing constituents in PM1. This work provides new insights into the aging-induced transformations of NOCs in urban PM1, and their changing role in light absorption, highlighting the need for further investigation of the aging mechanisms of NOCs.

Aerosols

Comparative effectiveness of torsemide vs furosemide in the management of heart failure patients: Win-ratio reanalysis of the TRANSFORM-HF trial.

BACKGROUND: Loop diuretics are widely used for managing congestion in patients with heart failure (HF). The TRANSFORM-HF trial is a multicenter randomized study that enrolled heart failure patients, comparing a strategy of torsemide vs furosemide. The time-to-event analysis demonstrated neutral effects on all-cause death at 30 months and the composite of all-cause death and first rehospitalization at 12 months. We evaluated whether a hierarchical win-ratio (WR) framework integrating mortality, recurrent hospitalization, and patient-reported health status provides additional interpretive insight. METHODS: This study is a secondary analysis of the pragmatic, multicenter, open-label, randomized TRANSFORM-HF trial, conducted across 60 US hospitals that randomized 2,859 patients hospitalized with HF to torsemide or furosemide. The primary 12-month hierarchical composite outcome was defined as (1) all-cause mortality, (2) recurrent all-cause hospitalizations, and (3) lack of improvement in the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS). The primary statistical method was a WR analysis adjusting covariates via inverse probability weighting. Subgroup analyses evaluated potential heterogeneity across patient demographics and clinical characteristics. RESULTS: In the primary 12-month intention-to-treat analysis, the adjusted WR was 1.07 (95% CI, 0.98-1.16; P = .13), indicating no significant difference between torsemide and furosemide. A supplementary 30-month analysis with extended mortality follow-up yielded a similar estimate (adjusted WR, 1.06; 95% CI, 0.98-1.16; P = .14); hospitalization and KCCQ-CSS components were assessed through 12 months. As-treated sensitivity analyses were consistent with the neutral primary findings. Exploratory subgroup analyses were not adjusted for multiplicity and should be considered hypothesis-generating. CONCLUSIONS: The overall WR comparison between torsemide and furosemide showed no statistically significant difference in the primary 12-month analysis. The WR framework provided an interpretive decomposition across outcome domains but did not establish superiority of either loop diuretic strategy. All findings should be considered exploratory. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03296813, https://clinicaltrials.gov/study/NCT03296813.

Aged

Coupling of spectroscopy and nitrogen-oxygen isotopes unveils the mechanisms of dissolved organic matter and nitrate pollution in lakes within the agro-pastoral transition zone.

Lakes in arid and semi-arid regions are subjected to severe ecological stress, such as organic pollution, eutrophication, and salinization, due to climate change and human activities. This study investigates Chagannur Lake, a typical arid-region lake that is representative and ecologically sensitive in Northern China's agro-pastoral ecotone, to uncover its pollution characteristics and mechanisms. We employed fluorescence spectroscopy and stable isotope analysis to trace dissolved organic matter (DOM) and nitrate sources. The DOM composition was dominated by microbial metabolic byproducts and protein-like substances, suggesting that microbial processes are key to organic matter transformation. Source apportionment revealed that pollutants primarily originated from livestock and poultry manure (37.6 %), agricultural fertilizers (35.6 %), and soil erosion (24.7 %), with agricultural fertilizers contributing most significantly in the Gogstai River (63.3 %). A structural equation model (SEM) coupling spectral and mass spectrometric data revealed that microbial transformation significantly impairs the lake's self-purification capacity, thereby promoting pollutant accumulation (path coefficient = 0.91,*p < 0.05). Moreover, microbial processes link endogenous and exogenous pollution, a mechanism effectively traced by isotopic and fluorescence indices (path coefficient = 0.55, &#x204e;&#x204e;p < 0.01). These findings enhance the understanding of pollution sources and transformation mechanisms in arid-region lakes and offer foundational theoretical support for policymakers engaged in pollution control strategies.

Lakes

Strategy for enhanced production of A40926B0 in Nonomuraea gerenzanensis using an efficient CRISPR/AsCas12f1 system.

The global emergence of vancomycin-resistant Gram-positive pathogens underscores the urgent need for efficient production of novel lipoglycopeptide antibiotics. Dalbavancin, a last-resort therapeutic agent, relies on its key biosynthetic precursor A40926B0, whose industrial manufacture is severely limited by the low yield of wild-type Nonomuraea gerenzanensis and inefficient genetic tools for this rare actinomycete. Here, we developed a high-efficiency CRISPR/AsCas12f1 genome editing system and applied systematic metabolic engineering to boost A40926B0 biosynthesis. First, conjugation conditions were optimized to elevate the transfer efficiency in N. gerenzanensis D11. The hypercompact AsCas12f1 nuclease showed markedly lower cytotoxicity than SpCas9 and enabled 100% gene deletion efficiency with preferred PAMs (TTTG, CTTG, GTTG). Second, we strengthened the shikimate pathway via multiple genetic strategies: overexpressing feedback-resistant DAHP synthase (aroG fbr ) and chorismate mutase/prephenate dehydrogenase (tyrA fbr ), as well as knocking out pheA. This manipulation blocks the phenylalanine synthetic branch and redirects metabolic flux toward the l-tyrosine branch. Third, we engineered the branched-chain fatty acid (BCFA) pathway via promoter replacement of bkdA2B2C2, LipAB, fabF and deletion of acdH to enhance isododecanoyl side-chain supply. The combinatorial engineering yielded strain B-13, which produced 1740&#x202f;mg/L A40926B0 in shake flasks. Finally, 50-L fed-batch fermentation with continuous maltodextrin feeding further increased the titer to 1817&#x202f;mg/L, the highest reported titer to date. This work establishes a robust CRISPR editing tool for N. gerenzanensis and provides valuable engineering references for precursor-oriented strain improvement targeting lipoglycopeptide antibiotics, offering insights for the industrial scale production of A40926B0.

A40926B0

New insights into soil amendment: Impact of humic acid on typical antibiotic resistance in agricultural soil.

Humic acid (HA) addition can improve agricultural soil, but little is known about how it affects the soil resistome. In this study, we used selective agar plate combined with quantitative PCR (qPCR) and 16S rRNA gene sequencing to investigate how HA influences antibiotic resistant bacteria (ARB) and antibiotic resistant genes (ARGs) in soil contaminated with erythromycin and kanamycin. 0.1 % HA reduced the abundance of culturable erythromycin-resistant bacteria (ERB), while promoting the growth of kanamycin-resistant bacteria (KRB). Lysinibacillus and Paenibacillus were the dominant genera in ERB and KRB, respectively, governing the changes in their abundances. At this concentration, the Lysinibacillus abundance in ERB decreased from 96.74 % to 70.57 %. Meanwhile, that of Paenibacillus in KRB increased from 33.40 % to 77.44 %. The copy number of ermF decreased after HA addition, while that of ermB increased. Furthermore, 0.1 % HA significantly reduced the copy number and relative abundance of aadA1 and aac(6')-Ib (aka aacA4)-03 in the soil. Changes in these two types of ARB and ARGs were primarily driven by shifts in the microbial community structure. Soil physicochemical properties, particularly increased organic matter (OM), altered the absolute abundance of ermB. Meanwhile, changes in intI1 abundance determined the risk associated with aadA1 and aac(6')-Ib (aka aacA4)-03. These findings emphasize the dual role of HA in the dissemination of antibiotic resistance in agricultural soils and highlight the necessity of considering dose-dependent effects when applying HA as a soil amendment.

Soil Microbiology

Tracking microplastic contamination across seasons in a freshwater reservoir: Evidence from surface water, sediments, and fishes.

Microplastics (MPs) are prevalent contaminants in aquatic environments, posing substantial ecological and health risks. These particles migrate within the different layers of aquatic bodies with time and affect the respective biota. Thus, to get an in-depth understanding of the particles, this current study investigated the seasonal distribution, morphological and chemical characteristics, along with potential ecological and human health impacts in the samples including surface water, sediment, and fish from a drinking water supplying reservoir in eastern India. Across three different seasons, pre-monsoon, monsoon, and post-monsoon samples were collected using optimized methods. Results revealed distinct seasonal trends: MP abundance in surface water peaked during the monsoon (mean: 1.15 MPs/L), while sediment showed the highest concentrations in the pre-monsoon (mean: 596 MPs/kg), indicating temporal accumulation dynamics influenced by runoff, hydrodynamics, and sedimentation. Fish gut analysis confirmed ingestion of MPs across five species, with concentrations ranging from 26 to 100 MPs/kg, depending on feeding habits. The most dominant MP type were fragments, followed by fibers, films, and beads. Polymer analysis via &#xb5;FTIR identified polyethylene, polypropylene, and polyvinyl chloride as prevalent, with hazard assessments (i.e., Polymer Hazard Index (PHI)) indicating medium to very high ecological risks. Heavy metal association was more dominant in the MPs isolated from sediments than the waterborne MPs. Pollution Load Index (PLI) values were > 1 in most seasons, confirming contamination. Health risk analysis suggested potential exposure through both drinking water and fish consumption. This study emphasizes the need for seasonal monitoring, improved waste management, and mitigation strategies to address MP pollution in freshwater ecosystems.

Microplastics

Association of Age at Menarche With Depression in Adulthood in NHANES 2015-2023: A Cross-Sectional Study.

PURPOSE: The primary objective of this study is to elucidate the role of age at menarche in depression in adulthood and explore the implications of this association. METHODS: We conducted a study involving 9,826 adult female participants from the National Health and Nutrition Examination Survey (NHANES) between 2015 and August 2023. Age at menarche was categorized as early (<12 years), normal (12-14 years), or late (&#x2265;15 years). Depression was assessed using the 9-item Patient Health Questionnaire (PHQ-9) and clinical diagnoses. Logistic regression and restricted cubic spline analyses were performed to address the study objectives. In addition, subgroup analyses were conducted based on demographic, lifestyle, and clinical characteristics. RESULTS: The depression group had a significantly higher proportion of young adults (aged 18-30 years) compared to the nondepression group (26.46% vs. 20.52%, p < .001). Conversely, the nondepression group included a greater proportion of older adults (over 60 years) than the depression group (29.53% vs. 23.98%, p < .001). After comprehensive adjustments, early menarche was significantly associated with increased depression risk (adjusted odds ratio [aOR] = 1.224, 95% confidence interval [CI]: 1.003-1.493, p = .047). Restricted cubic spline analyses revealed an L-shaped nonlinear pattern (p for nonlinearity = 0.006), with optimal age at menarche around 12 years. Subgroup analyses confirmed consistent associations without significant interactions. DISCUSSION: Early menarche is linked to increased depression risk, especially among women aged 18-30 years. Menarche at 12 years may serve as a key point for early intervention to prevent depression in young women.

Humans

An integrated multiscale air quality modelling framework for industrial park pollution: Linking local emissions to regional transport.

Capturing the spatiotemporal distribution of pollutants in industrial parks remains challenging for regional air quality models because of their coarse resolution (3 km), resulting in uncertainties in local emission quantification. To address this, we developed the Integrated Multiscale Air Quality Modelling System for Industry (IAQMS-Industry), coupling the regional Nested Air Quality Prediction Modelling System (NAQPMS) with a city-scale chemical transport model. This framework integrates point-source locations and Gaussian plume dispersion to simulate particulate matter with a diameter smaller than 2.5 micrometres (PM2.5) at 100 m resolution. Applied to the Beijing Yi Zhuang and Tangshan industrial parks and evaluated against observations. The coupled model achieved a normalized mean bias (NMB) ranging from 3.1 % to 6.2 %, improving upon NAQPMS (-16.9 % to -7.7 %). Spatial analysis revealed that coarse regional grids underestimated the PM2.5&#x200b; concentrations at industrial sites by smoothing gradients, whereas IAQMS-Industry successfully resolved spatial patterns. Industrial point emissions accounted for 22.9 %-26.4 % of PM2.5 in the coupled model, which was significantly greater than the regional model estimates of 1.6 %-13.7 %. These findings indicate that regional models overestimate pollutant dispersion processes in industrial parks while underestimating local industrial impacts. By explicitly resolving point-source dynamics and linking them to regional transport, IAQMS-Industry provides a robust tool for designing targeted emission controls in industrial cities and balancing local air quality improvements with minimized regional pollution outflow. This study underscores the necessity of multiscale modelling for accurate source apportionment and informed environmental governance in industrial zones.

Air Pollution

Effect of different liposomal bupivacaine concentrations in ultrasound-guided superior trunk block on postoperative analgesia and mobility: a randomized double-blind controlled trial protocol for shoulder arthroscopy.

BACKGROUND: Shoulder arthroscopy frequently causes severe postoperative pain that may impede recovery. Liposomal bupivacaine provides prolonged analgesia, and ultrasound-guided superior trunk block (STB) offers comparable analgesia to interscalene block with a lower risk of hemidiaphragmatic paralysis. However, the optimal concentration of liposomal bupivacaine for STB remains unknown. METHODS: This randomized, double-blind, controlled trial will enrol 282 adult patients scheduled for elective arthroscopic rotator cuff repair. Patients will be randomly allocated (1:1:1) to receive ultrasound-guided STB with liposomal bupivacaine 66&#x2009;mg (Group A), 44&#x2009;mg (Group B) or 33&#x2009;mg (Group C), each diluted to 10&#x2009;mL. The co-primary outcomes are (1) rest pain Numeric Rating Scale (NRS) score at 48&#x2009;h post-surgery and (2) cumulative oral morphine milligram equivalents (MME) consumption within 0-48&#x2009;h after surgery. Secondary outcomes include rest pain NRS scores at 6, 24 and 72&#x2009;h; motor function assessed by Muscle Balance Scale, Bromage score and American Shoulder and Elbow Surgeons (ASES) score at 6, 24, 48 and 72&#x2009;h; and Quality of Recovery-15 (QoR-15) score at 24 and 48&#x2009;h. DISCUSSION: This study will provide evidence on the optimal concentration of liposomal bupivacaine for STB in arthroscopic shoulder surgery, aiming to achieve effective and prolonged analgesia without compromising shoulder mobility.

Humans

Transcriptomic changes in the gut mucosa of fasting northern elephant seal pups reveal immune modulation during early microbiome establishment.

Fasting is an integral component of the life-history of many species. Following abrupt weaning, northern elephant seal pups (Mirounga angustirostris) undergo an extended post-weaning fast of approximately 60&#xa0;days. During this period, enteric bacterial diversity increases, suggesting that host immune regulation may facilitate the establishment of microbial communities. However, the molecular processes occurring within the intestinal mucosa during this transition remain poorly understood. To investigate these mechanisms, we characterized transcriptional changes in the enteric mucosa of male and female northern elephant seal pups sampled at weaning and after one month of fasting. Total RNA isolated from rectal swabs was sequenced and aligned to the Mirounga angustirostris reference genome. Differential gene expression and gene set enrichment analyses were used to identify genes and pathways associated with fasting and sex-specific responses. Fasting was accompanied primarily by transcriptional downregulation, including genes involved in antimicrobial defense, inflammation, protein turnover, and epithelial remodeling. In contrast, several genes associated with B-cell activity and immune recognition were upregulated. Gene Set Enrichment Analysis revealed coordinated activation of immune-regulatory pathways indicating dynamic modulation of intestinal immunity rather than generalized immune suppression. Pronounced sex-specific differences were also observed. Male pups exhibited transcriptional patterns consistent with enhanced immune tolerance, whereas females showed broader immune-pathway activation, including enrichment of pro-inflammatory and stress-response pathways. Several non-coding RNAs also displayed sex-specific changes in expression. Together, these findings suggest that fasting induces transcriptional remodeling of the gut and may contribute to immune regulation during a critical period of microbiome establishment in northern elephant seal pups.

Animals

Effectiveness of psychosocial and lifestyle interventions in promoting behaviour change and improving cognitive outcomes in older people with memory concerns: A systematic review.

BACKGROUND: Older adults with mild cognitive impairment or subjective cognitive decline have a greater dementia risk, particularly those from minority ethnic and socioeconomically disadvantaged backgrounds. Psychosocial and lifestyle interventions targeting modifiable risk factors offer hope for reducing risk, yet behavioural mechanisms remain unclear. This systematic review examines these mechanisms and associated outcomes. METHOD: We searched PubMed, Embase (Ovid), PsycINFO (Ovid), Web of Science, and Scopus for randomised control trials testing interventions that aimed to improve lifestyle and cognition in older adults with memory concerns. We explored behavioural mechanisms using the COM-B model and synthesised intervention effectiveness, overall and within underserved groups. We prioritised lower risk of bias studies. RESULTS: 26 studies described 23 randomised controlled trials (14 multidomain, 9 single domain interventions). Certainty of evidence that behaviour change was associated with cognition was low. Moderate-certainty evidence indicated that interventions providing a socially supportive environment and combining nutritional education and counselling for 6&#x202f;+&#x202f;months improved diet. Physical activity improved primarily in interventions incorporating education, structured training, and enablement strategies (e.g., tailored programmes, providing tools). Interventions simultaneously targeting capability, opportunity and motivation showed greater overall effectiveness. Few studies recorded ethnicity (13%) or sociodemographic status (9%), and none explored their impact. CONCLUSIONS: Non-pharmacological interventions can help this population improve their lifestyles if they feel capable, equipped and motivated, highlighting the value of careful design and implementation. There is scarce evidence on how these interventions work for underserved populations. Future research should explore this to inform tailored interventions and develop equitable dementia prevention strategies.

Humans

The effect of combining visuo-vestibular exercises with manual therapy and exercise on sensorimotor function in chronic neck pain: A randomized controlled trial.

OBJECTIVE: To investigate whether adding visuo-vestibular exercises to standard manual therapy and exercise produces superior improvements in sensorimotor function, pain, balance, and functional disability in adults with chronic neck pain. METHODS: This prospective, randomized controlled trial enrolled 58 adults with chronic neck pain (&#x2265;3 months) allocated to a manual therapy and exercise group (MtE; n&#x202f;=&#x202f;29) or MtE plus visuo-vestibular exercises (MtE-VVE; n&#x202f;=&#x202f;29). Both groups completed 12 supervised sessions over six weeks with a daily home exercise programme. Outcomes were assessed at baseline, 6 weeks, and 12 weeks, and included pain intensity (Visual Analog Scale [VAS]), upper extremity reaction time, computerized posturography, the Neck Disability Index (NDI), and cervical muscle endurance. RESULTS: Fifty-four participants (27 per group) completed the study. Both groups improved significantly across all outcomes (p&#x202f;<&#x202f;0.001). At 12-week follow-up, the MtE-VVE group demonstrated superior outcomes: activity-related pain was reduced by an additional 2.00&#x202f;cm (95% CI: 0.75-3.25; p&#x202f;=&#x202f;0.005), bilateral reaction time improved by 1.70&#x202f;s (p&#x202f;=&#x202f;0.001), eyes-open mediolateral sway decreased by 0.50&#x202f;mm (p&#x202f;<&#x202f;0.001), NDI score was 6.30 points lower (95% CI: 3.42-9.18; p&#x202f;<&#x202f;0.001), and cervical flexion and extension endurance improved by 12.00&#x202f;s and 27.70&#x202f;s, respectively (p&#x202f;&#x2264;&#x202f;0.020). CONCLUSION: Adding visuo-vestibular exercises to standard manual therapy and exercise produces clinically meaningful and sustained improvements in activity-related pain, sensorimotor function, postural control, and functional disability in adults with chronic neck pain, and may be recommended as an effective adjunctive intervention.

Humans

Anti-inflammatory agents after hip and shoulder arthroplasty: A systematic review and meta-analysis.

BACKGROUND: Postoperative inflammation after arthroplasty contributes to pain, delayed mobilization and prolonged hospitalization. Recent randomized trials have evaluated pharmacological anti-inflammatory strategies within contemporary enhanced recovery pathways, but evidence after hip and shoulder arthroplasty remains scattered across different drug classes and perioperative regimens. OBJECTIVES: To synthesize recent randomized controlled trial (RCT) evidence on perioperative anti-inflammatory agents after hip and shoulder arthroplasty. METHODS: PubMed, Embase, Cochrane Library and Web of Science were searched for English-language RCTs published from January 2020 to March 2026. The 2020-2026 window was selected to update evidence generated under modern arthroplasty, anesthesia, multimodal analgesia and enhanced recovery after surgery (ERAS) pathways. Eligible trials included adults undergoing hip or shoulder arthroplasty and compared corticosteroids, cyclooxygenase-2 (COX-2) inhibitors, nonsteroidal anti-inflammatory drug (NSAID)-based/local anti-inflammatory regimens, or related anti-inflammatory interventions with placebo, saline, no treatment, or the same regimen without the target component. Weighted mean differences (WMDs) were pooled using random-effects models. RESULTS: Nine RCTs involving 800 patients were included. Anti-inflammatory interventions significantly reduced postoperative C-reactive protein (CRP) [WMD=-32.18, 95% confidence interval (CI) (-41.16, -23.21), P<0.001], interleukin-6 (IL-6) [WMD=-31.25, 95% CI (-41.79, -20.77), P<0.001], rest pain [WMD=-0.41, 95% CI (-0.58, -0.23), P<0.001], activity pain [WMD=-0.56, 95% CI (-0.83, -0.29), P<0.001] and hospital stay [WMD=-0.54, 95% CI (-0.92, -0.15), P=0.006]. CONCLUSION: Recent RCT evidence suggests that perioperative anti-inflammatory interventions can attenuate early inflammatory responses and improve short-term pain and recovery after hip and shoulder arthroplasty. Because data were limited and clinically heterogeneous, the findings should not be interpreted as evidence favoring a specific drug class, dose, route, or timing.

Humans

Integrative machine learning and transcriptomic analysis reveals molecular mechanisms underlying low survival rate in larval Chinese Bahaba (Bahaba taipingensis).

Chinese Bahaba (Bahaba taipingensis) is a Class I protected marine fish endemic to China. Low larvae survival during artificial breeding severely hinder population recovery. To investigate the molecular mechanism of high mortality in larval fish, this study performed RNA-seq on liver from naturally deceased (ND) and mass-dead (MD) individuals, combined with least absolute shrinkage and selection operator (LASSO) regression and random forest (RF) algorithms to screen for core signature genes. A total of 873 differentially expressed genes (DEGs) were identified, including 112 upregulated and 761 downregulated genes. GO and KEGG enrichment analyses revealed significant enrichment in amino acid metabolism disorders, one&#x2011;carbon folate pool impairment, PPAR signaling abnormalities, ECM-receptor interaction, focal adhesion pathway, indicating widespread metabolic suppression accompanied by extracellular matrix remodeling and signaling disturbances in the livers of MD fish. MAD pre-filtering combined with dual machine learning algorithms yielded 18 robust core signature genes, among which SLC38A4, MMP1, FADD, FKBP5, and APOB were consistently identified as high-frequency core genes by both algorithms. SLC38A4 exhibited the highest importance score in the RF model and was significantly downregulated, making it the primary molecule distinguishing ND from MD phenotypes. ROC curve analysis showed that both models achieved an AUC of 1.000 (95% CI lower bound: 0.610), confirming the precise discriminatory ability of the core genes. GSEA further demonstrated significant enrichment of this core gene set in ND samples. This study provides the first systematic elucidation of the molecular mechanisms underlying liver dysfunction in low survival rate B. taipingensis, characterized by amino acid transport impairment, metabolic reprogramming, and structural remodeling, offering theoretical foundations for health assessment, early mortality risk warning, and artificial breeding conservation of this species.

Animals

Effects of multistrain probiotic supplementation on hepatic function and anthropometric parameters in patients with metabolic dysfunction-associated steatotic liver disease: a double-blind, randomized controlled trial.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly prevalent on a global scale. The gut microbiota is integral to its pathogenesis, prompting extensive research into microbiota modulation as a potential adjunctive therapeutic strategy. AIM: The study aimed to evaluate the effect of multistrain probiotics supplementation on hepatic function in patients with MASLD in a double-blind, randomized, controlled trial. The primary outcomes were changes in Fibrosis-4 index (FIB-4) and fatty liver index (FLI). Secondary outcomes included changes in anthropometric parameters, selected biochemical markers, and other liver-related indices. METHODS: A total of 64 patients with MASLD were randomly assigned to two groups receiving either placebo (C) or a probiotic mixture (PRO) containing the following bacterial strains: 50% Lactococcus lactis Rosell-1058, 25% Lacticaseibacillus casei Rosell-215, 12.5% Lactobacillus helveticus Rosell-52, 12.5% Bifidobacterium bifidum Rosell-71 for 12 wk. RESULTS: Significant group &#xd7; time interactions were observed for FIB-4 (Q = 0.007), with reduction in the PRO group and increase in the C group (-0.05 vs. 0.10; P = 0.002). No significant interaction was found for FLI (Q = 0.942). Significant group &#xd7; time interactions were also observed for aspartate aminotransferase (-2.87 vs. 1.87 U/L; Q = 0.003) and APRI (-0.03 vs. 0.02; Q = 0.001), favoring the PRO group (P < 0.001 for both). No significant changes were observed in anthropometric parameters, glucose levels, or lipid profile. CONCLUSIONS: In patients with MASLD, the 12-wk probiotic supplementation had a modest but statistically significant effect on FIB-4, aspartate aminotransferase, and APRI, with no significant effect on FLI or anthropometric and metabolic parameters. These findings suggest that this probiotic formulation may have potential benefits for liver function in MASLD. However, long-term studies incorporating imaging-based and histological endpoints are required to determine the clinical significance of these findings.

Humans