SAMe (Depression)

Excitatory junction potentials (e.j.ps) evoked by nerve stimulation with 15 pulses at 1 Hz were recorded from muscle cells of rabbit isolated jejunal arteries. LY 171555 1 mumol/l, SKF 38393 10 mumol/l, dopamine 10 mumol/l and clonidine 0.1 mumol/l depressed all e.j.ps in the train. The percentage inhibition was inversely related to the number of pulses. S- and R-sulpiride, 10 mumol/l, domperidone 1 mumol/l, SCH 23390 1 mumol/l and rauwolscine 1 mumol/l did not change, or even depressed the first e.j.ps. Of these compounds only S- and R-sulpiride, 10 mumol/l and rauwolscine 1 mumol/l facilitated the late e.j.ps. The percentage facilitation increased with the number of pulses until a maximum was reached; rauwolscine 1 mumol/l had the largest effect. S- and R-sulpiride, 10 mumol/l, as well as domperidone 1 mumol/l antagonized the action of LY 171555 1 mumol/l. S-Sulpiride was more potent than its R-isomer. SCH 23390 1 mumol/l and rauwolscine 1 mumol/l blunted the effect of SKF 38393 10 mumol/l. Rauwolscine 1 mumol/l slightly reduced the inhibition by dopamine 10 mumol/l; S-sulpiride 10 mumol/l was antagonistic only in the presence of rauwolscine 1 mumol/l. When rauwolscine 1 mumol/l, prazosin 0.1 mumol/l, propranolol 1 mumol/l and cocaine 10 mumol/l was added to the medium, dopamine 10 mumol/l continued to produce the same depression of e.j.ps, as in the absence of these compounds. Under such conditions S-sulpiride 10 mumol/l also counteracted dopamine 10 mumol/l. Rauwolscine 1 mumol/l prevented the effect of clonidine 0.1 mumol/l. The antagonists were not absolutely selective against only one type of agonist. We suggest that both presynaptic DA2- and postsynaptic DA1-receptors are present in rabbit jejunal arteries. The activation of either receptor-type may depress the e.j.ps. Dopamine interferes with neuroeffector transmission due to alpha 2-adrenoceptor agonist properties; its DA2-effect is unmasked only after alpha 2-adrenoceptor blockade. There was no evidence for a co-transmitter function of dopamine.

INTRODUCTION: While recent trials have shown daily prenatal low-dose 500 mg calcium supplementation to be noninferior to the recommended high-dose 1500 mg regimen for prevention of preeclampsia, its effects on maternal anemia and iron status remain unclear. METHODS: We conducted two individually randomized, non-inferiority trials in India and Tanzania (N=11,000 each) comparing daily 500 mg to 1500 mg calcium supplementation during pregnancy. All participants received standard IFA (60 mg iron) and were counseled to take calcium supplements several hours apart from the IFA. All participants had hemoglobin measured at baseline and at 32 weeks of gestation, while a random subset of participants had ferritin quantified at the same time points. Using an intention-to-treat approach, we assessed effects of 500 mg compared to 1500 mg calcium supplementation on mean hemoglobin and inflammation-adjusted serum ferritin (log-scale) using generalized linear models, and on anemia and iron deficiency anemia using log-binomial models. RESULTS: Third-trimester hemoglobin and serum ferritin were measured in 8,953 and 1,336 participants in India, respectively. In Tanzania, 8,496 participants had hemoglobin, and 882 had ferritin assessed. In both trials, there was no difference between 500 and 1500 mg calcium supplementation on third-trimester hemoglobin [India: mean difference (MD) 0.01 (95% confidence interval (CI): -0.03, 0.04); Tanzania: MD -0.02 (95% CI: -0.07, 0.03)], anemia [India: relative risk (RR) 1.01 (95% CI: 0.95, 1.07); Tanzania: RR 1.00 (95% CI: 0.96, 1.05)], or iron deficiency anemia [India: RR 1.20 (95% CI: 0.93, 1.57); Tanzania: RR 0.94 (95% CI: 0.77, 1.15)]. CONCLUSION: Low and high-dose calcium supplementation showed no differences in third-trimester hematologic outcomes. Future studies should assess the effects of co-administering or combining calcium and IFA into a single tablet on adherence and bioavailability of iron. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov identifier, NCT03350516; Clinical Trials Registry India number, CTRI/018/2/12119; and Tanzania Medicines and Medical Devices Authority Trials Registry number, TFDA0018/TR/010/.

BACKGROUND: Cataract surgery is the most frequently performed surgery worldwide, crucial for restoring sight in millions. The COVID-19 pandemic and an aging population have increased barriers to timely surgery. Missed preoperative instructions and poor adherence to postoperative care contribute to surgery cancellations, delays, and potential complications. Mobile digital health interventions could enhance adherence and reduce cancellations. OBJECTIVE: This study assessed the effectiveness of the Sharp Health Companion smartphone app, built on the CareKit health platform, compared with printed instructions. The aim was to evaluate its impact on medication adherence, surgery delays and cancellations, visual outcomes, and patient experience among older adults undergoing cataract surgery. METHODS: In this randomized controlled trial, 200 patients aged 41-87 (mean 69, SD 8.2) years were enrolled at a high-volume ophthalmology practice between December 2022 and January 2024. Most participants (145/200, 73%) were 65 years or older. Patients were randomized to group 1 (printed instructions with phone reminders, n=104) or group 2 (Sharp Health Companion app supplemented with backup printed instructions, n=96). Both groups received identical perioperative instructions and medications. Data included demographics, visual acuity, medication adherence (self-reported by paper checklist or Sharp Health Companion app care-card checklist and eye medication bottle weights), surgery cancellations and delays, and satisfaction surveys administered preoperatively, on postoperative day 1, and at 30 days. RESULTS: Sharp Health Companion app users had fewer same-day surgery delays (1/96, 1%) than those receiving printed instructions (10/104, 10%; P=.01), while cancellation rates were similar (P=.33). Patient-reported preparedness for surgery was high and comparable between groups on postoperative day 1 (group 1: mean 9.56, SD 1.19; group 2: 9.77, SD 0.73; P=.16). Preparedness for recovery at postoperative month 1 was similarly high (mean 9.92, SD 0.37 vs mean 9.85, SD 0.47; P=.28). At 30 days postoperatively, visual acuity improvement was similar (mean 0.14, SD 0.17 vs mean 0.11, SD 0.13

Sarcopenia in older adults increases fall risk and frailty. Improving muscle mass and function enhances balance and supports basic activities of daily living. Leucine-enriched essential amino acid supplementation combined with resistance training has been shown to enhance muscle performance. The present study evaluated muscle performance outcomes after 6 mo of these treatments. In an open-label randomized controlled trial, 66 participants were randomized equally to control and intervention groups (n = 33 each). Both groups consumed daily leucine-enriched essential amino acid supplements after exercise. The intervention group performed resistance training, and the control group followed regular walking and strengthening exercises. Primary outcomes were appendicular skeletal muscle mass index (ASMI), gait speed, and hand grip strength. Safety was assessed by adverse event reporting and laboratory tests. The results of this study show no significant improvement in ASMI in either group after 6 mo. Both groups demonstrated significant gait speed improvements, with no between-group difference. Hand grip strength improved only in the non-dominant hand of the control group. No serious adverse events occurred, and kidney function remained stable. In conclusion, 6 mo of daily leucine-enriched essential amino acid supplementation combined with exercise did not increase ASMI among healthy older adults. Gait speed showed a positive association with supplementation and daily exercise regardless of regimen. Improvement in hand grip strength was observed only in the non-dominant hand, warranting further investigation to clarify the effect of supplementation combined with exercise. Additional clinical studies are required to establish the effectiveness of this regimen in preserving muscle mass and enhancing functional performance. Clinical trial registration: This study has been registered with the Thai Clinical Trials Registry (ID: TCTR20210824002). © The Author(s) 2026. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.

INTRODUCTION: Environmental enteropathy (EE) is a syndrome affecting the gut characterised by villus blunting, reduced nutrient absorption and microbial translocation in children and adults experiencing a high burden of enteric infection due to inadequate access to clean water and sanitation. METHODS AND ANALYSIS: We will conduct coordinated randomised controlled trials in six countries to determine if supplementation with indispensable amino acids (IAAs) can improve intestinal barrier dysfunction in six geographically diverse populations of 18-36 months old children with stunting or severe stunting. All trials will measure the same primary outcomes while secondary outcomes will be measured on a per-trial basis using standardised protocols across the project. The primary endpoint will be change in gut permeability as assessed by the lactulose/rhamnose ratio. Secondary endpoints include changes in amino acid and carbohydrate absorption using novel, isotope tracer tests. Other prespecified outcome measures include changes in EE biomarkers and child weight. IAA supplementation will be given daily for 28 days and evaluation of the major endpoints will be at baseline and after 28 days of supplementation. ETHICS AND DISSEMINATION: Ethical approval will be obtained from the Research Ethics Committee at each participating site. Caregivers will provide written informed consent for each participant. Findings will be disseminated through peer-reviewed journals, conference presentations and face-to-face meetings with participant caregivers. TRIAL REGISTRATION NUMBER: CTRI: CTRI/2024/06/069187 (India); ClinicalTrials.gov (NCT06617130, Malawi; NCT06676215, Philippines and NCT07256028, Morocco); Ongoing (Zambia); Ongoing (Morocco); PACTR: (PACTR202311714091884, Ghana). © Author(s) (or their employer(s)) 2026. Re-use permitted under CC BY. Published by BMJ Group.

BACKGROUND: The obturator nerve block (ONB) is commonly performed using anterior and posterior branch blocks at the inguinal crease level. However, in practical situations, we have found that variable adductor muscle twitching can remain even after a successful main branch block. OBJECTIVES: This study evaluates how much an additional twitching block affects the complete adductor motor block compared to the classic ONB. Additionally, the study analyzes the patterns of residual twitching sites. STUDY DESIGN: A randomized, controlled trial. SETTING: The Department of Anesthesiology and Pain Medicine at the Gachon University Gil Medical Center. METHODS: In the classic group (n = 35), posterior and anterior branch blocks were performed by ultrasound with a nerve stimulator at the inguinal crease. In the sub-branch group (n = 35), the main branch block was performed in the same way as in the classic group. Fifteen minutes later, additional twitching blocks were performed. The primary outcome was the extent of the obturator reflex-graded adductor motor block, which was measured 15 minutes after the ONB in both groups, and the secondary outcome was the analysis of twitching site patterns. RESULTS: The total dose of local anesthetic was higher in the sub-branch group, but the quality of obturator reflex grading was statistically significantly better than in the classic group. No patient in either group required general anesthesia to complete surgery. Residual twitching was usually observed in the adductor brevis, adductor magnus, or pectineus muscles or at the inner portion of the fascial line through which the anterior or posterior branch passed. LIMITATION: The success of the ONB was evaluated using obturator reflex grades, which might not have provided an accurate measure of success. CONCLUSIONS: Although a main branch block alone does not usually result in inadvertent adductor muscle contraction severe enough to cause complications such as bladder perforation, partial residual muscle movement is observed. Therefore, supplementing the main branch block with an additional sub-branch block can be a reasonable strategy to achieve more complete motor blockade. Copyright

BACKGROUND: Tobacco use and its smoke produces oxidative stress in the body, which eventually triggers cell damage by lipid peroxidation. Smokers report lower levels of omega-3 fatty acids (FAs) in their serum as compared to nonsmokers. Omega-3 deficiency impairs neurotransmission, resulting in hypofunctioning of the mesocortical system, which is a reward and dependency system that can raise tobacco cravings, disrupting tobacco quitting efforts. Omega-3 polyunsaturated fatty acid (PUFA) regulates stress, anxiety, and negative emotions that are associated with tobacco urges. Limited research has assessed the supplementation effect of omega-3 PUFA [in the form of alpha-linolenic acid (ALA)] on tobacco craving. AIM: We aimed to explore the effects of omega-3 PUFA (ALA) on the frequency of tobacco use per day, tobacco dependence, and tobacco craving when compared to placebo in regular tobacco users. MATERIALS AND METHODS: Regular tobacco users (n = 83) recruited from the Tobacco Cessation Clinic were randomly allocated to two groups. Group I was the omega-3 PUFA group, supplemented with 10 mL/day of omega-3 PUFA in the form of ALA (5.1 gm) for 180 days, and the other group received a placebo for the same duration. The outcome was evaluated by means of a case record form (for demographic parameters), self-reports of tobacco use (for frequency of tobacco use per day), as well as psychometric measures (for tobacco dependence and tobacco craving). The evaluations were carried out at baseline and after 180 days of intervention. RESULTS AND CONCLUSION: The frequency of tobacco use per day, tobacco dependence, and tobacco craving were found to be significantly decreased (p < 0.0001) in the group receiving omega-3 PUFA (ALA) at the end of supplementation. This is a novel approach that ALA supplementation reduces tobacco cravings in regular tobacco users in comparison to a placebo. Thus, omega-3 FAs may be an adjuvant tool in quitting tobacco use by reducing nicotine dependence and tobacco craving. Further studies are necessary with large samples to understand the possible association and explore the probable nonpharmacological approaches for tobacco cessation. © Journal of

BACKGROUND: Whether the incorporation of Saccharomyces boulardii (S. boulardii) into vonoprazan-amoxicillin dual therapy contributes to improved eradication rate and a lower frequency of adverse events in rescue regimens for Helicobacter pylori (H. pylori) infection has yet to be established. METHODS: In a single-center, randomized controlled trial, 190 adults with previous H. pylori treatment failure were assigned to receive either vonoprazan (20 mg twice daily) plus amoxicillin (750 mg three times daily) (VA group) or the same regimen with S. boulardii (250 mg twice daily) (VAS group) for 14 days. Eradication rates, compliance, adverse events, and safety were assessed. Risk factors influencing the eradication rate were explored. RESULTS: Based on intention-to-treat analysis, H. pylori eradication rates were 80.0% in the VA group and 92.6% in the VAS group (P = 0.011), and per-protocol analysis yielded eradication rates of 85.4% and 94.6%, respectively (P = 0.037). There were no significant differences in eradication rates for either the VA regimen (P = 0.736) or the VAS regimen (P = 0.431) based on the number of previous treatment failures. However, a history of prior furazolidone use reduced the eradication rate of VAS therapy. The incidence of adverse events was significantly lower in the VAS group (11.6%) than it was in the VA group (32.6%; P < 0.001). Both groups showed similar good compliance and safety. CONCLUSION: Supplementing vonoprazan-amoxicillin dual therapy with S. boulardii significantly increases H. pylori eradication rates and reduces adverse events, offering an effective and simple rescue treatment unaffected by previous treatment failures. TRIAL REGISTRATION: Chinese Clinical Trial Registry No. ChiCTR2300075382, September 4, 2023. © 2026 Qu et al.

OBJECTIVE: Identifying eligible patients for precision oncology clinical trials is challenging, particularly for rare molecular subpopulations. To address this challenge, A2 Biotherapeutics developed BASECAMP-1 (NCT04981119), a non-interventional master screening study to identify patients eligible for interventional studies of logic-gated Tmod chimeric antigen receptor T-cell therapies. Eligible patients for these interventional trials have an advanced solid malignancy and are germline human leucocyte antigen (HLA)-A*02 heterozygous, with tumour-associated HLA-A loss of heterozygosity (LOH). HLA-A LOH occurs in ~16% of advanced solid malignancies; therefore, an efficient screening strategy is required. This report describes BASECAMP-1; compares the efficiency of two screening methods; and discusses the broader advantages of BASECAMP-1 beyond efficient enrolment. METHODS AND ANALYSIS: Patients are identified for BASECAMP-1 using two approaches. In the traditional approach, common for clinical trials, investigators consent and screen all patients who might be good candidates for cell therapy trials, with no prior knowledge of patient HLA-A type or LOH status. To further optimise our approach, we co-developed with Tempus AI (Tempus) the bioinformatic programme Aware, which identifies potentially eligible patients with tumour-associated HLA-A*02 LOH within a clinico-genomic database that includes linked genomic and transcriptomic sequencing and clinical data collected during routine care. RESULTS: Over 42 months of using a traditional approach to identify eligible patients, 1918 patients at 13 study sites were consented and screened for BASECAMP-1; of these, 30 patients with tumour-associated HLA-A*02 LOH were enrolled (~0.7 participants per month). Over the last 30 months of that same period, Tempus Aware screening was implemented and 55 patients with tumour-associated HLA-A*02 LOH were enrolled (~1.8 participants per month). The bioinformatic approach identified more patients than the traditional approach and used sequencing results produced as part of the standard clinical tumour sequencing workflow, reducing resource use and study staff burden. Additional advan

Glutathione (GSH), often referred to as the "master antioxidant," plays a vital role in protecting cells against oxidative stress. This human pilot study aimed to evaluate the oral absorption and safety profile of a novel formulation of micellar glutathione (LipoMicel®, LMG) compared with two commonly used dietary supplement forms: standard glutathione (STD) and liposomal glutathione (Setria® Glutathione, LSG). In the first phase, a randomized, double-blind, crossover study was conducted in healthy adults (n = 14) to assess whole-blood GSH following single oral doses using baseline-adjusted pharmacokinetic parameters (incremental AUC0-24 [iAUC0-24], Cmax, Tmax) and a targeted panel of glutathione-related metabolites. In the second phase, a 30-day, single-arm follow-up assessed the safety and tolerability of the most bioavailable formulation (LMG) in the same participants. Compared with STD (500 mg), LMG (300 mg) produced significantly higher baseline-adjusted systemic GSH exposure and peak response (iAUC0-24: 1287.5 ± 179.0 vs. 517.8 ± 180.0 µg·mL·h; p = 0.0064; ΔCmax: 103.9 ± 11.8 vs. 42.8 ± 11.5 µg/mL; p = 0.0003), corresponding to ~2.49-fold higher incremental exposure and ~2.43-fold higher peak response at the administered doses. When dose-normalized to a 300 mg equivalent, the incremental exposure (iAUC) and Cmax were up to 4-fold higher for LMG than STD. In the targeted metabolite panel, most analytes showed no formulation-dependent differences; however, dose-normalized methionine exposure was significantly higher with LMG than STD (iAUC: 149.9 ± 30.8 vs. 32.7 ± 28.3 µg·mL·h; p = 0.0151; ~4.58-fold). No significant differences were observed in oxidized glutathione (GSSG) exposure, while the GSH/GSSG ratio was higher following LMG versus STD (p = 0.001). No significant changes in clinical safety markers (e.g., ALT, AST, ALP, creatinine) were observed following 30 days of daily LMG administration at 600 mg/d. The novel micellar glutathione formulation demonstrated enhanced oral bioavailability compared with a standard glutathione preparation and was well tolerated over 30 days in healthy adults. These findings present LipoMicel® as a promising approach for o

PURPOSE: To compare and evaluate the clinical performance and fit success of lehfilcon A and lotrafilcon B multifocal soft contact lenses (MfSCLs). PATIENTS AND METHODS: This was a prospective, randomized, double-masked, crossover, dispensing clinical study. Eligible wearers were fitted and wore study MfSCLs bilaterally (≥8 hours/day, ≥5 days/week) over 30 days. Endpoints: binocular visual acuity (VA) at distance (4 m), intermediate (80 cm), and near (40 cm) at day 30; fit rate success; eye care professional (ECP) rating, study dispensed lens power at visit 1; lens fit, and surface characteristics at dispense and day 30; safety assessments. RESULTS: Overall, 101 subjects were enrolled. At day 30, lehfilcon A MfSCLs were noninferior to lotrafilcon B MfSCLs for distance, intermediate, and near VA (non-inferiority margin: 0.05; 95% UCL of LSM difference 0.00, 0.02, 0.04; mean VA, lehfilcon A: -0.10 ± 0.08, -0.10 ± 0.08, and 0.01 ± 0.12; lotrafilcon B: -0.09 ± 0.07, -0.11 ± 0.08, and -0.02 ± 0.11). At visit 1, ≥99.5% of both MfSCLs achieved successful fit with 1-2 lenses/eye. Mean ECP ratings for ease of fit: lehfilcon A 9.8 ± 0.6; lotrafilcon B: 9.7 ± 0.6. About 96.0% of subjects had same sphere (D) power and 100.0% had same ADD power in both eyes for both lenses. All MfSCLs had optimal/acceptable fit. Majority of MfSCLs (>96%) had grade 0/1 front surface wettability and front/back surface deposits. No serious AEs were reported, and all biomicroscopy findings were graded 2 (mild) or lower. CONCLUSION: Lehfilcon A multifocal contact lenses combine excellent visual performance, high fit success, and a stable, comfortable wearing experience over 30 days of daily wear. With their water-gradient surface, favorable safety profile, and ease of fit, they represent a reliable and beneficial option for clinicians to consider when selecting multifocal lenses for presbyopic patients. © 2026 Bickle et al.

BACKGROUND AND AIMS: Systemic inflammation is an independent predictor of cardiovascular events, and nut-enriched diets are often recommended after acute myocardial infarction (AMI). However, the effects of mixed nuts on inflammatory biomarkers in secondary prevention remain unclear. This study evaluated the impact of incorporating mixed nuts into the Brazilian Cardioprotective Diet (DICA Br) on systemic inflammation and dietary inflammatory potential in post-AMI patients. METHODS AND RESULTS: This secondary analysis of the DICA-NUTS randomized controlled trial included 170 adults post-AMI, assigned to receive either the DICA Br diet alone (n = 85) or the same diet supplemented with 30 g/day of mixed nuts (10 g each of peanuts, cashews, and Brazil nuts; n = 85) for 16 weeks. Plasma concentrations of interleukins (IL-2, IL-4, IL-6, IL-10), tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), and C-reactive protein (CRP) were measured at baseline and post-intervention. Dietary inflammatory potential was assessed using the Dietary Inflammatory Index (DII®) and the energy-adjusted DII (E-DII™). No significant between-group differences were observed for any inflammatory biomarker or for DII and E-DII scores. Within the DICA group, IL-4 levels decreased (-4.56 pg/mL; 95% CI -9.00 to -0.11; p = 0.045), with a concurrent increase in the IFN-γ/IL-4 ratio (0.035; 95% CI 0.003 to 0.067; p = 0.04). IFN-γ concentrations were higher in the lowest DII tertile (p = 0.046) and inversely correlated with DII scores (ρ = -0.15; p = 0.006). CONCLUSION: Supplementation with 30 g/day of mixed nuts did not significantly modify inflammatory biomarkers or improve the anti-inflammatory potential of the diet over 16 weeks in post-AMI patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03728127.

BACKGROUND: The structure and function of human tissue, such as bone, muscle and tendon, can be improved with targeted exercise training. However, the effects of exercise training on intervertebral disc tissue remain unclear. OBJECTIVE: We aimed to examine the impact of physical loading exposure (exercise training, sport and physical activity) on intervertebral disc (IVD) health compared to non-physical loading (or lower volume of the same physical loading) controls. METHODS: We conducted a systematic review and meta-analysis. Seven electronic databases (PubMed, CINAHL, SPORTDiscus, EMBASE, CENTRAL, Web of Science and Scopus) and two trial registries (World Health Organization International Clinical Trials Registry Platform and National Institutes of Health) were searched from inception to 3 June, 2025. Forward and backward citation tracking was conducted for included reports. Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation criteria (GRADE). Risk of bias was assessed using Cochrane RoB2 and Johanna Briggs Institute critical appraisal checklists. We included randomised controlled trials (n = 2), cohort (n = 9) and cross-sectional studies (n = 28) of any physical loading compared to controls with continuous measurements of IVD health (e.g. T2-relaxation, IVD height) via magnetic resonance imaging and/or categorically graded measures of IVD degeneration (e.g. Pfirrmann grade). RESULTS: Forty-five reports of 39 studies (participants: 4152) were included. The pairwise random-effects meta-analysis estimated the standardised mean difference (Hedges' g) of continuous outcomes for combined physical loading and independent subgroups and odds ratios (Paule-Mandel estimator) of categorical outcomes for combined physical loading only. A meta-analysis revealed upright bipedal loading (mostly running; Hedges' g [95% confidence interval] 0.31 [0.12, 0.50]; P = 0.002; n = 7, GRADE: very low) was associated with better IVD health; however, no other subgroup of physical loading was associated with better or worse IVD health. Combined physical loading revealed greater odds of IVD degeneration via reduced signal intensit

Folate is an essential nutrient that supports the formation of S-adenosyl methionine (SAM) in the pathway of one carbon metabolism. Dietary folate intake has been shown to affect the SAM-dependent methylation of diverse substrates, including DNA and inorganic arsenic (iAs). The methylation of iAs by arsenic methyltransferase (AS3MT) plays a key role iAs detoxification in both humans and mice. Our recent studies using wild-type C57BL/6N mice showed that preconception exposure to iAs resulted in heritable changes in DNA methylation in paternal sperm and differential expression of genes in tissues of the offspring that developed a diabetic phenotype. The goal of the present study was to determine if dietary folate can modify the iAs-induced differential methylation of DNA in sperm of male C57BL/6 mice expressing the human AS3MT and exhibiting a human-like pattern of iAs metabolism. Mice were fed folate deficient (FD, 0 mg folic acid/kg) or folate supplemented (FS, 10 mg folic acid/kg) diet for 6 weeks, followed by exposure to 0 (controls) or 400 ppb iAs (arsenite) in drinking water for 5 weeks while on the same types of diet. Reduced Representation Bisulfite Sequencing was used to identify CpG sites and genes that were differentially methylated in response to iAs exposure, followed by analysis of pathways enriched for these genes. Genes and pathways associated with cell morphology and function, and neural structure and function were the top pathways enriched by iAs exposure in both FD and FS mice. Notably, pathways associated with diabetes, regulation of insulin secretion and signaling were enriched for differentially methylated genes only in the sperm of iAs-exposed FS mice. These results suggest that folate intake modifies the effects of iAs exposure on DNA methylation in sperm of the humanized mice, providing strong rationale for studies that will examine the role of folate in modulation of adverse effects of preconception exposure to iAs. © 2026. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

RESEARCH QUESTION: Does combined treatment with hyaluronic acid and prolactin (PRL) for post-warming culture and embryo transfer increase the live birth rate after single vitrified-warmed blastocyst transfer (SVBT)? DESIGN: A three-arm, double-blind, randomized controlled trial (RCT) was conducted between October 2020 and May 2021. Overall, 1236 couples undergoing SVBT were randomized using a 1:1:1 ratio into three groups: after removing the zona pellucida, warmed blastocysts were incubated in a medium without hyaluronic acid or PRL (control group), a hyaluronic-acid-enriched transfer medium (EmbryoGlue group), or EmbryoGlue supplemented with PRL (EGP group) for 2-4 h prior to transfer in the same medium. The primary outcome was the live birth rate. RESULTS: The live birth rate was higher in the EGP group compared with the control (OR 1.40; P = 0.0219) and EmbryoGlue (OR 1.38; P = 0.0266) groups. Although positive pregnancy and clinical pregnancy rates were comparable among the three groups, the ongoing pregnancy rate was higher in the EGP group compared with the control (P = 0.0142) and EmbryoGlue (P = 0.0249) groups. Furthermore, the rate of early pregnancy loss was lower in the EGP group compared with the control (P = 0.0073) and EmbryoGlue (P = 0.0053) groups. Subgroup analysis demonstrated significant interactions for embryo culture time (P = 0.0494) and serum progesterone (P = 0.0045): EGP treatment was effective for day 4-5 blastocysts and patients with insufficient serum progesterone. CONCLUSIONS: This RCT suggests that combined treatment with hyaluronic acid and PRL is effective for improving the live birth rate in good-prognosis patients by reducing early pregnancy loss.

BACKGROUND: The Colorectal Cancer (CRC) pathogenesis and therapeutic efficacy are influenced by the gut microbiome, making it a promising biomarker for predicting treatment responses and adverse effects. This systematic review aims to outline the gut microbiome composition in individuals with CRC undergoing the same therapeutic regimen and evaluate interindividual microbiome profile variations to better understand how these differences may influence therapeutic outcomes. METHODS: Key studies investigating the microbiome's role in therapeutic approaches for CRC were searched in both PubMed and Cochrane databases on 12 and 22 March 2025, respectively. Eligible studies included free full-text English-language randomized clinical trials and human observational studies reporting on gut microbiome composition and treatment outcomes. RoB 2 and ROBINS-I were employed in the evaluation of bias for randomized trials and observational studies, respectively. Data extracted was narratively analyzed. RESULTS: Six studies involving a total of 361 individuals were included. Therapeutic interventions, either standard treatments and/or those targeting the gut microbiome, generally increased probiotic taxa and reduced pro-carcinogenic bacteria. However, no consistent pattern of improved clinical outcomes was observed, suggesting that treatment mechanisms, the tumor's nature, and individual characteristics play critical roles in microbiome modulation. CONCLUSION: The gut microbiome holds significant potential in clinical settings. Nonetheless, further research is needed to better understand its functional aspects and to consider the influence of treatment mechanisms, the tumor's nature, and individual characteristics as modulators, in order to optimize clinical outcomes. © 2026 The Authors. Published by Tech Science Press.