From A to E: Uniting vitamins against stroke risk-A systematic review and network meta-analysis.

BACKGROUND AND AIM: Stroke represents a significant public health challenge, necessitating the exploration of preventive measures. This network meta-analysis aimed to assess the efficacy of different vitamin treatments compared to a placebo in preventing stroke. METHODS: A systematic electronic search in databases including PubMed, EmBASE, Web of Science, clinicaltrials.gov, and Google Scholar until 31 May 2023 was conducted, to identify published studies investigating the association between vitamin intake and the risk of stroke. Pooled risk ratio (RR) with 95% confidence intervals (CIs) was calculated using a frequentist network meta-analysis. Furthermore, we ranked vitamins based on p-scores, facilitating a comparative assessment of their effectiveness in preventing stroke. RESULTS: A total of 56 studies, including 17 randomized controlled trials (RCTs) and 39 cohort studies were analyzed. Direct estimates obtained from network meta-analysis, we found that vitamin A (RR: .81 [.72-.91]), vitamin B-complex (RR: .85 [.74-.97]), vitamin B6 (RR: 79 [.68-.92]), folate (RR: .86 [.75-.97]), vitamin C (RR: .77 [.70-.85]) and vitamin D (RR: .73 [.64-.83]) were significantly associated with a decreased stroke risk. However, no significant association was observed for vitamin B2, vitamin B12, and vitamin E. Subsequent to network meta-analysis, vitamins were ranked in decreasing order of their efficacy in stroke prevention based on p-score, with vitamin D (p-score = .91), vitamin C (p-score = .79), vitamin B6 (p-score = .70), vitamin A (p-score = .65), vitamin B-complex (p-score = .53), folate (p-score = .49), vitamin B2 (p-score = .39), vitamin E (p-score = .28), vitamin B12 (.13) and placebo (.10). CONCLUSION: Our study has established noteworthy connections between vitamin A, vitamin B-complex, vitamin B6, folate, vitamin C, and vitamin D in the realm of stroke prevention. These findings add substantial weight to the accumulating evidence supporting the potential advantages of vitamin interventions in mitigating the risk of stroke. However, to solidify and validate these observations, additional research is imperative. Well-designed clinical trials or cohort studies are needed to further explore these associations and formulate clear guidelines for incorporating vitamin supplementation into effective stroke prevention strategies.

The impact of pre-pregnancy folic acid intake on placental DNA methylation in a fortified cohort.

Folate plays an important role in the modulation of one-carbon metabolism and DNA methylation through a complex biosynthesis pathway. Folate deficiency during pregnancy has been associated with an increased risk for birth defects. This study investigates the extent to which the availability of folate and S-Adenosylmethionine (SAM) affects placental DNA methylation. We hypothesized that maintaining sufficient levels of folate and SAM is particularly important in individuals carrying the MTHFR C677T polymorphism. Maternal- and cord blood was analyzed to genotype the MTHFR rs1801133 SNP. Red blood cell (RBC) folate, vitamin B12, SAM, and S-Adenosylhomocysteine (SAH) were analyzed in cord blood. Epigenome-wide methylation analyses were performed on 90 placenta tissue samples isolated from the fetal side of the placenta; 45 originating from mother-infant dyads homozygous for the MTHFR C677T variant and 45 originating from mother-infant dyads with the homozygous wild type MTHFR677 genotype. Verification of the results was performed using pyrosequencing assays. Genome-wide placental DNA methylation patterns were relatively stable and not significantly affected by levels of one-carbon metabolites. MTHFR genotype was associated with DNA methylation of several loci, including a locus in the MTHFR region. RBC folate and particularly the SAM:SAH ratio did affect overall CpG DNA methylation in some CpG regions when the loci were split according to their CpG island relation. This was most evident in participants carrying the MTHFR C677T variant suggesting a stronger influence of the biosynthesis pathway on the overall placental DNA methylation in MTHFR TT individuals than in MTHFR CC individuals.

Prescribing patterns for higher dose folic acid in pregnant women with epilepsy treated with antiseizure medication.

OBJECTIVE: This study was undertaken to characterize the use of higher doses of folic acid (≥1 mg daily) in relation to pregnancy in Denmark, Norway, and Sweden in women with epilepsy treated with antiseizure medication (ASM). METHODS: In this observational study, we used data from national medical birth, patient, and prescription registers in Denmark, Norway, and Sweden to retrospectively identify pregnancies in women with epilepsy treated with ASM from 2006 to 2017. The proportion of higher dose folic acid supplementation in pregnancies among women receiving ASM for epilepsy was calculated according to country of origin, time period, and type of ASM. Logistic regression with restricted cubic splines was used to model country-specific time trends. RESULTS: Among a total of 2 748 882 pregnancies, we identified 8695 (.3%) pregnancies after restricting the population to women with ASM-treated epilepsy. A prescription for higher dose folic acid was filled in 4719 (54.3%) of these pregnancies. The proportion supplemented with higher dose folic acid was highest in Sweden (74.3%) and lower in Norway (41.4%) and Denmark (34.3%). Furthermore, we observed a decreasing trend of higher dose folic acid use in Denmark and Norway from year 2012 to 2017. Among those who used higher dose folic acid, 42% did not start preconception supplementation with higher dose folic acid. SIGNIFICANCE: Supplementation with higher dose folic acid occurred in approximately half of pregnancies in women with ASM-treated epilepsy, with many not starting supplementation until after becoming pregnant. Considerable variability was observed in the use of higher dose folic acid across the countries, despite similar population characteristics and health care systems. Future guidelines should be simplified with clear recommendations developed in a collaborative manner by relevant specialists including neurologists, obstetricians, pediatricians, and public health specialists to enhance real-world applicability.

Maternal periconceptional folic acid supplementation and risk for fetal congenital genitourinary system defects.

BACKGROUND: Taking folic acid supplementation could reduce the risk of neural tube defects for offspring in the maternal periconceptional period, but the relationship between folic acid use and other birth defects remains unclear, such as genitourinary system birth defects. METHODS: The data from a Prenatal Health Care System and Birth Defects Surveillance System in Tongzhou, Beijing, China, were collected from 2013 to 2018. We adjusted for differences in characteristics between comparison groups using propensity score inverse probability weighting and assessed associations with Poisson regression modeling. RESULTS: A total of 65,418 live births and stillbirths were included, and there were 194 cases with congenital genitourinary defects among them. The prevalence of genitourinary system birth defects was 29.2 (34.9) per 10,000 for FA/MMFA users (nonusers). Compared to nonusers, FA/MMFA users had a lower risk for genitourinary system birth defects (adjusted risk ratio [aRR] 0.81, 95% confidence interval [CI] 0.67, 0.98), and for hypospadias (aRR 0.55, 95% CI 0.40, 0.76). CONCLUSIONS: FA or MMFA supplementation during the maternal periconceptional period could reduce the risk for genitourinary system birth defects in offspring. More mechanisms should be explored for the protective effect. IMPACT: Folic acid (FA) or multiple micronutrients containing folic acid (MMFA) supplementation during the maternal periconceptional period could reduce the risk for genitourinary system birth defects in offspring. Maternal FA/MMFA supplementation during the periconceptional period may reduce the risk for hypospadias.

Population pharmacokinetics of mirvetuximab soravtansine in patients with folate receptor-α positive ovarian cancer: The antibody-drug conjugate, payload and metabolite.

AIMS: Mirvetuximab soravtansine is a first-in-class antibody-drug conjugate recently approved for the treatment of folate receptor-α positive ovarian cancer. The aim of this study was to develop a population pharmacokinetic model to describe the concentration-time profiles of mirvetuximab soravtansine, the payload (DM4) and a metabolite (S-methyl-DM4). METHODS: Mirvetuximab soravtansine was administered intravenously from 0.15 to 7 mg/kg to 543 patients with predominantly platinum-resistant ovarian cancer in 3 clinical studies, and the plasma drug concentrations were analysed using a nonlinear mixed-effects modelling approach. Stepwise covariate modelling was performed to identify covariates. RESULTS: We developed a semi-mechanistic population pharmacokinetic model that included linear and nonlinear routes for the elimination of mirvetuximab soravtansine and a target compartment for the formation and disposition of the payload and metabolite in tumour cells. The clearance and volume of the central compartment were 0.0153 L/h and 2.63 L for mirvetuximab soravtansine, 8.83 L/h and 3.67 L for DM4, and 2.04 L/h and 6.3 L for S-methyl-DM4, respectively. Body weight, serum albumin and age were identified as statistically significant covariates. Exposures in patients with renal or hepatic impairment and who used concomitant cytochrome P450 (CYP) 3A4 inhibitors were estimated. CONCLUSION: There is no need for dose adjustment due to covariate effects for mirvetuximab soravtansine administered at the recommended dose of 6 mg/kg based on adjusted ideal body weight. Dose adjustment is not required for patients with mild or moderate renal impairment, mild hepatic impairment, or when concomitant weak and moderate CYP3A4 inhibitors are used.

The association of preconceptional folic acid supplementation with gestational age and preterm birth risk in twin pregnancies: a prospective cohort study in China.

PURPOSE: This study aims to explore the association of maternal preconceptional folic acid (FA) supplementation with gestational age and preterm birth in twin pregnancies, and whether the association varies by chorionicity or conception mode. METHODS: From November 2018 to December 2021, the information of FA supplementation and pregnancy outcomes were collected in twin pregnant women. The linear regression models and the logistic regression were used to test the association of preconceptional FA supplementation with gestational age at delivery and preterm birth and premature rupture of membranes (PROM). RESULTS: A total of 416 twin pregnancies were included. Compared with no use in twins, maternal preconceptional FA use was associated with a 0.385-week longer gestational age (95% CI 0.019-0.751) and lower risk of preterm birth < 36 weeks (adjusted OR 0.519; 95% CI 0.301-0.895) and PROM (adjusted OR 0.426; 95% CI 0.215-0.845). The protective effect on preterm birth < 36 weeks and PROM is similar whether taking FA supplements alone or multivitamins. However, the associations varied by chorionicity and conception mode of twins or compliance with supplementation. The positive associations between preconceptional FA use and gestational age only remained significant among twins via assisted reproductive technology or dichorionic diamniotic twins. Significant protective effects on preterm birth < 36 weeks and PROM were only found among women who took FA at least 4 times a week before conception. CONCLUSION: Maternal preconceptional FA supplementation was associated with longer gestation duration and lower risk of preterm birth < 36 weeks and PROM in twin pregnancies. To improve the success of their pregnancies, reproductive women should start taking FA supplements well before conception and with good compliance.

Arsenic modifies the effect of folic acid in spina bifida prevention, a large hospital-based case-control study in Bangladesh.

BACKGROUND: Spina bifida, a developmental malformation of the spinal cord, is associated with high rates of mortality and disability. Although folic acid-based preventive strategies have been successful in reducing rates of spina bifida, some areas continue to be at higher risk because of chemical exposures. Bangladesh has high arsenic exposures through contaminated drinking water and high rates of spina bifida. This study examines the relationships between mother's arsenic exposure, folic acid, and spina bifida risk in Bangladesh. METHODS: We conducted a hospital-based case-control study at the National Institute of Neurosciences & Hospital (NINS&H) in Dhaka, Bangladesh, between December 2016 and December 2022. Cases were infants under age one year with spina bifida and further classified by a neurosurgeon and imaging. Controls were drawn from children seen at NINS&H and nearby Dhaka Shishu Hospital. Mothers reported folic acid use during pregnancy, and we assessed folate status with serum assays. Arsenic exposure was estimated in drinking water using graphite furnace atomic absorption spectrophotometry (GF-AAS) and in toenails using inductively coupled plasma mass spectrometry (ICP-MS). We used logistic regression to examine the associations between arsenic and spina bifida. We used stratified models to examine the associations between folic acid and spina bifida at different levels of arsenic exposure. RESULTS: We evaluated data from 294 cases of spina bifida and 163 controls. We did not find a main effect of mother's arsenic exposure on spina bifida risk. However, in stratified analyses, folic acid use was associated with lower odds of spina bifida (adjusted odds ratio [OR]: 0.50, 95% confidence interval [CI]: 0.25-1.00, p = 0.05) among women with toenail arsenic concentrations below the median value of 0.46 µg/g, and no association was seen among mothers with toenail arsenic concentrations higher than 0.46 µg/g (adjusted OR: 1.09, 95% CI: 0.52-2.29, p = 0.82). CONCLUSIONS: Mother's arsenic exposure modified the protective association of folic acid with spina bifida. Increased surveillance and additional preventive strategies, such as folic acid fortification and reduction of arsenic, are needed in areas of high arsenic exposure.

Knowledge, awareness, and use of folic acid among women of childbearing age living in a peri-urban community in Ghana: a cross-sectional survey.

BACKGROUND: Folic acid, a water-soluble B-complex vitamin, plays a crucial role in DNA synthesis and maintenance, making it particularly significant during reproduction. Its well-known ability to reduce the risk of congenital anomalies during the periconceptional period underscores its importance. The increased requirement for folate during pregnancy and lactation is essential to support the physiological changes of the mother and ensure optimal growth and development of the foetus and offspring. This study assessed the knowledge, awareness, and use of folic acid among pregnant and lactating women of reproductive age residing in Dodowa in the Shai Osu-Doku District, Accra, Ghana. METHODS: The study was a cross-sectional design that involved 388 randomly selected participants (97 pregnant and 291 lactating women). Structured questionnaires were administered to gather information on the socioeconomic demographic characteristics, knowledge, awareness, and use of folic acid of the participants. Dietary intake was assessed using a food frequency questionnaire. The data were analysed using descriptive statistics and Pearson's chi-square analysis tests and are presented as frequencies and percentages, means, standard deviations, bar graphs, and pie charts. The significance of the results was determined at a 95% confidence interval. RESULTS: The mean age of the participants was 31 ± 5.0 years. Among the study participants, 46.1% demonstrated knowledge of folic acid deficiency, while approximately 68.3% had a high awareness of folic acid supplementation. Approximately 75% of the participants indicated that they had not used folic acid supplements within the week, and 15.5% reported consuming folic acid-fortified food per week. CONCLUSIONS: The women exhibited high awareness but poor knowledge regarding the usage of folic acid supplementation during pregnancy and lactation. Consequently, this lack of knowledge influenced the low use of folic acid supplements and low intake of folate-rich foods among pregnant and lactating mothers.

Prognostic Impact of Serum Homocysteine-Lowering Therapy on Patients with Hemorrhagic Stroke and Its Influence on National Institutes of Health Stroke Scale and China Stroke Scale Scores.

Objective: This study aimed to investigate the prognostic impact of serum homocysteine-lowering therapy on patients with hemorrhagic stroke (HS) and its influence on their National Institutes of Health Stroke Scale (NIHSS) and China Stroke Scale (CSS) scores. Methods: A double-blind study involving 120 patients with HS and hyperhomocysteinemia (Hhcy) who were admitted to our hospital was conducted in 2021. They were evenly divided into two groups: the control group (n=60) received low-dose folic acid, methylcobalamin, and vitamin B6 as part of serum homocysteine-lowering therapy, while the study group (n=60) received high-dose folic acid, methylcobalamin, and vitamin B6. The prognosis of each group was compared using the NIHSS and CSS to assess the neurological function of the patients. Results: Before treatment, the levels of oxidative stress markers and vascular endothelial function markers were comparable between the two groups (t = 0.051, 0.015, 0.010, 0.011, 0.013, 0.022, P = .960, .988, .992, 0.991, .989, 0.982). However, after treatment, the study group exhibited higher levels of MDA and ET-1 compared to the control group (t = 3.418, 1.978, P < .001). Additionally, SOD, GSH-Px, and PON1 levels were lower in the study group (t = 3.435, 3.783, 2.735, 3.893, P < .001). The NIHSS scores before treatment were comparable among patients (t = 0.058, P = 0.954), but after treatment, the study group showed significantly lower NIHSS scores (t = 20.105, P < .001). Similarly, the CSS scores before treatment were comparable (t = 0.046, P = .963), but the CSS scores in the study group after treatment were significantly lower (t = 5.027, P < .001). Conclusions: High-dose folic acid, methylcobalamin, and vitamin B6 as part of serum homocysteine-lowering therapy can improve oxidative stress and vascular endothelial function in HS patients. This treatment also enhances prognosis and ameliorates neurological deficits. Therefore, it holds significant clinical potential and should be considered for broader adoption.

Developing Folate-Conjugated miR-34a Therapeutic for Prostate Cancer: Challenges and Promises.

Prostate cancer (PCa) remains a common cancer with high mortality in men due to its heterogeneity and the emergence of drug resistance. A critical factor contributing to its lethality is the presence of prostate cancer stem cells (PCSCs), which can self-renew, long-term propagate tumors, and mediate treatment resistance. MicroRNA-34a (miR-34a) has shown promise as an anti-PCSC therapeutic by targeting critical molecules involved in cancer stem cell (CSC) survival and functions. Despite extensive efforts, the development of miR-34a therapeutics still faces challenges, including non-specific delivery and delivery-associated toxicity. One emerging delivery approach is ligand-mediated conjugation, aiming to achieve specific delivery of miR-34a to cancer cells, thereby enhancing efficacy while minimizing toxicity. Folate-conjugated miR-34a (folate-miR-34a) has demonstrated promising anti-tumor efficacy in breast and lung cancers by targeting folate receptor α (FOLR1). Here, we first show that miR-34a, a TP53 transcriptional target, is reduced in PCa that harbors TP53 loss or mutations and that miR-34a mimic, when transfected into PCa cells, downregulated multiple miR-34a targets and inhibited cell growth. When exploring the therapeutic potential of folate-miR-34a, we found that folate-miR-34a exhibited impressive inhibitory effects on breast, ovarian, and cervical cancer cells but showed minimal effects on and targeted delivery to PCa cells due to a lack of appreciable expression of FOLR1 in PCa cells. Folate-miR-34a also did not display any apparent effect on PCa cells expressing prostate-specific membrane antigen (PMSA) despite the reported folate's binding capability to PSMA. These results highlight challenges in the specific delivery of folate-miR-34a to PCa due to a lack of target (receptor) expression. Our study offers novel insights into the challenges and promises within the field and casts light on the development of ligand-conjugated miR-34a therapeutics for PCa.

Pancytopenia Due to Folate Deficiency.

We found the article on "The Digital Technology in Clinical Medicine: From Calculators to ChatGPT" interesting.1 According to Kulkarni et al., humanity has witnesses four important social system changes, starting with the primitive huntersgatherers and progressing to horticultural, agricultural, industrial, and the current fifth, which is based on digital information technology and has altered the way we present, recognize, and utilize different factors of production. In clinical medicine, digital technology has advanced significantly since the days of computations. According to Kulkarni et al., we have to benefit from these advancements as we all improve the lives of our patients while being cautious not to overturn the doctor-patient relationship. If technology, clinical expertise, and humanistic values are properly balanced, Kulkarni et al. concluded that the future is quite glorious.1 Regulatory organizations are pushing for improvements through clinical trials as a result of recognition of the expanding influence of digital technology in healthcare delivery. The "World Health Organizations Guidelines for Digital Interventions" and the "Food and Drug Administration's Digital Health Center of Excellence" are only two of the projects that are currently being highlighted in the study as efforts to analyze and implement digital health services.

Beyond Weight Loss: A Comprehensive Review of Pregnancy Management following Bariatric Procedures.

The increasing prevalence of bariatric surgery among women of childbearing age raises critical questions about the correct management of pregnancy following these procedures. This literature review delves into the multifaceted considerations surrounding pregnancy after bariatric surgery, with a particular focus on the importance of preconception counselling, appropriate nutrition assessment, and the necessity of correct folic acid supplementation. Key areas of investigation include nutrient absorption challenges, weight gain during pregnancy, and potential micronutrient deficiencies. Examining the relationship between bariatric surgery and birth defects, particularly heart and musculoskeletal issues, uncovers a twofold increase in risk for women who underwent surgery before pregnancy, with the risk emphasized before folic acid fortification. In contrast, a nationwide study suggests that infants born to mothers with bariatric surgery exhibit a reduced risk of major birth defects, potentially associated with improved glucose metabolism. In addition, this review outlines strategies for managing gestational diabetes and other pregnancy-related complications in individuals with a history of bariatric surgery. By synthesizing existing literature, this paper aims to provide healthcare providers with a comprehensive framework for the correct management of pregnancy in this unique patient population, promoting the health and well-being of both mother and child.

Can supplementing vitamin B12 improve mental health outcomes?: a literature review.

AIM: This study reviews research into the effects of the supplementation of B12 in the prevention and recovery of mental illness, and the potentiation of psychotropic medication. METHODOLOGY: This literature review follows a systematic approach to searching databases CINAHL, EMBASE, Medline, and PsycINFO where 287 non-duplicated articles results were received. Appropriate articles were identified through title and abstract screening and inclusion and exclusion criteria were applied. Five articles were chosen to address the research question following critical appraisal. Thematic analysis was then conducted. FINDINGS: This review identified five randomised controlled trials into the supplementation of various doses of B12 in conjunction with folic acid and B6. The supplement was measured against post-stroke depression prevention, the reduction of symptoms of depression in woman with cardiovascular disease, the effect on negative symptoms in schizophrenia, the reduction and prevention of depression in older adults, and the potentiation of psychotropic interventions. The papers reviewed showed inconclusive results, but evidence to support sub-groups and specific high-risk groups. Strong evidence showed supplementation of B12, folic acid and B6 has high rates of preventing post-stroke depression. CONCLUSION: The findings show that this area of research is still to be developed. The effects of B12 supplementation with other B vitamins on mental health have shown to be inconclusive. There is a case for its use to be considered within certain patient groups to aid recovery of mental health or in some high-risk patient groups. Recommendations are made for further research into high-risk groups of people that may have symptoms or symptoms that could be improved through the supplementation of B12.

Folic acid attenuates chronic visceral pain by reducing clostridiales abundance and hydrogen sulfide production.

Irritable bowel syndrome (IBS) related chronic visceral pain affects 20% of people worldwide. The treatment options are very limited. Although the scholarly reviews have appraised the potential effects of the intestinal microbiota on intestinal motility and sensation, the exact mechanism of intestinal microbiota in IBS-like chronic visceral pain remains largely unclear. The purpose of this study is to investigate whether Folic Acid (FA) attenuated visceral pain and its possible mechanisms. Chronic visceral hyperalgesia was induced in rats by neonatal colonic inflammation (NCI). 16S rDNA analysis of fecal samples from human subjects and rats was performed. Patch clamp recording was used to determine synaptic transmission of colonic-related spinal dorsal horn. Alpha diversity of intestinal flora was increased in patients with IBS, as well as the obviously increased abundance of Clostridiales order (a main bacteria producing hydrogen sulfide). The hydrogen sulfide content was positive correlation with visceral pain score in patients with IBS. Consistently, NCI increased Clostridiales frequency and hydrogen sulfide content in feces of adult rats. Notably, the concentration of FA was markedly decreased in peripheral blood of IBS patients compared with non-IBS human subjects. FA supplement alleviated chronic visceral pain and normalized the Clostridiales frequency in NCI rats. In addition, FA supplement significantly reduced the frequency of sEPSCs of neurons in the spinal dorsal horn of NCI rats. Folic Acid treatment attenuated chronic visceral pain of NCI rats through reducing hydrogen sulfide production from Clostridiales in intestine.

Mechanisms of folate metabolism-related substances affecting Staphylococcus aureus infection.

Staphylococcus aureus (S. aureus) is one of the critical clinical pathogens which can cause multiple diseases ranging from skin infections to fatal sepsis. S. aureus is generally considered to be an extracellular pathogen. However, more and more evidence has shown that S. aureus can survive inside various cells. Folate plays an essential role in multiple life activities, including the conversion of serine and glycine, the remethylation of homocysteine to methionine, and the de novo synthesis of purine /dTMP, et al. More and more studies reported that S. aureus intracellular infection requires the involvement of folate metabolism. This review focused on the mechanisms of folate metabolism and related substances affecting S. aureus infection. Loss of tetrahydrofolic acid (THF)-dependent dTMP directly inhibits the nucleotide synthesis pathway of the S. aureus due to pabA deficiency. Besides, trimethoprim-sulfamethoxazole (TMP/SMX), a potent antibiotic that treats S. aureus infections, interferes in the process of the folate mechanism and leads to the production of thymidine-dependent small-colony variants (TD-SCVs). In addition, S. aureus is resistant to lysostaphin in the presence of serine hydroxymethyltransferase (SHMT). We provide new insights for understanding the molecular pathogenesis of S. aureus infection.

Similar effect of co-administration of methotrexate and folic acid for the treatment of arthritis compared to separate administration.

OBJECTIVES: MTX is the recommended first-line treatment for RA associated with folic acid (FA) to reduce side effects related to MTX. Here, we proposed to test a co-administration of MTX with FA in the rat adjuvant-induced arthritis (AIA) on efficacy. MATERIAL AND METHODS: AIA was induced in female Lewis rats and treated with MTX in three groups. The first group of rats received only MTX (n = 13), whereas the second received MTX and FA on the same day (n = 14). The third group received FA one day after MTX (n = 14). Arthritic index (AI), ankle circumference (AC), ankle microcomputed tomography, and blood tests assessed arthritis severity and MTX tolerance. RESULTS: AI and AC were similar in MTX groups at various time points. Bone erosion and bone loss parameters were similar in all groups. MTX-PG1 was found at similar levels in various MTX groups and correlated negatively with arthritis severity. Finally, haematology and metabolic parameters were found at a similar level in MTX groups. CONCLUSION: Co-administration of MTX with FA on the same day did not reduce efficacy compared with FA application one day after MTX. Thus, co-administration of MTX and FA could be more convenient and improve compliance in patients.

Nutritional Status of Pediatric Patients With Acute Lymphoblastic Leukemia Under Chemotherapy: A Pilot Longitudinal Study.

BACKGROUND: The study investigates the nutritional status in children with acute lymphoblastic leukemia (ALL) during chemotherapy treatment because nourishment is substantial, as much as chemotherapy in children with malignant diseases. MATERIAL AND METHOD: We enrolled 17 children with ALL (between 1 to 16 year-old, mean age 6.03 ± 4.04 y) from 5 different centers in Istanbul between September 2013 and May 2014. Anthropometric data, prealbumin, B12, and folate levels were assessed, at diagnosis, after the induction phase of chemotherapy, and before maintenance phases of chemotherapy in a longitudinal and prospective study. RESULTS: Patients remarkably lost weight at the end of the induction phase ( P =0.064) and regained this loss before maintenance chemotherapy ( P =0.001). At the end of induction chemotherapy serum prealbumin level ( P =0.002), weight for height ratios ( P =0.016), weight for age ratios ( P =0.019) significantly decreased. From the end of the induction phase to the beginning of maintenance chemotherapy, weight ( P =0.001) and weight for age ( P =0.017) significantly, and weight for height were remarkably elevated ( P =0.076). At the end of the induction phase, serum prealbumin levels were significantly lower ( P =0.048) and below laboratory reference values ( P =0.009) in children younger than 60 months compared with those older. Serum folate levels increased from the end of the induction phase to the beginning of the maintenance phase ( P =0.025). Serum vitamin B12 levels did not alter significantly. CONCLUSION: There is malnutrition risk at the end of the induction phase of the ALL-BFM chemotherapy regimen; therefore, clinicians should follow up on nutrition closely, especially in under 5-year-old patients. However, before the beginning of the maintenance phase, children start to gain weight, and obesity risk occurs. Thus , further studies are needed to evaluate nutritional status during childhood ALL chemotherapy.

Application of curcumin nanoformulations to target folic acid receptor in cancer: Recent trends and advances.

Curcumin, derived from turmeric, has a strong anticancer potential known for millennia. The development of this phytochemical as a medicine has been hampered by several significant deficiencies, including its poor water solubility and low bioavailability. This review article discusses possibilities to overcome these bottlenecks by focusing on this natural polyphenol's nanoformulation. Moreover, preparation of curcumin conjugates containing folates as ligands for folic acid receptors can add a new important dimension in this field, allowing specific targeting of cancer cells, considering the significantly higher expression of these receptors in malignant tissues compared to normal cells. It is highly expected that simultaneous improvement of different aspects of curcumin in fighting against such a complex and multifaceted disease like cancer. Therefore, we can better comprehend cancer biology by developing a mechanistic understanding of curcumin, which will also inspire the scientific community to develop new pharmacological models, and exploration of emerging directions to revitalize application of natural products in cancer therapy.

L-Methylfolate in Diabetic Peripheral Neuropathy: A Narrative Review.

OBJECTIVE: One of the most frequently occurring complications of diabetes mellitus is peripheral neuropathy. Despite the painful symptoms associated with diabetic peripheral neuropathy (DPN), the current treatment landscape focuses on managing symptoms without addressing the underlying causes of DPN. This narrative review describes the mechanistic effects and clinical trial data supporting the use of L-methylfolate calcium (LMF), the bioactive form of folate, which is available in the United States as a prescription medical food that also contains other B vitamins for the dietary management of DPN. METHODS: Preclinical and clinical trial data evaluating the impact of LMF on DPN were identified using PubMed searches for articles published between 2010 and 2023. Search terms included: folate, LMF, diabetes, neuropathy, and neuropathic pain. Additionally, a literature search was conducted to identify studies related to LMF, genetic polymorphisms, and DPN pathophysiology. RESULTS: Several studies show that the C677T variant of the methylenetetrahydrofolate reductase gene is linked to greater risk of DPN than other methylenetetrahydrofolate reductase variants due to its inhibitory effects on several folic acid metabolic pathways. One double-blind, randomized controlled trial, 5 open-label studies, and 1 retrospective study found that LMF has a significant beneficial effect on DPN that extends beyond symptomatic relief to include modulating the underlying pathophysiology that leads to the progression and symptoms of DPN. LMF also significantly improves patient quality of life, with minimal adverse effects. CONCLUSION: Preclinical and clinical studies have found that LMF can be used to treat the underlying causes of DPN and provide long-lasting symptomatic relief.

Determinants of neural tube defects among women who gave birth in hospitals in Eastern Ethiopia: evidence from a matched case control study.

INTRODUCTION: Neural tube defects (NTDs) are severe birth defects caused by nutritional, genetic or environmental factors. Because NTDs continue to have a significant health and economic impact on children and community at large, it is crucial to investigate potential risk factors in order to develop novel approaches to NTDs prevention. Determinants for the development of NTDs differ by country, region as well as within the country. The objective of this study was to identify the determinants of NTDs among newborns delivered in three hospitals found in eastern Ethiopia. METHODS: A hospital-based matched case-control study was conducted among 138 cases and 138 control women who delivered in three teaching hospitals in Eastern Ethiopia in 2021. Data were collected using a structured and pre-tested interviewer-administered questionnaire. Cases were mothers who delivered a neonate with any type of NTDs regardless of gestational age or fetal viability, whereas controls were mothers who delivered an apparently healthy newborn. Chi-square was used to assess the significant difference between the two groups. Conditional logistic regression model was used to generate adjusted odds ratio with its corresponding 95% confidence intervals and compare the two groups. RESULTS: Anencephaly (51.4%) and spinal bifida (34.1%) were the most frequently observed NTDs. None of study participants took preconception folic acid supplementation. Being a non-formal mothers (AOR = 0.34, 95% CI: 0.12-0.92, P = 0.034), rural residence, (AOR = 3.4, 95% CI: 1.18-9.78, P = 0.023), history of spontaneous abortion (AOR = 2.95, 95% CI: 1.15-7.55, P = 0.023), having severe anemia (AOR = 3.4, 95% CI: 1.17-9.87, P = 0.024), history of fever or cold (AOR = 2.75; 95% CI: 1.05-7.15, P = 0.038), and an exposure to various agro-chemicals (AOR = 3.39, 95% CI: 1.11-10.3, P = 0.032) were independent determinants of NTDs. CONCLUSION AND RECOMMENDATION: In this study, NTDs were associated to several determinant factors in the area, including residential area, history of spontaneous abortion, severe anemia, fever/cold, antibiotic use before or during early pregnancy, and exposure to agrochemicals. Addressing the identified determinants is critical in averting the incidence of NTDs in the study area. Moreover, more research is needed to investigate women's dietary practices as well as the practice of preconception folic acid supplementation for pregnant women in Ethiopia's current health care system.