Apple Cider Vinegar (Digestion)

BACKGROUND AND AIMS: GLP-1 receptor agonists (GLP-1RAs) promote significant weight loss, but their impact on muscle mass, strength, and quality in metabolic dysfunction-associated steatotic liver disease (MASLD), a condition prone to muscle impairment, remains uncertain. METHODS: We conducted a systematic review of MEDLINE/PubMed, Embase, and the Cochrane Library up to 2 December 2025. Interventional and observational studies assessing GLP-1RA therapy and muscle-related outcomes in adults with MASLD were included. Muscle mass was assessed by computed tomography or magnetic resonance imaging, dual-energy X-ray absorptiometry, or bioelectrical impedance analysis; lean mass and fat-free mass were considered proxies. Muscle strength was evaluated using handgrip strength (HGS) or sit-to-stand (STS) tests. Muscle quality was assessed by imaging-based quantification of intramuscular fat infiltration (myosteatosis) or functionally based on performance relative to muscle mass. Results were synthesised narratively. RESULTS: Twelve studies were included (n = 810). Eleven assessed muscle mass (n = 785) across different GLP-1RA regimens and treatment durations (12-52 weeks). Findings suggested relative preservation of muscle mass, with modest reductions generally proportional to overall weight loss. Muscle strength was evaluated in three studies (n = 477), with no evidence of deterioration in HGS or STS performance despite meaningful weight loss. Muscle quality was assessed in four studies (n = 139) using imaging or functional metrics, with results suggesting preserved or improved muscle quality. Evidence was limited by small sample sizes and heterogeneous assessment methods. CONCLUSION: Current evidence suggests that GLP-1RA therapy is not associated with clinically meaningful loss of muscle mass or strength in adults with MASLD, with early data indicating possible improvements in muscle quality. © 2026 The Author(s). Liver International published by John Wiley & Sons Ltd.

Exogenous substances (including additives and pollutants), as key factors influencing anaerobic digestion (AD) systems, exert dual effects on microbial activity, community structure, and metabolic function. This review systematically evaluates the adaptability and limitations of existing mathematical models in predicting their complex mechanisms. On this basis, it emphasizes the modeling processes and applications of machine learning (ML) in AD, and outlines the progress and predictive performance of ML in research related to exogenous substances. The study summarizes the limitations of mathematical models in quantifying the impact of exogenous substances, provides a systematic review of analytical frameworks applying ML technology to the regulation of such substances in the field of AD, and clarifies both the potential and current constraints of ML in predicting exogenous substance effects. This work offers a theoretical reference for a deeper understanding of the mechanisms of exogenous substances and for constructing intelligent prediction models, while also providing methodological support for the optimization and regulation of AD processes.

This study conducted the meta-analysis of interactive effects of dietary total sulfur amino acids (TSAA) and crude protein (CP) on average daily feed intake (ADFI), average daily gain (ADG), and feed conversion ratio (FCR) in broiler chickens, aiming to estimate phase-dependent optimal digestible TSAA levels across dietary CP levels. Moreover, the optimal digestible TSAA levels with different CP levels, which were identified in the meta-analysis, were further validated using a broiler feeding trial. In the meta-analysis, a total of 37 studies published between 2007 and 2024 were included. An initial full quadratic model with CP and digestible TSAA showed limited significance of model coefficients with little biological interpretation across growth phases. Therefore, a simplified quadratic model was employed, incorporating the product of digestible TSAA and CP (TSAA × CP) as a single interactive term with quadratic effects. The results indicated significant coefficients (P < 0.05) for ADG and FCR in the starter phase, ADFI and FCR in the grower phase, FCR in the finisher phase, and ADG and FCR in the overall growth phase. Nonlinear interactions for FCR were consistent across all phases. Model performance evaluations also indicated that FCR was the most reliable variable for predicted responses, exhibiting the least prediction errors and between-study heterogeneity. Model simulations across fixed CP levels from 16.0% to 24.0% revealed that optimal digestible TSAA levels for ADFI, ADG, and FCR increased as dietary CP decreased, with an increment of approximately 0.02 to 0.07 percentage points in digestible TSAA for each 0.5-percentage point reduction in dietary CP. Experimental validation trial further supported these predictions, demonstrating that diets formulated with the model-derived optimal digestible TSAA levels decreased FCR (P < 0.05) compared with diets following their commercial recommendations, particularly under reducing CP levels. In conclusion, this meta-analysis suggested that optimal digestible TSAA levels required to maximize growth performance in broiler chickens consistently increased with reducing CP levels in diets across all growth phases.

Phosphorus (P) has several vital functions, and its excretion may have environmental impacts. Thus, an adequate P supply is of utmost importance to meet the requirements of the animals while avoiding unnecessary excretion. Calculation of the P requirement of dairy cows considers factors such as P secretion via milk and P deposition in growing or pregnant animals. Furthermore, a value for the efficiency of P utilisation is applied, which should be determined in animals fed at a marginal P supply to maximise absorption. The objective of the present meta-analysis was thus to estimate the efficiency of P utilisation, accounting for P supply in dairy cows. The dataset included 399 observations published in 77 studies on dairy cows. Data on P intake and faecal P excretion were used to calculate standardised P digestibility, corrected for faecal endogenous P losses. Furthermore, the P requirement and the P supply relative to the requirement were calculated. Linear and non-linear regressions were performed to analyse the relationship between P excretion via faeces and urine and standardised P digestibility with P intake and P supply. Phosphorus intake exceeding the net requirement of dairy cows was excreted with faeces to a large extent, while urinary P excretion had only minor quantitative importance below 5.2 g P/kg DM of feed. The estimated standardised P digestibility at a marginal P supply was 83% and was interpreted as the estimate for efficiency of P utilisation. The data did not indicate that differentiation in P utilisation efficiency between mineral and organic P sources in the feed or by lactation stage is helpful for adequate P supply of dairy cows.

BACKGROUND: Chronic hepatitis B (CHB) affects an estimated 254 million people globally. Historically, WHO and professional society guidelines have recommended treatment for individuals at high risk of disease progression, including those with hepatitis B virus (HBV) DNA concentrations >20 000 IU/mL. Whether individuals at lower risk, including those with HBV DNA <20 000 IU/mL and normal alanine aminotransferase concentrations, benefit from treatment remains uncertain. To inform 2024 WHO guidelines and the potential expansion of treatment threshold recommendations, we conducted two linked systematic reviews and meta-analyses; this analysis examines the incidence of clinical outcomes in untreated adults with non-cirrhotic CHB stratified by baseline HBV DNA and ALT concentrations. METHODS: In this systematic review and meta-analysis, we searched PubMed, Embase, Web of Science, and the Cochrane Library for longitudinal prospective and retrospective cohort studies, randomised controlled trials, and non-randomised studies of interventions, published in any language, from Jan 1, 2000, to Feb 6, 2023. We also reviewed the reference lists of included studies and systematic reviews and consulted networks of experts to identify other data sources. Included studies followed up adults (≥18 years) with non-cirrhotic CHB who had no history of antiviral therapy at enrolment, had baseline HBV DNA quantification and ALT measurement, had a follow-up period of at least 48 weeks, and assessed one or more of six key clinical outcomes (hepatocellular carcinoma, cirrhosis, liver-related mortality, all-cause mortality, liver decompensation, and indication for liver transplantation) or six additional outcomes (advanced liver fibrosis, progression of liver fibrosis, becoming eligible for antiviral treatment, hepatitis flare, and HBsAg and HBeAg seroclearance). Outcomes were required to be stratified by HBV DNA concentrations (<200 IU/mL, <2000 IU/mL, 2000-19 999 IU/mL, 20 000-199 999 IU/mL, and ≥200 000 IU/mL) or ALT concentrations (less than the upper limit of normal [ULN], 1·0-1·9 × ULN, and ≥2·0 × ULN). We excluded studies that focused solely on individuals who were pregnant; were co-i

Microplastics (MPs) are pervasive contaminants in organic waste streams destined for anaerobic digestion (AD), yet their net effect on resource recovery remains a contentious issue with contradictory findings. To resolve this ambiguity, we conducted a robust three-level random-effects meta-analysis, synthesizing data from 55 studies, for disentangling the product-specific impacts of MPs on AD performance. Our analysis revealed that MPs shift carbon flow within AD: they suppress methanogenesis (-6.29% methane yield) while promoting acidogenesis (+23.73% total VFAs), with propionic, butyric, and valeric acids increasing by 12.74%, 14.55%, and 22.18%, respectively. This demonstrates that MPs do not simply inhibit AD but rather redirect its carbon flow, and this carbon rerouting is determined by polymer type. The effects of MPs on AD process could be conceptualized as novel hypothetical "Toxic Stress vs. Substrate Perturbation" models. Conventional polymers (e.g., polyvinyl chloride, polyethylene terephthalate) exert toxic stress, inhibiting methanogens and causing upstream VFA accumulation. Conversely, biodegradable polymers (e.g., polylactic acid, polybutylene adipate terephthalate) act as slow-release carbon sources, perturbing substrate availability to enhance methanogenesis. Furthermore, these effects are strongly modulated by MP concentration, size, and operational conditions like temperature, which can even reverse the inhibitory effects. This study reframes MPs from being simple inhibitors to active biogeochemical agents within engineered ecosystems. By clarifying MPs' product-specific effects, this study provides theoretical foundation of MPs affecting AD process, improving resilience and efficiency of AD-based resource recovery.

BACKGROUND: Pediatric Pi*ZZ alpha-1 antitrypsin deficiency (A1ATD) can cause hepatocyte A1AT polymer retention and progressive liver injury, but estimates of childhood liver morbidity vary across studies and remain poorly defined. AIM: To quantify liver-specific outcomes in pediatric Pi*ZZ A1ATD. METHODS: We systematically reviewed studies reporting liver-specific outcomes in children with confirmed Pi*ZZ/ZZ A1ATD (PROSPERO CRD42022335666). We extracted prevalence of fibrosis and cirrhosis, elevated liver enzymes, and liver transplantation. Random-effects meta-analysis pooled logit-transformed proportions (with sensitivity analyses assessing robustness to model assumptions). RESULTS: Thirteen studies including 398 children met inclusion criteria. Pooled prevalence was 41.3% (95% CI 29.6-54.0) for fibrosis and 17.3% (7.2-35.9) for cirrhosis, with substantial heterogeneity for cirrhosis (I2 78.6%). Liver transplantation prevalence was 10.7% (6.3-13.0). Elevated liver enzymes occurred in 43.0% (19.2-70.5) with high heterogeneity (I2 89.4%). Across cohorts, the proportion with elevated liver enzymes declined with increasing mean age, despite ongoing liver disease in reported histology-based outcomes. CONCLUSIONS: Clinically important liver disease occurs in a substantial subset of children with Pi*ZZ A1ATD. Declining rates of elevated liver enzymes with age should not be interpreted as disease resolution. Standardized registries are needed for longitudinal surveillance, to identify disease modifiers, and to guide early intervention in this high-risk population.

The presence of β-mannans in poultry feed ingredients and their associated negative effects on nutrient utilization and production performance remain a concern for the poultry industry. Despite efforts to address these effects by exploiting commercial enzymes, like β-mannanase, responses across reported studies remain inconsistent. Hence, this meta-analysis, with a focus on phase feeding, aimed to determine whether β-mannanase supplementation improves growth performance, nutrient digestibility, histomorphology, and immune organ weight in broilers fed low-energy diets. It also explored the source of between-study variation. A literature search from 2004 to August 2024 identified 27 eligible studies. Data from these studies were pooled using Hedges' g to estimate the standardized mean difference (SMD) with 95% confidence intervals. Heterogeneity was addressed through subgroup and meta-regression analyses based on β-mannan source, mannan degrader, β-mannanase dose, trial duration, and broiler strain. The quality of the eligible studies was also assessed using the risk of bias checklists for animal studies (SYRCLE) of the Cochrane Collaboration. The random-effects model's SMD estimates revealed that BWG and FCR are markedly improved by β-mannanase in the starter phase compared to the grower phase. However, the dose effect on FCR is influenced by an interaction with duration, which gradually diminishes as the later phase of grow-out progresses. In addition, β-mannanase improved DM and CP digestibility and increased VH, the VH-to-CD ratio, and innate activation (spleen) to maintain intestinal function and efficient nutrient utilization. However, the enzyme's effects on responses can be influenced by dose, its interaction with trial duration, and, to a lesser extent, by mannan source, degrader type, and the broiler strain. This meta-analysis demonstrates that β‑mannanase supplementation is a reliable strategy for mitigating the antinutritive effects of β‑mannans in broiler diets. Supplementation of the enzyme at 968 g/ton within reduced‑energy, phase‑feeding programs consistently improves growth performance, particularly during the starter phase, while maintaining key

INTRODUCTION: Dietary factors, including fermentable oligo-, di-, monosaccharides, and polyols (FODMAPs), have been implicated in symptom generation among patients with functional dyspepsia (FD). Accordingly, a low-FODMAP diet (LFD) has been proposed as a potential therapeutic approach. However, no systematic review has yet been conducted. This study aimed to evaluate the effects of an LFD on gastrointestinal symptoms and quality of life (QoL) in patients with FD. METHODS: Following PRISMA guidelines, Medline, Embase, and Central were searched through October 2025. Studies involving adults or children diagnosed with FD and treated with a structured LFD or lower habitual FODMAP intervention were included. Randomized controlled trials (RCTs) and non-RCTs were assessed for methodological quality using the Cochrane RoB 2 tool and the Newcastle-Ottawa Scale, respectively. RESULTS: Ten studies involving 4,329 patients (two RCTs and eight non-RCTs) met the inclusion criteria. Both RCTs demonstrated significant improvements in dyspeptic symptoms and QoL following an LFD compared with the control or baseline. Non-RCTs consistently showed symptom relief and improved QoL in adults and children under dietitian supervision, whereas lower habitual FODMAP intake was associated with a higher risk of FD prevalence in cross-sectional studies. Overall, the studies exhibited a predominantly moderate risk of bias. CONCLUSION: Current evidence suggests that an LFD may alleviate gastrointestinal symptoms and enhance QoL in patients with FD. However, existing studies remain few and heterogeneous. High-quality, adequately powered clinical and mechanistic studies are warranted to confirm its therapeutic efficacy and clarify the underlying physiological mechanisms. © 2026 S. Karger AG, Basel.

BACKGROUND: Approximately 80% of individuals diagnosed with major depressive disorder (MDD) report symptoms of insomnia. Glutamatergic modulators, such as ketamine, are reported to be effective for the treatment of depressive symptomatology in adults with MDD. Disrupted glutamate homeostasis is linked to poor sleep quality and sleep disorders. Herein, we sought to systematically determine the effect of glutamatergic modulators on sleep mechanisms in preclinical and clinical studies. METHODS: In accordance with the PRISMA guidelines, a systematic search was performed using the following electronic databases: PubMed, Medline, Cochrane Library, PsycInfo, Embase, Scopus, and Web of Science. Databases were searched from inception to November 27, 2024. Study screening and selection was performed by three reviewers (K.V., B.S., and W.C.). Included studies reported on the effects of glutamatergic modulators on sleep behaviors, architecture, and mechanisms. RESULTS: Preclinical studies reported that glutamatergic modulators, notably ketamine impact mechanistic pathways known to subserve sleep. Including serotonergic, dopaminergic, and GABAergic systems. It was reported that ketamine effects on electroencephalogram (EEG) delta power during non-rapid eye movement (NREM) sleep, and normalizes clock suppressor gene expression. Furthermore, while esketamine enhances delta power during NREM sleep, arketamine does not exhibit a similar effect. Separately, mGlu2/3 activators are suggested to reduce rapid eye movement (REM) sleep. Clinical studies indicate that improved sleep in patients with MDD can mediate ketamine's antidepressant effects. CONCLUSION: Our findings indicate that glutamatergic modulators, primarily ketamine, are associated with improvement across several sleep behaviors commensurate in MDD, suggesting that mechanisms subserving sleep are potential targets for depression treatment.

Comment in doi: 10.1001/jamanetworkopen.2026.2995. IMPORTANCE: Adrenal insufficiency is conventionally treated with daily multiple-dose hydrocortisone, and once-daily low-dose prednisolone is an alternative for glucocorticoid replacement. Clinical trials comparing once-daily low-dose prednisolone with thrice-daily hydrocortisone are lacking. OBJECTIVE: To examine the differences in metabolism and bone turnover in patients receiving hydrocortisone vs prednisolone for adrenal insufficiency. DESIGN, SETTING, AND PARTICIPANTS: This double-blind, crossover randomized clinical trial of multiple-daily standard-dose hydrocortisone vs once-daily low-dose prednisolone (2-5 mg), performed from September 3, 2019, to December 14, 2023, involved adults with adrenal insufficiency. Anthropometrics, biochemical data for cardiometabolic and bone health, and subjective health survey data were collected at days 1, 30, and 120 of each study period for both medications. INTERVENTION: Individuals were randomized to receive 4 months of once-daily prednisolone in the morning (with placebos at noon and afternoon) or hydrocortisone at the same times. All participants were crossed over to the alternative treatment for an additional 4 months. MAIN OUTCOME AND MEASURES: The primary outcome was assessment of bone turnover, detected by change in carboxylated and undercarboxylated osteocalcin between days 1 and 120 in each treatment period. Secondary outcomes included change in weight, body mass index, waist circumference, glycated hemoglobin, and subjective heath survey responses. RESULTS: Forty-seven participants were randomized, with 46 participants included in the analysis (median [IQR] age, 55.0 [46.5-62.8] years; 24 [52.2%] male). Twenty-four received prednisolone first and 22 received hydrocortisone first. Bone turnover was significantly slowed with prednisolone compared with hydrocortisone as evidenced by a significantly lower level of multiple bone markers, including carboxylated osteocalcin (mean treatment difference, -1.22 ng/mL; 95% CI, -2.35 to -0.10 ng/mL; P = .04), undercarboxylated osteocalcin (mean treatment difference, -1.38 ng/mL; 95% CI, -2.32 to -0.44 ng/mL; P = .005) (to

Dairy consumption may influence cognitive performance through its macronutrient composition and subsequent release of bioactive components during digestion. The objective of the study was to evaluate the effect of dairy form on cognitive performance, glycemic response, and subjective emotions in children. A repeated measures randomized controlled trial was conducted with 54 children (31 girls and 23 boys; age: 12.0 ± 0.2 years) who completed five experimental visits. Upon arrival at the laboratory, consumption of a standardized breakfast, and collection of baseline measures, children consumed an isocaloric (180 kcal) snack of milk, yogurt, cheese, sugar-sweetened beverage (SSB) or snack skipping. Cognitive performance, glycemic response, and subjective emotions were measured over 120 min. Corsi Block Tapping Test (CBTT) (forward) (p = 0.007) was higher after milk compared to yogurt, cheese, SSB and snack skipping. CBTT (backward) (p = 0.001) was higher after milk and yogurt compared to snack skipping. Immediate word recall (p = 0.003) was higher after SSB compared to yogurt but did not differ from other treatments. Blood glucose (p < 0.001) (mmol/L) was lower after milk, cheese, yogurt, and snack skipping compared to SSB. Subjective average emotions (p < 0.001) were higher after milk, yogurt, cheese and SSB compared to snack skipping. Both milk and yogurt affected short-term cognitive performance in children, and the mechanism was explained, in part, by changes in glycemic response. Future studies are needed to explore the long-term effect of dairy form on cognitive performance and the role of the gut-brain axis and varying nutrient compositions. Clinicaltrials.gov, #NCT05767983 (registered on 23 November 2022).

BACKGROUND AND AIM: Plant-based meat analogues (PBMA) are rising in popularity, yet its nutritional efficacy remains unclear. This study examined the impact of protein-matched animal-based meat diets (AD) and PBMA diets (PD) on nutrient intake and biological micronutrient status among Singaporean adults. METHODS: A parallel-design randomized controlled trial among 89 participants compared the substitution of habitual protein-rich foods with fixed quantities of either animal-based meats (n = 45) or their corresponding PBMA (n = 44) over 8 weeks. Cooked intervention foods were nutritionally profiled and assessed using the Nutrient Rich Food index. Micronutrients intake was examined by 3-day food records with corresponding blood biomarkers, as well as bone mineral density assessments by dual-energy x-ray absorptiometry (DEXA). The primary outcomes are vitamin B12 and folate micronutrient intake and status. RESULTS: Statistical comparisons by analysis of covariance with baseline data as a covariate revealed that dietary thiamine, folate, vitamin B6, sodium, calcium, potassium, magnesium and iron intake in the PD group was significantly higher as compared to the AD group. A corresponding difference in biological status was observed at week 8 for plasma vitamin B12 (PD: 382.56 (19.38) pmol/L, AD: 357.76 (17.50) pmol/L, P = 0.004), folate (PD: 32.13 (2.34) nmol/L, AD: 23.62 (2.02) nmol/L, P = 0.003) and selenium (PD: 1.61 (0.03) μmol/L, AD: 1.57 (0.03) μmol/L, P = 0.006). Marginal changes in bone mineral density (0.06 g/cm2, 95 % CI, 0.01-0.12 g/cm2, P = 0.030) were observed among participants in the PD group but no significant effects in its associated outcomes of β-crosslaps and P1NP. Sex-specific effects of β-crosslaps were suggested among females with higher concentrations in the PD group than the AD group observed. CONCLUSION: While the fortification of certain micronutrients like folate and vitamin B12 may improve the nutritional status, calcium and iron supplementation did not translate to observable changes in circulating micronutrient status. Future PBMA development must prioritize bioavailability and physiological factors such as digestion, absorption, bioava

BACKGROUND: Automated insulin delivery (AID) systems have been shown to improve glycaemic outcomes in people with type 1 diabetes managed with insulin pump therapy. No randomised studies have evaluated the benefits of tubeless AID in both adults and children with suboptimal glycaemia compared with multiple daily injections. We aimed to evaluate the safety and efficacy of a tubeless AID system compared with multiple daily injections in this population. METHODS: RADIANT was a multicentre, international, parallel-group, open-label, randomised, controlled trial done in 19 hospitals in the UK, Belgium, and France. Participants aged 4-70 years with type 1 diabetes managed with multiple daily injections and continuous glucose monitoring and who had HbA1c levels of 7·5-11% (58-97 mmol/mol) were randomly assigned (2:1) to tubeless AID or control (multiple daily injections) using a permuted-block design. Participant and study teams were not masked to group allocation. The primary outcome was the adjusted between-group difference in HbA1c at 13 weeks assessed for superiority. Primary and safety outcomes were assessed in the modified intention-to-treat population (all randomly assigned participants). The study is registered with ClinicalTrials.gov, NCT05923827, and has been completed. FINDINGS: Between Sept 11, 2023, and April 26, 2024, 188 participants were randomly assigned to the AID group (n=125) or the control group (n=63). The AID group had a greater reduction in HbA1c, from 8·1% (SD 0·7; 65 mmol/mol [SD 7·7]) at baseline to 7·2% (0·6; 55 mmol/mol [6·6]) at 13 weeks, compared with the control group, from 8·1% (0·6; 65mmol/mol [6·6]) at baseline to 8·0% (0·7; 64 mmol/mol [7·7]) at 13 weeks, with an adjusted mean difference of -0·8% (95% CI -1·0 to -0·6; -8·7 mmol/mol [95% CI -10·9 to -6·6]; p<0·0001). During the 13-week trial, no episodes of severe hypoglycaemia or diabetic ketoacidosis occurred in either treatment group. 39 adverse events were reported among 28 participants in the AID group, and three adverse events among three participants in the control group. Two serious adverse events (Kawasaki disease and acute coronary syndrome) occurred in the AID group unrelat

BackgroundParkinson's disease is (PD) a progressive neurodegenerative disorder. This study investigated the effects of an individualized nutritional intervention based on the Ketoflex 12/3 protocol, in addition to standard medical treatment, on motor and non-motor symptoms in PD.Methods40 individuals with PD were included in the study, and participants were randomly assigned to intervention and control. All individuals were classified according to inflammatory, glycotoxic, toxic, and vascular biotypes. The intervention group was assigned a plant-rich diet with a low glycemic index, consistent with ketogenic principles, free of inflammatory effects, and including intermittent fasting. The primary endpoint was the change in motor symptoms measured by the Unified Parkinson's Disease Rating Scale part III (UPDRS-III) from baseline to six months. Secondary endpoints included apathy (Starkstein Apathy Scale), activities of daily living (ADL/IADL), and gastrointestinal function (Bristol stool scale).ResultsCompared with the control group, the intervention group showed a significantly greater improvement in motor symptoms as measured by UPDRS-III (-11.0 vs +2.1 points from baseline to six months; p < 0.001). Significant between-group differences were also observed for secondary endpoints, including apathy (Starkstein Apathy Scale), activities of daily living (ADL/IADL), and gastrointestinal function (Bristol stool scale), all favoring the intervention group. Spearman correlation analyses revealed significant negative correlations with ADL and UPDRS-III scores, particularly in individuals with an inflammatory phenotype.ConclusionsThe findings suggest an individualized nutritional approach may contribute to improvement in both motor and non-motor symptoms in PD. Larger, multi-center trials with extended follow-up are needed. Plain Language Summary: Parkinson's disease is a complex condition that affects both movement and non-motor functions such as digestion, sleep, and mood. In this study, we examined whether a personalized, plant-rich eating approach, in which participants ate their daily meals within a fixed time window, could improve selected motor and non-motor symp

BACKGROUND: Age-related decline in digestive function increases malnutrition risk. Supplementing meals with digestive enzymes may improve macronutrient digestion and bioavailability in adults reaching older ages. OBJECTIVES: To assess postprandial plasma nutrient concentrations after co-ingestion of a mixed meal and a mixture of 6 enzyme preparations (ENZ), including proteases, lipase, amylase, and glucoamylase. METHODS: Thirty middle-aged and older adults (56 ± 11 y; 18 females, 12 males) ingested chicken, peas, potatoes, and butter (435 kcal; 34 g protein, 51 g carbohydrate, 11 g fat) with either ENZ or placebo (PLA) in a randomized crossover fashion. Blood samples were collected at baseline and throughout a 0-5 h postprandial period for measurement of plasma amino acid, insulin, glucose, and nonesterified fatty acid (NEFA) concentrations. Clustering of postprandial amino acid responses was conducted in MFuzz, and logistic regression for response groups was conducted in JMP 18.2.0 (JMP Statistical Discovery LLC). RESULTS: Plasma amino acid concentrations were not statistically different between treatments (PLA compared with ENZ) over the postprandial period (all P > 0.05). Leucine time to maximum concentration was significantly faster (P = 0.047) with ENZ (121.2 ± 55.9 min) compared with PLA (141.0 ± 49.2 min). Postprandial plasma glucose concentrations (P = 0.04) and total NEFA (P = 0.001) were higher with ENZ compared with PLA. Three distinct response patterns (clusters) were detected within and across all postprandial amino acid categories. Differences in habitual macronutrient intake and interactions between sex, lean mass, and BMI distinguished participants with an earlier time to maximum postprandial leucine concentration when consuming ENZ compared with PLA from those with stable responses. CONCLUSIONS: Multienzyme supplementation improved macronutrient digestion of a mixed meal in middle-aged and older adults. For plasma amino acids, this benefit was most pronounced in adults with lower BMI and higher lean mass, and the effect was sex-dependent. This study was registered at clinicaltrials.gov as NCT05211440.

BACKGROUND: Systematic reviews have reported conflicting evidence to confirm if macrolides reduce rates of chronic lung disease of prematurity in at-risk preterm-born infants, including in those colonised with pulmonary Ureaplasma spp. Since an adequately powered trial has been lacking, we conducted a double-blind, randomised, placebo-controlled trial to assess if the macrolide azithromycin improved survival without the development of physiologically defined moderate or severe chronic lung disease of prematurity in infants born at < 30 weeks' gestation. METHODS: Infants recruited from 30 neonatal units (median gestational age 27.0 weeks, interquartile range 25.3-28.6) requiring respiratory support within 72 hours of birth were randomised to intravenous azithromycin 20 mg/kg/day for 3 days followed by 10 mg/kg for 7 days or to placebo. Primary outcome was survival without development of physiologically defined moderate/severe chronic lung disease of prematurity at 36 weeks' postmenstrual age. A total of 796 infants were required to detect 12% improvement in survival without development of moderate or severe chronic lung disease of prematurity, including 10% dropout, with two-sided α-level of 5% and 90% power. The primary outcome was analysed using three-level logistic regression to account for clustering of multiple births and participants within centres and was adjusted for gestational age as a fixed effect. Secondary outcomes included death, chronic lung disease of prematurity severity, treatment interaction with Ureaplasma spp. colonisation, days of invasive and days of non-invasive respiratory support, treatment for nosocomial infections, treated patent ductus arteriosus, severe intraventricular haemorrhage, necrotising enterocolitis, treated retinopathy of prematurity and emergence of azithromycin resistance in stool and respiratory samples. Quantitative polymerase chain reaction identified respiratory Ureaplasma spp. and antibiotic resistance genes. Safety was also monitored. FINDINGS: After three withdrawals, 796 randomised infants were included in the final analyses. Survivors without physiologically defined moderate/severe chronic lung disease of prematu

OBJECTIVES: To determine the safety and efficacy of ruxolitinib (RUX) and fostamatinib (FOS) compared with standard of care (SOC) in patients requiring hospital admission for the treatment of COVID-19 pneumonia. DESIGN: Adaptive multiarm, multistage, randomised, open-label trial (three arm, two stage). SETTING: Five hospitals in England between October 2020 and September 2022. PARTICIPANTS: Hospitalised patients (≥18 years) with COVID-19 pneumonia defined by a modified WHO COVID-19 severity grade of 3 or 4. INTERVENTIONS: Participants were randomly assigned 1:1:1 to receive RUX (10 mg two times per day for 7 days then 5 mg two times per day for 7 days), FOS (150 mg two times per day for 7 days then 100 mg two times per day for 7 days) or SOC. MAIN OUTCOME MEASURES: Primary outcome was development of severe COVID-19 pneumonia (modified WHO severity grade≥5) within 14 days of randomisation. Secondary outcomes included mortality, invasive and non-invasive ventilation, venous thromboembolism, duration of hospital stay, readmissions, inflammatory markers and serious adverse events (SAEs). RESULTS: At stage 1, 181 patients were randomised, with 4 assessed as ineligible post randomisation. FOS was stopped early for futility with 16 participants (27.6%, n=58) developing severe COVID-19 pneumonia compared with 15 (25.0%, n=60) in the SOC arm (adjusted odds ratio (aOR) compared with SOC: 1.12; 95% CI 0.49 to 2.58; p=0.608). RUX progressed to stage 2 but the trial was stopped early due to slow recruitment. At the final analysis, 10 participants (16.1%, n=62) developed severe COVID-19 pneumonia in the RUX arm compared with 15 (24.6%, n=61) in the SOC arm (aOR: 0.63; 95% CI 0.25 to 1.57; p=0.161). Four (7.4%) participants in the FOS arm, none in the RUX arm and three (5.5%) in the SOC arm died within 14 days of randomisation. Infections were the most frequently reported SAE and were numerically higher in the FOS (10, 17.2%) and RUX (10, 16.1%) arms compared with SOC (7, 11.5%). Two unexpected serious adverse reactions occurred in the RUX arm only. CONCLUSIONS: We found no evidence that FOS was superior to SOC for the treatment of COVID-19 pneumonia in patients requiring hosp

INTRODUCTION: Faecal elastase-1 testing is the most commonly used method for diagnosing pancreatic exocrine insufficiency (PEI), but has poor diagnostic precision and cannot guide titration of pancreatic enzyme replacement therapy (PERT). An alternative is 13C-mixed triglyceride breath test. We investigated concordance between breath test and faecal elastase-1, and response to bicarbonate-buffered enzymes. METHODS: In this prospective study, adults with faecal elastase <100 µg/g using PERT performed a baseline breath test without enzyme treatment. Participants with normal baseline exhalation (≥29%) were enrolled in Substudy I, where they discontinued pancreatic enzyme replacement therapy (PERT) and were clinically reassessed after 6 months. Participants with abnormal exhalation (<29%) were enrolled in Substudy II, a three-arm crossover study where breath test was repeated on three separate days while receiving 24,000, 48,000, and 72,000 IU PERT, in random order. Primary outcomes were PERT reinstatement at follow-up (substudy I) and differences in cumulative 13CO2 exhalation (substudy II). RESULTS: Baseline tests where performed in 25 participants. Thirteen participants had normal breath test, 11 agreed to pause PERT, but only five participants did not reinitiate treatment (substudy I). 12 participants were included in substudy II (mean age 65, all males). All had significant breath test improvements on lowest enzyme dose (24,000 IU) versus baseline (mean difference 21.5%, p < 0.001), yet higher enzyme doses did not improve results significantly. DISCUSSION: About half of participants previously categorised with PEI had normal 13C-mixed triglyceride breath test, questioning diagnosis. Most participants demonstrated normal breath test with lowest enzyme dose during standardised test meal. However, this finding may not generalise to habitual meals.

BACKGROUND: Vaginal cervical cerclage and progesterone are established treatments for prevention of pregnancy loss and prematurity. There is limited data to assess the effect of these treatments in combination. The objective of this study was to investigate the association between progesterone and no progesterone treatment on pregnancy outcomes in women at high risk of preterm birth who had received a vaginal cervical cerclage. METHODS AND FINDINGS: This is a secondary post-hoc analysis of women recruited to the C-STICH randomised controlled trial, which recruited in 75 obstetric units in the UK between 2015 and 2021. In the C-STICH trial, women with a singleton pregnancy, receiving a vaginal cervical cerclage due to a history of pregnancy loss or premature birth, or if indicated by ultrasound, were randomised to cerclage with braided or monofilament suture, with a primary outcome of pregnancy loss, defined as miscarriage, stillbirth, or neonatal death in the first week of life. In this secondary analysis, the primary outcome was pregnancy loss, defined as miscarriage and perinatal mortality, including any stillbirth or neonatal death in the first week of life. Secondary maternal outcomes included miscarriage and previable neonatal death; stillbirth; gestational age at delivery; preterm pre labour rupture of membranes, and sepsis. Secondary neonatal outcomes included early/late neonatal death and sepsis. For each outcome, regression models were fitted adjusting for prespecified prognostic variables. From the 2,048 women recruited to C-STICH, 1943 (95%) women had a vaginal cerclage placed and available progesterone data. Of these, 834 (43%) women received progesterone and 1,109 (57%) did not receive progesterone. In women with primary outcome data available, in our predefined analysis pregnancy loss occurred in 49 (5.9%) of 832 women who received progesterone and 91 (8.3%) of 1,103 women who did not receive progesterone (adjusted* risk ratio 0.70 (95% confidence interval (CI) [0.50, 0.99]); adjusted risk difference -0.02 (95% CI [-0.04, -0.001], *adjusted for indication, obstetric history, surgical technique, and maternal age). Further exploratory analysis exclud

Yeast culture (YC), a complex functional feed additive containing fermentation metabolites, has demonstrated potential in dairy production systems. However, its mechanistic effects on rumen function and host metabolism in lactating dairy cattle warrant further investigation. This study evaluated the impacts of YC supplementation on production performance, systemic antioxidant status, and rumen function in late-lactation Holstein cows. Fourteen multiparous Holstein cows (body weight 655 ± 28 kg; days in milk 270.4 ± 1.6 d) were randomly allocated into two groups, a control group (CON, basal diet) and a YC-supplemented group (YC, basal diet + 50 g/d YC), in a 28-day feeding trial. YC supplementation significantly increased dry matter intake (p < 0.01), nutrient digestibility (p < 0.01 for DM, CP, EE, NDF, and ADF), and milk yield (p < 0.05) compared to CON. Systemic antioxidant capacity was enhanced, as evidenced by elevated serum superoxide dismutase activity (p < 0.01) and total antioxidant capacity (p < 0.05). Rumen fermentation was improved with higher concentrations of total volatile fatty acids (p < 0.01) and microbial protein (p < 0.01) and reduced ammonia nitrogen levels (p < 0.01). Macrogenomic analysis revealed a YC-mediated restructuring of the rumen microbiota, characterized by an increased relative abundance of Firmicutes and decreased Bacteroidota. Untargeted metabolomic profiling identified significant alterations in rumen metabolite profiles, with differential metabolites enriched in pyrimidine metabolism and vitamin digestion and absorption pathways. These results indicate that YC supplementation improves production performance in late-lactation dairy cows through multi-faceted mechanisms involving rumen microbial community modulation and metabolic pathway activation, ultimately enhancing nutrient utilization and metabolic efficiency.

Background/Objectives: Beta amyloid (Aβ) aggregates play a central role in the pathophysiology of Alzheimer's disease (AD), and their detection and modulation remain major challenges in developing effective therapeutic and diagnostic strategies. Previously, gold nanoparticles with plasmonic and optical properties in the near-infrared (NIR) region and photothermal capabilities have been designed for detecting and disaggregating Aβ aggregates. However, these systems often face limitations related to biodegradability, long-term accumulation, and safety. In this work, a degradable NIR-responsive nanosystem based on small gold nanoparticles (sAuNPs), potentially excretable due to their small size, encapsulated within bovine serum albumin (BSA) and functionalized with the all-D peptide D3, was developed to inhibit Aβ aggregation. Methods: sAuNPs (~5-6 nm), functionalized with HS-PEG-NH2, were encapsulated into BSA nanoparticles using a desolvation method and subsequently conjugated to D3, resulting in the nanosystem f-sAuNPs-BSANPs-D3. The nanosystem was characterized by UV-Vis-NIR spectroscopy, dynamic light scattering, zeta potential analysis, electron microscopy, and nanoparticle tracking analysis. The effects of the nanosystem on Aβ1-42 aggregation were evaluated using a thioflavin T assay and electron microscopy. Additionally, the effects of f-sAuNPs-BSANPs-D3 on cell viability and its stability against trypsin digestion were assessed. Results: The nanosystem exhibited a measurable photothermal response under NIR irradiation and significantly reduced fibril formation. It did not affect the viability of SH-SY5Y neuronal cells at the tested concentrations. Trypsin incubation experiments demonstrated that the nanosystem remained stable at low enzyme concentrations mimicking plasma conditions, whereas higher enzyme concentrations induced degradation of the albumin matrix and subsequent disaggregation of sAuNPs. Conclusions: Overall, this study presents a degradable, albumin-based sAuNP nanosystem with NIR-responsive properties and potential for nanomedicine applications to inhibit Aβ aggregation in AD.

Background/Objectives: Recent studies have shown that the solubilisation of poorly water-soluble drugs can be enhanced by using infant formula as a lipid-based formulation. In those studies, digestion of the triglycerides in infant formula to produce more polar lipids, namely fatty acids and monoglycerides, produced a high-capacity solubilisation environment for weakly basic drugs such as clofazimine, driven mainly by ion-pairing of the fatty acid with the drug. However, digestion of lipid-based formulations is not expected to provide the same effect for nonionised or acidic drugs and in fact may present a reduced solubilisation capacity for weakly acidic drugs. Methods: In this study, a weakly acidic drug, tolfenamic acid, was dispersed in reconstituted infant formula, and the infant formula was digested under in vitro simulated intestinal conditions. The quantity of tolfenamic acid that was solubilised in the infant formula during digestion was determined by high-performance liquid chromatography and small-angle X-ray scattering. Results: Unexpectedly, digestion of the infant formula increased the solubilisation capacity for tolfenamic acid. Reconstituting infant formula at a higher fat content also increased the rate and extent of solubilisation of tolfenamic acid during digestion. The quantity of tolfenamic acid that was solubilised during digestion correlated approximately linearly with the quantity of free fatty acids produced during digestion. Conclusions: These results show that a weakly acidic drug can also exhibit digestion-driven solubilisation in a lipid-based formulation in the absence of ion-pairing and highlights the need to better understand drug response to digestion of lipid-based foods and formulations, and their versatility as a formulation option even for poorly water-soluble acidic drugs. Influence of Diet on Bioaccessibility of Iron from Dietary Supplements and Medicinal Products-Results of In Vitro Digestion Model and Analytical Determinations. Bawiec P(1), Jaworowska A(1), Sawicki J(2), Czop M(3), Tokarczyk J(1), Helon P(4), Koch W(1). Author information: (1)Department of Food and Nutrition, Medical University of Lublin, 4a Chodźki St

38. Nutrients. 2026 Apr 13;18(8):1219. doi: 10.3390/nu18081219. Influence of Diet on Bioaccessibility of Iron from Dietary Supplements and Medicinal Products-Results of In Vitro Digestion Model and Analytical Determinations. Bawiec P(1), Jaworowska A(1), Sawicki J(2), Czop M(3), Tokarczyk J(1),

The efficient resource utilization of duck manure and agricultural/forestry wastes (AFW) plays a significant role in environmental protection and promoting the sustainable development of the economy and society. This study examined the effects of hydrochar derived from AFW in the anaerobic digestion (AD) process, determining the optimal addition ratio. This research systematically investigated the impact of hydrochar on methane yield, as well as changes of short-chain fatty acids, microbial community dynamics, and metabolic pathways during AD of duck manure. The underlying mechanisms were clarified by metagenomic and metabolomic analyses. This experiment used duck manure as substrate and added hydrochar of four different dosage levels. Laboratory batch tests ran for 32 days at 37 ± 0.5 °C, with three parallel samples for each group. The results indicated that hydrochar additive significantly improved methane yield (p < 0.05), with a maximum increase of 27.13% at an optimal dosage of 10.91 g·L-1. This amendment enhanced the abundance of Firmicutes, Bacteroidota, Chloroflexota, Halobacteriota, and Methanosarcina significantly. Compared to the control group, the abundances of functional genes involved in hydrolysis, acidogenesis, and acetogenesis pathways increased by 28-254% in the optimal treatment group, with methanogenesis-related genes showing a 16-155% enhancement (p < 0.05).

The gut microbiota plays a central role in digestion, metabolism, immune regulation, and inflammatory processes, and is highly responsive to dietary factors, including food additives. With the increasing consumption of ultra-processed foods, growing attention has been directed toward the long-term effects of commonly used additives on gut health. This review examines the interactions between food additives and the gut microbiota, with a specific focus on the emulsifiers carboxymethyl cellulose (CMC) and carrageenan (CGN), which are widely used in processed foods. Evidence from in vitro, animal, and limited human studies indicates that both CMC and CGN can alter gut microbiota composition, disrupt intestinal barrier integrity, and promote pro-inflammatory responses, although their mechanisms of action differ. CGN has been more consistently associated with direct activation of inflammatory signalling pathways and epithelial stress, whereas CMC primarily induces microbiota-mediated effects, including altered microbial spatial organisation and mucus barrier disruption, leading to low-grade inflammation. The magnitude of these effects appears to depend on dosage, duration of exposure, and the experimental model employed. Overall, the findings summarised in this review suggest that chronic exposure to CMC and CGN may contribute to gut dysbiosis and increased inflammatory susceptibility, particularly within dietary patterns rich in ultra-processed foods. These observations highlight the need for harmonised research methodologies, more human-relevant long-term studies, and reconsideration of current food safety assessment frameworks to better account for microbiota-related outcomes.

Corn, paddy, wheat, sorghum, and cassava serve as the primary energy sources in both human and animal diets. This study aimed to evaluate their nutrient release patterns in a simulated gastrointestinal environment and to assess the in vitro biological activity of the metabolites produced during digestion. The results showed that wheat exhibited the highest dry matter degradation in the stomach-jejunum-ileum digestion stage, while wheat and paddy showed the highest crude protein degradation compared with the other starch sources. In addition, wheat had a higher total free sugar concentration than paddy, sorghum, and cassava. Among the individual free sugars, such as D-sorbitol and D-(+)-trehalose, were found to have the highest concentrations in wheat, whereas cassava had the highest D(-)-fructose concentration. Several differential metabolites, including valeric acid, caproic acid, octanoic acid, and azelaic acid were highly released in paddy, whereas glucaric acid, threonic acid, phenylacetic acid, and shikimic acid were highly released in cassava, and 4-hydroxycinnamic acid was highly released in paddy and sorghum. Four unique metabolites were identified during the digestion process of five starch sources. Particularly, isocitric acid and trans-Cinnamic acid were released only from cassava; caffeic acid was released only from sorghum and corn; and pimelic acid was released only from paddy and wheat. Furthermore, cassava was distinct from the other starch sources, displaying a higher abundance of differential metabolites within the glucagon signaling pathway as mapped in KEGG pathway analysis. In summary, compared with other starch sources, wheat provides more dry matter, protein, and sugars for the body. Cassava is unlikely to offer any advantage in glycemic regulation, while paddy and cassava possess stronger biological activity in terms of differential metabolites.

Astaxanthin (AST), despite its high bioactivity, exhibits poor stability and low bioavailability due to its strong lipophilicity and inherent degradation susceptibility. To overcome such a challenge, we developed a food-grade oleogel delivery system using a soy protein-arabinoxylan (SA) glycosylated complex modulated by different concentrations (0.5-3%) of sucrose ester (SE) or soy lecithin. We show that the emulsifier concentration has a non-linear effect on the oleogel microstructure: an optimal level of 1% had a significant impact on the interfacial compactness and network density, giving rise to improved thermal stability, rheological strength and AST encapsulation efficiency (81.27%). During in vitro digestion, the SA matrix in combination with emulsifiers allowed gastric protection and intestinal-targeted release of AST with a bioaccessibility of up to 88.84% (SAO-SE-AST). This controlled release profile directly translated into enhanced in vivo antioxidant efficacy in wild-type Bristol N2 Caenorhabditis elegans, as evidenced by reduced lipofuscin accumulation, elevated thermotolerance (survival rate: 64.44-73.33%), suppressed reactive oxygen species levels and activation of endogenous antioxidant enzymes (superoxide dismutase as well as glutathione peroxidase). Collectively, this research has uncovered that food-grade emulsifiers are not only stabilizers, but also key regulators of oleogel architecture and bioactive functionality. These results provide a structure-digestion-bioactivity correlation for protein-polysaccharide oleogels, representing a rational design strategy for high-performance delivery systems of lipid-soluble nutraceuticals.

There is an increasing interest in functional food formulations with added bioactive compounds, such as vitamins, probiotics, polyphenols and bioactive peptides, specifically in dairy and plant-based foods, bakery, and beverages. However, their stability in the food system, release rates and biological activity after consumption/digestion play an important role in the effectiveness of functional foods. There are technical challenges in maintaining the stability and acceptability of added compounds in the formulation design of food items. A novel approach to delivering bioactive compounds in functional foods is their microencapsulation, where stability-sensitive compounds are protected against their degradation during processing and physiological digestion, with targeted release in the gastrointestinal tract (GIT) and elicited cellular responses. Microencapsulation of bioactive compounds has been proven to be beneficial in in vitro models for the stability, antioxidant and immunomodulatory action, and acceptability compared to free (non-capsulated) forms. This technology is worth considering relative to the protection of health benefits of compounds used in food products, with their necessary bioactivity after physiological digestion in GIT. This article reviews important bioactive compounds, challenges, and strategies in the development of functional foods to ensure the required stability for the bioavailability of added compounds.

This study aimed to evaluate the effects of lowering crude protein (CP) levels in the diet of dairy cows alone or in combination with a yeast probiotic on nitrogen utilization, digestion, and rumen microbial protein synthesis. In total, six cows were included in a 3 × 3 Latin square design. Each study period consisted of 23 days of diet adaptation and 5 days for sampling and data collection. Cows were randomly assigned to one of the three diets according to protein level and supplementation: control diet with 16.5 CP%DM (CTR), a diet with 14.5 CP%DM without Actisaf Sc 47 supplementation (LCP), and a diet with 14.5 CP%DM with Actisaf Sc 47 supplementation at 5 g/cow/day (LCPActisaf). Reducing protein content from 16.5 to 14.5 CP%DM alone or in combination with Actisaf Sc 47 significantly reduced nitrogen intake. Regarding fecal nitrogen (FN), no difference was observed between the CTR and LCP groups. However, FN was significantly lower in the LCPActisaf group compared with that of the CTR group. There was a tendency for lower FN in the LCPActisaf group compared with the LCP group. Compared with CTR, urinary nitrogen (UN) was not impacted by LCP but tended to decrease with LCPActisaf (p = 0.1). Compared with CTR and LCP, supplementation with Actisaf Sc 47 increased nitrogen use efficiency (NUE) (p < 0.05). A tendency for higher NUE was observed in the LCP group compared with the CTR group (p = 0.07). Crude protein digestibility was similar between the CTR and LCP groups and tended to increase with Actisaf Sc 47 supplementation. Compared with CTR, neutral detergent fiber (NDF) digestibility was not impacted by LCP but increased by LCPActisaf (p = 0.05); LCPActisaf did not impact NDF digestibility compared with LCP. Organic matter (OM) digestibility was similar among treatments. Although there was no difference between the three groups on rumen microbial protein synthesis (RMP), supplementation with Actisaf Sc 47 increased RMP. Reducing protein content in combination with Actisaf Sc 47 appears to be a good strategy, enabling both the environmental footprint linked to nitrogen losses to be reduced, and fiber digestibility and rumen microbial protein synthesis to incr