Vitamin B9 (Folic Acid)

BACKGROUND: Neural tube defects (NTDs), particularly spina bifida, contribute significantly to pediatric mortality and disability in Africa. Limited healthcare resources and variation in management strategies across regions contribute to disparate outcomes. This systematic review and meta-analysis evaluate the epidemiological profile, clinical presentation, management, and outcomes of spina bifida across African regions. METHODS: A PRISMA-guided systematic review was conducted using PubMed, Google Scholar, Cochrane, and Scopus databases. Retrospective studies and case reports reporting spina bifida case volume, presentation, management, and outcomes in African countries were included. Random-effects meta-analysis estimated pooled prevalence rates with 95% confidence intervals (CI). RESULTS: A total of 32 studies from 10 African countries, encompassing 4,779 patients, met inclusion criteria. The mean age at presentation was 40.26 months (95% CI: 0---86.73). Myelomeningocele was the most common subtype (61.39%, 95% CI: (47.43---75.35). Overall pooled mortality was 33.8% (95% CI: (6.18---37.83), with significant regional variation (p < 0.01): Southern Africa 15% (95% CI: 0-38%), West Africa 39% (95% CI: 4-50%), East Africa 10% (95% CI: 7-13%), and North Africa 100% (95% CI: 99-100%). Surgical intervention was performed in 80.1% of cases (95% CI: 71.57-92.08), with ventriculoperitoneal shunting (17.61%, 95% CI: 5.48-29.75) and endoscopic third ventriculostomy (11.54%, 95% CI: 0-24.23) among the most common procedures. Clinical improvement was noted in 38.2% (95% CI: 23-71%), with significant differences between regions (p < 0.01), while 14.5% (95% CI: 7.47-24.31) showed no change or worsening. CONCLUSIONS: This study highlights significant variability in spina bifida presentation and outcomes across Africa. Myelomeningocele is the most common subtype, with substantial morbidity and mortality. Regional disparities underscore the need for standardized surgical protocols and increased access to neurosurgical care. Given the low rates of maternal folate supplementation, strengthening public health measures, including folic acid fortification and prenatal screening, is c

Congenital abnormalities (CAs) are a major contributor to perinatal mortality and morbidity in India, particularly among abortuses and stillbirths. Despite the Ministry of Health and Family Welfare, India, introducing stillbirth surveillance guidelines, national data on the burden of CAs remain limited. This systematic review and meta-analysis aimed to estimate the pooled prevalence of CAs in fetal losses and assess variations by organ system, region, and diagnostic approach. A comprehensive search following PRISMA 2020 guidelines was conducted in PubMed and Google Scholar. Twenty-two hospital-based studies published between 1967 and 2024 were included. Data were critically appraised using the Joanna Briggs Institute's Critical Appraisal checklist. Meta-analysis was performed in Review Manager software using a random-effects model. Subgroup analyses explored differences by fetal outcome, publication year, diagnostic method, and geographic region, while publication bias was assessed using funnel plots and Egger's test. The pooled prevalence of CAs in fetal losses was 0.21 (95% CI: 0.17-0.25), higher among abortuses (0.38) than stillbirths (0.12) and in autopsy-based studies (0.26) than non-autopsy studies (0.09). Central nervous system anomalies were most frequent (0.42), followed by multiple anomalies (0.37). The Central region reported the highest prevalence (0.66) and the North-East the lowest (0.03). The findings highlight the need for consistent surveillance, improved diagnostic methods, and preventive strategies-particularly periconceptional folic acid supplementation and integration of CA reporting into national programmes-to reduce fetal losses and enhance maternal and child health outcomes in India and similar low- and middle-income settings. © 2026 Japanese Teratology Society.

Background and Purpose: The effects of B-vitamin combinations on the prevention of cardiovascular diseases, such as myocardial infarction (MI) and stroke, remain controversial. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) over three decades to evaluate the association between B-vitamin combinations and mortality and arterial thrombotic outcomes. Methods: PubMed, Embase, Web of Science, and the Cochrane Library were systematically searched for RCTs with minimal duration over 24 months published between January 1996 and November 2025. Two reviewers independently screened studies, extracted data, and assessed risk of bias using the Cochrane Risk of Bias 2.0 tool. Random-effects models were used in this meta-analysis to calculate pooled risk ratios (RRs) and 95% confidence intervals (CIs). Results: Thirteen randomized trials enrolling 68,363 participants across both primary and secondary prevention populations were included. B-vitamin combinations were associated with a nonsignificant reduction in stroke and 3-point major adverse cardiovascular events (MACE) (stroke: RR 0.91, 95% CI 0.81-1.04; MACE: RR 0.93, 95% CI 0.86-1.01). No significant effects were observed for all-cause mortality (RR 1.01, 95% CI 0.96-1.06), cardiovascular mortality (RR 0.97, 95% CI 0.88-1.07), or MI (RR 0.97, 95% CI 0.91-1.03). In primary prevention populations, B-vitamin combinations were associated with significant reductions in stroke (RR 0.79, 95% CI 0.68-0.93) and MACE (RR 0.80, 95% CI 0.69-0.92). A modest reduction in MACE was also observed in secondary prevention populations (RR 0.91, 95% CI 0.83-0.99). Between-study heterogeneity was minimal to low for ischemic outcomes, supporting the robustness of these estimates, whereas substantial heterogeneity was observed for mortality outcomes in secondary prevention populations. Conclusions: The evidence is limited by heterogeneity in trial populations, vitamin formulations and doses, and outcome definitions, with substantial between-study inconsistency for mortality outcomes and imprecision in subgroup estimates derived from a small number of contributing trials. Overall, B-vitamin combinations d

BACKGROUND: Malaria is an infectious disease transmitted by female Anopheles mosquitoes, with ongoing transmission in over 80 countries. The malaria parasite requires folate for survival and growth; antifolate antimalarial medications used for prevention and treatment target enzymes in folate metabolism as their mechanism of action. Periconceptional folic acid (synthetic form of folate) supplementation (400 μg/day) is the standard of care for neural tube defect prevention. Concerns have been raised about the potential effects of folic acid (including above the tolerable upper intake level (UL) >1.0 mg/day) in the context of malaria prevention and treatment, including the efficacy of antimalarial medications. Examining the potential impact of folic acid on malaria risk and severity amongst people taking antifolate antimalarial medications may inform public health programmes in malaria-endemic areas. OBJECTIVES: To examine the effects of folic acid supplementation on the risk and severity of malaria infection amongst people taking antifolate antimalarials and living in areas with malaria endemicity. PREVENTION: Amongst uninfected people taking antifolate antimalarial medications for malaria prevention, does folic acid supplementation increase susceptibility or severity of malaria infection? TREATMENT: Amongst people with malaria infection who are being treated with antifolate antimalarial drugs, does folic acid supplementation reduce parasite clearance or increase the risk of treatment failure? SEARCH METHODS: We searched databases including CENTRAL, MEDLINE, Embase, CINAHL, Scopus, and trial registries (September 13, 2024), grey literature, and reference searches to identify additional studies. SELECTION CRITERIA: Randomised trials evaluating the effects of folic acid supplementation (alone or in combination with iron or other vitamins and minerals) amongst individuals taking antifolate antimalarial medications in malaria-endemic areas. DATA COLLECTION AND ANALYSIS: Primary outcomes included uncomplicated malaria or severe malaria, parasite clearance, and treatment failure. Cochrane RoB 2 was used to evaluate the risk of bias. Certainty of evidence was assessed u

BACKGROUND: Small vulnerable newborn (SVN) types, defined by combinations of being born too soon or too small, have distinct determinants, health consequences, and prevention strategies. The effects of prenatal balanced energy and protein (BEP) supplementation on SVN types remain unknown. METHODS AND FINDINGS: We conducted a systematic review and meta-analysis of individual participant data from eight randomized controlled trials of prenatal BEP supplements (N = 10,252, with 5,164 in the BEP arm and 5,088 in the control arm) in low- and middle-income countries were used. The control arms varied across studies and included context-specific standards of care, iron and folic acid supplements, or multiple micronutrient supplements. Newborns were classified into 10 groups through the combinations of preterm birth, small for gestational age (SGA) birth, and low birthweight (LBW), such as term-appropriate-for-gestational-age (AGA)-nonLBW, preterm-SGA-LBW, preterm-large-for-gestational-age-LBW, term-SGA-LBW, preterm-AGA-nonLBW, and other permutations. Newborns were also analyzed using a four-group categorization that included term-nonSGA, preterm-nonSGA, term-SGA, and preterm-SGA. Log-binomial models were used to estimate study-specific risk ratios (RRs), which were pooled using meta-analyses. Subgroup analyses were conducted by maternal age, parity, gestational age at enrollment, early pregnancy body mass index, and maternal anemia status. In the 10-group categorization of SVNs, on average, prenatal BEP supplementation led to a 30% lower risk of preterm-SGA-LBW (RR: 0.70; 95% CI [0.53, 0.91]; P = 0.009), a 25% lower risk of preterm-AGA-LBW (RR: 0.75; 95% CI [0.60, 0.93]; P = 0.009), and a 20% lower risk of term-SGA-LBW (RR: 0.80; 95% CI [0.72, 0.90]; P < 0.001). In the four-group categorization, prenatal BEP supplementation led to a 31% lower risk of preterm-SGA (RR: 0.69; 95% CI [0.52, 0.91]; P = 0.008) and a 12% lower risk of term-SGA (RR: 0.88; 95% CI [0.81, 0.96]; P = 0.005). The protective effect of prenatal BEP supplementation on preterm-SGA was stronger among multiparous women and women without anemia. The protective effects on all three SVN types under the four

BACKGROUND: Neural tube malformation is a common congenital malformation and its influencing factors were still unclear. This paper aims to explore the main influencing factors of neural tube malformation, and provide reference for the primary prevention of neural tube malformation. METHODOLOGY: Case-control literatures on the influencing factors of neural tube malformation from 1990 to 2021 were searched from Chinese and English websites. The quality of the included literatures was evaluated according to Newcastle-Ottawa Scale (NOS) scale and data were extracted. Meta-analysis was performed on the data using funnel plot and Egger's est evaluated publication bias, and sensitivity analysis was performed by eliminating individual studies one by one. RESULTS: A total of 49 case-control studies were included. Meta-analysis showed that the main influencing factors of neural tube malformation were folic acid (odds ratio (OR)OR=0.31, 95%CI: 0.20-0.47), fever (OR=3.02, 95%CI: 2.38-3.83), obesity (OR=1.76, 95%CI: 1.39-2.21), passive smoking (OR=1.91, 95%CI: 1.52-2.40). Antiepileptic drugs (OR=6.10, 95%CI: 2.58-14.43); Heavy metals (Zinc: OR=2.37, 95%CI: 1.06-5.30, mercury: OR= 4.61, 95%CI: 2.85-7.47). CONCLUSION: Prenatal supplementation with folic acid and zinc has been shown to reduce the risks of neural tube defects. It is recommended that women of childbearing age take folic acid and zinc supplements before and during pregnancy. Other factors such as fever, obesity, passive smoking, antiepileptic drugs, and mercury exposure have been associated with an increased incidence of neural tube abnormalities. Neurological tube abnormalities can be reduced by folic acid and zinc, which act as protective factors. The incidence of neural tube abnormalities is increased by fever, obesity, passive smoking, antiepileptic drugs, and mercury. © 2025 Wu X et al.

OBJECTIVE: Hyperhomocysteinemia (Hcy) independently predicts coronary heart disease (CHD) and adverse cardiovascular events. Although folic acid plays a key role in Hcy metabolism, the effect of combined B-vitamin supplementation (folic acid, VB6, and VB12) on clinical outcomes in CHD remains uncertain. METHODS: A systematic search of PubMed, Embase, and the Cochrane Library was conducted from inception through April 2025 using MeSH terms including "folic acid," "vitamin B6," "vitamin B12," "coronary heart disease," and "homocysteine." A random-effects model was used for meta-analysis. RESULTS: Thirteen studies involving 14,539 participants were included in the meta-analysis (7,338 patients treated with folic acid combined with vitamin B complex and 7,301 controls). Combined B-vitamin supplementation significantly reduced serum Hcy levels [mean difference: -2.36; 95% confidence interval (CI): (-3.09 to -1.62); p < 0.01] compared with any single-nutrient regimen. The incidence of vascular restenosis was lower in the intervention group than in the control group (risk ratio: 0.65; 95% CI: 0.44-0.95; p < 0.05). However, no significant differences were observed in the incidence of major cardiovascular events (p = 0.78) or cardiovascular-related mortality (risk ratio: 0.96; 95% CI: 0.85-1.07; p = 0.44). CONCLUSION: Combined B-vitamin supplementation effectively lowers serum Hcy levels and the incidence of vascular restenosis in patients with CHD. However, its impact on cardiovascular events and mortality remains inconclusive. Plain Language Summary: Meta-analysis of 13 RCTs (n = 14,539): combined B vitamins lower serum HcyCombined B-vitamin supplementation lowers vascular restenosis in CHD patientsExerts no significant impact on major CV events or mortalityHcy-lowering appears CHD-specific; broader CV benefits remain unproven.

Update of Cochrane Database Syst Rev. 2016 Feb 27;2:CD006589. doi: 10.1002/14651858.CD006589.pub4. RATIONALE: Iron deficiency anaemia is a common nutritional disorder among children in malaria-endemic regions and is associated with adverse developmental and health outcomes. However, concerns have been raised that iron supplementation might increase the risk of malaria by enhancing parasite growth, particularly in areas lacking adequate malaria prevention and treatment services. OBJECTIVES: To evaluate the effects and safety of iron supplementation, with or without folic acid, in children living in areas with hyperendemic or holoendemic malaria transmission, where malaria is intense and occurs year-round. SEARCH METHODS: We searched CENTRAL (Wiley), MEDLINE (Ovid), Embase (Ovid), and Global Index Medicus (WHO) up to 30 April 2024. We also searched two trial registries, ClinicalTrials.gov and WHO ICTRP, to 30 April 2024. We conducted a top-up search on 20 May 2025. We contacted trial investigators and scanned references of included trials and reviews for relevant studies. ELIGIBILITY CRITERIA: We included individual and cluster-randomised controlled trials (RCTs) conducted in malaria-endemic regions that enrolled children under 18 years of age. We included trials that compared: (1) oral iron alone versus placebo or no treatment; (2) oral iron plus folic acid versus placebo or no treatment; (3) oral iron (with or without folic acid) versus placebo or no treatment, grouped by malaria prevention and management services for the outcome of clinical malaria only; and (4) oral iron plus antimalarial treatment versus placebo or no treatment. Iron or fortified interventions had to provide ≥ 80% of age-appropriate Recommended Dietary Allowance (RDA). Antihelminthics and micronutrients other than iron and folic acid had to be administered equally to both groups. OUTCOMES: The critical outcomes were clinical malaria, severe malaria, and death from any cause. Important outcomes included hospitalisations and clinic visits. RISK OF BIAS: We assessed risk of bias in the included trials using the Cochrane RoB 1 tool. SYNTHESIS METHODS: We used fixed-effect meta-analysis (Mantel-H

This study aimed to evaluate the relationship between folate intake and breast cancer risk in adult women. A blinded paired-matched search was conducted in Embase, PubMed/Medline, and Web of Science. Cohort and case-control studies assessing folate intake or supplementation and breast cancer risk were included. The search yielded 377 studies. After exclusion of duplicates and reading of the titles and abstracts, 13 were selected for full-text reading, and 11 met the eligibility criteria. Most studies (n = 8) found a direct association between folate intake and reduced breast cancer risk, with one study observing a U-shaped relationship between dietary folate intake and breast cancer risk. Conversely, three studies found no association with breast cancer risk. Some studies report inconsistencies in the literature. A meta-analysis comparing mean folate intake between case and control groups revealed no statistical significance. Some studies have indicated a possible association between folate consumption and the risk of breast cancer, however the meta-analysis of this study did not confirm this relationship. Results were inconsistent, and the meta-analysis indicated no significant effect. © 2025 The Author(s). Molecular Nutrition & Food Research published by Wiley‐VCH GmbH.

BACKGROUND: Low folate levels in women of childbearing age can cause various health issues. Additionally, low perinatal folate concentrations are a significant cause of neural tube defects. Currently, folic acid supplements mainly consist of folic acid and the active form of folate. Therefore, this systematic review and meta-analysis aimed to evaluate the effectiveness and safety of the active form of folate in women of childbearing age. METHODS: We searched the published literature in PubMed, Medline, EMBASE, The Cochrane Library, China National Knowledge Infrastructure, and Wanfang. Randomized controlled trials (RCTs) were obtained to assess the effects of the active form of folate versus folic acid in women of childbearing age. The random or fixed effects model was used to analyze the data in meta-analysis. The results were expressed as standardized mean differences or risk ratios along with their corresponding 95% confidence intervals. RESULTS: Eleven RCTs were identified in our systematic review. The results indicated that the active form of folate supplementation might significantly increase plasma folate (P = .04), increase erythrocyte folate (P = .01), and decrease unmetabolized folic acid (P < .0001). Supplementation with the active form of folate might increase the subsequent pregnancy rates (P = .0005) and might decrease the incidence of adverse pregnancy outcomes (P = .0003) in women with a history of adverse pregnancy outcomes. However, there were no significant differences in homocysteine, vitamin B12, and betaine. In addition, subgroup analyses showed a significant increase in plasma folate and erythrocyte folate in the active form of folate supplementation group, specifically in subgroups with dosage ≥0.4 mg, intervention of the active form of folate supplementation versus the equimolar mass of folic acid, and intervention duration ≥12 weeks. CONCLUSION: Active form of folate supplementation might contribute to higher plasma folate, erythrocyte folate, and subsequent pregnancy rates, lower unmetabolized folic acid, and lower incidence of adverse pregnancy outcomes in women of childbearing age. Due to the limitation in the quality of involved stud

This prospective, randomized, double-blind, placebo-controlled trial investigated the efficacy and safety of thiamin and folic acid for cognitive impairment in maintenance hemodialysis (MHD) patients. A total of 215 MHD patients aged 18-75 with cognitive impairment were randomized to receive either oral thiamin (90 mg/day) plus folic acid (30 mg/day) or a placebo for 96 weeks. The primary endpoint was the change in the Alzheimer's Disease Assessment Scale-Cognitive section (ADAS-Cog) score. After 96 weeks, the treatment group showed a significant improvement in ADAS-Cog scores (from 21.25 ± 9.2 to 15.07 ± 8.38, p < 0.001), whereas the placebo group showed a non‑significant improvement (from 24.53 ± 11.01 to 26.53 ± 14.43, p = 0.077). The treatment group also demonstrated significantly increased blood levels of thiamin (from 5.59 ± 0.95 to 18.21 ± 3.91 ng/mL) and folate (from 12.37 ± 4.62 to 63.33 ± 16.02 ng/mL), and a reduction in homocysteine levels (from 4709.06 ± 353.15 to 2962.68 ± 158.87 ng/mL, p < 0.001), with no significant changes in the placebo group. While mortality was similar between the two groups (12.1% vs. 12.0%, p = 0.978), the incidence of adverse events was significantly lower in the treatment group (31.8% vs. 62.0%, p = 0.0017), particularly cardiovascular and cerebrovascular events (13.1% vs. 25.9%, p = 0.001). The study concludes that combined thiamin and folic acid supplementation improves cognitive function in MHD patients with a favorable safety profile.

Objective: To investigate the efficacy and safety of mFOLFOXIRI combined with bevacizumab plus cytoreductive surgery (CRS) in patients with resectable peritoneal metastasis of colorectal cancer (CRC). Methods: A single-center, prospective randomized controlled design was conducted. Inclusion criteria: confirmed synchronous or metachronous peritoneal metastasis of CRC, aged >18 years, adequate organ function and tolerance to chemotherapy, resectable peritoneal lesions with peritoneal cancer index (PCI) <20, Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1, and tolerance to CRS. Exclusion criteria: intolerance or inefficacy to oxaliplatin, distant unresectable metastasis, emergency surgery, active malignancy, history of thromboembolism, pregnancy or lactation, and other severe comorbidities. Between August 2022 and December 2024, eligible patients with resectable peritoneal metastasis of CRC treated at the Sixth Affiliated Hospital, Sun Yat-sen University were enrolled and randomly assigned at a 1:1 ratio to the neoadjuvant therapy group (mFOLFOXIRI plus bevacizumab followed by CRS) or the direct CRS group. The primary endpoint was the 1-year progression-free survival rate. Secondary endpoints included the response to neoadjuvant therapy, completeness of cytoreduction (CC) score, length of postoperative hospital stay, and postoperative complications. Results: A total of 53 patients who underwent surgery were included, with 19 in the neoadjuvant therapy group and 34 in the direct CRS group. There were no statistically significant differences between the two groups in age, sex, BMI, primary tumor location, pathological type, pattern of peritoneal metastasis (synchronous/metachronous), extraperitoneal metastasis, history of prior systemic therapy, baseline radiological PCI score, or tumor markers (CEA, CA19-9, CA125) (all P>0.05). In the neoadjuvant therapy group, post-treatment radiological PCI score was significantly lower than baseline [M(Q1,Q3): 6.0 (4.0, 12.0) vs. 8.0 (5.0, 12.0), Z=-3.086, P=0.002], and CEA was significantly reduced [3.9 (2.8, 7.3) μg/L vs. 7.7 (4.1, 16.1) μg/L, Z=-2.809, P=0.005]. Hemoglobin and albumin levels were als

Managing unresectable metastatic colorectal cancer (mCRC) requires a comprehensive strategy. While chemotherapy, anti-angiogenic, and anti-epidermal growth factor receptor (EGFR) agents are available, strategy trials are needed to optimize their use and sequencing. The STRATEGIC-1 phase III trial (NCT01910610) was designed to determine the optimal treatment sequence in patients with untreated, unresectable wild-type RAS/BRAFV600E mCRC. Patients were randomized (1:1) to FOLFIRI-cetuximab then mFOLFOX6-bevacizumab (arm A) or OPTIMOX-bevacizumab then FOLFIRI-bevacizumab followed by EGFR monoclonal antibody +/- irinotecan (arm B). The primary endpoint was the duration of disease control (DDC). Secondary endpoints were overall survival (OS), time to failure of strategy (TFS), progression-free survival (PFS), overall response rate (ORR), salvage surgery rate, safety, and health-related quality of life (HRQoL). Overall, 263 patients (arm A:131, arm B:132) were randomized. After 68.4 months of median follow-up (95% CI, 76.5-98.0), the median DDC was 22.8 months (95% CI, 20.4-28.8) in arm A and 23.5 months (95% CI, 17.9-26.3) in arm B (HR = 1.01, 95% CI, 0.76-1.34; log-rank P = 0.945). The median OS was 40.4 months (95% CI, 32.4-51.1) in arm A and 34.4 months (95% CI, 27.5-42.2) in arm B (HR = 1.30, 95% CI, 0.99-1.72). The ORR was higher in arm A (82.4% versus 65.4%) in the first-line group but not in the second-line group (20.7% versus 16.4%). Adverse events were consistent with the well-known safety profiles. STRATEGIC-1 did not meet its primary endpoint and was inconclusive in identifying the optimal treatment strategy in wild-type RAS/BRAFV600E mCRC. © 2026. The Author(s).

An adequate intake of folates is primarily dependent on the amount ingested, but also on the bioavailability of these water-soluble vitamins belonging to the vitamin B9 group. Therefore, we here present a human pilot study with a novel dual isotope design to assess the bioavailability of brewer's yeast folate as a model food. The particular advantage of the study design is the use of yeast intrinsically labeled with N-15, and a new reference folate specifically labeled with C-13. In this trial, 6 volunteers consumed (1) the intrinsically 15N-labeled yeast, (2) a 13C6-labeled (6S)-5-methyltetrahydrofolate as the reference dose and (3) a folate-free food on one of the three study days. On each study day, 21 plasma samples were taken and analyzed for three different isotopologues of (6S)-5-methyltetrahydrofolate using a 13C5-labeled (6S)-5-methyltetrahydrofolate as quantitation standard in stable isotope dilution assays. The main outcome of the study was that the yeast folates revealed for the five assessed volunteers a mean bioavailability of 74 % relative to 5-methyltetrahydrofolate as the reference dose. The study allows to conclude that intrinsically labeled foods are best suited to accurately measure the bioavailabilities of natural food folates embedded in their natural food matrix. © 2026 The Author(s). Molecular Nutrition & Food Research published by Wiley‐VCH GmbH.

BACKGROUND: Fortified bouillon cubes offer a scalable strategy to address micronutrient deficiencies in West Africa. However, success depends on household members' perceptions and acceptance. This study assessed changes in perception and acceptance of fortified bouillon cubes over time and explored factors influencing these outcomes among non-index household members (NIHMs) from trial households in Northern Ghana. METHODS: This longitudinal mixed-methods study was nested within a double-masked randomised controlled trial. Households received micronutrient-fortified bouillon cubes (vitamin A, vitamin B12, folic acid, iron, zinc, iodine) or control cubes (iodine only) for nine months. One NIHM (≥15 years) per household (n = 1,047) was enrolled. Structured interviews were conducted during early (months 1-2; n = 731) and late (months 7-9; n = 796) phases. Composite perception (8 items) and acceptance (10 items) scores (range: 1-5; higher scores = more positive perceptions/greater acceptance) were derived from an 18-item validated instrument. Bayesian linear mixed-effects models assessed temporal changes and associated individual and household factors. Twenty-four focus group discussions (months 4-5) explored drivers and barriers. RESULTS: Mean age of NIHMs was 40 ± 14.7 years; 59% were female. Perception scores increased over seven months, from 3.4 to 4.1 (adjusted posterior mean difference [aPMD] = 0.69; 95% credible interval [CrI]: 0.57, 0.81). Acceptance remained high (4.59 to 4.58; aPMD = -0.02; 95% CrI: -0.07, 0.03). No differences were observed between trial arms. At early timepoint, perception scores were lower among household heads compared with other household members, and lower among formal employees compared with farmers. Acceptance was higher among individuals from severely food-insecure households and lower among those from mildly food-insecure households. Focus groups revealed that perceived health benefits, sensory appeal, and cultural fit drove acceptance, while infertility-related myths and food colour changes were barriers. CONCLUSION: Fortified bouillon cubes were accepted, with perceptions improving over time. Public education will be essential t

BACKGROUND: This study aimed to determine the optimal second-line treatment strategy in patients with metastatic pancreatic cancer, hypothesizing that liposomal irinotecan (nal-IRI) combined with S-1 would be superior to nal-IRI with 5-fluorouracil (5-FU)/leucovorin (LV). METHODS: This was an international, multi-center, open-label, randomized phase I/II superiority trial. Patients with pancreatic adenocarcinoma, previously treated with gemcitabine-based treatment, were enrolled. Patients were randomly allocated to receive either nal-IRI plus S-1 (S-1 arm) or nal-IRI plus 5-FU/LV (5-FU arm). The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), (serious) adverse events (SAEs), response rate, and health-related quality of life. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using a Cox model. This trial is registered with ClinicalTrials.gov (NCT03986294) and is completed. RESULTS: Between November 10, 2021 and May 23, 2023, 120 patients were randomized to the S-1 arm (n = 61) or the 5-FU arm (n = 59). Three patients were excluded due to ineligibility. Median PFS was 2.2 months in the S-1 arm vs. 3.3 months in the 5-FU arm (HR 1.27; 95% CI 0.84-1.91, p = 0.26). Median OS was 6.0 months in the S-1 arm vs. 9.1 months in the 5-FU arm (HR 1.47; 95% CI 0.99-2.17, p = 0.054). The most common grade 3-4 AEs were diarrhea (13.8%) and nausea (10.3%) in the S-1 arm, and diarrhea (14.0%), asthenia and mucositis (both 7.0%) in the 5-FU arm. CONCLUSION: Second-line treatment with nal-IRI plus S-1 did not improve PFS and OS compared to nal-IRI plus 5-FU/LV in patients with metastatic pancreatic cancer following first-line gemcitabine-based chemotherapy.

IMPORTANCE: The poor prognosis and limited treatment options in patients with locally advanced pancreatic cancer (LAPC) highlight the need for novel therapies to increase survival. OBJECTIVE: To assess whether the addition of radiofrequency ablation (RFA) to chemotherapy improves survival when compared with chemotherapy only in patients with nonprogressive LAPC. DESIGN, SETTING, AND PARTICIPANTS: This international randomized clinical trial was performed from April 7, 2015, through December 6, 2022, in patients with unresectable LAPC with at least stable disease after 2 months of induction chemotherapy. The predefined study protocol reported a follow-up period of 18 months. Data analysis was performed from February 1, 2024, through January 15, 2025. INTERVENTION: Randomization to receive either RFA with chemotherapy or chemotherapy alone. MAIN OUTCOMES AND MEASURES: Primary outcome was overall survival. Secondary outcomes included progression-free survival, adverse events, and quality of life using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire and pancreatic cancer module. RESULTS: Overall, 188 patients (median [IQR] age, 65 [57-70] years; 100 [53%] men) were randomized, 95 to RFA with chemotherapy and 93 to chemotherapy only. Before randomization, induction chemotherapy had consisted of modified FOLFIRINOX (fluorouracil, oxaliplatin, irinotecan, and leucovorin) in 81 patients (85%) and a gemcitabine-based regimen in 14 patients (15%) in the RFA group vs 80 patients (86%) and 13 patients (14%) in the chemotherapy group, respectively. After a median follow-up of 55 months, median overall survival from randomization was 12.1 months (95% CI, 9.9-14.3 months) in the RFA group vs 11.6 months (95% CI, 9.4-13.9 months) in the chemotherapy group (hazard ratio, 1.07; 95% CI, 0.80-1.45; P = .64). Median progression-free survival was 5.8 months (95% CI, 4.4-7.2 months) in the RFA group and 6.9 months (95% CI, 5.3-8.5 months) in the chemotherapy group (P = .47). Grade 3 or higher serious adverse events were reported more often in the RFA group: 26 patients (27%) vs 10 patients (11%) (P = .004). Mean changes from baseline of -14

BACKGROUND: Fluoropyrimidines + angiogenesis inhibitor or dose-reduced doublets are used for (frail) elderly patients with metastatic colorectal cancer (mCRC). This non-comparative trial evaluated two 1st line regimens for patients not eligible for full-dose combinations. METHODS: This open-label, multicenter, phase II study randomized untreated mCRC patients ≥ 70 years ± frailty 1:1 to dose reduced mFOLFOX7 in Arm A or aflibercept (4 mg/kg) plus dose reduced mLV5FU2 in Arm B. Primary endpoint was the 6-months PFS rate (PFS@6), secondary endpoints included safety, overall survival (OS), overall response rate (ORR), patient reported outcomes and overall treatment utility (OTU). FINDINGS: The full analysis population comprised 120 patients (62 Arm A, 58 Arm B; 63% male), with a median age of 78.5 years. 82% frail patients were included. PFS@6 was 68% [95%CI 56%;80%] in Arm A and 46% [32%;59%] in Arm B. Median PFS was 7.9 and 5.5 months, median OS was 20.4 and 19.0 months and ORR was 47% and 22% in Arm A and B, respectively. At 3 months, 52% in Arm A and 35% in Arm B had a good OTU. Most frequent grade ≥ 3 AEs in Arm B were hypertension (41%) and proteinuria (10%). More patients in arm B had treatment-related SAEs grade ≥ 3 (17% in arm B and 5% in arm A). INTERPRETATION: Both regimens were feasible in this (frail) elderly population. Dose-reduced mFOLFOX7 and, to a lesser extent, 5-FU/aflibercept showed good PFS and 3-month OTU. Although most patients were regarded frail, survival rates were promising, most likely due to effective further-line treatments.

BACKGROUND: FOLFOXIRI plus bevacizumab improved efficacies and increased some adverse events in untreated metastatic colorectal cancer (mCRC), compared with the doublet plus bevacizumab. The clinical outcomes of ramucirumab (RAM) in combination with FOLFIRI or FOLFOXIRI as a first-line treatment are unknown. In this randomized phase II study (WJOG9216G), we compared the efficacy and safety of these regimens to determine which is more promising. METHODS: Patients with untreated mCRC were randomly assigned to the FOLFIRI-RAM or FOLFOXIRI-RAM arms. The primary endpoint was a confirmed objective response rate (ORR), and secondary endpoints included early tumor shrinkage (ETS), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: In total, 122 patients were randomized. The confirmed ORR was 59.3% and 60.3% in the FOLFIRI-RAM and FOLFOXIRI-RAM arms, respectively (odds ratio 1.04; P = 0.91). With a median follow-up period of 42.1 and 40.4 months, PFS was comparable between the FOLFIRI-RAM and FOLFOXIRI-RAM arms (median, 11.5 and 10.5 months). ETS rate (71.2% and 52.4%) and OS (median, 32.6 and 28.2 months) were significantly better in the FOLFIRI-RAM arm than in the FOLFOXIRI-RAM arm. The major grade ≥ 3 adverse events in the FOLFIRI-RAM and FOLFOXIRI-RAM arms were neutropenia (44.1% and 72.6%), anorexia (3.4% and 14.5%), and febrile neutropenia (3.4% and 11.3%). CONCLUSIONS: FOLFOXIRI plus RAM was not superior to FOLFIRI plus RAM in terms of efficacy, including ORR, in patients with untreated mCRC. Instead, first-line FOLFIRI plus RAM showed clinical efficacy and safety profiles comparable to those of doublet chemotherapy plus bevacizumab.

BACKGROUND: Standard adjuvant chemotherapy for stage III colon cancer consists of a fluoropyrimidine-plus-oxaliplatin regimen. Whether the addition of atezolizumab (an anti-programmed death ligand 1 agent) to a modified FOLFOX6 regimen (fluorouracil, oxaliplatin, and leucovorin; called mFOLFOX6) would improve outcomes in patients with stage III colon cancer with mismatch repair-deficient (dMMR) status is unclear. METHODS: In a phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with resected stage III dMMR tumors to receive either adjuvant atezolizumab plus mFOLFOX6 for 6 months, with atezolizumab continued as monotherapy (for a total of 12 months of therapy), or mFOLFOX6 alone for 6 months. The primary end point was disease-free survival. Secondary end points were overall survival and the adverse-event profile. RESULTS: A total of 355 patients were assigned to receive atezolizumab plus mFOLFOX6 and 357 to receive mFOLFOX6 alone. The median age of the patients was 64 years, 55.1% were women, and 53.9% had tumors that were T4, N2, or both (indicating high risk). At a median follow-up of 40.9 months, the 3-year disease-free survival was 86.3% (95% confidence interval [CI], 81.8 to 89.8) in the atezolizumab-mFOLFOX6 group, as compared with 76.2% (95% CI, 70.9 to 80.6) in the mFOLFOX6 group (hazard ratio for disease recurrence or death, 0.50; 95% CI, 0.35 to 0.73; P<0.001). Adverse events of grade 3 or 4 occurred in 84.1% of the patients who received atezolizumab plus mFOLFOX6 and in 71.9% of those who received mFOLFOX6 alone. CONCLUSIONS: The addition of atezolizumab to mFOLFOX6 significantly improved disease-free survival among patients with stage III dMMR colon cancer. (Funded by the National Cancer Institute of the National Institutes of Health and Genentech; ATOMIC ClinicalTrials.gov number, NCT02912559.).

RATIONALE: Non-small cell lung cancer (NSCLC) continues to impose a significant global mortality burden, due to limited therapies, drug resistance, and treatment-related toxicity. Exosomes offer promise for the targeted delivery of therapeutic agents. METHODS: Exosomes were isolated from bovine colostrum and characterized for size, polydispersity index, and surface charge. Celastrol (CEL) was loaded onto exosomes (ExoCEL), and Folic Acid (FA)-functionalized exosomes (FA-ExoCEL) and validated using fluorescence quenching and protease sensitivity assay. Anticancer activity was assessed in NSCLC cell lines using colony formation, cell migration and uptake assays. Transcriptomic (RNA-seq) and protein analysis were performed to analyze gene expression changes. Biodistribution, oral uptake and potential toxicity were evaluated in wild-type mice, while oral antitumor efficacy was tested in orthotopic lung tumor models comparing CEL, ExoCEL and FA-ExoCEL. Synergistic activity with paclitaxel was assessed in chemoresistant cells. RESULTS: Exosomes were isolated, characterized and efficiently loaded with CEL. ExoCEL demonstrated superior antiproliferative effects in NSCLC cell lines and enhanced potency in drug-resistant A549TR cells compared to free CEL. ExoCEL significantly inhibited colony formation and cell migration in a dose-dependent manner. RNA Seq and protein analyses showed that CEL and ExoCEL reversed TGF-β-induced EMT, restored epithelial markers, suppressed mesenchymal, oncogenic and extracellular matrix related markers. In orthotopic lung tumor models, FA-ExoCEL achieved approximately 80-90% tumor inhibition, outperforming both free CEL and ExoCEL. Oral delivery of FA-ExoCEL resulted in efficient gastrointestinal uptake, selective tumor targeting, recovery of exosomal markers in circulation and no observed systemic toxicity. CEL exhibited strong synergy with paclitaxel, with exosomal delivery further enhancing paclitaxel efficacy in resistant cells. CONCLUSIONS: FA-ExoCEL represents a safe, scalable, and effective oral therapeutic strategy for NSCLC. By combining exosome-mediated delivery with folate-targeted tumor accumulation, this platform enhances CEL bi

BACKGROUND/AIM: Colorectal cancer (CRC) continues to pose substantial clinical challenges owing to the limited response and emergent resistance to standard chemotherapeutic regimens, including FOLFOX. The present investigation explored the antitumor efficacy of JI-CJ002, a standardized herbal formula consisting of Angelica gigas, Aconitum carmichaeli, and Zingiber officinale (2:1:3 ratio), and its combined effects with FOLFOX in in vitro settings. MATERIALS AND METHODS: Cytotoxic activities were assessed in HT29 and HCT116 human colorectal cancer cell lines by conducting MTT assays, Annexin V/7-AAD staining, and western blotting. Network pharmacology techniques were employed to identify common targets among JI-CJ002, FOLFOX, and CRC-associated gene profiles. RESULTS: JI-CJ002 exhibited broad-spectrum cytotoxicity that was both time- and dose-dependent in HT29 and HCT116 cell lines. Network analysis identified 89 common targets predominantly involved in DNA repair, apoptosis, and chemoresistance pathways. The combination treatment led to a significant, synergistic reduction in cell viability and elevated apoptotic markers, including Annexin V/7-AAD positivity and cleaved PARP. Mechanistically, co-treatment inhibited ATM, ATR, p-CHK1, p-CHK2, p-Cdc2, and p-p53, while sustaining γ-H2AX accumulation, signifying persistent DNA damage and inadequate activation of cell cycle arrest checkpoints. Immunofluorescence revealed a further increase in γ-H2AX nuclear foci. CONCLUSION: JI-CJ002 augments the therapeutic effect of FOLFOX by suppressing DNA damage response and inducing aberrant cell cycle progression, thereby supporting its development as a chemo-sensitizing agent for colorectal cancer therapy.

Globally and within Egypt, obesity fuels a growing health crisis, demanding novel therapeutic approaches rooted in systems medicine. This framework promotes the classification of diseases based on causal molecular mechanisms and use multi-target interventions to achieve synergistic effects within these pathways. Our previous research identified a dysregulated interaction among fatty acid synthase (FASN), arginase (ARG), and endothelial nitric oxide synthase (eNOS) as a potential mechanistic driver of obesity and its sequelae. To address this, we designed a targeted therapeutic approach targeting malfunctioning at this dysfunctional FASN/ARG/eNOS network to enhance outcomes in obesity-related cardiovascular complications. We induced obesity in rats using a high-fructose, high-salt diet for 10 weeks, then randomized them into six groups: control, obese, and four obese treatment arms receiving orlistat (FASN inhibitor), norvaline (ARG inhibitor), citrulline/folic acid (eNOS recoupling), or their combination for 5 weeks. Although individual treatments offered benefits - orlistat reducing adiposity and improving some metabolic and cardiac markers, norvaline improving blood pressure (BP) and glycemic control, and citrulline/folic acid enhancing antioxidant defense and vascular function - the combined intervention yielded a striking synergistic effect. This multi-pronged approach most effectively reduced adiposity, normalized key metabolic parameters, conferred robust protection against cardiac remodeling (both structural and functional), significantly improved BP regulation, and modulated cardiac oxidative stress and inflammation. Our findings strongly indicate that simultaneously targeting the FASN/ARG/eNOS axis with mechanism-based therapies represents a novel and highly promising approach to comprehensively mitigate obesity and its devastating cardiovascular consequences.

Methotrexate is an antifolate agent used for the treatment of various malignancies and is mainly secreted via human organic anion transporter 3 (hOAT3) in the proximal tubular cells. Coadministration of the xanthine oxidase inhibitor, febuxostat, in patients receiving methotrexate has been reported to be associated with an elevated risk of hematological toxicity and increased plasma methotrexate levels. Because febuxostat has an inhibitory effect against hOAT3, it may inhibit renal elimination of methotrexate via hOAT3. However, the drug interaction between methotrexate and febuxostat via hOAT3 remains to be clarified. In the present study, we investigated the effect of febuxostat on pharmacokinetics of methotrexate in rats and drug interaction between methotrexate and febuxostat using hOAT3-expressing cultured cells. In the pharmacokinetics study using rats, concomitant administration of febuxostat significantly increased plasma concentration of methotrexate and prolonged its half-life. In vitro studies showed that febuxostat inhibited hOAT3-mediated transport of methotrexate in a concentration-dependent manner. Dixon plot indicated that inhibitory constant value of febuxostat against methotrexate transport via hOAT3 was 0.63 ± 0.01 μM. Moreover, the inhibitory effect of febuxostat was of noncompetitive type. Taken together, these results suggest that concomitant administration of febuxostat delayed elimination of methotrexate, at least in part, by noncompetitive inhibition of hOAT3-mediated methotrexate transport at clinical concentrations. The findings of this study provide novel information on drug interactions associated with febuxostat. © 2025 The Author(s). Biopharmaceutics & Drug Disposition published by John Wiley & Sons Ltd.

PURPOSE: To address celastrol(Ce)'s efficacy and toxicity challenges in breast cancer, we first developed a carrier-free, self-targeting nanosystem with synergistic anti-tumor action by leveraging methotrexate (MTX)'s intrinsic folate moiety for active tumor targeting. METHODS: Ce-MTX nanoparticles (NPs) were prepared using a solvent precipitation method, with formulation parameters optimized. Characterization included particle size, polydispersity index (PDI), encapsulation efficiency (EE), loading efficiency (LE), and TEM. Drug release was investigated under physiological and tumor-mimetic conditions via a dialysis method. Cellular uptake and in vitro anti-tumor effects were evaluated in A549 and 4T1 cell lines. In vivo, tumor distribution and normal tissue accumulation were analyzed in 4T1 tumor-bearing mice. Anti-tumor efficacy and biosafety were evaluated through tumor growth curves, tumor inhibition rates, body weight changes, organ indices, histological analysis, and serum biochemistry. RESULTS: The optimized Ce-MTX NPs exhibited a particle size of 90.20 nm, PDI of 0.062, and spherical morphology. The EE and LE were 95.15% and 66.53% for Ce, and 95.74% and 33.6% for MTX, respectively. The NPs demonstrated excellent stability over 7 days. Notably, Ce-MTX NPs exhibited pH-dependent drug release, with accelerated release at pH 5.5. Qualitative and quantitative cellular uptake assays revealed significantly higher uptake of Ce-MTX NPs compared to the free drugs, with enhanced folate receptor-targeting in 4T1 cells. Cytotoxicity assays showed stronger anti-tumor activity of Ce-MTX NPs in 4T1 cells compared to the free drug mixture, thus demonstrating the superior synergistic anti-cancer effects achieved by the nanoparticle formulation. Importantly, in vivo studies confirmed substantial tumor growth inhibition and an excellent biosafety profile. CONCLUSION: The carrier-free Ce-MTX NPs demonstrated enhanced stability, tumor targeting, and rapid drug release within tumor cells, significantly improving the efficacy and biosafety of breast tumor treatment. These nanoparticles offer a promising strategy for combined cancer therapy and hold great potential for further

BACKGROUND: The potential of marine algae as a source of antibacterial chemicals has been very promising. Numerous bioactive compounds produced by these organisms can fight off harmful microorganisms. Two marine algae (Chlorophyta: Ulva lactuca, Rhodophyta: Pterocladiella capillacea) were screened for their antibacterial activity against distinct multidrug-resistant bacteria Klebsiella pneumoniae. This efficiency is ascribed to the bioactive substances found in these algae, which have the ability to stop the growth of this harmful bacteria. Pterocladiella capillacea is a viable target for the development of novel antibacterial medications since its chemicals function by interfering with bacterial processes. RESULTS: A mixture of (U. lactuca + P. capillacea. + Nitrofurantoin) increased the inhibition zone on K. pneumoniae by 100%. Our docking findings demonstrated that benzo[h]quinoline, 2, 4-dimethyl-, and 4, 4'-Bis [4-methyl-2-pyrimidylsulfamido] terephthalanilide have a high affinity (-10 and - 11 respectively) to dock with the cell wall proteins of Klebsiella pneumoniae. It can cause cell lysis and death by interfering with the integrity of bacterial cell walls. Furthermore, it may disrupt DNA replication and vital bacterial enzymes. The molecule 4, 4'-Bis [4-methyl-2-pyrimidylsulfamido] terephthalanilide is a member of the sulfonamide class, which is well-known for its broad-spectrum antibacterial properties. This compound's capacity to prevent bacteria from synthesizing folic acid is the main source of its antibacterial action. Bacterial cell division and DNA synthesis depend on folic acid. The substance successfully stops bacterial growth and multiplication by blocking this pathway. CONCLUSION: These two substances are interesting candidates for the development of novel antimicrobial drugs due to their efficacy against strains of bacteria that are resistant to antibiotics. © 2025. The Author(s).

Reactive oxygen species (ROS) generated by cold atmospheric plasma (CAP) cause irreversible damage to cancer cell DNA, RNA, mitochondria, and antioxidant defense systems, leading to apoptosis. Plasma-induced disruption of the antioxidant defense system of cancer cells by cystine uptake via xC- antiporter has been widely studied, while folate uptake by cancer cells via high expression of hSLC19A1, which generates Nicotinamide Adenine Dinucleotide Phosphate (NADPH) via one-carbon metabolism, is also an important component of the antioxidant defense mechanism of cancer cells. Disrupting folate transport in cancer cells is an important potential pathway for synergizing with pemetrexed (PMX) to induce apoptosis in cancer cells, which is of great research value. In this paper, classical molecular dynamics simulations were employed to study the effect of plasma oxidation of hSLC19A1 on the uptake of 5-Methyltetrahydrofolate (5-MTHF), which is the predominant dietary and circulatory folate, and the antifolate chemotherapeutic agent PMX by cancer cells. The results showed that the channel radius of hSLC19A1 for transporting 5MTHF after oxidation became narrower and the conformation tended to be closed, which was unfavorable for the transport of 5-MTHF; hydrogen bonding and hydrophobic interactions between hSLC19A1 and 5-MTHF decreased, the predicted docking affinity decreased, and the binding energy decreased from -28.023 kcal/mol to -16.866 kcal/mol, while that with PMX was stable around -28 kcal/mol, suggesting that the oxidative modification reduced the binding capacity of hSLC19A1 and 5-MTHF while barely affecting the transport of PMX, which contributed to weakening the antioxidant defense system of cancer cells and synergizing with PMX to induce apoptosis in cancer cells. Our simulations provide theoretical insights for CAP-induced apoptosis in cancer cells at the microscopic level and help promote the further development of cold atmospheric plasma in the field of cancer therapy.

Peptidoglycan (PG) is an important bacterial macromolecule that confers cell shape and structural integrity, and is a key antibiotic target. Its synthesis and turnover are carefully coordinated with other cellular processes and pathways. Despite established connections between the biosynthesis of PG and the outer membrane, or PG and DNA replication, links between PG and folate metabolism remain comparatively unexplored. Folate is an essential cofactor for bacterial growth and is required for the synthesis of many important metabolites. Here we show that inhibition of folate synthesis in the important Gram-negative pathogen Pseudomonas aeruginosa has downstream effects on PG metabolism and integrity that can manifest as the formation of a subpopulation of round cells that can undergo explosive lysis. Folate inhibitors potentiated β-lactams by perturbation of PG recycling, reducing expression of the AmpC β-lactamase. Supporting this mechanism, folate inhibitors also synergized with fosfomycin, an inhibitor of MurA, the first committed step in PG synthesis that can be bypassed by PG recycling. These insights led to the design of a dual-active inhibitor that overcomes NDM-1 metallo-β lactamase-mediated meropenem resistance and synergizes with the folate inhibitor, trimethoprim. We show that folate and PG metabolism are intimately connected, and targeting this connection can overcome antibiotic resistance in Gram-negative pathogens. IMPORTANCE: To combat the alarming global increase in superbugs amid the simultaneous scarcity of new drugs, we can create synergistic combinations of currently available antibiotics or chimeric molecules with dual activities, to minimize resistance. Here we show that older anti-folate drugs synergize with specific cell wall biosynthesis inhibitors to kill the priority pathogen, Pseudomonas aeruginosa. Anti-folate drugs caused a dose-dependent loss of rod cell shape followed by explosive lysis, and synergized with β-lactams that target D,D-carboxypeptidases required to tailor the cell wall. Anti-folates impaired cell wall recycling and subsequent downstream expression of the chromosomally encoded β-lactamase, AmpC, which normally destroys

Diabetic cognitive dysfunction (DCD) refers to the cognitive impairment observed in individuals with diabetes. Epidemiological studies have suggested that supplementation with n-3 polyunsaturated fatty acid (PUFA) or B vitamins may prevent the development of diabetic complications. Post hoc studies indicate a potential synergistic effect of n-3 PUFA and B vitamins in preventing cognitive impairment. However, the precise effect and underlying mechanism of this combination on DCD remain unclear. In case-control study, we compared fatty acid composition of erythrocyte membrane and serum homocysteine levels between diabetic individuals with and without DCD. We found that insufficient levels of n-3 PUFA, along with elevated serum homocysteine, significantly increase the risk of developing DCD. Treatment with a combination of fish oil, folate, and vitamin B12 improved cognitive impairment and aberrant neuronal morphology in streptozotocin-induced DCD mice. Folic acid and vitamin B12 enhanced the efficiency of exogenous docosahexaenoic acid (DHA) transportation to the brain by preventing the accumulation of homocysteine and S-adenosylhomocysteine, thereby inhibiting neuronal apoptosis in diabetic brains. Furthermore, folic acid and vitamin B12 supplementation can provide sufficient 5-methylcytosine for diabetic brains by promoting DNA methylation, while increased DHA levels maintain TET-mediated active DNA demethylation in diabetic brains through enhancing TET2 function. Overall, our study provides novel insights into molecular mechanisms underlying the synergistic preventive effects of the combined supplementation with fish oil, folic acid and vitamin B12 on DCD, suggests that combining n-3 PUFA and B vitamins could be a promising strategy for preventing DCD among individuals with diabetes.

Green tea (Camellia sinensis) is a commonly consumed beverage or dietary supplement. As a natural product with a myriad of proposed health benefits, patients are likely to consume green tea while taking their medications unaware of its potential to interact with drugs and influence drug efficacy and safety. Catechins are the abundant polyphenolic compounds in green tea (e.g., (-)-epigallocatechin-3-gallate), which are reported to influence determinants of drug pharmacokinetics, such as drug solubility and the activity of drug transporters and drug metabolizing enzymes. This review summarized the results of clinical studies investigating the influence of green tea catechins on the pharmacokinetics of clinically used medications. The majority of analyses (72%) reported significant decreases (by 18-99%) in systemic drug exposure with green tea consumption (atorvastatin, celiprolol, digoxin, fexofenadine, folic acid, lisinopril, nadolol, nintedanib, raloxifene, and rosuvastatin). One analysis (6%) reported a 50% increase in drug systemic exposure (sildenafil) and for 22% of analyses drug pharmacokinetics were not affected by green tea consumption (fluvastatin, pseudoephedrine, simvastatin, and tamoxifen). For most drugs reporting an interaction, green tea catechins were proposed to decrease intestinal drug absorption by inhibiting OATP uptake (particularly OATP1A2), enhancing P-gp efflux activity or reducing drug solubility. Case reports have associated changes in drug pharmacokinetics with green tea consumption to changes in drug efficacy or safety (e.g., nadolol and erlotinib). These findings prompt the need for further research in relating evidence from existing literature to predict additional clinically important green tea-drug interactions and to provide appropriate recommendations for patients and clinicians. © 2025 The Author(s). Clinical Pharmacology & Therapeutics © 2025 American Society for Clinical Pharmacology and Therapeutics.

PURPOSE: Folic acid (vitamin B9) plays a vital role in DNA synthesis, repair, and methylation, supporting both normal cellular functions and the proliferation of cancer cells. This review aims to explore the complex interplay between folic acid metabolism, antifolate chemotherapy (particularly methotrexate), and chemotherapy-induced malabsorption, with an emphasis on the need for nutritional interventions. METHODS: A comprehensive literature review was conducted using databases such as PubMed, Scopus, and Google Scholar to identify studies addressing folic acid deficiency, chemotherapy-related malabsorption, methotrexate toxicity, and nutritional support strategies in cancer patients. RESULTS: Evidence indicates that methotrexate-induced inhibition of dihydrofolate reductase disrupts folate pathways, contributing to folic acid deficiency and malabsorption syndromes. This can lead to clinical complications such as anaemia, mucositis, immune suppression, and reduced treatment tolerance. Nutritional deficiencies further exacerbate drug toxicity and impair patient outcomes. While folic acid supplementation has shown benefit in reducing toxicity, its dosing must be carefully managed to avoid interference with chemotherapeutic efficacy. CONCLUSION: Folic acid deficiency and malabsorption are significant concerns in cancer therapy involving antifolate drugs. Targeted nutritional strategies, including judicious folic acid supplementation, are essential to improving patient outcomes and minimizing treatment-associated complications. Future clinical approaches should integrate personalized nutritional support alongside chemotherapy regimens. © 2026. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Iron-deficiency anemia is the most common micronutrient deficiency and a leading cause of disability-adjusted life years among adolescent girls and young women (AGYW) globally. Although multiple micronutrient supplementation (MMS) provides a broader range of micronutrients than iron-folic acid supplementation (IFAS) prior to conception, the acceptability of MMS and home-based supplementation strategies remains underexplored. We assessed the acceptability of MMS, IFAS, and a contextualized nutrition curriculum delivered via school clubs in a two-arm cluster-randomized trial across three rural secondary schools in Monapo District, Mozambique. Fourteen teachers (clusters) were randomized to deliver either weekly school-based IFAS or daily home-based MMS. A total of 492 AGYW aged 13-20 years were enrolled (240 IFAS; 252 MMS); both arms received the same nutrition curriculum. Participants in both arms reported increased energy, improved appetite, and relief from menstrual symptoms. IFAS was significantly more acceptable than MMS for smell, and some participants perceived the once-weekly IFAS regimen as less burdensome than daily MMS. Some AGYW also reported that male peers perceived MMS as birth control, or assumed the girls were pregnant, due to the image of a pregnant woman on the pill bottle. Ratings of the nutrition curriculum and teachers' facilitation were positive in both arms. Participants generally preferred the regimen they were assigned, and family support facilitated adherence. These findings suggest home-based supplementation may be a feasible and acceptable strategy for reaching in-school and out-of-school AGYW in Mozambique. Including boys in future interventions and redesigning the MMS label could help reduce misconceptions and enhance acceptability. © 2026 The Author(s). Maternal & Child Nutrition published by John Wiley & Sons Ltd.

Spina bifida (SB) is a neurodevelopmental disorder characterised by the incomplete closure of the embryonic neural tube, resulting in a neural tube defect (NTD) that affects the development of the spine and spinal cord. Both genetic and non-genetic factors contribute to the occurrence of SB, including deficiencies in folic acid and vitamin B12, maternal obesity, smoking, epilepsy, alcohol consumption, drug use, and a history of previous pregnancies affected by SB. Complications associated with SB include meningitis, hydrocephalus, neonatal paralysis, and urinary or faecal incontinence. Considerable advancements have been made in raising awareness, improving diagnostic capabilities, and establishing specialised clinics and multidisciplinary teams (MDTs) dedicated to SB management. However, several gaps persist in its management. These include inadequate awareness and education among healthcare professionals, limited access to healthcare services, a scarcity of surgical workforce and MDTs, social stigma and discrimination, and research and data accessibility gaps. The implications of these management gaps in SB care encompass diminished quality of life, increased morbidity and mortality rates, and economic consequences related to surgical management. To improve SB management outcomes in Africa, strategic interventions should focus on enhancing healthcare infrastructure and resources, strengthening education and awareness programs for SB prevention and support, addressing cultural concerns, improving neonatal surgical care, and enhancing research and guidelines. By addressing these gaps through targeted, equity-focused interventions in healthcare infrastructure, education, cultural adaptation, neonatal surgical care, research, and policy, substantial improvements can be made in SB care and outcomes in Africa, reducing the disproportionate burden of disability in low-resource settings. © The Author(s) 2026.

Background Nutritional deficiencies persist as a major public health challenge in India alongside a rising non-communicable disease burden. The Center for Nutritional Health at AIIMS Mangalagiri provides comprehensive nutritional services including counseling, anthropometric assessment, and laboratory diagnosis of key deficiencies. We aimed to determine the prevalence of anemia, vitamin D and vitamin B12 deficiencies, and malnutrition (underweight and overweight/obesity); examine gender-based differences in nutritional parameters; identify patterns of multiple concurrent deficiencies; and analyze their age-wise distribution among patients attending the center, to inform targeted intervention strategies. Methodology We conducted a cross-sectional study using retrospective clinical data from 2,303 patients attending the Center for Nutritional Health at AIIMS Mangalagiri over 30 months. Demographic, anthropometric, hemoglobin, 25-hydroxyvitamin D (25(OH)D), vitamin B12, calcium, and 24-hour dietary recall data were obtained from routine clinical records. Deficiencies were defined using World Health Organization (WHO) anemia criteria, standard international vitamin reference ranges, and Asian-specific body mass index (BMI) cutoffs. Analyses included Pearson chi-square, Mann-Whitney U, Spearman rank correlation, and multivariable binary logistic regression. Results Among 2,303 participants (1,681 women (73.0%); mean age, 42.4 ± 13.9 years), anemia affected 1,195 of those tested (74.2%), of whom 764 (47.5%) had moderate-to-severe anemia. Vitamin D deficiency (<20 ng/mL) was present in 658 participants (59.5%), vitamin B12 deficiency in 250 (41.9%), overweight/obesity in 1,240 (78.0%), and underweight in 88 (5.5%). Women had higher odds of anemia (OR, 3.64; 95% CI, 2.83-4.68; P < 0.001) and suboptimal vitamin D status (insufficient/deficient, <30 ng/mL vs. sufficient, ≥30 ng/mL) (OR, 2.11; 95% CI, 1.17-3.81; P = 0.018). Multivariable regression identified female sex (adjusted OR, 1.60; 95% CI, 1.16-2.21; P = 0.004) and younger age (adjusted OR, 0.98 per year; 95% CI, 0.97-0.99; P = 0.001) as independent predictors of vitamin D deficiency (<20 ng/mL). Multiple concurren

INTRODUCTION: Anaemia remains a major public health concern among Indian adolescents, particularly girls. National-level and state-level initiatives led by the Government of India, such as the Weekly Iron and Folic Acid Supplementation, Anaemia Mukt Bharat and the Intensified National Iron Plus Initiative, aim to control iron-deficiency anaemia through systematic supplementation and behaviour change communication strategies. However, implementation challenges persist. Given the limited evidence on barriers, facilitators and interventions implemented to improve the outlined national schemes, we have designed a systematic review to inform future research and programmes. This review aims to systematically identify and synthesise evidence on barriers and facilitators influencing the implementation of national iron and folic acid supplementation programmes targeting adolescents aged 10-19 years in India. METHODS AND ANALYSIS: A comprehensive search will be conducted using five databases, namely PubMed, EMBASE, Web of Science, CINHAL and Scopus, from inception to 30 September 2025. To capture grey literature, we will also search government portals, international agency repositories, clinical trial registries and the Google platform. Eligible studies include experimental, observational, qualitative and implementation research conducted in school-based, community-based or combined delivery settings. Screening, data extraction and quality appraisal will be performed independently by two reviewers using the Covidence platform. The Joanna Briggs Institute tool will be used to assess methodological quality of included studies. Quantitative data will be synthesised descriptively following the Synthesis Without Meta-analysis guidelines, and qualitative data will be analysed using thematic synthesis. ETHICS AND DISSEMINATION: Ethical approval is not required as there is no human participation. The results will be published in a peer-reviewed journal and presented at scientific conferences. PROSPERO REGISTRATION NUMBER: CRD420251153248. © Author(s) (or their employer(s)) 2026. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ G

INTRODUCTION: Tubulointerstitial fibrosis represents the final common pathway to kidney failure, with tubular epithelial cell (TEC) injury playing a critical role. Current methods for assessing TEC injury rely on invasive biopsies or lack temporal resolution, limiting real-time monitoring of disease progression and therapeutic responses. METHODS: Near-infrared (NIR) autofluorescence was evaluated for non-invasive TEC injury assessment in three mouse models: unilateral ureteral obstruction (UUO; consistent tubulointerstitial injury), folic acid nephropathy (variable injury severity), and unilateral ischemia-reperfusion injury (IRI; acute tubular injury), without exogenous probes. Mechanistic studies used BALB/c-Cpoxnct mice, which harbor a spontaneous missense mutation reducing coproporphyrinogen oxidase activity, an enzyme that metabolizes coproporphyrinogen III in heme biosynthesis. Kidney slice cultures were treated with the mitochondrial complex III inhibitor antimycin A or the mitochondrial reactive oxygen species scavenger MitoTEMPO. Human kidney samples (non-cancerous region of nephrectomies) were examined ex vivo. RESULTS: NIR autofluorescence correlated with TEC injury, oxidative stress markers, and fibrosis across all three models. Spectroscopic analysis identified coproporphyrin III as the likely primary fluorophore. Cpox mRNA and CPOX protein were consistently reduced in injured kidneys. CPOX was expressed in proximal tubules and lost in damaged cells. BALB/c-Cpoxnct mice showed elevated baseline autofluorescence, which increased further after UUO, with HPLC confirming accumulation of the porphyrin metabolite coproporphyrin III. In kidney slice cultures, antimycin A reduced CPOX protein and enhanced autofluorescence; MitoTEMPO reversed both effects. To test whether autofluorescence can track therapeutic responses, finerenone (non-steroidal, mineralocorticoid receptor antagonist) was administered in UUO and bilateral IRI models; treated mice showed reduced autofluorescence that correlated with improved histology. In 34 human samples, autofluorescence correlated inversely with eGFR and positively with periodic acid-Schiff stain injury scores. CONCLUSION

BACKGROUND: Government of India launched Anemia Mukt Bharat (AMB) program in 2018. Despite its implementation, the prevalence of anemia remains high. To address the gaps in coverage, adherence and effective implementation, the Indian Council of Medical Research (ICMR) initiated the Precision driven Response for Anemia Control and Sustainable Health (PRAKASH) study. It is an implementation research study aimed at co-developing and optimizing a district-level model of evidence-based anemia control interventions. The intended goal is to reduce anemia prevalence to 20% or lower through scalable, context-specific, and sustainable strategies. METHODS: This multi-site study targets six key population groups: children (aged 6-59 months and 5-9 years), adolescents boys and girls (10-19 years), women of reproductive age (20-49 years) and pregnant women. Interventions are anchored in six pillar i. Test-Treat-Track until resolution, ii. prophylactic iron and folic acid supplementation, ensuring high complianceiii. anemia-relevant health interventions, iv. fortified rice distribution, v. dietary diversification and promotion of iron-rich foods, and vi. behavior change communication through Jan Andolan. Anemia prevalence will be estimated through a series of community-based cross-sectional surveys. Mixed methods approach will be employed to assess barriers and enablers at the individual, household, facility, and community levels. The study will utilize implementation science frameworks, including Consolidated Framework for Implementation Research (CFIR) and Expert Recommendations for Implementing Change (ERIC), to guide iterative implementation, real-time model refinement, and monitoring of performance. Information on outcome indicators will be collected to evaluate anemia prevalence, fidelity, feasibility, and service delivery improvements. CONCLUSION: The study will try to readdress the implementation challenges across diverse regions and aims to develop a comprehensive and replicable model for the AMB 2.0 program. The study is likely to contribute to the global evidence base on implementation science for anemia reduction in low- and middle-income countries. Copyright: © 2

BACKGROUND: Inadequate nutrition of the dams, even if recognized as a possible cause of infertility, it is usually underestimated during the common diagnostical procedures (i.e., clinical examination, vaginal cytology, ultrasound, blood and urine analysis). Although the diet may meet adult maintenance requirements, several nutrients can be suboptimal during the pre-gestation period and may influence reproductive performance. This case report describes the use of an oral supplement to increase fertility in a German Sheperd breeding center experiencing prolonged secondary anoestrus. CASE PRESENTATION: Fifteen German Shepherd bitches with secondary anoestrus (>12 months) underwent standard reproductive workup (vaginal cytology, hormone assays, ultrasound, and semen testing of sires). Abdominal ultrasound of the bitches did not present any signs of cystic endometrial hyperplasia (CEH). Similarly, metabolic disorders (hypothyroidism and Cushing's disease) were ruled out. It was hypothesized that the kennel diet might have provided suboptimal bioavailability of nutrients; as such the nutritional plan was reviewed, and a multi-component "fertility mix" (liquid and powder phases dosed daily at 0.8 g/kg0.75 and 0.4 g/kg0.75, respectively) was added to the usual complete maintenance ration. RESULTS: Within 6 months of supplementation, 12/15 bitches resumed cyclicity and were confirmed pregnant or gave birth; whereas three underweight bitches with chronic enteropathies did not resume cyclicity. CONCLUSION AND LIMITATIONS: The diagnostic approach to infertility is complex and involves both male and female factors, while dietary adequacy is often overlooked. Nutrients such as eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid, folic acid, vitamin E, selenium, and zinc may influence ovarian steroidogenesis and antioxidant systems, and maintenance diets may not always be optimal for bitches intended for reproduction. These observations are hypothesis-generating; baseline and follow-up nutrient biomarkers were not obtained and no untreated control group was available, precluding causal inference.

Maternal nutrition can influence genetic health during pregnancy, increasing the risk of DNA damage in both the mother and fetus. This study investigated the effect of maternal nutritional factors on DNA damage biomarkers in the mother-infant dyad. A cross-sectional study was conducted with pregnant women residing in Northeast Brazil. Participants included women aged ≥18 years in the third trimester, excluding those with non-communicable chronic diseases and smokers. Data collection included sociodemographic, lifestyle, anthropometric information, and a 76-item Food Frequency Questionnaire. The micronucleus cytome assay was performed on oral mucosa cells, with DNA damage biomarkers expressed per thousand cells (‰). Statistical analysis involved hierarchical clustering and Generalized Linear Models using Jamovi 2.5.6. The median age of the pregnant women (n = 209) was 26 years. Only 44.5% had adequate pre-pregnancy nutritional status, with a 9.5% increase in low birth weight. Total energy intake was 1842 (588-5709) kcal, with 72% consuming less than 90% of their caloric needs. The diet was predominantly hyperproteic and hyperlipidic, with over 60% showing inadequate intake of magnesium and folic acid. Among 209 participants, 80 consented to oral mucosa cell collection, and 59 mother-infant pairs were analyzed. Three maternal nutritional profiles were identified: Cluster 1 ("Multiple Burdens of Malnutrition"), Cluster 2 ("Low Burdens of Malnutrition"), and Cluster 3 ("High Nutritional Intake"). While maternal nutritional profiles did not affect nuclear abnormalities in mothers, they influenced newborns. Infants of mothers in Clusters 1 and 2 exhibited more nuclear abnormalities than those in Cluster 3. Maternal nutritional inadequacy was associated with increased nuclear abnormalities in newborns, suggesting an impact on fetal genomic stability. © The Author(s) 2026. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For commercial re-use, please contact [email protected] for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permission

Micronutrient deficiencies remain widespread across sub-Saharan Africa, reflecting not only inadequate diets but also limitations in how current interventions are designed and delivered. Universal salt iodization (USI) has achieved broad population coverage and represents one of the most successful large-scale nutrition interventions globally. However, most fortification strategies continue to target single nutrients in isolation, missing opportunities to address overlapping deficiencies. Recent evidence from Ethiopia demonstrates that folic acid can be co-fortified with iodized salt without compromising iodine status, offering proof-of-concept that existing platforms can be leveraged for integrated micronutrient delivery. This perspective argues that integrated fortification strategies combining iodine, folic acid, and potentially other micronutrients into widely consumed vehicles offer a more efficient, scalable, and equitable pathway to improve population-level nutritional status. However, translating proof-of-concept into public health impact requires addressing key challenges: biological effectiveness, product stability, implementation feasibility, quality assurance, and population heterogeneity. We propose a policy agenda that includes regulatory reform, investment in surveillance systems, and coordinated action across health, trade, and food safety sectors. Integrated fortification should complement, not replace, broader strategies like dietary diversification and supplementation, while offering a pragmatic pathway to address overlapping micronutrient deficiencies at scale across Africa and other low- and middle-income settings. © 2026 The New York Academy of Sciences.

OBJECTIVE: To assess the availability of folic acid fortified corn masa (CM) products across selected areas/regions in the United States for neural tube defects (NTD) prevention 8 years after voluntary fortification of CM products was permitted. METHODS: Geographic selection using US census data included areas with majority Hispanic census tracts in California (CA), Georgia, and Texas (TX). A largely rural county in CA, an urban county in TX, and the metropolitan Atlanta area were selected as study sites. Stores selling groceries and snacks in the selected areas were visited and surveyed for CM products. A mobile application was used to record product data, including product identifiers (e.g., brand name, product type) and folic acid information (e.g., presence and amount of folic acid, folic acid graphical design element). Analyses were performed using R studio. RESULTS: In the 111 stores surveyed, products identified included 50 distinct retail CM flour bags, 178 distinct corn tortilla products, 88 distinct tostada products, and 223 other distinct CM products. Fifty percent of distinct CM flour bags (25/50) were fortified with folic acid. Additionally, 1% (2/178) of tortillas and about 3% (3/88) of tostadas were fortified. No other fortified products were identified. CONCLUSION: Almost a decade after voluntary folic acid fortification of CM flour was allowed, very few ready-made CM products assessed in this study were fortified. As states work to initiate changes to increase the availability of fortified products, continued assessment can help monitor the availability of fortified products for NTD prevention. Published 2026. This article is a U.S. Government work and is in the public domain in the USA.

Age-related renal function decline may contribute to other physiological alterations. This study aimed to examine the associations of kidney function, assessed by estimated glomerular filtration rate (eGFR), and nutritional factors with homocysteine levels in community-dwelling older adults. This cross-sectional study enrolled participants aged ≥ 65 years. Demographic characteristics were collected using questionnaires. Biochemical parameters, including homocysteine, folic acid, vitamin B12, and metabolic disorder indicators, were measured, and eGFR was calculated and categorized into three groups. Homocysteine concentrations were significantly higher in the low and moderate eGFR groups compared with the high eGFR group (median: 16.9 vs. 11.9 vs. 9.3 μM, p < 0.01). Regression analyses indicated that each 1-unit decrease in eGFR was associated with higher homocysteine (β = -0.13, p < 0.01). Conversely, higher folic acid (β = -0.29, p < 0.01) and vitamin B12 (β = -0.003, p < 0.01) levels were significantly associated with lower homocysteine concentrations. These associations remained significant after mutual adjustment, indicating distinct effects of renal function and nutritional factors on homocysteine levels. Moreover, homocysteine levels were positively correlated with waist circumference (r = 0.38, p < 0.01) and triglycerides (r = 0.18, p < 0.05) and inversely correlated with high-density lipoprotein cholesterol (r = -0.27, p < 0.01). The results suggest that renal function and nutritional status are independently associated with homocysteine levels and may contribute to metabolic risk profiles in older adults.

BACKGROUND: Lactoferrin is an iron-binding glycoprotein present in secretions, including breast milk, with anti-inflammatory and antimicrobial properties. Previous studies suggest bovine lactoferrin (bLF) may improve hemoglobin and iron status; however, most evidence comes from high-income countries, and data from resource-limited settings remain limited. OBJECTIVES: This study aimed to determine whether oral bLF is noninferior to ferrous sulfate for improving hemoglobin among nonpregnant women with iron-deficiency anemia (IDA) in Bangladesh. We hypothesized that 200 mg or 400 mg bLF would be noninferior to 60 mg elemental iron as ferrous sulfate after 12 wk, using a prespecified noninferiority margin of -0.25 g/dL. METHODS: We conducted a double-blind, randomized, parallel-group, noninferiority trial in Dhaka, Bangladesh. Women aged 18 to 49 y with IDA were randomized 1:1:1 to receive 60 mg elemental iron as ferrous sulfate, 200 mg bLF, or 400 mg bLF, each given daily with 400 μg folic acid for 12 wk. Ferrous sulfate was the active control. The primary outcome was hemoglobin change from baseline to 12 wk in the per-protocol population. RESULTS: Of 3722 women screened, 555 were randomly assigned to receive 186 to 200 mg bLF, 185 to 400 mg bLF, and 184 to ferrous sulfate. Mean hemoglobin change at 12 wk was -0.2 ± 0.8 g/dL, 0.0 ± 0.9 g/dL, and 1.1 ± 1.3 g/dL, respectively. Compared with ferrous sulfate, mean differences were -1.2 g/dL (95% CI: -1.6 to -0.9) and -1.1 g/dL (95% CI: -1.4 to -0.8) for 200 mg and 400 mg bLF, respectively (P < 0.0001). Adverse events were comparable across groups. CONCLUSIONS: In nonpregnant Bangladeshi women aged 18 to 49 y with IDA, both bLF doses were inferior to ferrous sulfate for improving hemoglobin after 12 wk. These findings do not support bLF as a substitute for ferrous sulfate in similar settings. This trial is registered with the Australian New Zealand Clinical Trials Registry as ACTRN12617001455358 (https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=373059).

BACKGROUND: Patients with anemia preparing for abdominal cancer surgery in whom transfusion is not an option require careful preoperative management. Cancer-related anemia is often multifactorial. Therefore, we applied a blood augmentation protocol based on patient blood management (PBM), which optimizes the patient's own red cell mass. We aimed to evaluate the effect of this protocol on surgical outcomes in patients with gastrointestinal and hepato-biliary-pancreatic cancers requiring transfusion-free surgery by comparing outcomes between patients with and without preoperative anemia (the anemic and non-anemic groups). All participants were Jehovah's Witnesses for whom transfusion was not an option. METHODS: We retrospectively analyzed consecutive Jehovah's Witness patients admitted to Shonan Atsugi Hospital between January 2017 and December 2020. Patients with preoperative anemia underwent a blood augmentation protocol from their first visit until surgery. They received iron and vitamin supplementation (folic acid, vitamin C, B12, and B6), and an erythropoiesis-stimulating agent. The primary outcomes were 30-day postoperative mortality and complications (Clavien-Dindo grade >IIIa). The secondary outcomes included waiting time to surgery and perioperative hemoglobin (Hb) values measured at protocol initiation, 1 to 3 days before surgery, and postoperative days (PODs) 1, 3, and 7. RESULTS: Of the 125 registered cases, 100 patients were analyzed (44 patients in the anemic group receiving blood augmentation (mean ± standard deviation [SD] age 70.9 ± 7.8 years; 26 [59.1%] female); 56 patients in the nonanemic group (age 66.4 ± 10.4 years; 35 [62.5%] female). The 30-day mortality rate (0/44 [0%] vs 0/56 [0%]) and the incidence of severe complications (9/44 [20.6%] vs 11/56 [19.6%]) did not differ between the two groups. Age-adjusted logistic regression for complications confirmed no significant difference (unadjusted odds ratio [OR] = 1.05; 95% confidence interval [CI], 0.39-2.82, P =.92 and age-adjusted OR = 0.94; 95% CI, 0.34-2.64, P =.91). The waiting time to surgery-which corresponds to the blood augmentation period for the anemic group-did not differ significan

BACKGROUND AND AIMS: Methylene-tetrahydrofolate dehydrogenase 1 (MTHFD1) deficiency is a rare inborn error of immunity (IEI) involving defects in folate metabolism. It can present with combined immunodeficiency and variable phenotypic features, including recurrent bacterial infections, megaloblastic anemia, and failure to thrive. METHODS: We describe 2 unrelated Kuwaiti children with MTHFD1 deficiency caused by a homozygous pathogenic variant [c.517C>T (Arg173Cys)]. RESULTS: Both cases presented with unexplained megaloblastic anemia, recurrent sinopulmonary infections, failure to thrive, and developmental delay. The first patient, a 10-year-old girl, was diagnosed with combined immunodeficiency and autoimmune thyroiditis. Treatment with folic acid resulted in significant clinical improvement. The second patient, a 3-year-old girl, presented with sepsis secondary to progressive lobar pneumonia and bone marrow failure. Despite intensive treatment, including broad-spectrum antibiotics, antifungals, IVIG, and dexamethasone for suspected hemophagocytic lymphohistiocytosis, she developed severe complications and passed away on day 18 of PICU admission. CONCLUSION: As there is no specific clinical or laboratory phenotype for most IEIs, we emphasize the importance of molecular diagnosis through urgent genetic testing in patients with suspected MTHFD1 deficiency. Precision therapy with prompt folate or folinic acid supplementation can significantly improve outcomes, as evidenced by the survival of one patient with minimal intervention.

Gadolinium nanoparticles (GdNPs) have been studied extensively due to their lower toxicity and better magnetic resonance imaging (MRI) detection capabilities than Gd-chelates. Their surfaces are conveniently modified with several molecules to enhance their accumulation in the cancer of interest, thereby enabling more accurate diagnosis and treatment. In this study, hydrothermal GdNPs were functionalized with folic acid (FA) (for active targeting), polyethylene glycol (to improve biocompatibility), and azide molecules (for subsequent click reaction) via a silane ligand exchange conjugation method. Results showed a hydrodynamic diameter of 7.90 nm and a zeta potential of -6.80 mV for Azide-PEG-Folate-modified GdNPs. UV spectra confirmed the presence of FA in NPs at UV absorption of 284 and 353 nm. Typical FTIR spectra also appeared at wavenumbers of 2950 and 2150 cm- 1, confirming the presence of PEG and azide molecules on modified NPs, respectively. Additionally, modified NPs maintained good stability for up to 3 weeks at 25 and 4 °C. A preliminary click in vitro investigation also showed the NPs' good viability even after incubation at 132 µg/mL, followed by the click reaction with 300 µg/mL of Holmium(III)-complexed-DOTA-BCN on HeLa cancer cells. This first click-combination finding serves as a promising candidate for Gd/Ho-MRI agents, thereby enabling a more accurate diagnosis due to their simultaneous T1/T2 contrast enhancement. © 2026 The Authors. ChemistryOpen published by Wiley‐VCH GmbH.

This multicohort, single-center, phase II trial explored the efficacy and safety of a biomarker-driven total neoadjuvant therapy (TNT) regimen in high-risk locally advanced rectal cancer (LARC) patients. The regimen included induction chemotherapy (4 cycles of mFOLFOX6) with targeted agents (bevacizumab for cohort B and cetuximab for cohort C), followed by short-course radiotherapy (25 Gy/5Fx) and consolidation chemotherapy (2 cycles of mFOLFOX6, with cetuximab in cohort C). The primary endpoint was complete response (CR; sustained clinical CR [cCR] + pathological CR [pCR]). Secondary endpoints included compliance, safety, pathological outcomes, and survival. Between April 2021 and October 2024, 90 of 96 patients completed the prescribed treatment. CR was achieved in 36 (18 in cohort B and 18 in cohort C) patients (40%). No grade IV-V toxicity was observed, although three and 41 patients experienced targeted agent-related adverse effects in cohort B and C, respectively. In the two cohorts, 43 and 38 patients underwent curative surgery with sphincter preservation in 39 (90.7%) and 34 (89.5%) patients, respectively. Postoperative complications occurred in seven (16.3%) and five (13.2%) patients, of whom one (2.6%) patient in cohort C received reoperation. This intensified TNT regimen with targeted agents for high-risk LARC patients achieved a satisfactory CR rate with acceptable toxicities and complications. © 2026. The Author(s).

BACKGROUND: The global burden of neuropsychiatric disorders has been increasing rapidly. Folate has been studied in the context of these disorders due to its role in cellular methylation capacity, which is crucial for normal neuronal gene expression and neurotransmitter syntheses. Epidemiological evidence linking folate and neuropsychiatric disorders is growing, yet inconclusive. METHODS: We searched MEDLINE, Embase, CINAHL, the Cochrane Library, and the Database of Abstracts of Reviews of Effects from inception to February 2024 for systematic reviews and meta-analyses investigating the associations between folate exposure and any neuropsychiatric disorders. Two independent reviewers screened the syntheses in two stages and extracted relevant data. Evidence was categorised into unique associations (unique exposure measure - unique outcome - unique setting). We identified evidence for each category of unique associations. We evaluated the risk of bias of all included syntheses using ROBIS and assessed the credibility of evidence using predefined criteria. RESULTS: From a total of 76 syntheses, we identified 44 unique associations from meta-analyses and 18 unique associations from qualitative syntheses across 14 outcome categories. Most of the reviews consisted of case-control studies or cross-sectional studies, and most were at high risk of bias. We identified two associations at a suggestive level of credibility: folic acid supplementation during or before pregnancy was associated with a reduced risk of perinatal depression, while prenatal maternal folic acid use was associated with a reduced risk of autism spectrum disorder in offspring. Seven associations were downgraded to weak due to unavailable data. Other associations were at a weak level of credibility due to insufficient statistical power. CONCLUSIONS: The available evidence on the relationship between folate status and neuropsychiatric disorders primarily comprised data from observational studies, limiting causal inference on folate exposure and the risk of onset or progression of neuropsychiatric disorders. Prospective studies and sex-stratified analyses could add to the evolving knowledge on this topi

Glioblastoma multiforme (GBM) remains one of the most aggressive central nervous system malignancies, with therapeutic efficacy severely constrained by the blood-brain barrier (BBB), which limits drug delivery to the tumor site, and by the lack of tumor-specific targeting, leading to off-target effects and inadequate intratumoral accumulation. To address these interconnected challenges, we designed a dual-targeted biomimetic nanoplatform (GIM@Lip-Bio/FA) using glycogen as a biodegradable core for co-loading methotrexate (MTX) and IR780, followed by coating with a lipid layer sequentially modified with biotin and folic acid (FA) to enable active transport across the BBB and selective recognition by glioma cells. The resulting nanoparticles exhibited a uniform size, excellent stability, and significantly enhanced cellular uptake mediated by SMVT and folate receptor α (FRα). Notably, the nanoplatform demonstrated efficient BBB penetration and precise tumor accumulation in orthotopic GBM models. Upon nea

BACKGROUND: Preconception care (PCC) is a set of biomedical, behavioural, and social interventions provided before pregnancy to improve maternal and neonatal outcomes. Despite its proven benefits, PCC uptake remains low in Nigeria and other sub-Saharan African countries, largely due to limited awareness, poor health system integration, and socio-cultural barriers. This study assessed awareness and prior utilization of PCC among pregnant women attending primary health centres (PHCs) in Ogbomoso, Southwest Nigeria, and examined factors associated with its uptake. METHODOLOGY: A descriptive cross-sectional study was conducted among 152 pregnant women attending antenatal clinics in three randomly selected PHCs in Ogbomoso North LGA. A multistage sampling technique was used. Data were collected using a structured, pretested questionnaire and analysed using SPSS version 26. Descriptive

Rice, a global staple, often lacks essential nutrients due to milling, leading to micronutrient deficiencies or "hidden hunger." This study aimed to optimize the fortification of rice analogues with essential vitamins, focusing on nutrient retention during cooking. Using cold extrusion technology, rice analogues were produced from a mixture of rice flour, sodium alginate (1%), water (30%), and a nutrient ready mix (NRM) in varying proportions: low-dose (100%), intermediate-dose (125%), and High-dose (150%) of recommended levels. The fortification level was statistically optimized using Design Expert software, with high-dose fortification (150% NRM) yielding the highest cooking retention, achieving a desirability value of 0.961. Post-co

Cancer remains a major global health challenge, with its growing incidence highlighting the critical need for effective and accessible treatments. Current therapeutic approaches, including surgery, chemotherapy, radiation therapy, hormone therapy, and immuno-therapy, are often limited by toxicity, poor targeting, and suboptimal efficacy. These challenges have driven the development of nanotechnology-based strategies aimed at improving tumor selectivity and therapeutic outcomes. Among the most promising are extracellular vesicles, particularly exosom

Spina bifida occulta (SBO) refers to a split in the spine that is concealed beneath the skin. The biomechanical impact of complete sacral SBO has often been underappreciated. This case highlights the potential effects of complete sacral SBO on the spine. A 12-year-old girl presented with truncal asymmetry and intermittent neck and lumbar pain lasting for two years. Initially, she was diagnosed with mild scoliosis during a school health screening and was placed under medical observation, but her symptoms worsened over time. Imaging studies revealed an inverted cervical lordosis along with a 25-degree left thoracolumbar curvature. Additionally, the laminae of all five sacral vertebrae were intact yet failed to fuse into a median crest, consistent with a diagnosis of complete sacral SBO. This anomaly was not noted in the patient's earlier medical documentation. The treatment aimed to improve spinal stability. Chiropractic care was provided weekly for 58 months, incorporating rhythmic massage, flexion-distraction techniques, and spinal manipulation. The patient reported complete resolution of neck and back pain, and her scoliotic curve was reduced to 17 degrees. This case unde

This study investigated the effects of dietary folic acid (FA) on growth performance, lipid metabolism, one-carbon metabolism, and gut microbiota of juvenile mud crab (Scylla paramamosain). Six isonitrogenous and isolipidic diets were formulated: one antibiotic basal diet control with 1% succinylsulfathiazole (0.00 + 1% SST), one basal diet control (0.00 mg/kg FA), and four diets with graded FA levels (1.37, 2.43, 4.26, and 9.84 mg/kg). A total of 180 juvenile crabs (initial body weight: 15.21 ± 0.10 g) were individually reared for 8 weeks. Compared with the 0.00 mg/kg FA and 0.00 + 1% SST treatments, dietary supplementation with 4.26 mg/kg FA improved final weight (FW), percent weight gain (PWG), specific growth rate (SGR), survival, and feed efficiency (FE) (P < 0.05). The 4.26 mg/kg FA also enhanced eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) contents in hepatopancreas and muscle, whereas the 0.00 + 1% SST treatment significantly reduced

Acute kidney injury (AKI) is a critical clinical syndrome characterized by an abrupt decline in renal function and is associated with substantial morbidity and mortality. Current therapeutic options remain predominantly supportive. Cisplatin-induced AKI, a clinically relevant subtype of AKI, is driven by oxidative stress, mitochondrial dysfunction, inflammatory activation, and tubular epithelial cell injury. Rapamycin, a potent mechanistic target of rapamycin (mTOR) inhibitor, has shown renoprotective potential in preclinical AKI models; however, its therapeutic application is limited by poor renal accumulation, low aqueous solubility, a narrow therapeutic window, and potential systemic toxicity. To address these limitations, a kidney-targeted nanotherapeutic was engineered by loading rapamycin onto ultrasmall manganese oxide (Mn3O4) nanoparticles surface-functionalized with folic acid (RAP@Mn3O4-FA). This nanoplatform integrates the intrinsic ROS-scavenging activity of Mn3O4 with folate receptor (FR)-mediated renal targeting, thereby enhancing intrarenal drug delivery while reducing off-target exposure. In a cisplatin-induced AKI mouse model, RAP@Mn3O4-FA improved renal function, attenuated histological injury, activated AMPK/mTOR-associated autophagy, and showed a favorable preliminary biosafety profile. These findings suggest that RAP@Mn3O4-FA is a promising kidney-targeted nanotherapeutic candidate for cisplatin-induced AKI treatment.

STUDY QUESTION: Are periconception maternal modifiable lifestyle factors (i.e. smoking, alcohol consumption, caffeine intake, folic acid supplement use, and physical activity) associated with embryonic morphologic development and growth in a large population-based cohort study? SUMMARY ANSWER: Inadequate folic acid supplement use and insufficient serum folate levels were associated with delayed embryonic morphologic development and reduced growth, while no associations were observed for smoking, alcohol, caffeine intake, or physical activity. WHAT IS KNOWN ALREADY: Modifiable maternal lifestyle factors during the periconception period may influence embryonic growth and

BACKGROUND: Rational drug use in obstetrics is essential to ensure maternal safety and optimal pregnancy outcomes. Drug utilization studies help evaluate prescribing patterns and identify areas for improvement. OBJECTIVE: To assess the drug utilization pattern and evaluate maternal outcomes associated with obstetric medications in antenatal and postnatal women at a tertiary care hospital. METHODS: A prospective observational study was conducted over six months in a tertiary care hospital. A total of 200 antenatal and postnatal women receiving medications were included. Data on demographics, drug prescriptions, and maternal outcomes were collected. Statistical analysis was performed using SPSS version 25.0. Chi-square test, independent t-test, and multivariate logistic regression were applied. A P value < 0.05 was considered s

The increasing burden of Acute Kidney Injury (AKI) significantly impacts human health. Approximately 70% of septic patients develop AKI, which markedly increases the risk of in-hospital mortality. However, current treatment for Sepsis-Associated Acute Kidney Injury (SA-AKI) is mainly supportive, and no specific therapy is available. siRNA therapy is an emerging approach that inhibits mRNA of specific targets to exert therapeutic effects. Based on the gene silencing principle of siRNA, we developed a targeted bifunctional coloaded nanoparticle, PDA@Cur-PEI-PEG-FA/siRela (PCPPFS), using folic acid (FA) as a targeting moiety. In this system, curcumin acts as a therapeutic agent and

Human Papilloma Virus infection represents one of the most common sexually transmitted infections worldwide. While research on Human Papilloma Virus has traditionally focused on its role in cervical cancer pathogenesis, such infection is also highly prevalent in the male population. Despite this, the clinical management of Human Papilloma Virus in men still remains limited, with no universally accepted screening protocols or therapeutic guidelines. This clinical case series describes six male patients (aged 26-66 years) with Human Papilloma Virus infection detected in samples of urethral mucosa, anal mucosa, or seminal fluid. Each patient took the dietary supplement containing epigallocatechin gallate (200 mg), folic acid (400 μg), vitamin B12 (1 mg), and hyaluronic acid (50 mg)

OBJECTIVE: Recurrence affects 65%-75% of pancreatic cancer (PC) patient post-resection. Established salvage strategies for recurrent PC are lacking, and systemic chemotherapy offers limited survival benefits. This study aimed to evaluate the efficacy and safety of immune checkpoint inhibitors (ICIs) combined with different chemotherapy in patients with recurrent PC, specifically FOLFIRINOX (a combination of 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) and Gemcitabine plus Nab-paclitaxel (AG).Materials and methods: We retrospectively screened 201 patients with recurrent PC between March 2016 and September 2022. A total of 113 eligible patients were enrolled, including 23 in the chemotherapy combined with ICIs group and 90 in the chemotherapy-only group. The primary endpoint was overall survival (OS), and secondary endpoints included progression-free survival (PFS). Subgroup analyses were performed based on chemotherapy regimens (FOLFIRINOX vs. AG). RESULTS: In the overall cohort, the chemotherapy combined with ICIs group demonstrated a trend toward improved survival compared to the chemotherapy group. Subgroup analysis revealed that among patients receiving the FOLFIRINOX regimen, the addition of ICIs was significantly associated with improved OS (median OS: not reached vs. 14.9 months; HR = 0.266 [95% CI: 0.077-0.919]; log-rank P = 0.025; Cox P = 0.036) and showed a superior trend in PFS (P = 0.080) compared to FOLFIRINOX alone. Conversely, no significant survival benefit was observed in the AG subgroup (P > 0.05). CONCLUSION: Combining ICIs with FOLFIRINOX-based chemotherapy was significantly associated with improved OS in patients with recurrent PC with an acceptable safety profile. This combination strategy represents a promising therapeutic option for recurrent PC, particularly when paired with the FOLFIRINOX backbone.

The development of targeted and multifunctional anticancer nanoplatforms remains challenging due to limited selectivity, systemic toxicity, drug resistance, and off-target effects associated with conventional platinum-based chemotherapy. Zn(II) complexes have emerged as promising low-toxicity metal-based alternatives, exhibiting enhanced cytotoxicity toward cancer cells compared to healthy cells. In this study, a Schiff base ligand (K) was synthesized via condensation of 4-(1H-phenanthro[9,10-d]imidazol-2-yl)aniline and salicylaldehyde followed by complexation with Zn(II) to form a Zn(II) complex (S1). To enhance site-specific cellular uptake, Zn(II) complex S1 was encapsulated within folic acid-functionalized 10,12-pentacosadiynoic acid (FA-PCDA) and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC)-based liposomes via molecular co-assembly, significantly improving stability and targeting capability. The resulting liposomal formulation of Zn(II) complex S1 (Lip-S1) exhibited characteristic fluorescence properties, enabling potential imaging applications. Lip-S1 selectively targeted folate receptor-expressing cervical cancer (HeLa) cells, demonstrating enhanced anticancer efficacy with a half maximal inhibitory concentration (IC50) of 143.8 μg mL-1 compared to free S1 and bare liposomes. Functional assays revealed that Lip-S1 inhibited cell proliferation, migration, and tumor spheroid growth while inducing apoptosis through mitochondrial membrane depolarization, elevated intracellular reactive oxygen species (ROS), caspase 3/7 activation, and modulation of apoptotic proteins (Bax upregulation, Bcl-2 downregulation). ROS scavenging studies confirmed that apoptosis is primarily mediated by oxidative stress linked to the PI3K/AKT (phosphatidylinositol 3 kinase/protein kinase B) signaling pathway. Enhanced cellular internalization of Lip-S1 relative to controls was also observed. These results highlight Lip-S1 as a targeted, fluorescence-trackable nanoplatform for ROS-mediated anticancer therapy. © 2026 American Chemical Society.

Inflammation-driven disorders remain a major therapeutic challenge, partly because conventional anti-inflammatory drugs are often limited by adverse effects, poor target specificity, and incomplete modulation of oxidative and inflammatory pathways. This study developed a green, plant-based targeted nanoplatform using methanolic extracts of Cuminum cyminum and Carum carvi for the synthesis of ZnO NPs, followed by chitosan coating and folic acid functionalization to improve biocompatibility, stability, and inflammatory-cell targeting. The resulting ZnO, CS-ZnO, and FA-CS-ZnO NPs were characterized by FTIR, XRD, FESEM, TEM, and EDX analyses. Their anti-

Nutraceuticals and phytoceuticals are increasingly investigated for bipolar disorder (BD). We conducted a systematic review and network meta-analysis of randomized controlled trials (RCTs). PubMed/MEDLINE, EMBASE, Scopus, PsycINFO, and ClinicalTrials.gov were searched from inception to July 1, 2025. Co-primary outcomes were changes in depressive or manic symptoms (standardized mean difference [SMD]), treatment response, and acceptability (risk ratio [RR]); tolerability and remission (RR) were secondary outcomes. Heterogeneity, transitivity, inconsistency, small-study effects, risk of bias, and confidence in evidence (CINeMA) were assessed. Twenty-eight RCTs (n=2,222) evaluated 22 treatments. No treatment outperformed placebo for depressive symptoms; placebo outperformed palmitoylethanolamide (SMD=2.69, 95% CI 1.43-3.95), based on one trial, amid substantial heterogeneity (I²=86%) but no global inconsistency. For manic symptoms, palmitoylethanolamide (SMD=-4.58, 95% CI -6.24 to -2.92) and folic acid (SMD=-2.42, 95% CI -4.06 to -0.79) outperformed placebo, with substantial heterogeneity (I²=91.3%) and no global inconsistency. Sensitivity analyses supported palmitoylethanolamide, although the finding relied on one RCT from a region producing larger-than-average SMDs. Meta-regression indicated that larger effects were associated with lower adapted AMSTAR-Plus scores. Free-and-easy-wanderer-plus™ combined with carbamazepine outperformed placebo for response and acceptability. CINeMA ratings varied and were predominantly low or very low, particularly for manic symptoms. Current evidence does not support firm recommendations for any nutraceutical or phytoceutical in acute bipolar depression or mania, and further high-quality research is needed.

The capacity of health systems to provide quality care for pregnant adolescents remains underexplored. This study examined the quality, continuity, and experiences of maternal healthcare among pregnant adolescents (<20 years) compared with adult women (20 + years) in Ethiopia, Kenya, and South Africa. It also explored factors associated with mistreatment and obstetric complications among adolescents using data from the Maternal and Newborn Health eCohort study. We followed 3,051 pregnant women from their first antenatal care (ANC) visit until six weeks postpartum. We used descriptive analyses to compare care quality and outcomes and logistic regression to identify factors among adolescents. The study included 380 adolescents and 2,671 adults. Adolescents had lower first-trimester ANC attendance (22% vs. 30%, p = 0.003), fewer follow-up ANC visits (mean 3.1 vs. 3.8, p < 0.001), and lower adherence to iron-folic acid supplementation (59.0% vs. 69.4%, p < 0.001). Continuity of care was also lower (53% vs. 59%, p < 0.001). Adolescents experienced more mistreatment during delivery (26.9% vs. 18.6%, p = 0.003). Obstetric complications occurred in 31% of adolescents compared with 25.9% of adults. Mistreatment was associated with rural residence (adjusted odds ratio (aOR): 2.61, 95% CI: 1.11-6.13, p = 0.028), public facility use (aOR: 4.33, 95% CI: 1.44-13.1, p = 0.009) and intimate partner violence (IPV) (aOR: 3.31, 95% CI: 1.16-9.39, p = 0.025). Protective factors included being in Kenya (aOR: 0.19, 95% CI: 0.05-0.75, p = 0.018), privacy during delivery (aOR: 0.44, 95% CI: 0.21-0.92, p = 0.030) and high perceptions of quality of care (aOR: 0.37, 95% CI: 0.18-0.76, p = 0.007). Obstetric complications were associated with rural residence (OR: 2.25, 95% CI: 1.09-4.63; p = 0.028) and antenatal depression (OR: 2.43, 95% CI: 1.19-5.00, p = 0.015). These findings highlight gaps in adolescent maternal healthcare. Strengthening adolescent-responsive and respectful care within primary healthcare, alongside integrated mental health and IPV support, may improve adolescents' maternal healthcare experiences and outcomes. Copyright: © 2026 Amboko et al. This is an open access artic

BACKGROUND: Diabetes mellitus, a chronic metabolic disorder affecting over 537 million individuals worldwide, represents one of the most burdensome global health challenges of the 21st century. Despite the availability of numerous oral antidiabetic agents, their therapeutic effectiveness is significantly compromised by poor aqueous solubility, chemical instability in the gastrointestinal (GI) environment, extensive hepatic first-pass metabolism, low membrane permeability, and inadequate systemic bioavailability. Nanotechnology-based drug delivery systems have emerged as transformative platforms capable of circumventing these multifaceted physiological and biopharmaceutical limitations. OBJECTIVE: This comprehensive

Folates are essential metabolites of the cell and need to be acquired either by transport or biosynthesis. All metazoa including humans, some bacteria, and some protozoa acquire it solely through specific transporters. Plants and fungi, in contrast, have the capacity both for de novo biosynthesis and for uptake through plasma membrane folate transporters. These recently identified transporters belong to the oligopeptide transporter (OPT) family. Folate transporters from this family have been identified in yeasts and other fungi, including pathogenic fungi. They have also been observed in plants such as Arabidopsis thaliana and have the ability to transport both synthetic and natural folates including the naturally abundant 5-methyl tetrahydrofolate. In Saccharomyces cerevisiae, the folate transporter Opt1p (Hgt1p) is a proton-coupled transporter that was already known to transport glutathione (GSH). While in some organisms a single transporter is able to transport both substrates, in other organisms separate transporters in this family exist for folate and GSH. Mutational, kinetic, and

Bacterial infections are significant issues that endanger public health and deplete financial resources. A potential strategy to combat these infections is molecular hybridization, which combines pharmacophores from potential drugs to produce hybrid scaffolds that are more effective. The preparation of pyridines attached to pyrazolopyrimidine units with promising antimicrobial potency and dual inhibitory capacity against DNA gyrase and dihydrofolate reductase (DHFR) is the aim of this work. A green procedure was conducted by reacting the suitable 2-cyanoacetamides with aromatic aldehydes and malononitrile in refluxing ethanol for 5-8 h containing choline hydroxide to give pyrazolopyrimidine-linked 4-arylpyridine-3,5-dicarbonitrile hybrids 1 and 2 in 74%-94% yields. In general, 5,7-diphenylpyrazolopyrimidine-linked pyridines 2 showed slightly more increased antibacterial activity, particularly against methicillin-resistant Staphylococcus aureus (MRSA), compared to 5,7-di

BACKGROUND: Split cord malformation (SCM) is a rare congenital anomaly characterized by a longitudinal division of the spinal cord into two hemicords. Clinical manifestations are diverse, often including neurological, orthopedic, and cutaneous abnormalities. Surgical management remains the mainstay of treatment, though outcomes and complication profiles require further study. This study aimed to analyze the clinical spectrum, surgical management, and outcomes of pediatric and young adult patients with SCM. METHODS: A retrospective review was conducted of patients with SCM who underwent surgery at our tertiary care institute between 2018 and 2024. From 168 identified cases, 35 patients with complete clinical, radiological, and surgical data were included. Demographics, clinical features, radiological findings, operative details, and postoperative outcomes were recorded. Descriptive statistics were generated using GNU PSPP 2.0.0. RESULTS: Among 35 patients (18 males, 17 females; mean age 5.4 years, range 2 months-20 years), SCM

Children and adolescents in Indonesia are experiencing the triple burden of malnutrition (TBM), resulting from an increasing prevalence of overweight and obesity paired with persistent undernutrition and anemia. The extent to which the coronavirus disease 2019 (COVID-19) further exacerbated TBM within this group, because of lifestyle changes and increased food insecurity, has not been well documented. This narrative review aimed to fill that gap by exploring components of TBM (i.e., undernutrition, anemia, and overweight and obesity), its determinants (e.g., diet), and related nutrition policies and programs among school-aged children and adolescents in Indonesia during the pandemic. We reviewed a total of 10 peer-reviewed articles published between 2021 and 2025 on children and adolescents' nutrition status and TBM-related determinants. Results suggested that during COVID-19, children and adolescents in Indonesia experienced a high prevalence of undernutrition, overweight and obesity, and anemia. Most children

BACKGROUND: Aberrant p53 expression may have prognostic significance in colorectal cancer; however, its role in patients with colorectal liver metastases (CRLM) who receive neoadjuvant chemotherapy but do not achieve pathological complete response (pCR) remains unclear. AIMS: We evaluated whether aberrant p53 expression assessed by immunohistochemistry (IHC) predicts recurrence-free survival (RFS) in patients with

BACKGROUND: Excessive intake of exogenous vitamin A during pregnancy has been associated with congenital malformations. This experimental study aimed to evaluate whether vitamin B12, folic acid, and L-carnitine exert a protective or contributory effect on malformations induced by hypervitaminosis A. METHODS: Thirty-five healthy adult female Wistar albino rats and seven male rats were used. Pregnant rats received vitamin A alone or in combination with vitamin B12, folic acid, or L-carnitine for 21 consecutive days (GD 0-21). At the end of gestation, neonates were evaluated for gross congenital malformations. Brain, liver, and eye tissues were excised and processed for histopathological and morphometric analyses. RESULTS: No gross external malformations were observed in any group; however, significant growth restriction and multi-organ histopathological alterations were detected in the offspring. Histological examination revealed interstitial edema in brain tissue and retinal detachment in the eye. Hepatic alterations included sinusoidal dilatatio

BACKGROUND: Neural tube defects (NTDs) are congenital developmental anomalies resulting from incomplete neural tube closure during early embryonic development. They present a wide range of clinical manifestations along the craniospinal axis. OBJECTIVE: With only 6.2% of Lebanese women of childbearing age taking folic acid tablets during the adequate period, it is primordial to shed light on cases of NTDs in Lebanon. This case series presents four cases of NTDs that deviate from the conventional "zipper closure" model of neural tube development, aligning more with the modern multisite closure approach. This case series showcases the consequences of inadequate intake of folic acid prior to conception in addition to delayed prenatal diagnosis. The four cases are presented in accordance with CARE reporting guidelines. METHODS: The study presents four case rep

OBJECTIVE: To evaluate the nutritional profile, dietary intake, and feeding characteristics of Brazilian children and adolescents with infantile neuroaxonal dystrophy, comparing exclusively orally fed and gastrostomy-fed participants. METHODS: This retrospective cross-sectional study included 21 genetically confirmed patients with infantile neuroaxonal dystrophy between July 2023 and March 2024. Data collection involved 24-hour dietary recalls, anthropometric measurements, and assessment of dysphagia using the Functional Oral Intake Scale. Nutritional status and intake were compared using the Mann-Whitney U test (p<0.05). RESULTS: Twelve participants (57%) received gastrostomy feeding. Among orally fed participants (n=9), 66.7% required food texture modifications and 88.9% exhibited sympto

Aortic dissection (AD) is a life-threatening cardiovascular disease with an extremely high mortality rate. Excessive reactive oxygen species (ROS) production and inflammatory responses in diseased vascular regions are central drivers of AD pathogenesis, leading to destruction of the aortic wall structure and fatal hemorrhage. However, conventional clinical therapies for AD cannot effectively eliminate excessive ROS at lesion sites while simultaneously exerting anti-inflammatory effects. To address these limitations, we developed a biomimetic, inflammation-targeting nanoparticle, ZIF-8@Res@PEG-FA (ZRF), to attenuate AD progression through potent antioxidant and anti-inflammatory interventions. ZRF is constructed with ZIF-8 as the core carrier, loaded with the antioxidant and anti-inflammatory agent resveratrol, and surface-modified with PEG-folic acid (PEG-FA). This nanoparticle enhances resveratrol bioavailability and leverages the inflammation-targeting capability of folic acid to preferentially accumulate in AD lesions. Under mildly acidic conditions, ZRF

Triple-negative breast cancer (TNBC) is an aggressive subtype with limited therapeutic options and poor clinical outcomes. This study evaluated folic acid-functionalized solid lipid nanoparticles co-loaded with docetaxel and erlotinib (FA-DOC/ERL-SLNs) as an oral targeted therapy for TNBC. FA-DOC/ERL-SLNs exhibited the lowest IC₅₀ values of 0.82 ± 0.05 μM and 0.92 ± 0.03 μM in MDA-MB-231 and 4T1 cells, respectively, with enhanced cellular uptake compared with free drugs and non-targeted SLNs. The formulation also induced higher apoptosis (apoptosis indices of 1.42 and 1.45), greater G2/M cell-cycle arrest, autophagy inhibition, and reduced clonogenicity and migration. Pharmacokinetic studies demonstrated markedly improved oral bioavailability, with AUC₀-t increasing from 1.03 to 45.69 μg·h/mL for docetaxel and from 18.30 to 87.76 μg·h/mL for erlotinib. In