by Natsuhiro Takahashi, Akihiko Fujita, Yuki Azetsu, Akiko Karakawa, Mie Myers, Masamichi Takami, Masahiro Chatani
Bone loss occurs in astronauts during prolonged spaceflight, thus indicating the sensitivity of skeletal homeostasis to altered gravitational environments. Previous studies have shown that microgravity affects osteoclast differentiation and bone resorption, which suggests that osteoclasts possess mechanisms to sense and respond to gravity-generated mechanical forces. For testing of the related mechanisms, hypergravity can be experimentally reproduced with use of a centrifuge. In the present study, osteoclasts derived from mouse bone marrow were subjected to hypergravity under three conditions: 30G exposure using a non-CO2 centrifuge system, and short- or long-term exposure to 3G or 5G using an incubator-compatible centrifuge system. Cytoskeletal organization and resorptive function were assessed using TRAP (tartrate-resistant acid phosphatase) staining, F-actin visualization, and dentin pit assays. In addition, phosphoproteomic analysis was performed after short-term exposure to 5G hypergravity. Hypergravity exposure for as brief as 30 minutes compromised F-actin ring integrity, reduced fluorescence intensity, and promoted nuclear repositioning toward actin rings, whereas tubulin and vinculin localization remained unchanged, and the structural alterations corresponded to attenuated resorption pit formation. Quantitative phosphoproteomic profiling revealed coordinated hypergravity-dependent changes in phosphorylation across multiple cellular modules, including cytoskeletal organization, membrane trafficking, intracellular signaling, and nuclear regulatory pathways. Together, these results indicate that osteoclasts are sensitive to gravity-generated mechanical loading, with hypergravity rapidly modifying F-actin-associated cytoskeleton properties and reprogramming phosphorylation-dependent signaling networks, ultimately attenuating bone-resorptive activity. These findings provide mechanistic insight into how osteoclasts respond to altered gravitational loading conditions and have implications for skeletal adaptation during spaceflight and under altered mechanical loading conditions on Earth.by Tatsuya Yoshihara, So Owada, Harumasa Arita, Akiko Nakagomi, Kota Tanaka, Yosuke Ono, Osamu Yoshino
BackgroundTo investigate the association between menstrual-related disorders and sexually transmitted infections (STI) among young women in Japan, and to examine differences according to disorder type and hormonal therapy use.
MethodsThis cross-sectional study used the Japan Medical Data Center Claims Database and included women younger than 40 years who had at least one healthcare visit in 2023. Menstrual-related disorders were defined as endometriosis or dysmenorrhea based on ICD-10 codes. The prevalence of five STIs—gonorrhea, genital chlamydia infection, trichomoniasis, genital herpes, and other sexually transmitted conditions—was compared between women with and without menstrual-related disorders. Subgroup analyses were conducted for endometriosis, dysmenorrhea, and hormonal therapy (low-dose estrogen–progestin combinations or dienogest). Prevalence ratios (PR) and prevalence differences (PD) with 95% confidence intervals (CI) were estimated.
ResultsAmong 3,440,929 women, 257,897 (7.5%) had menstrual-related disorders. All STI were substantially more prevalent in this group than in women without menstrual-related disorders, with PRs ranging from 4.31 to 5.29. Endometriosis showed the highest prevalence, particularly for genital chlamydia infection (4.98%; PR 7.44). Dysmenorrhea was also associated with consistently elevated STI prevalence. Among women with menstrual-related disorders, STI prevalence differed only slightly according to hormonal therapy use, with differences generally within one percentage point.
ConclusionMenstrual-related disorders were strongly associated with increased diagnosis of STI in Japanese young women. These findings highlight the importance of integrating STI screening and reproductive health education into routine gynecologic care for women with endometriosis or dysmenorrhea. The influence of healthcare-seeking behavior and diagnostic patterns should be considered when interpreting claims-based STI data.
by Agatha Ribeiro Kalthof, Nikolas Dresch Ferreira, Caio Mateus Silva, Iuri Cordeiro Valadão, Iguaracy Pinheiro de Sousa, Ester Riserio Matos Bertoldi, Vanessa Morais Lima, Lauro Thiago Turaca, Ana Beatriz Ruiz Afonso Barbosa, Miriam Helena Fonseca-Alaniz, Jean-Paul Concordet, Elida Adalgisa Neri, Jose E. Krieger
Generating mature human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) remains a major obstacle to accurate disease modeling and cardiac repair. As the transcription factor Irx3 is a key determinant of ventricular conduction system fate in mice, we hypothesized that suppressing IRX3 expression accelerates human working cardiomyocyte differentiation. Here, we demonstrate that depleting IRX3 enhances hiPSC-CM differentiation. IRX3-knockout (KO) hiPSCs generated a greater number of cardiomyocytes with elevated expression of TNNI1 and CX43. Notably, IRX3-KO cardiomyocytes exhibited improved electrophysiological properties, more uniform mitochondrial distribution, better sarcomere organization, and enhanced intercellular connectivity. We observed that IRX3 expression peaks during the early stages of cardiomyocyte differentiation, whereas IRX3-KO cardiac progenitors have increased expression of GATA4, NKX2–5, and TBX5, as well as enhanced cell proliferation. These integrative analyses indicate that IRX3 influences cardiomyocyte differentiation by modulating the gene regulatory networks driven by GATA4, NKX2–5, and TBX5, providing functional evidence linking gene regulatory networks to the structural and electrophysiological development of cardiomyocytes. Collectively, these findings identify IRX3 as a key regulator of early cardiac commitment and highlight the potential of IRX3 suppression to enhance the molecular and functional phenotype of hiPSC-derived cardiomyocytes.by Juliana Ju Yun Hoo, Shumetha Sidhu, Kok Wei Tan
Rapid urbanization has increased disconnection from nature, especially in cities. While research on restorative environments has largely focused on non-tropical regions, little is known about the restorative potential of tropical urban green spaces (UGSs). This study assessed the perceived restorativeness of tropical UGSs in Malaysia using 120 environmental stimuli from nature, urban, and mixed urban-nature settings. 87 participants were randomly assigned to one of the three modalities: audio-only, visual-only, or bimodal. Each participant rated a subset of 30 stimuli on perceived restorativeness. Results showed that nature and mixed urban-nature scenes were in general rated as more restorative than urban scenes. An interaction effect indicated that, in the visual-only modality, mixed urban-nature scenes were perceived as more restorative than nature scenes, while no significant differences were observed in the audio-only and bimodal modalities. Moreover, perceived restorativeness for nature scenes was comparable across bimodal, visual-only, and audio-only presentations. These findings suggest that small pockets of urban nature (e.g., tree-lined streets, rooftop gardens) can offer greater psychological restoration than wild, untamed forests. In addition, high-quality nature sounds (e.g., birdsong, flowing water) can provide restorative benefits comparable to visual exposure when access to green views is limited. Such insights can inform urban planning strategies to design more restorative and liveable cities.To evaluate the effectiveness of multidisciplinary offloading versus standard care on one-year diabetic foot ulcer recurrence, amputation, mortality, and functional recovery. In this prospective cohort study, 232 patients with healed diabetic foot ulcers were stratified into a control group (76 patients) or an intervention group (156 patients) receiving offloading modalities ranging from felt padding to custom-made therapeutic footwear. Assignment was based on shared decision-making considering biomechanical needs and economic feasibility. Primary outcomes included recurrence, amputation, and mortality. Secondary outcomes assessed quality of life, working ability, and ankle function. The intervention group demonstrated significantly lower recurrence (10.9% vs. 25.0%; p = 0.007) and mortality (3.2% vs. 14.5%; p = 0.004). Multivariable analysis identified offloading as independently protective against recurrence (odds ratio 0.35) and mortality (odds ratio 0.24). Amputation rates did not differ significantly after adjustment. Functionally, the intervention group achieved superior recovery in quality of life, working ability, and ankle scores (p < 0.001). Subgroup analysis indicated that customized therapeutic footwear yielded the lowest complication rates and highest patient satisfaction. Multidisciplinary offloading significantly reduces recurrence and mortality while restoring physical function. Although financial barriers influence device selection, customized therapeutic footwear offers the optimal balance of biomechanical protection and functional outcomes.
An affordable heart-healthy dietary approach is essential for the management of familial hypercholesterolaemia (FH); however, the optimal dietary pattern and the role of adjunctive nutrient supplementation remain uncertain. This study aims to evaluate the effects of the Brazilian Cardioprotective Diet (DICA Br), adapted from the Portfolio Diet, with or without phytosterol and/or krill oil supplementation in individuals with probable or definite FH according to the Dutch Lipid Clinic Network (Dutch MEDPED) criteria.
The DICA-FH study is a national, multicentre, randomised, factorial, parallel-group, superiority, placebo-controlled clinical trial with a 1:1:1:1 allocation ratio. Participants aged ≥16 years receiving age-appropriate lipid-lowering therapy will be randomised into four groups: (1) adapted cardioprotective diet (DICA-FH) plus phytosterol placebo and krill oil placebo; (2) DICA-FH plus phytosterol 2 g/day and krill oil placebo; (3) DICA-FH plus phytosterol placebo and krill oil 2 g/day or (4) DICA-FH plus phytosterol 2 g/day and krill oil 2 g/day. All participants will undergo whole-genome sequencing and receive appropriate genetic counselling. Primary outcomes will be means of low-density lipoprotein cholesterol and lipoprotein(a) levels after 120 days. Secondary outcomes will include additional lipid biomarkers, adherence to protocol and adverse events. The planned sample size is 300 participants. Follow-up is expected to conclude in July 2026.
This study was registered under CAAE 65549622.2.1001.0060 and received ethical approval from the Hcor Research Ethics Committee (approval number 5.805.072) and the Brazilian National Research Ethics Commission (CONEP; approval number 6.864.951). Written informed consent will be obtained from all participants prior to enrolment. The study findings will be disseminated through peer-reviewed publications, scientific conferences and channels aimed at the general public.
Digital health interventions (DHIs) show considerable promise in supporting hypertension self-management by promoting preventative care and self-monitoring. While their efficacy is increasingly evident, the long-term uptake, acceptance and sustained engagement with these tools are frequently challenged by issues such as usability, trust and varying user experiences. This review aims to synthesise qualitative evidence to identify barriers and facilitators and the key factors that impact the adoption, acceptance and engagement with DHIs for hypertension self-management.
Systematic review of qualitative literature using thematic analysis following Cochrane’s qualitative and implementation methods guidance.
PubMed, PsycInfo, Web of Science and the Cochrane Library were searched in February 2025.
The searches included relevant qualitative and mixed-methods studies on the use of digital devices for hypertension management, which described the barriers and facilitators associated with these tools. We included studies published from 2015 to 2025 to capture relevant evidence. Only studies published in English with a qualitative approach were included.
From an initial 10 943 identified publications, 15 met our inclusion criteria, primarily originating from Europe and the USA, exploring diverse racial and ethnic group experiences. Our thematic synthesis revealed 7 analytical and 22 descriptive themes detailing barriers and facilitators encountered by patients with hypertension, healthcare providers (HCPs) and caregivers. These themes covered technology utilisation, design components, linguistic and cultural relevance, healthcare factors, trust and credibility and interpersonal interactions.
Our analysis underscores that factors such as the usability, design and relevance of social support profoundly influence the uptake and acceptance of DHIs in hypertension self-management among patients, caregivers and HCPs.
CRD42023480389.
Ophthalmic complaints account for a substantial proportion of presentations to emergency and acute eye care services, yet initial assessment or referral is frequently performed by non-ophthalmologist healthcare professionals. Previous single-centre studies suggest that one-third of referrals are incorrectly diagnosed, potentially delaying appropriate management of vision-threatening conditions. However, the overall magnitude of diagnostic error and patterns of misdiagnosis across healthcare settings remain unclear. This study aims to systematically review and synthesise the evidence on the diagnostic concordance of ophthalmic referral diagnoses made by non-ophthalmologists in acute eye care.
A systematic review and meta-analysis will be conducted following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols) guidance and registered with PROSPERO. MEDLINE (Ovid), Embase (Ovid) and the Cochrane CENTRAL database will be searched from inception to April 2025. Studies evaluating the diagnostic accuracy of referrals made by non-ophthalmologist healthcare professionals in emergency or acute eye care settings will be included. Two reviewers will independently screen studies, extract data and assess risk of bias using the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies-2) framework adapted for referral-diagnosis studies. The primary outcome will be diagnostic concordance between referral and final ophthalmologist diagnosis. Where appropriate, pooled concordance proportions will be synthesised using a random-effects meta-analysis. Condition-specific 2x2 diagnostic accuracy analyses will only be undertaken where valid binary target conditions and sufficient denominators are reported. Heterogeneity will be assessed using Cochran’s Q test and the I² statistic with subgroup analyses exploring differences by referring clinician type and anatomical location of ophthalmic pathology.
Ethical approval is not required for this study as it will synthesise data from previously published studies; findings will be disseminated through publication in a peer-reviewed journal and presentation at relevant academic conferences.
CRD420261352717.
To explore the impact of acute worsening events (AWEs), defined as clinically relevant deteriorations in peak expiratory flow, reliever use and/or symptoms, on patients’ daily lives and identify behaviours linked to their recognition and management.
A qualitative international substudy was conducted in the Netherlands, Spain, the USA, Canada and the UK (2023–2024).
19 patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) from a randomised clinical trial participated. Interviews, triggered by AWEs and repeated 6 weeks later, were audio-recorded, transcribed and analysed.
Patients varied in identifying bad days, reporting inability to perform physical activities, symptom worsening or the need for add-on treatment. Recognition of AWEs depended on their duration: shorter events (
AWEs significantly impact daily life but vary widely in recognition and thresholds for seeking care. Limited awareness of daily disease variations may contribute to both under-reporting of worsening events to healthcare providers and suboptimal self-management in COPD.
This study aims to explore the ability to identify high-grade intracranial arterial stenosis (ICAS) by an artificial intelligence (AI) designed to detect large vessel occlusions (LVO) and the clinical relevance of these ‘false positive’ findings.
We are presenting a retrospective cohort study.
The study was conducted at a supraregional stroke centre of an urban tertiary care provider.
Consecutive stroke cases treated between January 2023 and December 2023 of patients >18 years of both sexes and any ethnicity were eligible for inclusion. 934 patients (52.7% male) with a mean age of 71.7±13.6 years (25–101 years) were included.
CT angiographies were analysed by a deep learning algorithm for LVO detection of the anterior circulation. AI results were compared with radiology reports and secondary focused evaluation.
Diagnostic accuracies for ICAS detection by the AI were calculated.
Primary reports identified 30 ICAS and nine additional ICAS were detected during secondary evaluation (incidence 4.2%). The sensitivity of radiology reports was 77% (95% CI 0.61 to 0.89), the specificity 99% (95% CI 0.98 to 1.00), negative predictive value (NPV) 99% (95% CI 0.98 to 0.99) and positive predictive value (PPV) 79% (95% CI 0.65 to 0.88). The AI identified 13 of 39 ICAS correctly. 18 false positive cases (neither LVO nor ICAS) were flagged by the AI. The sensitivity of the algorithm was 33% (95% CI 0.19 to 0.50), the specificity 98% (95% CI 0.97 to 0.99), the NPV 97% (95% CI 0.96 to 0.98) and PPV 42% (95% CI 0.28 to 0.58).
Detection of high-grade ICAS by an algorithm trained to identify LVO is per se a false positive finding but occurred in 13 of 39 cases. Dedicated training for ICAS might lead to a beneficial tool during the diagnostic work-up for ischaemic stroke.
German Register for Clinical Trials (DRKS: DRKS00034019 https://drks.de/search/de/trial/DRKS00034019).
Asthma, chronic obstructive pulmonary disease (COPD) and obstructive sleep apnoea (OSA) are prevalent chronic respiratory diseases associated with increased comorbidity, mortality and healthcare costs. Physical activity and exercise are widely recommended as part of treatment for these conditions, yet the specific effects of Nordic walking (NW) remain underexplored. The aims of this randomised controlled trial (RCT) are to improve physical fitness, functional capacity and respiratory health and increase regular physical activity and quality of life of older adults with asthma and/or COPD and/or OSA through a supervised 3-month group-based NW intervention combined with resistance, balance and mobility training.
This single-blinded, parallel-group RCT will recruit 100 adults aged 55–80 years diagnosed with asthma and/or COPD and/or OSA in the Northern Savo region of Finland. Participants will be randomly allocated to either an intervention group or a control group.
The intervention group will participate in a 12-week supervised exercise programme consisting of progressive NW sessions twice per week and resistance, balance and mobility training once per week. The primary outcome is a change in cardiorespiratory endurance. Secondary outcomes include functional capacity, physical activity level, spirometry parameters and quality of life. The control group will continue their usual physical activity and receive physical activity guidance after 12 weeks. Measurements were conducted at baseline, three and 9 months. Data will be analysed according to the intention-to-treat principle. Group differences over time will be examined using appropriate parametric or non-parametric methods depending on data distribution.
Ethical approval was obtained from the Regional Medical Research Ethics Committee of Eastern Finland Collaborative Area (892/13.00/2023). Findings will be disseminated through publications in peer-reviewed journals and presentations at scientific conferences.
The trial is registered at ISRCTN12097135, registration date: 7 June 2024.
South African women are vulnerable to HIV acquisition during the postpartum period which can result in perinatal transmission via breastfeeding; many male partners do not know their HIV status. Biomedical approaches to preventing HIV for postpartum women include pre-exposure prophylaxis (PrEP) and antiretroviral treatment for male partners with HIV. Gaps in implementation include low uptake of PrEP among postpartum women and infrequent testing of men who may be motivated to test for HIV to protect the health of their infant.
We will conduct a randomised pilot trial in KwaZulu-Natal (KZN) Province, South Africa among postpartum women and their male partners. The study will pilot a combination intervention consisting of cognitive behavioural strategies (including communication skills training, motivational interviewing and problem-solving) to promote HIV self-testing (HIVST) for Partners and PrEP uptake for HIV-uninfected Postpartum Women, the ‘H4P’ intervention. The study aims to determine the feasibility, acceptability and preliminary effectiveness of the H4P intervention. We will enrol 60 HIV-uninfected women, aged 18 years and older, in their third trimester of pregnancy and reporting a partner whose HIV-serostatus is unknown. Sixty male partners will also be eligible to enrol. Enrolled women will receive three oral HIVST kits to distribute to their male partners and standard of care information on HIVST and PrEP. Women randomised to the intervention arm will receive additional counselling and reproductive health-centred HIVST information for the male partner, including information about why HIV testing is important during their partners’ postpartum period. To evaluate feasibility, we will calculate screening-to-enrolment ratios for women and men, the number of women who distribute HIVST kits to their male partners and the number of men who test. Acceptability will be evaluated using the Client Satisfaction Questionnaire and qualitative interviews. Effectiveness will be assessed at 3 months by measuring the proportion of women initiating PrEP via self-report and urine tenofovir measurements or receipt of injectable PrEP and the proportion of men who test positive who link to HIV care. Qualitative interviews will explore perceptions of the intervention.
Ethics approval for this study was obtained from the Human Research Ethics Committee at The University of the Witwatersrand, Johannesburg, South Africa (Reference number: 250612) and the Institutional Review Boards at Massachusetts General Brigham (2025P002271, Boston, Massachusetts, USA) and the University of Alabama at Birmingham (300015167, Birmingham, Alabama, USA) in the USA. Site support and approvals were obtained from the health facility and the KwaZulu-Natal Provincial Department of Health. Results will be disseminated through peer-reviewed manuscripts, reports and both local and international presentations.
Approximately 40% of women stop endocrine therapy for hormone-receptor-positive breast cancer within the first 5 years of prescribed treatment because of side effects. Musculoskeletal complaints are among the most frequently reported side effects. The Cancer Of the BReast Asanas (COBRA) study examines the effect of an 18-week yoga programme on endocrine therapy-associated musculoskeletal complaints in women with breast cancer.
In total, 140 women will be randomised in a 1:1 ratio to the intervention or waitlist control group. The intervention programme consists of two times a week 1-hour supervised Hatha or (easy) Vinyasa yoga classes at a yoga or sports centre for 18 weeks and once per week a half-hour at home using videos. The waitlist control group is asked to maintain their habitual lifestyle during the first 18 weeks and will participate in a similar yoga programme to the intervention group for the following 18 weeks. The control group yoga programme is offered live-remote. The primary outcome (musculoskeletal complaints) is assessed with the Brief Pain Inventory questionnaire at baseline and 18 weeks (primary comparison) and additionally at 36 weeks. Secondary outcomes include lower and upper extremity joint complaints, menopausal symptoms, fatigue, sleep, quality of life, anxiety and depression, cognitive complaints and habitual physical activity (all patient-reported), vital signs and anthropometrics, physical fitness, blood biomarkers, medication use, safety data and patient and teacher experiences. At baseline and 18 weeks, cognitive complaints are also assessed with an online neuropsychological test battery.
The COBRA study was approved by the Medical Ethical Committee of the University Medical Center Utrecht. The study started on 8 October 2024, and 65 participants have been included (20 January 2026). Results will be submitted to an international peer-reviewed journal.
To compare use of electronic nicotine delivery systems (ENDS) with nicotine replacement therapies (NRTs) on risk of cigarette smoking relapse by people who had already quit cigarettes.
Prospective cohort study.
The American Cancer Society Cancer Prevention Study-3, a nationwide US cohort with follow-up every 3 years beginning in 2015.
Adults who in 2015 had already quit smoking (n=3112) or were smoking (n=1018) and who in 2018 reported past or current exclusive use of ENDS or NRT and provided smoking status.
Relapse to cigarette smoking in 2018 among people who were already quit in 2015, and abstinence from cigarettes in 2018 among people who were smoking in 2015.
Among respondents who had already quit in 2015, the unadjusted risk of relapse in 2018 was approximately three times greater for those who reported past exclusive ENDS versus past exclusive NRT use (11.2% vs 3.9%; relative risk (RR)=2.90, 95% CI 2.12 to 3.98). This association remained significant in a multivariable-adjusted model (RR=2.09, 95% CI 1.49 to 2.92). Among those smoking in 2015, the unadjusted likelihood of abstinence in 2018 was higher for those who reported current ENDS versus NRT use (RR=1.35, 95% CI 1.01 to 1.80), but the multivariable model adjusted for smoking frequency indicated no difference in abstinence (RR=1.38; 95% CI 0.93 to 2.05).
ENDS use was associated with greater relapse risk than NRT among people who had already quit. Although ENDS may support shorter-term cessation, further long-term observational research is needed to clarify relapse risks associated with ENDS relative to NRT.
To estimate the global, regional and national burden of maternal haemorrhage (2000–2021) and its 2050 projections in 204 countries and territories.
This study systematic analysis of the burden of maternal haemorrhage sourced data from the Global Burden of Disease (GBD) 2021 study. We estimated the incidence, mortality, disability-adjusted life years (DALYs), years lived with disability (YLDs) and years of life lost (YLLs) due to maternal haemorrhage. Changes in the burden from 2000 to 2021 were computed using AAPC. To detect statistically notable changes in the trends of maternal haemorrhage metrics between 2000 and 2021, Joinpoint regression analysis using the Joinpoint Regression Programme was conducted. We also projected mortality rates, YLDs and YLLs through to 2050 using maps and trends generated by the GBD Foresight visualisation tool.
Globally, the incidence of maternal haemorrhage among women aged 15–49 years declined from 881.98 per 100 000 reproductive aged women (95% uncertainty interval (UI) 687.01 to –1150.23) in 2000 to 714.00 (95% UI 556.97 o t908.54) in 2021, with an average annual percentage change (AAPC) of –0.91 (–1.37 to –0.49). Similar downward trends were observed for maternal deaths, DALYs, YLDs and YLLs attributable to maternal haemorrhage, with AAPCs of –3.78 (–4.39 to –3.18), –4.68 (–4.83 to –4.55), –1.21 (–1.54 to –0.89) and –4.80 (–5.10 to –4.52), respectively. Sub-Saharan Africa, particularly Western Sub-Saharan Africa, recorded the highest burden in 2021, which is almost 300 times higher than in Western Europe. Elevated rates of mortality, DALYs and YLDs were also evident in Sierra Leone, Chad, Niger, Mali, Nigeria, Burkina Faso, Central African Republic, Somalia and South Sudan in 2021 and projections for 2050. However, the high-income Asia Pacific region had the lowest incidence, DALYs and YLDs at 151.32 (109.63–203.68), 2.21 (1.72–2.86) and 0.87 (0.46–1.38) per 1 00 000 women, respectively. Australasia recorded the lowest maternal death count and YLLs attributed to maternal haemorrhage at 0.69 (0.50–0.90) and 0.56 (0.41–0.74) per 1 00 000 women, respectively.
While the global burden of maternal haemorrhage has declined over time, significant regional and national inequities persist. Even though the 2050 projections show improvement in the burden of maternal haemorrhage, there is also regional and national variation in the rate of decrease in maternal haemorrhage burden. Targeted, context-specific interventions are urgently needed to reduce maternal haemorrhage-related mortality and morbidity.
Interstitial lung diseases (ILDs) represent a heterogeneous group of disorders, which have in common persistent inflammation and/or pulmonary fibrosis, involving mainly but not exclusively the interstitium. This results in restrictive ventilatory physiology and limited respiratory reserve. Patients with ILD can have frequent exacerbations of their disease, with subsequent acute respiratory failure that may require admission to the intensive care unit (ICU). The diagnosis and management of ILD in the ICU presents unique challenges due to the paucity of evidence supporting survival benefits of organ support in this cohort of patients.
This systematic review will be reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, and the protocol will follow the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guideline. MEDLINE, Embase, Emcare and CENTRAL will be searched for studies published from inception to 2026, involving adult patients with ILD requiring invasive mechanical ventilation (IMV), with or without comparison to non-invasive respiratory support such as high-flow oxygen, non-invasive ventilation (NIV), continuous positive airway pressure or bilevel positive airway pressure. Eligible studies will include randomised controlled trials and observational studies (cohort and case–control) in adults with ILD and acute respiratory failure requiring IMV in the intensive care setting. Case series with fewer than 10 patients, non-human or in vitro studies and studies involving perioperative lung transplant or lung cancer as the primary diagnosis will be excluded. The primary outcomes assessed will be in-hospital and 1-year mortality, and secondary outcomes will include ventilator-free days, ICU and hospital length of stay, NIV failure, reintubation and postdischarge respiratory outcomes where available. Where feasible, meta-analysis will be conducted using a random-effects model. Heterogeneity will be assessed using the I² statistic. Prespecified subgroup analyses will be performed, including ILD subtype (eg, idiopathic pulmonary fibrosis (IPF) vs non-IPF), presence of pulmonary hypertension, timing of IMV initiation (early vs late), baseline lung function (forced vital capacity ≥50% vs
This systematic review will be based on published data, and as such, no ethical approval is required. Findings from this study will be disseminated through peer-reviewed publications as well as presentations in healthcare-based settings.
CRD420251265836.
by Patricia Fiorino, Luigi Fernandes Rosa Cauduro, Danielle Silberspitz Konig, Leonardo Fernandes Rosa Cauduro, Caio de Araujo Santos, Juliana Alves Kavai, Isadora Durigan Duarte, Anna Laura Viacava Américo
Zebrafish (Danio rerio) are widely used as models in cardiovascular research due to their rapid development, optical transparency, and genetic similarity to humans. However, the lack of standardized experimental conditions, particularly regarding developmental stage and microenvironmental parameters, limits reproducibility across studies. This study aimed to characterize cardiovascular function in Zebrafish larvae and evaluate the impact of developmental stage and environmental factors. Wild-type AB embryos were maintained under standard conditions, and heart rate (HR), cardiac output (CO), and ejection fraction (EF) were measured at 24, 30, 48, 52, 56, 72, 78, and 80 hours post-fertilization (hpf). The effects of variations in temperature (27.0, 27.5, and 28.0 °C) and pH (7.0, 7.4, and 8.0) were also assessed. Results showed a progressive increase in HR from 24 to 72 hpf, stabilizing thereafter. CO exhibited two phases of elevation: an early rise between 24–48 hpf and a stronger increase between 48–56 hpf. EF remained generally stable, with a transient reduction at 48 hpf. Cardiovascular performance reached a physiologically stable state after 72 hpf, defining a reliable window for functional studies. Environmental conditions modulated these parameters: temperature variation induced approximately 20% difference in HR and reduced EF, while CO was minimally affected. In contrast, pH variations within the physiological range had no significant impact on HR, CO, or EF. These findings highlight developmental and environmental variables that may influence cardiovascular measurements in Zebrafish larvae and support the development of more consistent experimental approaches in cardiovascular and toxicological research.The Parent Support Team (PST) is an intensive early intervention home visiting programme delivered by child and family health nurses to families with infants aged 0–6 months experiencing psychosocial and health vulnerabilities. In contrast, mainstream services provide universal clinic-based care and scheduled developmental checks. This mixed-methods study aimed to: (1) describe demographic and psychosocial characteristics, service activity and well-baby check attendance among PST clients compared with mainstream service clients; (2) evaluate changes in maternal depressive symptoms following PST engagement; and (3) explore client experiences, including perceived outcomes and facilitators and barriers to change.
Convergent parallel mixed-methods study.
Retrospective data were extracted from electronic medical records for PST clients (909 mothers; 1038 children) and mainstream service clients (17,707 mothers; 21,764 children) between August 2019 and December 2022. Quantitative analyses described demographics, psychosocial characteristics, service use and maternal depressive symptoms. PST client experience surveys (166 mothers) were analysed using descriptive statistics and thematic analysis.
PST clients demonstrated greater psychosocial complexity and higher maternal depressive symptoms at entry than mainstream clients. PST mothers had more frequent service contacts and maintained stronger engagement with services after discharge. The proportion of mothers with clinically significant depressive symptoms decreased following programme participation. Survey findings indicated improved parenting confidence and practical skills. Positive outcomes were attributed to nurse qualities, opportunities to discuss concerns, a holistic care approach and the service model. Reported barriers included accessibility, scope of education topics and communication challenges.
The PST programme effectively engages vulnerable families, supports maternal mental health and promotes sustained connection with child and family health services.
Intensive early intervention home visiting programmes may improve outcomes for families with complex needs and warrant broader implementation.
SRQR guidelines were followed.
None.
by Kanae Kondo, Ichizo Morita, Shigemitsu Sakuma, Isao Ohsawa
ObjectivesThis study aimed to longitudinally examine nationwide changes in smoking behavior among the Japanese population in response to the COVID-19 pandemic.
Design and settingA secondary analysis was conducted using cigarette sales data from the Tobacco Institute of Japan, monthly tobacco expenditures from the Family Income and Expenditure Survey conducted by the Ministry of Internal Affairs and Communications, and smoking prevalences from the National Database of Open Data Japan. An interrupted time-series segmented regression model adjusted for seasonality and autocorrelation was used to examine changes in cigarette sales and monthly tobacco expenditures before and after the first declaration of a state of emergency.
ParticipantsDepending on the data source, data from 2014 to 2022, from 2015 to 2025, or from 2015 to February 2026 were used.
Primary and secondary outcome measuresChanges in level and slope were evaluated before and after the first state of emergency and after COVID-19 was downgraded to a common infectious disease.
ResultsCigarette sales declined at a significantly slower rate after the first state of emergency than before. Price-adjusted monthly tobacco expenditures increased significantly by 132 JPY compared with the previous month, although the expenditure findings were less robust in the quadratic sensitivity analysis. The smoking prevalence among men declined slightly each year, from 34.2% in 2014 to 31.9% in 2022. In contrast, the smoking prevalence among women remained relatively stable, ranging between 9.4% and 9.9%.
ConclusionsAlthough cigarette sales declined more slowly and household tobacco expenditures increased during the first state of emergency in Japan, smoking prevalences did not change substantially. These findings suggest changes in tobacco purchasing patterns, including stockpiling, and possible changes in smoking intensity among continuing smokers, rather than a meaningful population-level decline in smoking behavior. There was no robust evidence of a clear reversal after May 2023.
by Kethmany Ratsavong, Dirk Essink, E. Pamela Wright, Somphou Sayasone, Sengchanh Kounnavong, Jacqueline E. W. Broerse
Child undernutrition remains a significant public health challenge in many low and middle-income countries (LMICs), including Lao PDR, where high levels persist even in urban areas with generally available and accessible food. This study aimed to explore factors underlying the persistently high rates of undernutrition among young children in urban (Saysetha) and peri-urban (Pakgneum) districts of the Vientiane Capital in Lao PDR. A cross-sectional survey employed a sequential explanatory mixed-methods approach, combining a structured questionnaire of 333 mother–child pairs for quantitative analysis with semi-structured interviews of 47 caregivers for qualitative insights. The prevalence of malnutrition among children under 24 months in Vientiane Capital was 27.3% for stunting, 4.2% for wasting, 14.4% for underweight, and 5.11% for overweight. Multiple logistic regression was applied to identify factors associated with malnutrition, while qualitative data were thematically analyzed. The principal findings revealed that, beyond food access, the quality of caregiving and, critically, caregivers’ capacity to translate nutrition knowledge into effective practices distinguished well-nourished from undernourished children. Caregivers of better-nourished children obtained health and nutrition information from diverse sources, whereas those of undernourished children relied mainly on health services. In conclusion, strengthening practical nutrition communication in various methods and channels, such as through videos and demonstrations, and enhancing caregivers’ ability to apply nutritional knowledge, are central to improving child nutritional outcomes in urban and peri-urban settings in Lao PDR.