Musculoskeletal disorders impose a substantial global disability burden. Conventional 3D bioprinting cannot replicate the dynamic, anisotropic architecture of bone, cartilage, skeletal muscle, and cardiac muscle. Four-dimensional (4D) bioprinting addresses this by integrating stimuli-responsive materials into constructs, enabling programmed shape transformation and adaptive behavior following implantation.

This narrative review examines primary experimental research on stimuli-responsive 4D-bioprinted musculoskeletal constructs, drawing on in vitro, in vivo, and combined outcomes from leading peer-reviewed journals.

Evidence spans four stimuli modalities - magnetic actuation, near-infrared (NIR) photothermal response, thermoresponsive swelling-shrinking transitions, and shape memory polymer (SMP) recovery - applied across bone, cartilage, skeletal muscle, and cardiac constructs. Bioink formulations from silk fibroin-gelatin composites and alginate-polydopamine inks to GelMA-based hydrogels and polyester SMPs present trade-offs between printability, shape fidelity, and cellular compatibility. Cross-study synthesis identifies stiffness trajectory, architectural anisotropy, and dynamic deformation as primary mechano-biological axes directing cell fate decisions. Preclinical studies document encouraging ossification and chondrogenesis outcomes, though constructs fall short of native tissue mechanical benchmarks.

Translational barriers range from fundamental physical constraints - including the mechanical performance gap and stimulus penetration depth limitations - to incremental engineering challenges amenable to near-term resolution. Passive hydration-driven deployment represents the most clinically tractable strategy, while multifunctional bioinks integrating stimuli-responsiveness, bioactive factor presentation, and cell-instructive surface chemistry define the primary material development direction.

The World Health Organization package of essential non-communicable disease interventions (PEN) comprises evidence-based interventions for primary healthcare systems in low- and middle-income countries (LMICs). Implementation fidelity, defined as the degree to which an intervention is delivered as intended, is crucial for intervention effectiveness. Yet, across LMICs, evidence on fidelity to PEN is scarce and mostly limited to pilot studies.

We evaluated fidelity to PEN during national scale-up in Nepal using a convergent parallel mixed methods study design based on the Conceptual Framework for Implementation Fidelity. Data were collected in 2021 from 105 randomly selected primary healthcare facilities across all seven provinces of Nepal. Using direct observation of 172 non-communicable disease (NCD) patient visits, we quantified health service providers' adherence to PEN protocol 1 (hypertension and diabetes management) and protocol 2 (lifestyle counselling). We calculated overall fidelity scores and examined their potential determinants in multivariable regression models using generalized estimating equations. Moreover, we conducted semi-structured interviews with 47 providers and 33 NCD patients to elicit their views on factors affecting fidelity. We analyzed verbatim interview transcripts using thematic analysis.

PEN-trained health service providers managing hypertension and diabetes patients (protocol 1) mainly focused on asking about medication (76% of patient visits), measuring blood pressure (82%), and adjusting medication (85%). Blood glucose was measured in 28% of eligible patient contacts. Other care steps, including cardiovascular risk estimation, were mostly skipped. Lifestyle counselling for NCD patients (protocol 2) most frequently entailed salt restriction advice (41%) and instructions on medications (62%) and follow-up appointments (69%). Overall fidelity scores for protocols 1 and 2 were 20.8 and 22.1 out of 100, respectively. In multivariable regressions, prior PEN training was associated with 25% (95%-CI: 1-54%; p = 0.04) and 32% (95%-CI: -4-80%; p = 0.08) higher fidelity scores for protocols 1 and 2, respectively. Qualitative data suggested that providers and patients were generally engaged by the intervention, though various factors impede fidelity, including negative user experiences and limited availability of medical supplies. Strategies to improve fidelity to PEN that participants suggested were intervention manuals, supervision and monitoring visits, brief refresher trainings, and community outreach programs.

Implementation fidelity to PEN during scale-up in Nepal was often limited to a few diagnostic and therapeutic actions. Next to enhancing user experience, ensuring a reliable supply of diagnostic equipment and medicines will likely be crucial to sustainably improve NCD care. Fidelity assessments in resource-limited settings should examine the availability of key implementation resources.

Mental health disorders pose a critical burden globally, 400 million incident and 1.1 billion prevalent cases; and in Bangladesh, 10.38 million incident and 24.05 million prevalent cases in 2023. Despite the mental health burden in Bangladesh, the majority of the people (> 90%) do not receive required services, due to the concentration of service providers in big cities, leaving rural and marginalized people disproportionately affected. Therefore, to address these barriers, the Non-Communicable Disease Control (NCDC) programme established tele-mental health services in government facilitated Wellbeing Centers at district and sub-district level. Thus, our study aimed to assess early implementation outcomes of the Wellbeing Center model.

The Wellbeing Centers implementation model was established in January 2023 in two district and five sub-district level hospitals to provide mental health services. We measured WHO's implementation research outcomes comparing with preset benchmark. Data were collected using a structured questionnaire from healthcare providers (n = 167) and service recipient (n = 7825).

The findings revealed that the majority of the service providers perceived (96.4%, 95% CI: 92.3-98.6) the Wellbeing Centers fit well with the existing infrastructure of their facility. Whereas, half of the service providers (49.7%, 95% CI: 41.8-57.5) highlighted the shortages of staff in implementation. Besides, 99.8% (95% CI: 99.6-99.8) of user participants perceived that the WBC improved their access to mental health services, mental health services from WBC were acceptable (99.8%, 95% CI: 99.6-99.8), and the WBC was useful (99.9%, 95% CI: 99.7-99.9). Moreover, high prevalence of moderate to severe anxiety (85.1%, 95% CI: 84.1-85.8) and depression (84.3%, 95% CI: 83.4-85.1) highlights a clear requirement for mental health care among participants. Multiple logistic regression identified several determinants of accessibility (high income group had 24% higher access), acceptability (unmarried had 35% lower acceptability), and usefulness (people aged higher than 50 years had 22% lower usefulness) of the Wellbeing Centers.

This implementation study indicated high initial service uptake, feasibility, accessibility, acceptability, and usefulness of Wellbeing Center in addressing mental health challenges in low-resource settings like Bangladesh. Acknowledging human resource shortages, retention barriers, staff training, and infrastructural resilience will be required to scaling up the intervention.

Not applicable.

Nursing students frequently experience high levels of clinical stress, which can impair learning, reduce clinical competence, and hinder the development of self-efficacy and professional identity. Structured stress-management approaches may support student well-being.

In this study, we aimed to compare the effects of an adapted 4A-based stress-management intervention with a mobile self-help program on clinical stress, clinical self-efficacy, and professional identity.

A parallel randomized controlled trial was conducted with 105 undergraduate nursing students. Participants received either a 4A-based, in-person, 5-week intervention using a peer-teaching design or a 5-week mobile self-help program. Outcomes were measured at baseline and 4 weeks after the intervention.

The 4A-based intervention produced greater reductions in clinical stress and higher clinical self-efficacy at post-test compared with the mobile program. Neither intervention significantly improved professional identity.

The adapted 4A-based intervention was more effective than the mobile self-help program, supporting the value of structured, facilitator-led stress-management training in nursing education.

With the decline in the average age of menopause, increased life expectancy and rising longevity among women, a significant number face menopausal challenges including physical and psychological symptoms that adversely affect their quality of life (QoL). Given the growing preference for complementary therapies over menopausal hormone therapy (MHT) and promising evidence on auricular acupressure, this study aimed to investigate its effect on QoL in postmenopausal women.

The randomized sham-controlled clinical trial enrolled 120 eligible postmenopausal women visiting comprehensive health centers in Qazvin, Iran, between February and August 2024. Participants were randomized into intervention (n = 60) or sham (n = 60) groups using the balanced blocks randomization method. The intervention group received auricular acupressure using Vaccaria seed-embedded tapes on specific points (Chinese/European uterine, ovary, Shenmen, brain, gonadotropin and sympathetic points) over 10 sessions (4-day intervals). Participants were instructed to apply moderate pressure to each point for 20 s, three times daily. The sham group followed an identical protocol but used non-seeded tapes. Data were collected using demographic/fertility questionnaires and the Menopause-Specific Quality of Life Questionnaire (MENQOL), assessing vasomotor, physical, psychosocial and sexual domains (lower scores indicate improved QoL). QoL was evaluated at baseline, 1 month post intervention and 2 months post intervention. Data were analyzed using repeated-measures analysis of variance-analysis of covariance (SPSS version 27, α = 0.05).

Baseline QoL scores did not differ significantly between groups. Post intervention, the intervention group showed statistically significant reductions in total QoL scores and all subscales at 1-month and 2-month follow-ups (p < 0.05). Mean differences for intervention versus sham groups in the first and second follow-ups were -28.50, -48.87 for total QoL; -2.36, -5.92 for vasomotor subscale; -2.55, -9.75 for psychosocial subscale; -10.89, -28.41 for physical subscale; and -1.62, -4.78 for sexual subscale. Based on η²-values, auricular acupressure explained 63.4% of total QoL variance, and 61.6% (vasomotor), 39.9% (psychosocial), 66.2% (physical), and 42.4% (sexual) for the subscales.

Auricular acupressure significantly improved overall QoL and all specific domains (physical, psychosocial, vasomotor, sexual) in postmenopausal women. Healthcare providers may consider this non-pharmacological therapy particularly for MHT-ineligible patients to alleviate menopausal symptoms and enhance QoL. Some limitations such as potential social desirability bias from self-reported measures, the lack of objective biomarkers due to budget limits and unevaluated confounding factors related to living conditions highlight the need for future research with multimodal assessments.

Climate change poses significant public health challenges, particularly in low- and middle-income countries (LMICs), where ethical considerations are critical for equitable research. This systematic review synthesizes existing knowledge on climate change, public health, and research ethics in LMICs to identify key themes and research gaps.

A systematic search of PubMed and Medline (2001-2024) identified 643 articles, of which 86 met inclusion criteria. Studies were thematically synthesized, and keyword co-occurrence mapping and cluster analysis were used to explore associations between health and ethical themes. Data visualization, including keyword co-occurrence mapping and hierarchical clustering, was performed to highlight thematic associations and research gaps.

Out of 86 studies 53.48 % were were published after the year 2022. Research is predominantly focused on mortality, outbreaks, and epidemics, mostly associated in ethical contextss such as community rights and beneficence. Associations were strongest between "Rights and Liberties" and "Community Rights." However, ethical considerations were inconsistently integrated, with equity and justice particularly underrepresented in studies on non-communicable diseases and maternal health. Most of the studies relied on secondary data, reflecting gaps in localized, context-specific evidence. Geographically, South Asia and parts of Africa were represented, while Southeast Asia and Latin America were markedly underrepresented despite major climate-related health risks.

This review highlights increasing research interests in climate change and health but identifies gaps in ethical frameworks and LMIC representation. Strengthening research agendas with context-specific ethical considerations and prioritizing vulnerable populations is essential for equitable health responses towards climate change in resource-limited settings.

Cardiometabolic risk results from interactions between genetic and dietary factors. Variation in the adrenergic β-2 receptor gene (ADRB2 rs1042713) may influence responses to insulinogenic dietary patterns.

We aimed to assess whether the associations between dietary insulin indices (DIIs) and cardiometabolic risk factors differ by ADRB2 rs1042713 genotype.

In this cross-sectional study involving 369 adults, the energy-adjusted DII and dietary insulin loads (DILs) were derived from a validated food frequency questionnaire. The rs1042713 polymorphism was genotyped using the polymerase chain reaction-restriction fragment length method. Gene-diet interactions were assessed using multivariable general linear models.

Significant interactions were observed between both DII and DIL and the rs1042713 genotype on systolic blood pressure (SBP) (P-interaction < 0.05). In tertile analyses, among A-allele carriers, SBP was 7.8-7.9 mm Hg in the highest versus lowest tertiles of both DIL and DII (95% CIs = 2.5, 13.2 mm Hg). In contrast, among GG homozygotes, SBP was slightly lower in the highest DII tertile compared with the lowest tertile. A modest interaction between DIL and genotype was observed for HDL cholesterol (P = 0.035), which was attenuated after adjustment (P = 0.056). Interactions with diastolic blood pressure were inconsistent.

The associations between insulinogenic dietary patterns and SBP vary by ADRB2 rs1042713 genotype, with greater sensitivity among A-allele carriers and a more attenuated response among GG homozygotes. SBP emerged as the most consistent outcome, highlighting the need for confirmation in prospective studies.

To systematically and quantitatively assess the efficacy of phage therapy against multidrug-resistant Stenotrophomonas maltophilia in preclinical models.

A systematic search of PubMed, Scopus, ScienceDirect, Google Scholar, and Wiley Online Library was conducted for preclinical studies on phage therapy against established S. maltophilia infections with survival outcomes. Data were pooled using a fixed-effects model, with subgroup and sensitivity analyses.

www.crd.york.ac.uk/prospero identifier is CRD420251059693.

Among 6,277 references, six studies met the inclusion criteria; one study was excluded after sensitivity analysis. The overall pooled Odds Ratio (OR) for phage therapy efficacy was 21.10 (95% CI: 9.09-49.02; p < 0.001). Subgroup analysis by Multiplicity of Infection (MOI) showed dose-dependent effects, with the highest efficacy at MOI = 100 (OR =143.68, 95% CI: 11.95-1726.78; p < 0.001) followed by MOI = 10 (OR =60.13, 95% CI: 6.29-575.09; p < 0.001). Burst size analysis indicated larger burst sizes increased effect magnitude, with the highest at 41.67 (OR =31.27, 95% CI: 7.32-133.49; p < 0.001).

Phage therapy shows strong preclinical efficacy against multidrug-resistant S. maltophilia. It represents a rapid, targeted, and antibiotic-sparing approach, supporting future antimicrobial stewardship efforts and informing the design of clinical applications.

Legal blindness due to proliferative diabetic retinopathy (PDR) in patients with diabetes mellitus can be preventable if detected and treated in a timely manner. Although vitrectomy has traditionally been reserved for complicated cases, advances in surgical techniques and a better understanding of pathophysiology have driven its evaluation as an early or preventive strategy in selected patients. This article presents a systematic review in PubMed (2020-2025), with an emphasis on classic studies, on the safety and efficacy of vitrectomy as an early intervention in patients with PDR, before the onset of major complications, using the keywords "diabetic vitrectomy," "proliferative diabetic retinopathy," "retinal diseases," and "vitreous hemorrhage". Most of the specific evidence in Mexican or Latin American populations is limited, which is why general evidence used as a reference in the region was also included. Studies published in English and in open-access were included. The reviewed studies consistently report that early vitrectomy helps maintain or improve visual acuity during follow-up, reduces progression to severe complications, and shows low rates of intraoperative adverse events. It is concluded that early vitrectomy in selected patients with PDR represents a safe and effective strategy with the potential to preserve vision and alter the natural history of the disease. However, prospective multicenter clinical trials are needed to establish standardized selection criteria and validate its long-term impact.

Amino acids (AAs), tricarboxylic acid (TCA) cycle intermediates, and acylcarnitines (ACs) can reflect energetic metabolism. Metabolic dysfunction-associated steatotic liver (MASLD) has been associated with the modification of plasma AAs, ACs and TCA cycle intermediates' profiles, but the changes in advanced fibrosis without type 2 diabetes (T2D) are not well studied.

The objective of this pilot study was to describe the targeted plasma metabolomic profile in individuals with advanced fibrosis to test research hypotheses concerning hepatic energy metabolism.

We compared plasma fasting concentrations of 21 AAs, 11 organic acids (including ketone bodies and TCA cycle intermediates) and 14 ACs between individuals with advanced fibrosis stages (F3-F4/4) (n = 10) and individuals with no advanced fibrosis (n = 10), all without T2D and with similar clinical characteristics.

Median age (IQR) (51 [43-67] vs. 57 [43-66] years), sex (30 vs. 50% men) and BMI (35 [28-37] vs. 37 [32-39] kg/m²) were comparable between groups. The advanced fibrosis (AF) group presented higher plasma tyrosine (p = 0.04), α-ketoglutarate (p = 0.04), and a lower level of medium-chain ACs C8 and C10 (p = 0.04). The glutamate-glycine-serine (GSG) index, which combines AAs involved in glutathione metabolism, was higher in the AF group (p = 0.04).

Overall, our results suggest impaired AAs catabolism and mitochondrial dysfunction. While the limited sample size and study design preclude causal inferences, these findings highlight potential metabolic signatures of advanced fibrosis in MASLD. They also underscore the need for larger, longitudinal studies to clarify their origin, significance, and clinical implications.