A Predictive Model for Thiamine Responsive Disorders Among Infants and Young Children: Results from a Prospective Cohort Study in Lao People's Democratic Republic.

OBJECTIVE: To develop a predictive model for thiamine responsive disorders (TRDs) among infants and young children hospitalized with signs or symptoms suggestive of thiamine deficiency disorders (TDDs) based on response to therapeutic thiamine in a high-risk setting. STUDY DESIGN: Children aged 21 days to <18 months hospitalized with signs or symptoms suggestive of TDD in northern Lao People's Democratic Republic were treated with parenteral thiamine (100 mg daily) for ≥3 days in addition to routine care. Physical examinations and recovery assessments were conducted frequently for 72 hours after thiamine was initiated. Individual case reports were independently reviewed by three pediatricians who assigned a TRD status (TRD or non-TRD), which served as the dependent variable in logistic regression models to identify predictors of TRD. Model performance was quantified by empirical area under the receiver operating characteristic curve. RESULTS: A total of 449 children (median [Q1, Q3] 2.9 [1.7, 5.7] months old; 70.3% exclusively/predominantly breastfed) were enrolled; 60.8% had a TRD. Among 52 candidate variables, those most predictive of TRD were exclusive/predominant breastfeeding, hoarse voice/loss of voice, cyanosis, no eye contact, and no diarrhea in the previous 2 weeks. The area under the receiver operating characteristic curve (95% CI) was 0.82 (0.78, 0.86). CONCLUSIONS: In this study, the majority of children with signs or symptoms of TDD responded favorably to thiamine. While five specific features were predictive of TRD, the high prevalence of TRD suggests that thiamine should be administered to all infants and children presenting with any signs or symptoms consistent with TDD in similar high-risk settings. The usefulness of the predictive model in other contexts warrants further exploration and refinement. TRIAL REGISTRATION: Clinicaltrials.gov NCT03626337.

Association between dietary macronutrient composition and plasma one-carbon metabolites and B-vitamin cofactors in patients with stable angina pectoris.

Elevated plasma concentrations of several one-carbon metabolites are associated with increased CVD risk. Both diet-induced regulation and dietary content of one-carbon metabolites can influence circulating concentrations of these markers. We cross-sectionally analysed 1928 patients with suspected stable angina pectoris (geometric mean age 61), representing elevated CVD risk, to assess associations between dietary macronutrient composition (FFQ) and plasma one-carbon metabolites and related B-vitamin status markers (GC-MS/MS, LC-MS/MS or microbiological assay). Diet-metabolite associations were modelled on the continuous scale, adjusted for age, sex, BMI, smoking, alcohol and total energy intake. Average (geometric mean (95 % prediction interval)) intake was forty-nine (38, 63) energy percent (E%) from carbohydrate, thirty-one (22, 45) E% from fat and seventeen (12, 22) E% from protein. The strongest associations were seen for higher protein intake, i.e. with higher plasma pyridoxal 5'-phosphate (PLP) (% change (95 % CI) 3·1 (2·1, 4·1)), cobalamin (2·9 (2·1, 3·7)), riboflavin (2·4 (1·1, 3·7)) and folate (2·1 (1·2, 3·1)) and lower total homocysteine (tHcy) (-1·4 (-1·9, -0·9)) and methylmalonic acid (MMA) (-1·4 (-2·0, -0·8)). Substitution analyses replacing MUFA or PUFA with SFA demonstrated higher plasma concentrations of riboflavin (5·0 (0·9, 9·3) and 3·3 (1·1, 5·6)), tHcy (2·3 (0·7, 3·8) and 1·3 (0·5, 2·2)) and MMA (2·0 (0·2, 3·9) and 1·7 (0·7, 2·7)) and lower PLP (-2·5 (-5·3, 0·3) and -2·7 (-4·2, -1·2)). In conclusion, a higher protein intake and replacing saturated with MUFA and PUFA were associated with a more favourable metabolic phenotype regarding metabolites associated with CVD risk.

The association between dietary vitamin B1 intake and constipation: a population-based study.

BACKGROUND: Numerous researches have indicated a correlation between the intake of dietary micronutrients and the occurrence of constipation. Nevertheless, the correlation between constipation and vitamin B1 remains uninvestigated. The main aim of this research was to examine the association between chronic constipation and the consumption of vitamin B1 in the diet among adult participants of the National Health and Nutrition Examination Survey (NHANES). METHODS: This study used data from the NHANES, a survey on health and nutrition conducted between 2005 and 2010. The respondents' dietary information was gathered by utilizing the 24-hour dietary records. Various statistical analyses, such as multiple logistic regression, subgroup analysis, and curve-fitting analysis, were employed to investigate the correlation between dietary intake of vitamin B1 and chronic constipation. RESULTS: In the trial, there were 10,371 participants, out of which 1,123 individuals (10.8%) were identified as having chronic constipation. Fully adjusted multiple logistic regression analyses showed that increasing dietary intake of vitamin B1 (OR = 0.87, 95% CI: 0.77-0.99) was significantly associated with a reduced risk of constipation. Following adjustment for multiple variables in Model 3, the odds ratio (OR) and 95% confidence interval (CI) for the third tertile, in comparison to the first tertile (reference group), was 0.80 (0.65, 0.99). In addition, subgroup analyses and interaction tests showed a significant inverse association between vitamin B1 intake and the prevalence of constipation, especially among men, non-hypertensive, and non-diabetic individuals (all P-values less than 0.05). CONCLUSION: This research uncovered an inverse correlation between the consumption of vitamin B1 in the diet and the occurrence of chronic constipation. One potential explanation for this phenomenon is that the consumption of vitamin B1 in one's diet is linked to the softening of stools and an augmented occurrence of colonic peristalsis. Additional extensive prospective research is required to thoroughly examine the significance of thiamine in long-term constipation.

Intake of B vitamins and the risk of developing islet autoimmunity and type 1 diabetes in the TEDDY study.

PURPOSE: The aim was to study the association between dietary intake of B vitamins in childhood and the risk of islet autoimmunity (IA) and progression to type 1 diabetes (T1D) by the age of 10 years. METHODS: We followed 8500 T1D-susceptible children born in the U.S., Finland, Sweden, and Germany in 2004 -2010 from the Environmental Determinants of Diabetes in the Young (TEDDY) study, which is a prospective observational birth cohort. Dietary intake of seven B vitamins was calculated from foods and dietary supplements based on 24-h recall at 3 months and 3-day food records collected regularly from 6 months to 10 years of age. Cox proportional hazard models were adjusted for energy, HLA-genotype, first-degree relative with T1D, sex, and country. RESULTS: A total of 778 (9.2) children developed at least one autoantibody (any IA), and 335 (3.9%) developed multiple autoantibodies. 280 (3.3%) children had IAA and 319 (3.8%) GADA as the first autoantibody. 344 (44%) children with IA progressed to T1D. We observed that higher intake of niacin was associated with a decreased risk of developing multiple autoantibodies (HR 0.95; 95% CI 0.92, 0.98) per 1 mg/1000 kcal in niacin intake. Higher intake of pyridoxine (HR 0.66; 95% CI 0.46, 0.96) and vitamin B12 (HR 0.87; 95% CI 0.77, 0.97) was associated with a decreased risk of IAA-first autoimmunity. Higher intake of riboflavin (HR 1.38; 95% CI 1.05, 1.80) was associated with an increased risk of GADA-first autoimmunity. There were no associations between any of the B vitamins and the outcomes "any IA" and progression from IA to T1D.  CONCLUSION: In this multinational, prospective birth cohort of children with genetic susceptibility to T1D, we observed some direct and inverse associations between different B vitamins and risk of IA.

Efficacy of oral folinic acid supplementation in children with autism spectrum disorder: a randomized double-blind, placebo-controlled trial.

Oral folinic acid has shown potential to improve symptoms in children with autism spectrum disorder (ASD). However, randomized controlled trials (RCTs) are limited. This double-blind, placebo-controlled RCT aimed to compare changes in Childhood Autism Rating Scale (CARS) scores in children with ASD aged 2-10 years, among folinic acid (2 mg/kg/day, maximum of 50 mg/day) and placebo groups at 24 weeks, in comparison with baseline. Both the groups received standard care (ABA and sensory integration therapy). Secondary objectives included changes in behavioral problems measured by the Child Behavior Checklist (CBCL) and serum levels of anti-folate receptor autoantibodies and folic acid, correlated with changes in autism symptom severity. Out of the 40 participants recruited in each group, 39 and 38 participants completed the 24-week follow-up in the folinic acid and placebo groups, respectively. The change in CARS score was higher in the folinic acid group (3.6 ± 0.8) compared to the placebo group (2.4 ± 0.7, p < 0.001). Changes in CBCL total score and CBCL internalizing score were also better in the folinic acid group (19.7 ± 9.5 vs. 12.6 ± 8.4 and 15.4 ± 7.8 vs. 8.5 ± 5.7, p < 0.001 for both). High-titer anti-folate receptor autoantibodies were positive in 32/40 and 33/40 cases in the folinic acid and placebo groups, respectively (p = 0.78). In the placebo group, improvement in CARS score was comparable regardless of autoantibody status (p = 0.11), but in the folinic acid group, improvement was more pronounced in the high-titer autoantibody group (p = 0.03). No adverse reactions were reported in either group. CONCLUSIONS: Oral folinic acid supplementation is effective and safe in improving ASD symptoms, with more pronounced benefits in children with high titers of folate receptor autoantibodies. TRIAL REGISTRATION:  CTRI/2021/07/034901, dated 15-07-2021. WHAT IS KNOWN: • Folate receptor autoantibodies are more prevalent in children with autism spectrum disorder (ASD) compared to typically developing children. • Folate receptor autoantibodies play a significant role in the neuropathogenesis of autism spectrum disorder. WHAT IS NEW: • Add-on oral folinic acid supplementation is safe and effective in reducing the severity of symptoms in children with ASD. • The clinical benefits are more pronounced in children with high titers of folate receptor autoantibodies.

Bilateral hearing loss as the initial presentation of reversible Wernicke's encephalopathy with splenial lesion.

BACKGROUND: Wernicke's encephalopathy (WE) is an acute neurological syndrome resulting from thiamine (vitamin B1) deficiency. It has been recognized increasingly in non-alcoholic patients, such as in the condition of malnutrition. Recent literature has shed light on uncommon symptoms and neuroimaging findings. CASE REPORT: We reported a case of a 44-year-old male who initially presented with bilateral hearing loss, and exhibited abnormality in the splenium of the corpus callosum on magnetic resonance imaging (MRI) diffusion-weighted imaging sequence. On the following day the patient developed new symptoms, including unstable walking, double vision and hallucination. The subsequent brain MRI demonstrated lesions involving periaqueductal grey matter and bilateral medial thalamus, indicating the diagnosis of WE. Empirical treatment with intravenous thiamine resulted in complete clinical and radiological resolution. CONCLUSION: To the best of our knowledge, the current case is the first report of WE in literature with uncommon but reversible manifestations. This case warns us to maintain a heightened level of suspicion for WE in malnourished patients with neurological deficits, despite the possibility of atypical presentations encompassing bilateral hearing disturbances and unusual neuroradiological results. Early diagnosis and timely administration of thiamine in WE are likely to lead to a favorable outcome and full recovery.

Effect of dietary myo-inositol supplementation on the insulin resistance and the prevention of gestational diabetes mellitus: an open-label, randomized controlled trial.

PURPOSE: Myo-inositol (MI) is an insulin-sensitizing dietary supplement, enhancing the transfer of glucose into the cell. Gestational diabetes mellitus (GDM) is characterized by abnormal glucose tolerance, which is associated with elevated insulin resistance. The present study aimed to assess the effect of MI supplementation during pregnancy on the incidence of GDM. METHODS: We performed a single-center, open-label, randomized controlled trial. A cohort of 200 pregnant women at 11-13+6 weeks of gestation were randomly assigned in two groups: MI group (n = 100) and control group (n = 100). The MI group received MI and folic acid (4000 mg MI and 400 mcg folic acid daily), while the control group received folic acid alone (400 mcg folic acid daily) until 26-28 weeks of gestation, when the 75 g Oral Glucose Tolerance Test (OGTT) was performed for the diagnosis of GDM. Clinical and metabolic outcomes were assessed. RESULTS: The incidence of GDM was significantly higher in the MI group (14.9%) compared to the control group (28.5%) (P = 0.024). Women treated with MI had significantly lower OGTT glucose values, than those not treated with MI (P < 0.001). The insulin resistance as assessed by HOMA-IR was significantly lower in the MI group versus control (P = 0.045). Furthermore, MI group had significantly higher insulin sensitivity as measured by the Matsuda Index, compared to the control group (P = 0.037). CONCLUSION: MI supplementation seems to be an effective option to improve the glycemic control of pregnant women and prevent the onset of GDM. TRIAL REGISTRATION: ISRCTN registry: ISRCTN16142533. Registered 09 March 2017.

Phentolamine and B vitamins for feeding intolerance in late preterm infants: a randomised trial.

BACKGROUND AND OBJECTIVES: Feeding intolerance (FI) is a common problem in late preterm infants (34 weeks ≤ gestational age < 37 weeks). This study aimed to evaluate the efficacy and safety of phentolamine combined with B vitamins in treating FI in late preterm infants and to explore its effects on gastrointestinal symptoms, inflammation and complications. METHODS AND STUDY DESIGN: We randomly assigned 118 late preterm infants with FI to a treatment group (n = 56) or a control group (n = 62). The treatment group received intravenous phentolamine and intramuscular B vitamins, whereas the control group received basic treatment only. We measured the time of disappearance of gastrointestinal symptoms, the time of basal at-tainment, the time of hospitalisation, the incidence of complications, the concentrations of inflammatory markers and the overall effective rate of treatment. RESULTS: The treatment group had a shorter duration of gastrointestinal symptoms than did the control group (p < 0.01). The treatment group also had lower concentrations of inflammatory markers and a higher overall effective rate than did the control group (p < 0.05). There was no difference between the two groups in the time of hospitalisation, basal attainment, weight re-covery and the incidence of complications (p > 0.05). CONCLUSIONS: Phentolamine and B vitamins can reduce gastrointestinal symptoms and inflammation in late preterm infants with FI but do not affect the occurrence of complications.

CASE DEFINITION AND TREATMENT TRIAL OF TETANY SYNDROME IN PANAMANIAN GOLDEN FROGS (ATELOPUS ZETEKI).

The mass extinction of amphibians necessitates specialized programs to ensure species' survival. Maryland Zoo in Baltimore houses the largest assurance population of the critically endangered Panamanian golden frog (Atelopus zeteki). However, individuals in this population experience a tetany-like syndrome, characterized by rigid/inappropriately positioned limbs and difficulty hopping, swimming, and righting. In this study, a syndrome case definition was assigned and the associated clinical signs were described. Then, four different treatments were systematically assessed in order to find the most effective protocol for treatment and begin to elucidate its underlying causes. Eighty-three frogs fulfilled the case definition and were treated orally for 14 d with either calcium gluconate, magnesium chloride, supplemental gavage feeding, or combination of calcium, magnesium, and vitamin B complex. Frogs were tested with a defined protocol assessing hopping, righting, and swimming abilities. Testing was performed at symptom onset and repeated weekly until resolution occurred. Analyses revealed that combination treatment was significantly more effective in eliminating clinical signs of tetany syndrome. Results show the most effective way to treat this syndrome, but do not help elucidate the underlying cause. Future work will focus on examining factors (e.g., diet, husbandry) that may elicit the syndrome for a more complete understanding of its etiology.

Association between B-vitamins intake and frailty among patients with chronic obstructive pulmonary disease.

PURPOSE: Gain insight into the impact of B vitamins, including vitamin B1, vitamin B2, niacin, vitamin B6, total folate, and vitamin B12 on the risk of frailty in patients with chronic obstructive pulmonary disease (COPD). METHODS: This study was an American population-based cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES). A total of 1201 COPD patients were included in the analysis. Of these, the intake of B vitamins was determined by the two 24-h recall interviews. We followed the method constructed by Hakeem et al. to calculate the frailty index (FI), which is used as a reliable tool to assess the debilitating status of patients with COPD. Missing data were imputed by the MissForest method based on random forests. Multivariate logistic regression model and inverse probability weighted based on propensity scores were used to correct for confoundings. RESULTS: Logistic regression models showed that vitamin B6 intake was negatively correlated with frailty risk in COPD patients, while other B vitamins including B1, B2, niacin (vitamin B3), total folic acid and vitamin B12 were not. After adjusting for covariates, the association between vitamin B6 and frailty risk (adjusted OR = 0.80, 95%CI = 0.66-0.95, P = 0.013) remained significant. At the same time, sensitivity analysis proves the robustness of the results. CONCLUSION: COPD patients with lower vitamin B6 intake have a higher risk of frailty. However, intake of vitamin B1, B2, niacin, total folic acid, and vitamin B12 was not associated with frailty risk in COPD patients.

Methods and approaches to estimate B vitamin status in dairy cows: Knowledge, gaps and advances.

Clinical symptoms of B vitamin deficiency are rarely observed in ruminants because these vitamins are synthesized by the rumen microbiota. However, over the last decades, numerous reports of beneficial effects on production and metabolic efficiency of dairy cows have been published supporting that, under some conditions, B vitamin subclinical deficiency is present in these animals. Due to their roles as coenzymes or cofactors in major metabolic pathways, an adequate supply in B vitamins is critical to optimize metabolic efficiency. Nowadays, taking into account the growing interest for the Smart Farming concept, fulfilling ruminant requirements for B vitamins according to their physiological stage under different feeding management cannot be neglected. In dairy cows, B vitamin supply is greatly dependent of the activity of the ruminal microbiota. Indeed, the amount of vitamins reaching the small intestine is dependent of the utilization of the vitamins provided by the diet and their synthesis by the microorganisms present in the rumen. The two major challenges faced to determine B vitamin status of ruminants are the difficulty to estimate B vitamin supply due to the lack of knowledge on factors driving the fate of B vitamins in the digestive tract, especially in the rumen, and the choice and thresholds of biomarkers reflecting adequately the animal status. The present paper aims to present the actual state of knowledge on the methodological approaches used to estimate B vitamin supply and status of ruminant and to point out future research orientations.

The effect of metformin and myoinositol on metabolic outcomes in women with polycystic ovary syndrome: role of body mass and adiponectin in a randomized controlled trial.

PURPOSE: To compare the effects of insulin sensitizers metformin (MET) and myo-inositol (MI) on adiponectin levels and metabolic characteristics in women with polycystic ovary syndrome (PCOS) with respect to their body mass index (BMI). METHODS: In this open label, parallel randomized clinical trial, 66 women with PCOS (33 normal-weight and 33 overweight/obese) were randomized to either MI (4 g/day) or MET (1500 mg/day) for a period of 6 months. Serum concentration of adiponectin, hormonal and metabolic laboratory outcomes and clinical assessment of BMI, body composition and Ferriman-Gallwey score (FG score) were evaluated before and after treatment. RESULTS: After the 6-month intervention, comparison between MET and MI in time to treatment analysis showed no significant differences between the two treatments for all analyzed parameters. Only borderline significantly lower AUC glucose was found in the MET group in comparison to the MI group (p = 0.071). The main effect of treatment was shown for glucose concentration at 120 min OGTT (p = 0.032) and testosterone (p = 0.002). The main effect of time was shown for body mass (p = 0.004), waist circumference (p < 0.001), BMI (p = 0.003), body fat mass (p = 0.001), adiponectin (p = 0.020), fasting glucose (p = 0.001), testosterone (p = 0.015), SHBG (p = 0.013), 17OH progesterone (p = 0.008), LH (p = 0.004) and estradiol (p = 0.014). CONCLUSION: Our study showed similar effects of MET and MI on BMI, body composition, hormonal profile, metabolism of glucose and insulin, and adiponectin level. The two insulin sensitizers, MET and MI, were useful in reducing BMI and improving body composition without significant differences between the two treatments in PCOS women. TRIAL REGISTRATION: ISRCTN13199265. Trial registration date: 14.04.2021. (ISRCTN Registry), retrospectively registered.

High maternal folic acid intake around conception alters mouse blastocyst lineage allocation and expression of key developmental regulatory genes.

Folate, a cofactor for the supply of one-carbon groups, is required by epigenetic processes to regulate cell lineage determination during development. The intake of folic acid (FA), the synthetic form of folate, has increased significantly over the past decade, but the effects of high periconceptional FA intake on cell lineage determination in the early embryo remains unknown. Here, we investigated the effect of maternal high FA (HFA) intake on blastocyst development and expression of key regulatory genes. C57BL/6 adult female mice were fed either Control diet (1 mg FA) for 4 weeks before conception and during the preimplantation period (Con-Con); Control diet for 4 weeks preconception, followed by HFA (5 mg FA) diet during preimplantation (Con-HFA); or HFA diet for 4 weeks preconception and during preimplantation (HFA-HFA). At E3.5, blastocyst cell number, protein, and mRNA expression were measured. In HFA-HFA blastocysts, trophectoderm cell numbers and expression of CDX2, Oct-4, and Nanog were reduced compared with Con-Con blastocysts; Con-HFA blastocysts showed lower CDX2 and Oct-4 expression than Con-Con blastocysts. These findings suggest periconceptional HFA intake induces changes in key regulators of embryo morphogenesis with potential implications for subsequent development.

Subacute cutaneous lupus erythematosus triggered after measles vaccination.

Subacute cutaneous lupus erythematosus (SCLE) is a subtype of cutaneous lupus erythematosus that can be triggered by endogenous or exogenous factors. Among the exogenous factors are some medications, drugs, tobacco, infections, and vaccines. In this context, the benefits of vaccination are questioned because although it is important to prevent infections in immunosuppressed patients a theoretical risk of developing systemic lupus erythematosus (SLE) remains in these patients. This report presents a case of a previously healthy female patient who developed SCLE after measles vaccination and progressed to SLE and thereby suggests a possible trigger of the disease.

Exploring trajectories in dietary adequacy of the B vitamins folate, riboflavin, vitamins B6 and B12, with advancing older age: a systematic review.

Maintaining nutritional adequacy contributes to successful ageing. B vitamins involved in one-carbon metabolism regulation (folate, riboflavin, vitamins B6 and B12) are critical nutrients contributing to homocysteine and epigenetic regulation. Although cross-sectional B vitamin intake in ageing populations is characterised, longitudinal changes are infrequently reported. This systematic review explores age-related changes in dietary adequacy of folate, riboflavin, vitamins B6 and B12 in community-dwelling older adults (≥65 years at follow-up). Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, databases (MEDLINE, Embase, BIOSIS, CINAHL) were systematically screened, yielding 1579 records; eight studies were included (n 3119 participants, 2­25 years of follow-up). Quality assessment (modified Newcastle­Ottawa quality scale) rated all of moderate­high quality. The estimated average requirement cut-point method estimated the baseline and follow-up population prevalence of dietary inadequacy. Riboflavin (seven studies, n 1953) inadequacy progressively increased with age; the prevalence of inadequacy increased from baseline by up to 22·6 and 9·3 % in males and females, respectively. Dietary folate adequacy (three studies, n 2321) improved in two studies (by up to 22·4 %), but the third showed increasing (8·1 %) inadequacy. Evidence was similarly limited (two studies, respectively) and inconsistent for vitamins B6 (n 559; −9·9 to 47·9 %) and B12 (n 1410; −4·6 to 7·2 %). This review emphasises the scarcity of evidence regarding micronutrient intake changes with age, highlighting the demand for improved reporting of longitudinal changes in nutrient intake that can better direct micronutrient recommendations for older adults. This review was registered with PROSPERO (CRD42018104364).

Thiamine Treatment and Favorable Outcome in an Infant with Biallelic TPK1 Variants.

Episodic encephalopathy due to mutations in the thiamine pyrophosphokinase 1 (TPK1) gene is a rare autosomal recessive metabolic disorder. Patients reported so far have onset in early childhood of acute encephalopathic episodes, which result in a progressive neurologic dysfunction including ataxia, dystonia, and spasticity. Here, we report the case of an infant with TPK1 deficiency (compound heterozygosity for two previously described pathogenic variants) presenting with two encephalopathic episodes and clinical stabilization under oral thiamine and biotin supplementation. In contrast to other reported cases, our patient showed an almost normal psychomotor development, which might be due to an early diagnosis and subsequent therapy.

Thiamine Pyrophosphokinase Deficiency due to Mutations in the TPK1 Gene: A Rare, Treatable Neurodegenerative Disorder.

TPK deficiency due to TPK1 mutations is a rare neurodegenerative disorder, also known as thiamine metabolism dysfunction syndrome 5 (OMIM no.: 614458). Here, we report a new patient with compound heterozygous TPK1 mutations, of which one has not been described so far. The individual reported here suffered from acute onset encephalopathy, ataxia, muscle hypotonia, and regression of developmental milestones in early infancy, repeatedly triggered by febrile infections. Initiation of high-dose thiamine and magnesium supplementation led to a marked and sustained improvement of alertness, ataxia, and muscle tone within days. Contrary to the described natural history of patients with TPK deficiency, the disease course was favorable under thiamine treatment without deterioration or developmental regression during the follow-up period. TPK deficiency is a severe neurodegenerative disease. This case report demonstrates that this condition is potentially treatable. High-dose thiamine treatment should therefore be initiated immediately after diagnosis or even upon suspicion.

Folate Intake and Risk of Pancreatic Cancer: A Systematic Review and Updated Meta-Analysis of Epidemiological Studies.

INTRODUCTION: Pancreatic cancer is one of the most fatal malignancies and primary prevention strategies are limited. Epidemiological studies focusing on the association between folate intake and pancreatic cancer risk have reported inconsistent findings. METHODS: A systematic search of the literature was conducted using the PubMed and EMBASE databases. A systematic review and meta-analysis of eligible studies was performed to assess the association between folate intake and risk of pancreatic cancer. RESULTS: A total of 16 studies involving 5654 cases and 1,009,374 individuals were included. The result showed a significant association of folate intake with a decreased risk of pancreatic cancer, with a pooled OR of 0.82 (95% CI: 0.69-0.97, P = 0.019) for the highest category of intake vs. the lowest. The data suggested that high intake of folate may contribute to the prevention of pancreatic cancer. However, the association was observed only in case-control studies (OR = 0.78, 95% CI: 0.65-0.93, P = 0.006), but not in cohort studies (RR = 0.85, 95% CI: 0.66-1.09, P = 0.244). Dose-response meta-analysis showed that an increment of folate intake (100 µg/day) was marginally associated with the risk of pancreatic cancer, with a pooled OR of 0.97 (95% CI: 0.93-1.00, P = 0.053). CONCLUSION: High folate intake might be inversely associated with pancreatic cancer risk, which needs to be confirmed.

Preconception lifestyle advice for people with infertility.

BACKGROUND: Infertility is a prevalent problem that has significant consequences for individuals, families, and the community. Modifiable lifestyle factors may affect the chance of people with infertility having a baby. However, no guideline is available about what preconception advice should be offered. It is important to determine what preconception advice should be given to people with infertility and to evaluate whether this advice helps them make positive behavioural changes to improve their lifestyle and their chances of conceiving. OBJECTIVES: To assess the safety and effectiveness of preconception lifestyle advice on fertility outcomes and lifestyle behavioural changes for people with infertility. SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility Group Specialised Register of controlled trials, CENTRAL, MEDLINE, Embase, PsycINFO, AMED, CINAHL, trial registers, Google Scholar, and Epistemonikos in January 2021; we checked references and contacted field experts to identify additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs), randomised cross-over studies, and cluster-randomised studies that compared at least one form of preconception lifestyle advice with routine care or attention control for people with infertility. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures recommended by Cochrane. Primary effectiveness outcomes were live birth and ongoing pregnancy. Primary safety outcomes were adverse events and miscarriage. Secondary outcomes included reported behavioural changes in lifestyle, birth weight, gestational age, clinical pregnancy, time to pregnancy, quality of life, and male factor infertility outcomes. We assessed the overall quality of evidence using GRADE criteria. MAIN RESULTS: We included in the review seven RCTs involving 2130 participants. Only one RCT included male partners. Three studies compared preconception lifestyle advice on a combination of topics with routine care or attention control. Four studies compared preconception lifestyle advice on one topic (weight, alcohol intake, or smoking) with routine care for women with infertility and specific lifestyle characteristics. The evidence was of low to very low-quality. The main limitations of the included studies were serious risk of bias due to lack of blinding, serious imprecision, and poor reporting of outcome measures. Preconception lifestyle advice on a combination of topics versus routine care or attention control Preconception lifestyle advice on a combination of topics may result in little to no difference in the number of live births (risk ratio (RR) 0.93, 95% confidence interval (CI) 0.79 to 1.10; 1 RCT, 626 participants), but the quality of evidence was low. No studies reported on adverse events or miscarriage. Due to very low-quality evidence, we are uncertain whether preconception lifestyle advice on a combination of topics affects lifestyle behavioural changes: body mass index (BMI) (mean difference (MD) -1.06 kg/m², 95% CI -2.33 to 0.21; 1 RCT, 180 participants), vegetable intake (MD 12.50 grams/d, 95% CI -8.43 to 33.43; 1 RCT, 264 participants), alcohol abstinence in men (RR 1.08, 95% CI 0.74 to 1.58; 1 RCT, 210 participants), or smoking cessation in men (RR 1.01, 95% CI 0.91 to 1.12; 1 RCT, 212 participants). Preconception lifestyle advice on a combination of topics may result in little to no difference in the number of women with adequate folic acid supplement use (RR 0.98, 95% CI 0.95 to 1.01; 2 RCTs, 850 participants; I² = 4%), alcohol abstinence (RR 1.07, 95% CI 0.99 to 1.17; 1 RCT, 607 participants), and smoking cessation (RR 1.01, 95% CI 0.98 to 1.04; 1 RCT, 606 participants), on low quality evidence. No studies reported on other behavioural changes. Preconception lifestyle advice on weight versus routine care Studies on preconception lifestyle advice on weight were identified only in women with infertility and obesity. Compared to routine care, we are uncertain whether preconception lifestyle advice on weight affects the number of live births (RR 0.94, 95% CI 0.62 to 1.43; 2 RCTs, 707 participants; I² = 68%; very low-quality evidence), adverse events including gestational diabetes (RR 0.78, 95% CI 0.48 to 1.26; 1 RCT, 317 participants; very low-quality evidence), hypertension (RR 1.07, 95% CI 0.66 to 1.75; 1 RCT, 317 participants; very low-quality evidence), or miscarriage (RR 1.50, 95% CI 0.95 to 2.37; 1 RCT, 577 participants; very low-quality evidence). Regarding lifestyle behavioural changes for women with infertility and obesity, preconception lifestyle advice on weight may slightly reduce BMI (MD -1.30 kg/m², 95% CI -1.58 to -1.02; 1 RCT, 574 participants; low-quality evidence). Due to very low-quality evidence, we are uncertain whether preconception lifestyle advice affects the percentage of weight loss, vegetable and fruit intake, alcohol abstinence, or physical activity. No studies reported on other behavioural changes. Preconception lifestyle advice on alcohol intake versus routine care Studies on preconception lifestyle advice on alcohol intake were identified only in at-risk drinking women with infertility. We are uncertain whether preconception lifestyle advice on alcohol intake affects the number of live births (RR 1.15, 95% CI 0.53 to 2.50; 1 RCT, 37 participants; very low-quality evidence) or miscarriages (RR 1.31, 95% CI 0.21 to 8.34; 1 RCT, 37 participants; very low-quality evidence). One study reported on behavioural changes for alcohol consumption but not as defined in the review methods. No studies reported on adverse events or other behavioural changes. Preconception lifestyle advice on smoking versus routine care Studies on preconception lifestyle advice on smoking were identified only in smoking women with infertility. No studies reported on live birth, ongoing pregnancy, adverse events, or miscarriage. One study reported on behavioural changes for smoking but not as defined in the review methods. AUTHORS' CONCLUSIONS: Low-quality evidence suggests that preconception lifestyle advice on a combination of topics may result in little to no difference in the number of live births. Evidence was insufficient to allow conclusions on the effects of preconception lifestyle advice on adverse events and miscarriage and on safety, as no studies were found that looked at these outcomes, or the studies were of very low quality. This review does not provide clear guidance for clinical practice in this area. However, it does highlight the need for high-quality RCTs to investigate preconception lifestyle advice on a combination of topics and to assess relevant effectiveness and safety outcomes in men and women with infertility.

An Evaluation of Awareness, Knowledge, and Use of Folic Acid and Dietary Folate Intake among Non-Pregnant Women of Childbearing Age and Pregnant Women: A Cross-Sectional Study from Turkey.

This study was carried out to evaluate awareness, knowledge, and use of folic acid and dietary folate intake among non-pregnant women of childbearing age and pregnant women. A cross-sectional study was completed with 1442 women (1106 non-pregnant and 336 pregnant) in Ankara, Turkey. The individuals' awareness, knowledge, and use of folic acid were questioned and food consumption were taken. More than two-thirds of the non-pregnant and pregnant women had heard of folic acid (77.2% and 89.0%, respectively). The pregnant women (53.9%) knew more that folic acid should be used before conception in order to prevent congenital anomalies than non-pregnant women (41.4%). It was found that 70.2% of the pregnant women and only 15.1% of the non-pregnant women used folic acid supplementation. The pregnant women (1368.4 mcg; 330.4 mcg) significantly had higher folic acid and dietary folate intake than non-pregnant women (29.6 mcg; 289.3 mcg) (p < .01). Despite many public health campaigns, awareness, knowledge, and appropriate use of folic acid are still inadequate and not at the desired level in women of childbearing age.