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Scientific Reports Mar 2024Malaria is the leading parasitic disease worldwide, with P. vivax being a major challenge for its control. Several studies have indicated metabolomics as a promising...
Malaria is the leading parasitic disease worldwide, with P. vivax being a major challenge for its control. Several studies have indicated metabolomics as a promising tool for combating the disease. The study evaluated plasma metabolomic profiles of patients with recurrent and non-recurrent P. vivax malaria in the Brazilian Amazon. Metabolites extracted from the plasma of P. vivax-infected patients were subjected to LC-MS analysis. Untargeted metabolomics was applied to investigate the metabolic profile of the plasma in the two groups. Overall, 51 recurrent and 59 non-recurrent patients were included in the study. Longitudinal metabolomic analysis revealed 52 and 37 significant metabolite features from the recurrent and non-recurrent participants, respectively. Recurrence was associated with disturbances in eicosanoid metabolism. Comparison between groups suggest alterations in vitamin B6 (pyridoxine) metabolism, tyrosine metabolism, 3-oxo-10-octadecatrienoate β-oxidation, and alkaloid biosynthesis II. Integrative network analysis revealed enrichment of other metabolic pathways for the recurrent phenotype, including the butanoate metabolism, aspartate and asparagine metabolism, and N-glycan biosynthesis. The metabolites and metabolic pathways predicted in our study suggest potential biomarkers of recurrence and provide insights into targets for antimalarial development against P. vivax.
Topics: Humans; Malaria, Vivax; Metabolomics; Malaria; Metabolome; Antimalarials
PubMed: 38538661
DOI: 10.1038/s41598-024-54231-5 -
Brain & Development Jun 2024Infantile epileptic spasm syndrome (IESS), including West syndrome (WS) and infantile spasm (IS), causes a challenging prognosis, particularly when associated with...
OBJECTIVE
Infantile epileptic spasm syndrome (IESS), including West syndrome (WS) and infantile spasm (IS), causes a challenging prognosis, particularly when associated with metabolic etiologies.
METHODS
This study, conducted at a tertiary pediatric neurology center, explored the prevalence and clinical features of inborn errors of metabolism in 112 children with IESS over 10 years.
RESULTS
Most patients presented with seizures, primarily flexor spasms, and the median age at onset was 5 months. Comprehensive clinical evaluation and neuroimaging revealed structural-acquired causes as the most common etiology. Notably, inborn errors of metabolism were identified in 5.4 % of cases, with six distinct diagnoses including nonketotic hyperglycinemia, pyridoxine-dependent epilepsy, primary coenzyme Q10 deficiency 7, congenital disorder of glycosylation type IIM, 6-pyruvoyl tetrahydrobiopterin synthase deficiency, and argininosuccinate lyase deficiency. The prevalence of inborn errors of metabolism in this cohort was consistent with global variations reported in the literature. Genetic testing, including karyotype analysis and whole exome sequencing, was performed in a subset of cases with no clear diagnosis, revealing abnormalities in approximately 50 % of cases. Adrenocorticotropic hormone emerged as the most frequently prescribed antiseizure medication.
CONCLUSION
This study provides insight into the diagnostic challenges associated with IESS and highlights the importance of metabolic investigations, especially in cases without a clear etiology. The findings emphasize the need for further genetic and metabolic studies to enhance prognostic accuracy and guide potential treatment options for children with IESS, particularly in populations with high rates of consanguinity.
Topics: Humans; Infant; Female; Male; Spasms, Infantile; Child, Preschool; Tertiary Care Centers; Metabolism, Inborn Errors; Child; Prevalence
PubMed: 38493042
DOI: 10.1016/j.braindev.2024.03.003 -
Cell Host & Microbe Mar 2024Pyridoxine-unresponsive homocystinuria has lifelong implications for health. In this issue, Perreault and colleagues present evidence that orally delivered engineered...
Pyridoxine-unresponsive homocystinuria has lifelong implications for health. In this issue, Perreault and colleagues present evidence that orally delivered engineered probiotic Escherichia Coli Nissle SYNB1353 is a promising candidate in reducing homocysteine, with successful trials in mice, monkeys, and humans. However, further probiotic optimization and safety assessments are required.
Topics: Mice; Humans; Animals; Homocystinuria; Escherichia coli; Probiotics; Pyridoxine; Homocysteine
PubMed: 38484708
DOI: 10.1016/j.chom.2024.02.008 -
Alarming levels of inadequate intake of B group vitamins in tribal lactating women from South India.Journal of Public Health Research Jan 2024Micronutrients are necessary for proper growth and development of the human body, though required in small amounts. Dietary intake of these micronutrients by lactating...
BACKGROUND
Micronutrients are necessary for proper growth and development of the human body, though required in small amounts. Dietary intake of these micronutrients by lactating women is essential for their own health as well as children's overall growth and development. objective of present study is to assess the adequacy of dietary B-group vitamins intake during lactation and to find out the factors associated with their inadequate intake.
DESIGN AND METHODS
It was a analysis of data from prospective cohort study for 10 months carried out among 340 Scheduled Tribes mothers in 10 clusters in Guntur district, Andhra Pradesh, India. Data collection was done using a 24 h dietary recall questionnaire. A -value less than 0.05 was considered to be statistically significant.
RESULTS
All the mothers ( = 340) were not having adequate intake of Thiamine, Riboflavin, Niacin, Pyridoxine, Pantothenic acid, Biotin and Folic acid. Methyl cobalamin intake was inadequate in 37.5% mothers ( = 136). The mean intake of Vitamin B12 was 40.98 + 42.8 (SD) µg/day. Age at marriage, location and parity were significantly associated with inadequate intake of Vitamin B12.
CONCLUSIONS
The current diet pattern of mothers of vulnerable groups might affect the growth and development of the infant. We strongly recommend for supplementation of B-group vitamins to pregnant and lactating women in India.
PubMed: 38476323
DOI: 10.1177/22799036241234036 -
Nutrition Research (New York, N.Y.) May 2024In pregnant women, the Energy-adjusted Dietary Inflammatory Index (E-DII) is adopted to measure the inflammatory potential of the diet, but it does not predict the...
In pregnant women, the Energy-adjusted Dietary Inflammatory Index (E-DII) is adopted to measure the inflammatory potential of the diet, but it does not predict the quality of the diet. Our hypothesis is that a more pro-inflammatory diet during pregnancy is also a poorer quality diet. Thus, the objective of this study is to verify the association of the E-DII with the Diet Quality Index Adapted for Pregnancy (DQI-P) and the nutrient intake from the diet in terms of the second and third gestational trimesters. This is a cross-sectional study that took place in Brazil (2018-2019), with eligible adult women up to 72 hours' postpartum and in good health. Socioeconomic, gestational, anthropometric, and food consumption data were collected, enabling the calculation of E-DII, DQI-P, and nutrient intake. The sample (n = 260) had a median E-DII of 0.04 (-1.30 to 1.90) and DQI-P of 68.82 (18.82-98.22). There was no relevant difference between E-DII tertiles by sociodemographic, gestational, and anthropometric characteristics. The E-DII and the DQI-P showed agreement (55.7%) and inverse correlation (r = -0.53; P < .001). Each 1-unit increase in DQI-P, iron, iodine, magnesium, pyridoxine, and vitamin E decreased the E-DII score (P < .05). An increase of 1 unit in protein, saturated fatty acids, and vitamin C increased the E-DII score (P < .05). Thus, the results suggest that the E-DII can predict diet quality during pregnancy, with the added benefit of measuring the inflammatory potential of the diet.
Topics: Humans; Female; Pregnancy; Cross-Sectional Studies; Adult; Diet; Inflammation; Brazil; Young Adult; Energy Intake; Maternal Nutritional Physiological Phenomena
PubMed: 38460227
DOI: 10.1016/j.nutres.2024.02.004 -
Orphanet Journal of Rare Diseases Mar 2024This study aimed to assess medication adherence and demographic, clinical, and psychopathological parameters such as quality of life, depression, and anxiety levels that...
BACKGROUND
This study aimed to assess medication adherence and demographic, clinical, and psychopathological parameters such as quality of life, depression, and anxiety levels that can affect pediatrics with Wilson's Disease (WD).
METHODS
A prospective cohort study was conducted at an outpatient clinic in Turkey among pediatric patients (2 to 18 years) with WD between November 2022 and April 2023. The Medication Adherence Report Scale (MARS-5) as a subjective and Medication Possession Ratio (MPR) as an objective assessment were scored. Physical, genetic and biochemical parameters, the Pediatric Quality of Life Inventory (PedsQL) for both parents and patients, Childhood Depression Inventory, State Trait Anxiety Inventory were also administered.
RESULTS
A total of 30 pediatric outpatients who were prescribed D-penicillamine (n = 27) or trientine (n = 3) as chelators and zinc (n = 29) and pyridoxine (n = 19) as supplements were included. Proteinuria (n = 3), skin rash (n = 2), and gastrointestinal upset (n = 2) were observed. When the correlation between MARS-5 and duration of follow-up was examined, a significant negative correlation was found (p = 0.014). According to MPRs, non-adherence rates (missed doses ≥ 20%) were 29.6%, 17.2% and 5.3% for D-penicillamine, zinc and pyridoxine, respectively. PedsQL scores were higher than those of parents, with a positive correlation between them (p < 0.001). Also, there was a significant positive correlation between PedsQL and State Anxiety Inventory (p < 0.001). Comparing the change in urinary copper levels between different levels of treatment knowledge, significant differences were observed between high- and low levels (p = 0.043).
CONCLUSIONS
Overall, nonadherence rates were 23.3% based on MARS-5 and 5.3-29.6% based on MPR. It is essential to consider factors such as the duration of follow-up, biochemical parameters, treatment knowledge, quality of life and anxiety as potential influencers of medication adherence.
Topics: Adolescent; Child; Humans; Cohort Studies; Hepatolenticular Degeneration; Penicillamine; Prospective Studies; Pyridoxine; Quality of Life; Turkey; Zinc; Child, Preschool
PubMed: 38454433
DOI: 10.1186/s13023-024-03113-0 -
The FEBS Journal Jun 2024Vitamin B is a critical molecule for metabolism, development, and stress sensitivity in plants. It is a cofactor for numerous biochemical reactions, can serve as an...
Vitamin B is a critical molecule for metabolism, development, and stress sensitivity in plants. It is a cofactor for numerous biochemical reactions, can serve as an antioxidant, and has the potential to increase tolerance against both biotic and abiotic stressors. Due to the importance of vitamin B, its biosynthesis is likely tightly regulated. Plants can synthesize vitamin B de novo via the concerted activity of Pyridoxine Biosynthesis Protein 1 (PDX1) and PDX2. Previously, PDX proteins have been identified as targets for ubiquitination, indicating they could be marked for degradation by two highly conserved pathways: the Ubiquitin Proteasome Pathway (UPP) and the autophagy pathway. Initial experiments show that PDXs are in fact degraded, but surprisingly, in a ubiquitin-independent manner. Inhibitor studies pointed toward cathepsin B, a conserved lysosomal cysteine protease, which is implicated in both programed cell death and autophagy in humans and plants. In plants, cathepsin Bs are poorly described, and no confirmed substrates have been identified. Here, we present PDX proteins from Arabidopsis thaliana as interactors and substrates of a plant Cathepsin B. These findings not only describe a novel cathepsin B substrate in plants, but also provide new insights into how plants regulate de novo biosynthesis of vitamin B.
Topics: Cathepsin B; Arabidopsis; Vitamin B 6; Arabidopsis Proteins; Substrate Specificity; Ubiquitination; Gene Expression Regulation, Plant; Carbon-Nitrogen Lyases
PubMed: 38431778
DOI: 10.1111/febs.17110 -
Frontiers in Neurology 2024Pyridoxine-dependent epilepsy due to variants (PDE-ALDH7A1) is a rare disorder, presenting typically with severe neonatal, epileptic encephalopathy. Early diagnosis is...
PURPOSE
Pyridoxine-dependent epilepsy due to variants (PDE-ALDH7A1) is a rare disorder, presenting typically with severe neonatal, epileptic encephalopathy. Early diagnosis is imperative to prevent uncontrolled seizures. We have explored the role of EEG in the diagnosis and management of PDE.
METHODS
A total of 13 Norwegian patients with PDE-ALDH7A1 were identified, of whom five had reached adult age. Altogether 163 EEG recordings were assessed, 101 from the 1st year of life.
RESULTS
Median age at seizure onset was 9 h (IQR 41), range 1 h-6 days. Median delay from first seizure to first pyridoxine injection was 2 days (IQR 5.5). An EEG burst suppression pattern was seen in eight patients (62%) during the first 5 days of life. Eleven patients had recordings during pyridoxine injections: in three, immediate EEG improvement correlated with seizure control, whereas in six, no change of epileptiform activity occurred. Of these six, one had prompt clinical effect, one had delayed effect (< 1 day), one had no effect, one had uncertain effect, and another had more seizures. A patient without seizures at time of pyridoxine trial remained seizure free for 6 days. Two patients with prompt clinical effect had increased paroxysmal activity, one as a conversion to burst suppression. Autonomic seizures in the form of apnoea appeared to promote respiratory distress and were documented by EEG in one patient. EEG follow-up in adult age did not show signs of progressing encephalopathy.
CONCLUSION
A neonatal burst suppression EEG pattern should raise the suspicion of PDE-ALDH7A1. Respiratory distress is common; isolated apnoeic seizures may contribute. EEG responses during pyridoxine trials are diverse, often with poor correlation to immediate clinical effect. Reliance on single trials may lead to under-recognition of this treatable condition. Pyridoxine should be continued until results from biomarkers and genetic testing are available.
PubMed: 38419708
DOI: 10.3389/fneur.2024.1355861 -
European Journal of Nutrition Jun 2024The 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)... (Observational Study)
Observational 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.
Topics: Humans; Diabetes Mellitus, Type 1; Male; Female; Vitamin B Complex; Prospective Studies; Child; Autoimmunity; Child, Preschool; Infant; Islets of Langerhans; Autoantibodies; Risk Factors; Diet; Proportional Hazards Models; United States; Finland; Sweden; Germany; Dietary Supplements; Birth Cohort; Disease Progression
PubMed: 38413484
DOI: 10.1007/s00394-024-03346-6