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Milk fat globule membrane (MFGM) and its associated milk polar lipids (MPLs) are bioactive components of dairy fat with emerging relevance for cardiometabolic and cognitive health. This systematic review and meta-analysis evaluated the effects of bovine-derived MFGM/MPL on fasting and postprandial cardiometabolic disease risk markers and cognitive function in disease-free adults, compared with isoenergetic dairy products or supplements low in these components. Searches of PubMed (MEDLINE), Embase, and Cochrane Central identified randomized controlled trials (RCTs) comparing MFGM/MPL-containing foods or supplements with isoenergetic dairy comparators low in these components. Risk of bias (RoB) was assessed using Cochrane RoB 2.0 tool. Random-effects meta-analyses were performed for outcomes reported in ≥ 3 studies, and certainty of evidence for critical outcomes was evaluated using the GRADE approach. Of 730 records screened, 13 studies (14 articles) met inclusion criteria (RoB: low to some concerns). Pooled analyses demonstrated that 2-16 wk intake of MFGM/MPL (19.8 to 5000 mg/d) reduced fasting total cholesterol (weighted mean difference [WMD]: -0.18 mmol/L; 95% CI: -0.30, -0.07), LDL cholesterol (WMD: -0.12 mmol/L; 95% CI: -0.22, -0.03), apolipoprotein B concentrations (WMD: -0.05 g/L; 95% CI: -0.09, -0.01), and the total cholesterol:HDL cholesterol ratio (WMD: -0.17; 95% CI: -0.33, -0.01), with low heterogeneity (I2 = 0-9%) and moderate certainty of evidence. No clear effects were observed for fasting circulating HDL cholesterol, triacylglycerol, glucose, insulin, or blood pressure (low certainty). Evidence for emerging fasting cardiometabolic biomarkers, postprandial responses, and cognitive outcomes was limited and synthesized narratively. This review offers the strongest and most methodologically robust evidence to date that bovine-derived MFGM/MPL modestly improves atherogenic markers in adults, with implications for dietary guidance and future research. Limited data for novel biomarkers and cognitive outcomes highlight priorities for longer-term, adequately powered RCTs to clarify their broader health relevance. This systematic review protocol was registered at https://www.crd.york.ac.uk/PROSPERO/ as CRD42025636269.

As countries transition from implementing iron folic acid (IFA) to multiple micronutrient supplements (MMS) for pregnant women, they need accurate data on who is being reached with these interventions. The aim of our formative research in Ethiopia and Bangladesh was to design updated household survey questions, response options, and visual aids to measure coverage of prenatal micronutrient supplements. In phase I, we landscaped health providers and retailers to identify prenatal micronutrient products available in each country and interviewed currently pregnant women (CPW) and recently delivered women (RDW) about how they differentiated among micronutrient products. In phase II, we used these findings to draft survey questions and visual aids. In phase III, we iteratively tested and refined the draft tools through cognitive interviews with women. We had 73 participants in Ethiopia and 132 in Bangladesh, encompassing CPW, RDW, healthcare workers, and retailers. Women in both contexts distinguished among micronutrient products based on colour, shape, packaging, and perceived purpose. In cognitive tests, women generally understood the English term 'iron' as a catch-all term for any iron-containing supplement. Women did not recognise any specific term for multivitamins or MMS. Shorter recalls of seven days or one month for adherence were feasible for respondents. It is challenging for the measurement community to identify terms and images that help women distinguish between supplement types. The final set of survey questions developed as part of this research is comprehensible and can be feasibly adapted and used in multi-topic surveys in MMS contexts, but requires validation.

Water security ensures the availability, accessibility and acceptability of safe water for drinking, hygiene, and other purposes for individuals and communities to meet daily and future needs. An estimated 2.2 million Americans experience water insecurity linked to poor diet quality and adverse health outcomes. This perspective article summarizes the scientific evidence about water security and healthy hydration to understand the opportunities and challenges for government agencies to strengthen the links and policy coherence across both areas for the population. We focus on the United States (U.S.) context due to the complex policy landscape of government agencies with different regulatory oversight for promoting healthy hydration and water security, and a weakly regulated yet growing multibillion-dollar bottled water, functional beverage and hydration supplement industry marketed to Americans. First, we describe healthy hydration recommendations and U.S. fluid intake trends across the lifespan. Second, we examine the evolving industry that produces and markets hydration products including bottled water, soft drinks, non-alcoholic functional beverages, and dietary supplements. Third, we discuss the U.S. government agencies that have regulatory oversight to protect and educate the public to ensure the safety of bottled water and publicly supplied drinking water and enforce policies requiring that businesses use truthful advertising and marketing claims for functional beverages and supplements. We offer recommendations for U.S. government agencies and other stakeholders to strengthen policy coherence and improve coordination of guidelines and legislation to ensure affordable healthy hydration and water security for all Americans.

Medication literacy is critical for older adults managing complex medication regimens, yet few measures have been developed specifically for this population. The MEDication Literacy Assessment of Geriatric patients and informal caregivers (MED-fLAG) was developed as a multidimensional self-reported measure for older adults and informal caregivers. The instrument uniquely captures skills related to both prescribed and non-prescribed medications, including herbal and nutritional supplements. Although the MED-fLAG previously demonstrated satisfactory content validity, further evaluation of its psychometric properties was warranted. To evaluate the psychometric properties of the MED-fLAG using Rasch analyses. A cross-sectional study was conducted among French- and Dutch-speaking hospitalized older adults in Switzerland, Belgium, and the Netherlands. Hospitalized participants aged ≥ 65 years who had managed their medications for at least three months were included. Rasch modelling using the Partial Credit Model was applied to assess unidimensionality, item fit (goodness-of-fit), item hierarchy (item difficulty calibration), person separation reliability, and differential item functioning across language groups. Among the 582 respondents, the mean age was 73.9 years, with a standard deviation of 11.4 years. Analyses were conducted on 563 responses, including 356 from the Dutch-speaking sample and 207 from the French-speaking sample. Rasch analyses supported the measurement properties of the Functional subscale (with 19 items) and Interactive subscale (with 13 items), including satisfactory unidimensionality, item fit, and reliability. However, the Critical subscale (with 21 items) displayed signs of multidimensionality and substantial differential item functioning across languages. Person separation indices fell below the recommended threshold, indicating moderate discrimination, and Wright maps highlighted the need for more challenging Interactive items and easier Critical items. These findings support the MED-fLAG as a promising instrument while underscoring the need for further refinement, particularly within the Critical medication literacy subscale. In the future, this standardized measure may support the formal assessment of medication literacy among older adults and informal caregivers to ensure that medication regimens align with patients' abilities. In the context of early hospital discharge, the MED-fLAG may provide valuable information to guide individualized care planning and help prevent medication-related problems. Future research should also explore the development of an optimized and potentially shorter version of the MED-fLAG to enhance feasibility in routine clinical practice. Further psychometric evaluation of a revised version of the MED-fLAG is needed before the instrument can be confidently recommended for research and clinical use.

Cellular senescence is a fundamental mechanism of ageing, characterised by stable cell cycle arrest and the acquisition of a pro-inflammatory secretory phenotype. Nutritional interventions are widely proposed to modulate ageing biology, but their effects on cellular senescence in humans remain unclear. We systematically synthesised evidence from interventional human studies assessing the impact of nutritional strategies on biomarkers of cellular senescence. We searched MEDLINE, Embase, Cochrane Library, and Web of Science from inception to September 10, 2024. We included interventional studies in humans reporting biomarkers of cellular senescence, including markers of cell cycle arrest, DNA damage, telomere length, transcriptomic signatures, and factors of the senescence-associated secretory phenotype (SASP). Twenty-nine articles (27 trials; 3,811 participants) were included. Across studies, nutritional interventions modulated multiple senescence biomarkers to varying extents, with calorie restriction producing the most recurrent reductions in circulating inflammatory and secretory factors commonly included in SASP panels as well as senescence-associated transcriptomic signatures. Classical markers of cell cycle arrest (e.g., CDKN2A/p16, CDKN1A/p21) and telomere length were largely unchanged or highly variable. Calorie restriction mimetics, particularly metformin and rapamycin, showed context-dependent effects, most evident under conditions of metabolic or physiological stress. Among dietary supplements, n-3 polyunsaturated fatty acids may modulate selected inflammatory/SASP-related circulating markers, although the evidence for dietary supplements remains limited and heterogeneous. In humans, available evidence suggests that nutritional interventions may preferentially affect senescence-associated inflammatory and secretory biomarker profiles, particularly SASP-related mediators, rather than markers more directly related to senescent cell abundance. However, because SASP factors and circulating cytokines are heterogeneous and not specific to senescent cells, these findings should be interpreted as evidence for possible modulation of senescence-associated markers rather than definitive effects on senescence burden. These observations support the use of multi-marker and functionally relevant endpoints in future clinical studies targeting biological ageing and cellular senescence.

Pre-existing diabetes in pregnancy is rising globally and is associated with significant maternal and neonatal health risks, yet optimal dietary strategies remain uncertain. This systematic review evaluated evidence on dietary components, supplements and dietary patterns during pre-conception and pregnancy in women with pre-existing diabetes. Electronic databases were searched for eligible studies, and risk of bias was assessed using ROB-2, ROBINS-E and ROBINS-I-V2. A random-effects meta-analysis with GRADE assessment was conducted for folic acid supplementation. Twenty-six studies from ten countries met inclusion criteria. Higher diet quality characterised by greater intakes of vegetables, fruits, plant-based proteins, nuts, fish, and lower intakes of processed foods was associated with improved glycaemic outcomes. Low-glycaemic index and DASH dietary patterns, along with carbohydrate counting showed potential benefits, while evidence for low carbohydrate and high-fibre diets was mixed. Associations with gestational weight gain, pre-eclampsia, and neonatal outcomes were inconsistent. Meta-analysis suggested pre-conception folic acid supplementation reduced neural tube defect risk, however the certainty of evidence was very low. Diet quality appears more important than specific macronutrient targets and individualised dietitian led care is essential. Further high-quality research is needed to define optimal dietary approaches for pregnancies complicated by pre-existing diabetes.

Multiple sclerosis (MS) is a chronic neuroinflammatory disease affecting approximately 2.9&#xa0;million people worldwide. Disease-modifying therapies for MS effectively lower the risk of relapses and delay disability progression, but the increasing medication burden and ongoing adherence challenges complicate disease management. An improved understanding of predictors of medication-related risks is essential to optimize long-term safety, treatment effectiveness, and quality of life in patients with MS. In this longitudinal observational study, 206 adults with MS or clinically isolated syndrome were enrolled, of whom 175 completed the 5-year follow-up assessment. Sociodemographic, clinical, and comprehensive medication data were collected at baseline and follow-up through structured interviews and review of medical records. Polypharmacy was defined as the concurrent use of &#x2265;&#x2009;5 medications. Potential drug-drug interactions (pDDIs) were systematically identified using the DrugBank database, and medication non-adherence was defined based on patient self-reported missed medication. Over the 5-year follow-up period, the prevalence of polypharmacy increased from 53.1% to 62.3% (p&#x2009;=&#x2009;0.024), and pDDI exposure rose from 67.4% to 81.1% (p&#x2009;<&#x2009;0.001), mainly driven by the greater use of drugs for comorbid conditions and dietary supplements. In contrast, monthly medication non-adherence remained stable (25.7% to&#xa0;27.3%, p&#x2009;=&#x2009;0.855). Major interactions accounted for 7.1% of all identified pDDIs. Older age, disability pension status, higher disability levels, coexisting medical conditions, and lower educational attainment were associated with polypharmacy and the presence of pDDIs, whereas non-adherence was linked to prior non-adherent behavior and inpatient care at baseline. Over time, the prevalence of polypharmacy and pDDIs increased in patients with MS, whereas medication non-adherence emerged as a largely independent risk domain. Polypharmacy and the presence of pDDIs were mainly associated with aging- and disability-related factors, whereas medication non-adherence was more difficult to predict. Our findings emphasize the need for regular medication monitoring that considers both prescribed and non-prescribed drugs, alongside individualized adherence support to mitigate distinct medication-related risks in long-term MS care.

A 59-year-old woman presented with a 5-month history of an incidentally discovered pancreatic mass and episodic epigastric pain. Imaging studies revealed a mass in the pancreatic head/neck and tail with suspected vascular encasement, and the tumor marker CA19-9 was markedly elevated. Due to these findings, pancreatic malignancy was initially suspected. However, serum IgG4 was found to be extremely elevated at 10,022 &#x3bc;g/mL, and an ultrasound-guided pancreatic biopsy showed benign ductal epithelium with low proliferative activity and occasional plasmacytoid cells, with no evidence of adenocarcinoma. A diagnosis of IgG4-related autoimmune pancreatitis was established. The patient was started on oral methylprednisolone (32&#x202f;mg/day) and pancreatic enzyme supplements. Over 1 year of follow-up, her serum IgG4 level normalized to 489&#x202f;&#x3bc;g/mL, CA19-9 returned to 16&#x202f;U/mL, and serial MRI examinations demonstrated marked resolution of the pancreatic head/neck mass and improvement of the biliary stricture. This case underscores the clinical importance of including IgG4-AIP in the differential diagnosis of pancreatic masses, particularly when serologic or imaging features are equivocal, to prevent unnecessary surgical intervention.

Intensive farming of Nile tilapia (Oreochromis niloticus) heightens susceptibility to infectious diseases, including motile aeromonad septicemia caused by Aeromonas hydrophila, thereby necessitating sustainable alternatives to antibiotics. This study investigated the effects of dietary supplementation with Ocimum basilicum (sweet basil) essential oil (1% w/w) and Thymus vulgaris (thyme) essential oil (0.5% w/w) on growth performance, hematological parameters, serum biochemistry, innate immune responses, cytokine profiles, and resistance to experimental A. hydrophila challenge. A total of 180 juvenile Nile tilapia (initial weight 13.21&#x2009;&#xb1;&#x2009;0.16&#xa0;g) were randomly assigned to three dietary treatment groups (three replicates of 20 fish per treatment) and fed for 60&#xa0;days: (1) basal control diet, (2) basal diet supplemented with 1% O. basilicum essential oil, and (3) basal diet supplemented with 0.5% T. vulgaris essential oil. Fish then received intraperitoneal A. hydrophila challenge (0.1&#xa0;mL of 1.5&#x2009;&#xd7;&#x2009;108&#xa0;CFU&#xa0;mL&#x207b;1). Growth, hematological, serum biochemical, and innate immune parameters (lysozyme, nitric oxide, phagocytic index) were assessed at days 30, 60, and 75 (15&#xa0;days post-challenge). Differential leukocyte counts and cytokine concentrations (TNF-&#x3b1;, IL-1&#x3b2;, IL-6, IL-2, IL-10) were assessed at day 75, and histopathological analysis of hepatic and cephalic kidney tissues was performed to evaluate the protective effects of dietary supplementation against A. hydrophila-induced tissue damage. Both essential oil supplements significantly enhanced growth performance (final body weight and weight gain), hematological indices (hemoglobin concentration and erythrocyte and total leukocyte counts), serum protein profiles (total protein, albumin, and globulin), and innate immune function (lysozyme activity, nitric oxide production, and phagocytic index) compared to the control group (P&#x2009;&#x2264;&#x2009;0.05). Notably, the diet supplemented with 1% O. basilicum essential oil produced substantial responses than the diet supplemented with 0.5% T. vulgaris essential oil across several assessed parameters (P&#x2009;&#x2264;&#x2009;0.05). Fish fed the O. basilicum-supplemented diet had the highest levels of both pro-inflammatory (TNF-&#x3b1;, IL-1&#x3b2;, IL-6) and anti-inflammatory (IL-10) cytokines, and the lowest overall mortality rate (2.2&#x2009;&#xb1;&#x2009;2.2%; relative percent survival [RPS]&#x2009;=&#x2009;96.7&#x2009;&#xb1;&#x2009;3.3%). The T. vulgaris group had a mortality rate of 13.3&#x2009;&#xb1;&#x2009;3.9%; RPS&#x2009;=&#x2009;82.1&#x2009;&#xb1;&#x2009;6.4%, and the non-supplemented control group had a mortality rate of 77.8&#x2009;&#xb1;&#x2009;5.9%. Histopathology confirmed markedly diminished renal and hepatic lesions, coupled with increased activation of melanomacrophage centers in both essential oil-supplemented groups. These results suggest that adding 1% O. basilicum essential oil to the diet of Nile tilapia promotes growth, boosts the immune system, and provides greater protection against A. hydrophila infection than adding 0.5% T. vulgaris essential oil. The findings support the potential use of these phytogenic additives as components of health-management strategies in Nile tilapia culture. However, additional studies under commercial production conditions, including dose-optimization, long-term safety assessments, and economic evaluations, are required before practical application can be recommended.

Up to 75% of children treated for severe acute malnutrition (SAM) relapse within six months of recovery, yet evidence on post-discharge interventions remains limited. We conducted a formative assessment to understand how small-quantity lipid-based nutrient supplements (SQ-LNS) could be integrated in post-discharge care to prevent relapse. This study aimed to inform whether and how a program integrating SQ-LNS into post-discharge monitoring could be implemented in Mali. Specifically, we aimed to: 1) identify barriers and enablers to post-discharge monitoring, 2) develop one or more post-discharge models based on recommendations, 3) understand the feasibility of these model(s), 4) describe acceptability of the model(s) and product, and 5) propose a final model to be piloted at larger scale. This formative study comprised two iterative phases conducted between September 2024 and May 2025. In exploratory Phase One, we conducted semi-structured interviews with 12 caregivers of children with SAM and eight treatment providers, in triangulation with 13 focus groups among caregivers, health care workers (HCW's), and supervisors. Themes included current practices, anticipated challenges, and service delivery preferences. Findings informed a confirmatory Phase Two involving four direct observations of three delivery models implemented at four sites and 13 interviews with similar participants. Textual data were coded and thematically analyzed using Dedoose software. Although national guidelines recommend routine post-discharge monitoring for SAM children, it was rarely practiced due to limited awareness among HCW's. Both caregivers and HCW's supported the idea of post-SAM monitoring, preferring on-site over home visits for feasibility. Caregivers valued growth monitoring, interacting with HCW's, and nutritional supplementation. While unfamiliar with SQ-LNS, caregivers viewed it positively based on their experience with therapeutic foods. Three delivery models were tested: (1) weekly visits for one month transitioning to fortnightly thereafter, (2) fortnightly visits and program days, and (3) fortnightly visits for caregivers and weekly program days at the health site. Model three proved most feasible for caregivers and providers. This formative research informed a program design that aligns with caregiver preferences and health system capacity, requiring minimal external support. Fortnightly post-discharge monitoring paired with SQ-LNS supplementation at treatment sites is recommended.

There is an eminent association between human gut microbiota and health. The eventual footprint on the host depends heavily on the symbiotic relationship between the host and their gut microbiota. Current probiotics mostly available to consumers are drawn from a restricted arsenal of organisms, mostly belongs to various genera of Lactic acid bacteria (LAB). Ever expanding knowledge of gut microbiota and its related constituents is shifting this paradigm, specifically the phylogenetic range and the obscure characteristics of novel biotherapeutics currently under consideration. Due to this, and because their progress is more complaint to a pharmaceutical route with sole purpose of mitigating chronic ailments, rather than a food delivery as they are not designed for conventional use as food or dietary supplements, these microorganisms are repeatedly mentioned as Next Generation Probiotics (NGPs), a notion that coincides with the juvenile concept of live biotherapeutic products. Various nonconventional strains showing probiotic potential includes Akkermansia muciniphila, Prevotella copri, Faecalibacterium prausnitzii, Eubacterium halii, members of Clostridia cluster IV and XIV and Bacteroides fragilis. However, major challenge hindering their way to the market is viable intestinal delivery due to stringent survival conditions. In this review, present day outlook on the development and valuation of these strains are covered, along with suggested approaches which stakeholders and industries should consider for better outcomes.

It is generally known that kidney stone disease (KSD) is associated with alterations in urinary microbiome, but the roles of the urinary microbiome in KSD pathogenesis remain unclear. This study addressed the impact of Lactobacillus acidophilus (a commensal bacterium found in normal urine) on renal epithelial integrity, calcium oxalate monohydrate (COM) crystal-cell adhesion, expression of membrane receptors of COM crystals, and oxalate degradation under oxalate-induced stress (a known inducer of KSD). Inner medullary collecting duct cells (mIMCD-3) were cultured for 24 h under control or oxalate-induced (by 0.6 mM sodium oxalate; NaOx) conditions without or with L. acidophilus (at 1&#x2009;&#xd7;&#x2009;103 colony-forming unit (CFU)/ml) co-incubation. NaOx reduced transepithelial resistance (TER) of the mIMCD-3 monolayer and downregulated ZO-1, a tight junction (TJ) protein. Additionally, NaOx enhanced the COM crystal-binding capability of mIMCD-3 cells by upregulating a COM crystal receptor, annexin A2, on cell membranes. Such harmful effects of NaOx were abolished when mIMCD-3 cells were co-cultured with L. acidophilus. Moreover, culturing L. acidophilus in artificial urine (AU) supplemented with NaOx for 24 h revealed that the oxalate level in AU decreased, suggesting the oxalate-degrading activity of the bacterium in an AU environment. L. acidophilus prevented oxalate-mediated renal epithelial barrier disruption and COM crystal adhesion to renal epithelial cells by preserving ZO-1 and annexin A2 expression at their basal levels, at least in part, via its oxalate-degrading property. Not applicable (This is not a clinical trial).

Chyawanprash is an ancient Ayurvedic superfood described for its antioxidant, anti-ageing and immunity-boosting properties. Prolonged exposure to environmental stressors such as extreme heat, air pollution and toxins could lead to several diseases by triggering oxidative stress and inflammation. These stress response pathways, conserved in humans and C. elegans, play crucial roles in the progression of neurological and metabolic diseases. Present study examines the role of the ancient Ayurvedic superfood, Patanjali Special Chyawanprash (PSCP), on heat stress-induced behavioural and molecular damages, using C. elegans as the model organism. Phytochemical analysis of PSCP by high-performance liquid chromatography (HPLC) revealed the presence of several antioxidant and anti-inflammatory phytometabolites like gallic acid, corilagin, chebulagic acid, 5-HMF, cinnamic acid, eugenol, and ellagic acid. PSCP supplementation in C. elegans prevented the production of Advanced Glycation End products (AGEs) and heat stress-induced alterations in locomotory and feeding behaviours. Nuclear Localization of DAF-16, expression of SOD-3::GFP and MYO-3::GFP, along with sarcomeric F-actin arrangement in heat-stressed C. elegans, was analyzed using fluorescence microscopy. PSCP supplementation along with the food to the heat-stressed C. elegans resulted in ~2-fold increase in mitochondrial membrane potential and in MYO-3::GFP expression. Additionally, PSCP exhibited a strong antioxidant profile in heat-stressed worms, indicated by normalized ROS, GSH levels and SOD-3 activity. mRNA levels of thermo-tolerance genes like hsf-1 and heat-shock proteins: hsp-70, hsp-16.2 and hsp-12.6 in heat-stressed C. elegans were normalized by PSCP treatment. PSCP also promoted longevity and prevented heat stress-induced lifespan reduction in C. elegans. Overall, these findings indicate that Patanjali Special Chyawanprash (PSCP) could serve as an important food supplement for enhancing stress resistance in organisms including humans, potentially benefiting longevity and reducing disease susceptibility.

To explore the impact of cognitive frailty on falls, readmissions, and mortality in aged patients undergoing Maintenance Hemodialysis (MHD). A prospective cohort study. We collected baseline data from September 2023 to January 2024. We assessed cognitive frailty at baseline using the Frailty Scale and Montreal Cognitive Assessment. Older adults receiving MHD were followed for 12 months, with assessments at 6 and 12 months. Mortality was the primary outcome; falls and readmissions were secondary outcomes. We assessed adverse outcomes through multiple methods: mortality data were obtained via hospital electronic medical record system queries, dialysis registry platform verification, and confirmation by medical staff; falls and readmissions were ascertained through face-to-face interviews with patients during dialysis sessions, supplemented by hospital medical record system queries. We used the &#x3c7;&#xb2; test to compare group differences in adverse outcome rates, the Kaplan-Meier method with the log-rank test to estimate monthly cumulative event probabilities, and Cox regression to assess the association between cognitive frailty and the three adverse outcomes. Of 1,023 older adults on MHD, 300 (29.3%) had cognitive frailty. The other 723 (70.7%) did not. In 12 months, there were 101 deaths (9.8%), 190 falls (18.6%), and 299 readmissions (29.2%). The cognitive frailty group had higher incidences of death (59 [19.7%] vs. 42 [5.8%]), falls (94 [31.3%] vs. 95 [13.1%]), and readmissions (129 [43.0%] vs. 170 [23.5%]). After adjusting for confounders, cognitive frailty remained an independent risk factor for mortality (HR&#x2009;=&#x2009;2.716, 95% CI 1.754-4.205, P&#x2009;<&#x2009;0.001), falls (HR&#x2009;=&#x2009;2.021, 95% CI 1.471-2.777, P&#x2009;<&#x2009;0.001), and readmissions (HR&#x2009;=&#x2009;1.996, 95% CI 1.585-2.514, P&#x2009;<&#x2009;0.001). Cognitive frailty independently increases risk for mortality, falls, and hospital readmission in older adults undergoing MHD. Strengthen screening and assessment for cognitive frailty to help identify high-risk patients early and inform targeted interventions.

Midwifery care in Germany is currently neither systematically monitored nor managed. A&#xa0;central register and a&#xa0;standardized planning framework are lacking, resulting in limited reliable data on the actual provision of care. Regional analyses also indicate substantial differences in access to midwifery care. The aim of this study was to apply the methodology of the German Demand Planning Guideline (BPL-RL) to midwifery care and to conduct a&#xa0;nationwide small-area analysis of regional and social disparities. Address data from the German Midwives Association (DHV; August 2024) were geocoded using postal codes and aggregated at district level. Based on the BPL-RL framework, supply levels were calculated for women of reproductive age (15-49&#xa0;years), adjusted using the German Index of Socioeconomic Deprivation (GISD, 2022), and supplemented by travel-time analyses. The analyses revealed pronounced socio-spatial inequalities. Overall, 23.8% of districts were (potentially) undersupplied (supply level <&#x202f;75%), 45.8% were within the reference range of the BPL-RL framework (75-110%), and 30.5% showed high supply levels (>&#x202f;110%), including 7.5% with substantial oversupply (>&#x202f;140%). The average travel time to the nearest midwife was 9.6&#x202f;min; longer travel times were concentrated in sparsely populated regions with high levels of deprivation. Applying the BPL-RL to midwifery care enables a&#xa0;structured and data-driven assessment of service provision in Germany. The findings highlight regional and social inequalities and provide an empirical basis for value-based, socially equitable, and systematically managed demand planning for midwifery care. EINLEITUNG: Die Hebammenversorgung in Deutschland wird bislang weder systematisch erfasst noch gesteuert. Ein zentrales Register und eine standardisierte Planungsgrundlage fehlen, wodurch belastbare Daten zur Versorgungssituation nur begrenzt vorliegen. Regionale Analysen deuten zugleich auf erhebliche Unterschiede im Zugang zu Hebammenhilfe hin. Ziel der Studie war es, die Methodik der Bedarfsplanungsrichtlinie (BPL-RL) auf die Hebammenversorgung zu &#xfc;bertragen und regionale sowie soziale Disparit&#xe4;ten bundesweit kleinr&#xe4;umig zu analysieren. Adressdaten des Deutschen Hebammenverbands (DHV, Stand August 2024) wurden &#xfc;ber Postleitzahlen geokodiert und auf Kreisebene aggregiert. Auf Grundlage der Systematik der BPL-RL wurden Versorgungsgrade f&#xfc;r Frauen im geb&#xe4;rf&#xe4;higen Alter (15&#x2013;49&#xa0;Jahre) berechnet, anhand des German Index of Socioeconomic Deprivation (GISD, 2022) adjustiert und durch Fahrzeitanalysen erg&#xe4;nzt. Die Analysen zeigten eine ausgepr&#xe4;gte sozialr&#xe4;umliche Ungleichverteilung. 23,8&#x202f;% der Kreise waren (potenziell) unterversorgt (Versorgungsgrad <&#x202f;75&#x202f;%), 45,8&#x202f;% lagen im Referenzbereich der BPL-RL-Systematik (75&#x2013;110&#x202f;%) und 30,5&#x202f;% wiesen eine hohe (>&#x202f;110&#x202f;%) Versorgung auf, darunter 7,5&#x202f;% mit deutlicher &#xdc;berversorgung (>&#x202f;140&#x202f;%). Die mittlere Fahrzeit zur n&#xe4;chstgelegenen Hebamme betrug 9,6&#x202f;min; l&#xe4;ngere Wege konzentrierten sich auf d&#xfc;nn besiedelte Regionen mit hoher Deprivation. Die &#xdc;bertragung der BPL-RL auf die Hebammenhilfe erm&#xf6;glicht eine strukturierte und datenbasierte Bewertung der Versorgung in Deutschland. Die Ergebnisse verdeutlichen regionale und soziale Ungleichheiten und bilden eine empirische Grundlage f&#xfc;r eine wertorientierte, sozial gerechte und steuerbare Bedarfsplanung der Hebammenversorgung.

While neurofibromatosis type 1 (NF1)-associated malignant peripheral nerve sheath tumor (nfMPNST) is often considered to have a particularly poor prognosis compared to sporadic malignant peripheral nerve sheath tumor (sMPNST), this assumption remains insufficiently substantiated. This study aimed to compare clinical characteristics, treatment outcome, and survival between nfMPNST and sMPNST in a nationwide Danish cohort. We conducted a retrospective cohort study of patients with malignant peripheral nerve sheath tumor (MPNST) in Denmark from 2000 to 2020. NF1-associated cases were identified through a national NF1 registry, while sporadic cases of MPNST were extracted from the Danish Sarcoma Database. Clinical, pathological, and treatment data were supplemented by chart review and national pathology records. Survival outcomes were analysed using Kaplan-Meier estimates and Cox proportional hazards models. A total of 146 patients were included of which 42 had nfMPNST and 104 sMPNST. Patients with nfMPNST were significantly younger at diagnosis (median 37 (min-max: 12-73) vs. 58 (min-max: 5-93) years, p&#x2009;<&#x2009;0.001) and had larger tumors (>5&#x2009;cm in 88% vs. 50%, p&#x2009;<&#x2009;0.001). Wide margin resection was achieved less often in nfMPNST (35% vs. 66%, P&#x2009;=&#x2009;0.003), and adjuvant radiotherapy was more commonly administered (61% vs. 36%). Five-year overall survival for localized disease was significantly lower in nfMPNST (44% vs. 63%, P&#x2009;=&#x2009;0.03), with higher recurrence rates (69% vs. 49%, P&#x2009;=&#x2009;0.049) and shorter time to recurrence (median 2.2 vs 3.4&#x2009;years) Among 27 sMPNST tumors analysed by next-generations sequencing, 5 (19%) harbored pathogenic NF1 variants. nfMPNST presents at a younger age with more aggressive features and worse outcomes compared to sporadic cases. These findings support the need for tailored surveillance and treatment strategies in NF1 patients and highlight the potential role of NF1 alterations in sMPNST pathogenesis.

A theory- and practice-based implementation strategy bundle (ISB) was developed to support physical therapists and dieticians during implementation of the combined lifestyle intervention ProMuscle for community-dwelling older adults in multiple community-care settings. Alongside a 42-week hybrid type III stepped-wedge randomized cluster implementation effectiveness trial, a process evaluation was conducted to explore possible working mechanisms of the ISB on the adoption, reach, and fidelity of ProMuscle by describing a causal pathway. Additionally, barriers and facilitators for the use of the ISB were identified. During the 6-week transitional period in which clusters transitioned from the control to the intervention group and at the end of the 42-week trial, (group)interviews were held with physical therapists and dieticians. Interview guides were informed by the RE-AIM framework and supplemented with quantitative data from surveys and ISB tracking activity. Interviews were transcribed and thematically analyzed. Insights from the process evaluation informed a causal pathway diagram and the identification of barriers and facilitators for the use of the ISB. Twenty-five physical therapists and dieticians were interviewed during the transitional period, and fifteen participated in the group interviews at the end of the trial. The causal pathway diagram revealed that individual factors (knowledge and beliefs about the intervention, convincing others, and networking), and organizational- and system-level factors (facilitation, collaboration, and support) moderated the influence of the ISB on the implementation outcomes. Particularly organizational and system-level factors could not always be addressed by individual professionals. The fidelity of the ISB was low, according to the healthcare professionals, due to timing of receiving the ISB and lack of education on its use. The results highlight the complexity of real-world implementation in multiple community-care settings and address the need for organizational and policy-level facilitation to enhance the implementation, sustainment, and scale-up of lifestyle interventions for community-dwelling older adults. Additionally, low fidelity of the ISB probably contributed to the non-significant effect of the ISB on the adoption of ProMuscle. Future implementation studies should take the timely delivery of an ISB into account and provide adequate education to healthcare professionals about the use of implementation strategies. ClinicalTrials.gov (NCT05672004) registered at 12/07/2022 https://clinicaltrials.gov/ct2/show/NCT05672004.

Helicobacter pylori (H. pylori) is a Gram-negative gastric pathogen resistant to the acidic stomach environment through urease-mediated neutralization, enabling colonization of the gastric mucosa. It is a major cause of gastritis, peptic ulcer disease, and gastric cancer, and was classified as a Class I carcinogen by the International Agency for Research on Cancer (IARC) in 1994. Rising antibiotic resistance has limited the efficacy of conventional therapies, highlighting the need for alternative or adjunct antimicrobial strategies. Forty lactic acid bacteria (LAB) isolates were screened for anti-H. pylori activity against twenty clinical H. pylori isolates previously recovered from gastric biopsies of Egyptian patients using neutralized cell-free supernatants (CFSs). The CFSs were evaluated alone and in combination with standard therapeutic antibiotics. The most potent CFS was subsequently evaluated for cytotoxic activity against colorectal adenocarcinoma (Caco-2) cells as a preliminary assessment of its potential anticancer-related properties. The CFS was then subjected to fast protein liquid chromatography (FPLC), and the active fraction was further analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) to estimate its molecular weight. Following verification of its probiotic characteristics, the producer strain was identified by 16&#xa0;S rRNA gene sequencing. Nine out of forty LAB isolates demonstrated anti-H. pylori activity, with minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values ranging from 93.7 to 750&#xa0;&#xb5;g/mL. Combination assays demonstrated isolate-dependent interactions, with synergistic effects observed with clarithromycin (CLR), amoxicillin (AX), metronidazole (MET), tetracycline (TE), rifampicin (RA), and levofloxacin (LEV) against certain H. pylori isolate groups. L. fermentum strain M98, identified as the most potent isolate, exhibited the highest inhibitory activity both alone and in combination with antibiotics. The protein-enriched precipitate containing a putative bacteriocin exhibited cytotoxic activity against Caco-2 cells, with an IC&#x2085;&#x2080; value of 19.73&#x2009;&#xb1;&#x2009;0.16&#xa0;&#xb5;g/mL. FPLC of its CFS yielded 22 protein fractions, three of which exhibited anti-H. pylori activity, suggesting the presence of bacteriocin-like compounds. Subsequent SDS-PAGE analysis of the active fraction revealed a prominent protein band of approximately 34&#xa0;kDa. The CFS of L. fermentum strain M98 exhibits significant in vitro anti-H. pylori activity and enhances the efficacy of tested antibiotics, supporting its potential as an adjunct therapeutic agent against antibiotic-resistant H. pylori. In addition, LAB-precipitated proteins containing a putative bacteriocin demonstrated cytotoxic activity against Caco-2 cells, suggesting the presence of bioactive compounds with potential therapeutic value. Further in vivo investigations are warranted to confirm their safety, efficacy, and potential biomedical applications.