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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 Peoples 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.

The present study aimed to investigate the neuroprotective effects of the vitamin B complex (B1, B2, B3, B5, B6, and B12—VBC), by studying the changes in the femoral nerve, quadriceps muscle, popliteal lymph nodes and gut microbiota in the rat model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). VBC treatment attenuated clinical signs of EAE during the disease, and reduced the duration of EAE thereby contributing to a faster recovery. In VBC-treated EAE rats, a significant decrease in nerve and muscle nuclear density was revealed during the onset period of the disease, while a marked increase was detected at the end of the disease, compared with untreated EAE rats. In the lymph nodes of VBC-treated EAE rats, a fewer number of lymphoid follicles in the cortical area and smaller epithelioid granulomas were detected. The changes in microbiota composition were examined using 16S rRNA gene sequencing and bioinformatics analysis, which revealed the potential of VBC treatment in establishing and/or maintaining gut microbiota homeostasis. Finally, the present study demonstrated that VBC treatment ameliorated the cellular changes in the affected peripheral nerve, muscles innervated by this nerve, and the gut microbiota dysbiosis which occurred during the EAE.

The present study aimed to investigate the neuroprotective effects of the vitamin B complex (B1, B2, B3, B5, B6, and B12-VBC), by studying the changes in the femoral nerve, quadriceps muscle, popliteal lymph nodes and gut microbiota in the rat model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). VBC treatment attenuated clinical signs of EAE during the disease, and reduced the duration of EAE thereby contributing to a faster recovery. In VBC-treated EAE rats, a significant decrease in nerve and muscle nuclear density was revealed during the onset period of the disease, while a marked increase was detected at the end of the disease, compared with untreated EAE rats. In the lymph nodes of VBC-treated EAE rats, a fewer number of lymphoid follicles in the cortical area and smaller epithelioid granulomas were detected. The changes in microbiota composition were examined using 16S rRNA gene sequencing and bioinformatics analysis, which revealed the potential of VBC treatment in establishing and/or maintaining gut microbiota homeostasis. Finally, the present study demonstrated that VBC treatment ameliorated the cellular changes in the affected peripheral nerve, muscles innervated by this nerve, and the gut microbiota dysbiosis which occurred during the EAE.

The present study aimed to investigate the neuroprotective effects of the vitamin B complex (B1, B2, B3, B5, B6, and B12—VBC), by studying the changes in the femoral nerve, quadriceps muscle, popliteal lymph nodes and gut microbiota in the rat model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). VBC treatment attenuated clinical signs of EAE during the disease, and reduced the duration of EAE thereby contributing to a faster recovery. In VBC-treated EAE rats, a significant decrease in nerve and muscle nuclear density was revealed during the onset period of the disease, while a marked increase was detected at the end of the disease, compared with untreated EAE rats. In the lymph nodes of VBC-treated EAE rats, a fewer number of lymphoid follicles in the cortical area and smaller epithelioid granulomas were detected. The changes in microbiota composition were examined using 16S rRNA gene sequencing and bioinformatics analysis, which revealed the potential of VBC treatment in establishing and/or maintaining gut microbiota homeostasis. Finally, the present study demonstrated that VBC treatment ameliorated the cellular changes in the affected peripheral nerve, muscles innervated by this nerve, and the gut microbiota dysbiosis which occurred during the EAE.

The functional and genomic diversity of the human gut microbiome is shaped by horizontal transfer of mobile genetic elements (MGEs). Characterized MGEs can encode genes beneficial for their host's self-defense (e.g., antibiotic resistance) or ability to compete for essential or limited resources (e.g., vitamins). Vitamin B12 and related compounds (corrinoids) are critical nutrients that enable colonization by members of the common gut microbe phylum, the Bacteroidetes. Herein, we identify a distinct class of MGEs in the Bacteroidetes responsible for the mobilization and exchange of the genes required for transport of corrinoids, a group of cyclic tetrapyrrole cofactors including vitamin B12 (btuGBFCD). This class includes two distinct groups of conjugative transposons (CTns) and one group of phage. Conjugative transfer and vitamin B12 transport activity of two of the CTns were confirmed in vitro and in vivo, demonstrating the important role MGEs play in distribution of corrinoid transporters in the Bacteroidetes.

Our previously reported, first validated, UPLC-MS/MS-based simultaneous analysis of five human milk B-vitamins revealed severe matrix effects. High levels of endogenous lactose fouled the electrospray ionization source affecting the analysis. We evaluated solid-phase extraction (SPE), liquid-solid extraction (LSE), protein precipitation (PPT), and liquid chromatography effluent diversion for lactose-removal. SPE failed to separate lactose from vitamins; LSE using 2-propanol reduced lactose and vitamin recoveries. PPT-solvent, milk volume, and reconstitution solvent influenced flavin adenine dinucleotide, pyridoxal and nicotinamide recoveries. Using an optimized LC-gradient enabled chromatographic separation of lactose from vitamins and its removal using a post-column switch-valve. Only 40 µL milk was subjected to methanol-PPT and non-polar matrix removal by methyl tert-butyl ether. B-vitamin recoveries were established (81.9-118.6%; CV ≤ 11.9%; precision: 4.9-13.7%) with greatly reduced matrix effects, and improved process efficiency, and recovery.

BackgroundInfantile beriberi-related mortality is still common in South and Southeast Asia. Interventions to increase maternal thiamine intakes, and thus human milk thiamine, are warranted; however, the required dose remains unknown.ObjectivesWe sought to estimate the dose at which additional maternal intake of oral thiamine no longer meaningfully increased milk thiamine concentrations in infants at 24 wk postpartum, and to investigate the impact of 4 thiamine supplementation doses on milk and blood thiamine status biomarkers.MethodsIn this double-blind, 4-parallel arm randomized controlled dose-response trial, healthy mothers were recruited in Kampong Thom, Cambodia. At 2 wk postpartum, women were randomly assigned to consume 1 capsule, containing 0, 1.2 (estimated average requirement), 2.4, or 10 mg of thiamine daily from 2 through 24 weeks postpartum. Human milk total thiamine concentrations were measured using HPLC. An Emax curve was plotted, which was estimated using a nonlinear least squares model in an intention-to-treat analysis. Linear mixed-effects models were used to test for differences between treatment groups. Maternal and infant blood thiamine biomarkers were also assessed.ResultsIn total, each of 335 women was randomly assigned to1 of the following thiamine-dose groups: placebo (n = 83), 1.2 mg (n = 86), 2.4 mg (n = 81), and 10 mg (n = 85). The estimated dose required to reach 90% of the maximum average total thiamine concentration in human milk (191 µg/L) is 2.35 (95% CI: 0.58, 7.01) mg/d. The mean ± SD milk thiamine concentrations were significantly higher in all intervention groups (183 ± 91, 190 ± 105, and 206 ± 89 µg/L for 1.2, 2.4, and 10 mg, respectively) compared with the placebo group (153 ± 85 µg/L; P < 0.0001) and did not significantly differ from each other.ConclusionsA supplemental thiamine dose of 2.35 mg/d was required to achieve a mi

A middle-aged woman was diagnosed with postural orthostatic tachycardia syndrome based on her clinical symptoms, elevated norepinephrine levels and positive tilt-table test. The patient was refractory to conventional treatment and improved only after she was treated with methylated B vitamins for her heterozygous catechol-O-methyltransferase Val158Met polymorphism.

Vitamin B12 is the only known essential human micronutrient made exclusively by prokaryotes. Kennedy and Taga introduce us to the world of cobamides-those cobalt-containing compounds, like B12, that appear to be the proprietary domain of our microbial partners.

Symbionts can regulate animal reproduction in multiple ways, but the underlying physiological and biochemical mechanisms remain largely unknown. The presence of multiple lineages of maternally inherited, intracellular symbionts (the primary and secondary symbionts) in terrestrial arthropods is widespread in nature. However, the biological, metabolic, and evolutionary role of co-resident secondary symbionts for hosts is poorly understood. The bacterial symbionts Hamiltonella and Arsenophonus have very high prevalence in two globally important pests, the whiteflies Bemisia tabaci and Trialeurodes vaporariorum, respectively. Both symbionts coexist with the primary symbiont Portiera in the same host cell (bacteriocyte) and are maternally transmitted. We found that elimination of both Hamiltonella and Arsenophonous by antibiotic treatment reduced the percentage of female offspring in whiteflies. Microsatellite genotyping and cytogenetic analysis revealed that symbiont deficiency inhibited fertilization in whiteflies, leading to more haploid males with one maternal allele, which is consistent with distorted sex ratio in whiteflies. Quantification of essential amino acids and B vitamins in whiteflies indicated that symbiont deficiency reduced B vitamin levels, and dietary B vitamin supplementation rescued fitness of whiteflies. This study, for the first time, conclusively demonstrates that these two intracellular symbionts affect sex ratios in their whitefly hosts by regulating fertilization and supplying B vitamins. Our results reveal that both symbionts have the convergent function of regulating reproduction in phylogenetically-distant whitefly species. The 100% frequency, the inability of whiteflies to develop normally without their symbiont, and rescue with B vitamins suggests that both symbionts may be better considered co-primary symbionts.

Microbial communities are essential to fundamental processes on Earth. Underlying the compositions and functions of these communities are nutritional interdependencies among individual species. One class of nutrients, cobamides (the family of enzyme cofactors that includes vitamin B12), is widely used for a variety of microbial metabolic functions, but these structurally diverse cofactors are synthesized by only a subset of bacteria and archaea. Advances at different scales of study-from individual isolates, to synthetic consortia, to complex communities-have led to an improved understanding of cobamide sharing. Here, we discuss how cobamides affect microbes at each of these three scales and how integrating different approaches leads to a more complete understanding of microbial interactions.

BackgroundAngelman syndrome (AS) is a neurodevelopmental disorder that is caused by maternal genetic deficiency of a gene that encodes E6-AP ubiquitin-protein ligase (gene symbol UBE3A) mapping to chromosome 15q11-q13. AS leads to stiff and jerky gait, excess laughter, seizures, and severe intellectual disability. In some parts of the brain, the paternally inherited UBE3A gene is subject to genomic imprinting by the action of the UBE3A-antisense transcript (UBE3A-ATS) on the paternally inherited allele. Consequently, only the maternally inherited UBE3A gene is expressed in mature neurons. AS occurs due to deletions of the maternal 15q11 - 13 region, paternal uniparental disomy (UPD), imprinting center defects, mutations in the maternal UBE3A gene, or other unknown genetic malfunctions that result in a silenced maternal UBE3A gene in the specific imprinted regions of the brain.ResultsA potential treatment strategy for AS is to increase methylation of UBE3A-ATS to promote expression of the paternal UBE3A gene and thus ameliorate the clinical phenotypes of AS. We treated two sets of male identical twins with class I deletions with a 1 year treatment trial of either betaine and folic acid versus placebo. We found no statistically significant changes in the clinical parameters tested at the end of the 1 year trial, nor did we find any significant adverse events.ConclusionsThis study tested the hypothesis that by increasing the methylation of the UBE3A-antisense transcript in Angelman syndrome to promote expression of the silenced paternal UBE3A gene we may ameliorate the clinical phenotypes of AS. We treated two sets of identical twins with placebo versus betaine and folic acid. Although this study represented a novel approach to treating Angelman syndrome, the differences in the developmental testing results was not significant. This paper also discusses the value of monozygotic twin studies in minimizing confounding variables and its utility in conducting small treatme

The vitamin B12 family of cofactors known as cobamides are essential for a variety of microbial metabolisms. We used comparative genomics of 11,000 bacterial species to analyze the extent and distribution of cobamide production and use across bacteria. We find that 86% of bacteria in this data set have at least one of 15 cobamide-dependent enzyme families, but only 37% are predicted to synthesize cobamides de novo. The distribution of cobamide biosynthesis and use vary at the phylum level. While 57% of Actinobacteria are predicted to biosynthesize cobamides, only 0.6% of Bacteroidetes have the complete pathway, yet 96% of species in this phylum have cobamide-dependent enzymes. The form of cobamide produced by the bacteria could be predicted for 58% of cobamide-producing species, based on the presence of signature lower ligand biosynthesis and attachment genes. Our predictions also revealed that 17% of bacteria have partial biosynthetic pathways, yet have the potential to salvage cobamide precursors. Bacteria with a partial cobamide biosynthesis pathway include those in a newly defined, experimentally verified category of bacteria lacking the first step in the biosynthesis pathway. These predictions highlight the importance of cobamide and cobamide precursor salvaging as examples of nutritional dependencies in bacteria.

Sammanfattning Bakgrund Vitamin- och mineralbrister hos gravida kvinnor kan leda till missfall och allvarliga störningar i barnets utveckling. Moderns tarmflora överförs med stor sannolikhet till barnet under förlossningen och kan därför innebära ett viktigt steg i utvecklingen av barnets tarmflora. En tänkbar lösning för att säkra ett adekvat intag kan vara konsumtion av kosttillskott och probiotika. I dagsläget finns osäkra uppgifter om hur många gravida kvinnor som intar tillskott. Syfte Att undersöka hur många gravida kvinnor i Västerbottens län som valde att inta kosttillskott, främst järn och probiotika, samt om det fanns en skillnad mellan olika faktorer och intag. Metod En kvantitativ tvärsnittsstudie där gravida kvinnor (n=1473) från Northpop-studien i Västerbottens län svarade på ett frågeformulär gällande intag av kosttillskott och faktorer som ålder, utbildning, kostregim etc. De statistiska tester som användes var Chi-2-test, oberoende t-test och Mann Whitney U-test. Materialet analyserades i SPSS. Signifikansnivån sattes till p<0,05. Resultat Majoriteten av deltagarna svarade att de intog kosttillskott. Faktorer som ökade intaget av kosttillskott hos gravida kvinnor var högre ålder (p=0,030) jämfört med lägre ålder, högre utbildningsnivå (p=0,006) jämfört med lägre utbildningsnivå och vegetarisk/vegansk kost (p=0,021) jämfört med blandkost. Femtiofem procent uppgav att de intog järntillskott. De faktorer som ökade intaget av järntillskott hos gravida kvinnor var vegetarisk/vegansk kost (p=0,001) jämfört med blandkost. Probiotika intogs av 2 procent. Ett högre intag av probiotika sågs hos personer boende i stadsområde (p=0,024) jämfört med övriga boenderegioner samt de som åt vegetarisk/vegansk kost (p=0,001) jämfört med blandkost. Slutsats Majoriteten av deltagarna intog någon typ av kosttillskott, hälften intog järntillskott och en liten andel intog probiotika. Lågutbildade, yngre, de som äter blandkost och bor utanför stadsområde verkar vara, Background Vitamin and mineral deficiencies in pregnant women can lead to miscarriage and serious disturbances in children’s development. The intestinal flora of the mother is most likely transmitted to the child during childbirth and may lay the foundation for the child's health. One possible solution to ensure an adequate intake may be the consumption of dietary supplements and probiotics. At present, there is insufficient data on supplement consumption among pregnant women. Objective The purpose of the study was to examine how many pregnant women in Västerbotten County chose to consume dietary supplements, mainly iron and probiotics, and whether there was a difference between different factors and intake. Method A quantitative cross-sectional study where pregnant women (n=1473) from the Northpop-study in Västerbotten County responded to a questionnaire regarding consumption of dietary supplements and factors such as age, education, diet etc. The material was analyzed in SPSS with Chi-2-test, independent T-Test and Mann-Whitney U-Test. Using significance level <0.05. Results The majority of participants, 90 percent, responded that they consumed dietary supplements. The factors that increased the intake of dietary supplements in pregnant women were higher age (p=0.030), higher education (p=0.006) and vegetarian/vegan diet (p=0.021). Iron was reported to be consumed by 804 people, 55 percent. The factors that increased the intake of iron supplement in pregnant women were vegetarian/vegan diet (p=0.001). Probiotics were consumed by 25 people, 2 percent. Living in urban areas (p=0.024) and eating vegetarian/vegan diet (p=0.002) increased consumption of probiotics. Conclusion The majority of participants chose to consume some type of dietary supplement, half of the participants consumed iron supplements and a small part consumed probiotics. It appears that pregnant women who are low educated, younger, eating an omnivorous diet and living outside urban, Northpop

The vitamin B12 family of cofactors known as cobamides are essential for a variety of microbial metabolisms. We used comparative genomics of 11,000 bacterial species to analyze the extent and distribution of cobamide production and use across bacteria. We find that 86% of bacteria in this data set have at least one of 15 cobamide-dependent enzyme families, but only 37% are predicted to synthesize cobamides de novo. The distribution of cobamide biosynthesis and use vary at the phylum level. While 57% of Actinobacteria are predicted to biosynthesize cobamides, only 0.6% of Bacteroidetes have the complete pathway, yet 96% of species in this phylum have cobamide-dependent enzymes. The form of cobamide produced by the bacteria could be predicted for 58% of cobamide-producing species, based on the presence of signature lower ligand biosynthesis and attachment genes. Our predictions also revealed that 17% of bacteria have partial biosynthetic pathways, yet have the potential to salvage cobamide precursors. Bacteria with a partial cobamide biosynthesis pathway include those in a newly defined, experimentally verified category of bacteria lacking the first step in the biosynthesis pathway. These predictions highlight the importance of cobamide and cobamide precursor salvaging as examples of nutritional dependencies in bacteria.

BackgroundAngelman syndrome (AS) is a neurodevelopmental disorder that is caused by maternal genetic deficiency of a gene that encodes E6-AP ubiquitin-protein ligase (gene symbol UBE3A) mapping to chromosome 15q11-q13. AS leads to stiff and jerky gait, excess laughter, seizures, and severe intellectual disability. In some parts of the brain, the paternally inherited UBE3A gene is subject to genomic imprinting by the action of the UBE3A-antisense transcript (UBE3A-ATS) on the paternally inherited allele. Consequently, only the maternally inherited UBE3A gene is expressed in mature neurons. AS occurs due to deletions of the maternal 15q11 - 13 region, paternal uniparental disomy (UPD), imprinting center defects, mutations in the maternal UBE3A gene, or other unknown genetic malfunctions that result in a silenced maternal UBE3A gene in the specific imprinted regions of the brain.ResultsA potential treatment strategy for AS is to increase methylation of UBE3A-ATS to promote expression of the paternal UBE3A gene and thus ameliorate the clinical phenotypes of AS. We treated two sets of male identical twins with class I deletions with a 1 year treatment trial of either betaine and folic acid versus placebo. We found no statistically significant changes in the clinical parameters tested at the end of the 1 year trial, nor did we find any significant adverse events.ConclusionsThis study tested the hypothesis that by increasing the methylation of the UBE3A-antisense transcript in Angelman syndrome to promote expression of the silenced paternal UBE3A gene we may ameliorate the clinical phenotypes of AS. We treated two sets of identical twins with placebo versus betaine and folic acid. Although this study represented a novel approach to treating Angelman syndrome, the differences in the developmental testing results was not significant. This paper also discusses the value of monozygotic twin studies in minimizing confounding variables and its utility in conducting small treatme

Human RPE cell lines, especially the ARPE-19 cell line, are widely-used in eye research, as well as general epithelial cell studies. In comparison with primary RPE cells, they offer relative convenience and consistency, but cultures derived from these lines are typically not well differentiated. We describe a simple, rapid method to establish cultures from ARPE-19 cells, with significantly improved epithelial cell morphology and cytoskeletal organization, and RPE-related functions. We identify the presence of nicotinamide, a member of the vitamin B family, as an essential factor in promoting the observed differentiation, indicating the importance of metabolism in RPE cell differentiation.

Sammanfattning Bakgrund Vitamin- och mineralbrister hos gravida kvinnor kan leda till missfall och allvarliga störningar i barnets utveckling. Moderns tarmflora överförs med stor sannolikhet till barnet under förlossningen och kan därför innebära ett viktigt steg i utvecklingen av barnets tarmflora. En tänkbar lösning för att säkra ett adekvat intag kan vara konsumtion av kosttillskott och probiotika. I dagsläget finns osäkra uppgifter om hur många gravida kvinnor som intar tillskott. Syfte Att undersöka hur många gravida kvinnor i Västerbottens län som valde att inta kosttillskott, främst järn och probiotika, samt om det fanns en skillnad mellan olika faktorer och intag. Metod En kvantitativ tvärsnittsstudie där gravida kvinnor (n=1473) från Northpop-studien i Västerbottens län svarade på ett frågeformulär gällande intag av kosttillskott och faktorer som ålder, utbildning, kostregim etc. De statistiska tester som användes var Chi-2-test, oberoende t-test och Mann Whitney U-test. Materialet analyserades i SPSS. Signifikansnivån sattes till p<0,05. Resultat Majoriteten av deltagarna svarade att de intog kosttillskott. Faktorer som ökade intaget av kosttillskott hos gravida kvinnor var högre ålder (p=0,030) jämfört med lägre ålder, högre utbildningsnivå (p=0,006) jämfört med lägre utbildningsnivå och vegetarisk/vegansk kost (p=0,021) jämfört med blandkost. Femtiofem procent uppgav att de intog järntillskott. De faktorer som ökade intaget av järntillskott hos gravida kvinnor var vegetarisk/vegansk kost (p=0,001) jämfört med blandkost. Probiotika intogs av 2 procent. Ett högre intag av probiotika sågs hos personer boende i stadsområde (p=0,024) jämfört med övriga boenderegioner samt de som åt vegetarisk/vegansk kost (p=0,001) jämfört med blandkost. Slutsats Majoriteten av deltagarna intog någon typ av kosttillskott, hälften intog järntillskott och en liten andel intog probiotika. Lågutbildade, yngre, de som äter blandkost och bor utanför stadsområde verkar vara, Background Vitamin and mineral deficiencies in pregnant women can lead to miscarriage and serious disturbances in children’s development. The intestinal flora of the mother is most likely transmitted to the child during childbirth and may lay the foundation for the child's health. One possible solution to ensure an adequate intake may be the consumption of dietary supplements and probiotics. At present, there is insufficient data on supplement consumption among pregnant women. Objective The purpose of the study was to examine how many pregnant women in Västerbotten County chose to consume dietary supplements, mainly iron and probiotics, and whether there was a difference between different factors and intake. Method A quantitative cross-sectional study where pregnant women (n=1473) from the Northpop-study in Västerbotten County responded to a questionnaire regarding consumption of dietary supplements and factors such as age, education, diet etc. The material was analyzed in SPSS with Chi-2-test, independent T-Test and Mann-Whitney U-Test. Using significance level <0.05. Results The majority of participants, 90 percent, responded that they consumed dietary supplements. The factors that increased the intake of dietary supplements in pregnant women were higher age (p=0.030), higher education (p=0.006) and vegetarian/vegan diet (p=0.021). Iron was reported to be consumed by 804 people, 55 percent. The factors that increased the intake of iron supplement in pregnant women were vegetarian/vegan diet (p=0.001). Probiotics were consumed by 25 people, 2 percent. Living in urban areas (p=0.024) and eating vegetarian/vegan diet (p=0.002) increased consumption of probiotics. Conclusion The majority of participants chose to consume some type of dietary supplement, half of the participants consumed iron supplements and a small part consumed probiotics. It appears that pregnant women who are low educated, younger, eating an omnivorous diet and living outside urban, Northpop

Pregnant and post-partum women require increased nutrient intake and optimal cognition, which depends on adequate nutrition, to enable reasoning and learning for caregiving. We aimed to assess (a) differences in maternal cognition and caregiving between women in Malawi who received different nutritional supplements, (b) 14 effect modifiers, and (c) associations of cognition and caregiving with biomarkers of iron, Vitamin A, B-vitamin, and fatty acid status. In a randomized controlled trial (n = 869), pregnant women daily received either multiple micronutrients (MMN), 20 g/day lipid-based nutrient supplements (LNS), or a control iron/folic acid (IFA) tablet. After delivery, supplementation continued in the MMN and LNS arms, and the IFA control group received placebo until 6 months post-partum, when cognition (n = 712), caregiving behaviour (n = 669), and biomarkers of nutritional status (n = 283) were assessed. In the full group, only one difference was significant: the IFA arm scored 0.22 SD (95% CI [0.01, 0.39], p = .03) higher than the LNS arm in mental rotation. Among subgroups of women with baseline low hemoglobin, poor iron status, or malaria, those who received LNS scored 0.4 to 0.7 SD higher than the IFA arm in verbal fluency. Breastmilk docosahexaenoic acid and Vitamin B12 concentrations were positively associated with verbal fluency and digit span forward (adjusting for covariates ps < .05). In this population in Malawi, maternal supplementation with MMN or LNS did not positively affect maternal cognition or caregiving. Maternal docosahexaenoic acid and B12 status may be important for post-partum attention and executive function.

AimsIncreased epicardial adipose tissue (EAT), pericardial adipose tissue (PAT), periaortic adipose tissue (PaAT), and subcutaneous adipose tissue (SAT) are mediators of metabolic risk, and are associated with the severity of coronary artery calcium (CAC). Aged garlic extract (AGE) has been shown to reduce the progression of coronary atherosclerosis. This study evaluates the effect of AGE with supplements (AGE+S) on EAT, PAT, SAT, and PaAT.MethodsSixty asymptomatic participants participated in a randomized trial evaluating the effect of AGE+S versus placebo on coronary atherosclerosis progression, and underwent CAC at baseline and after 12 months of treatment. EAT, PAT, PaAT, and SAT volumes were measured on CAC scans. PAT was calculated as: intrathoracic adipose tissue-EAT. SAT was defined as the volume of fat depot anterior to the sternum and posterior to the vertebra. PaAT was defined as fat depot around the descending aorta.ResultsAt 1 year, the increase in EAT, PAT, PaAT, and SAT was significantly lower in the AGE+S as compared with the placebo group (P<0.05). The odds ratios of increase in EAT, PAT, PaAT, and SAT were 0.63 [95% confidence interval (CI): 0.43-0.90], 0.72 (95% CI: 0.45-0.93), 0.81 (95% CI: 0.65-0.98), and 0.87 (CI: 0.52-0.98), respectively, compared with the placebo group, which even remained significant (all P<0.05) after adjustment for cardiovascular risk factors and statin therapy and BMI.ConclusionThis study shows that AGE+S is associated with favorable effects on reducing the progression rate of adipose tissue volumes.

AimsIncreased epicardial adipose tissue (EAT), pericardial adipose tissue (PAT), periaortic adipose tissue (PaAT), and subcutaneous adipose tissue (SAT) are mediators of metabolic risk, and are associated with the severity of coronary artery calcium (CAC). Aged garlic extract (AGE) has been shown to reduce the progression of coronary atherosclerosis. This study evaluates the effect of AGE with supplements (AGE+S) on EAT, PAT, SAT, and PaAT.MethodsSixty asymptomatic participants participated in a randomized trial evaluating the effect of AGE+S versus placebo on coronary atherosclerosis progression, and underwent CAC at baseline and after 12 months of treatment. EAT, PAT, PaAT, and SAT volumes were measured on CAC scans. PAT was calculated as: intrathoracic adipose tissue-EAT. SAT was defined as the volume of fat depot anterior to the sternum and posterior to the vertebra. PaAT was defined as fat depot around the descending aorta.ResultsAt 1 year, the increase in EAT, PAT, PaAT, and SAT was significantly lower in the AGE+S as compared with the placebo group (P<0.05). The odds ratios of increase in EAT, PAT, PaAT, and SAT were 0.63 [95% confidence interval (CI): 0.43-0.90], 0.72 (95% CI: 0.45-0.93), 0.81 (95% CI: 0.65-0.98), and 0.87 (CI: 0.52-0.98), respectively, compared with the placebo group, which even remained significant (all P<0.05) after adjustment for cardiovascular risk factors and statin therapy and BMI.ConclusionThis study shows that AGE+S is associated with favorable effects on reducing the progression rate of adipose tissue volumes.

Pregnant and post-partum women require increased nutrient intake and optimal cognition, which depends on adequate nutrition, to enable reasoning and learning for caregiving. We aimed to assess (a) differences in maternal cognition and caregiving between women in Malawi who received different nutritional supplements, (b) 14 effect modifiers, and (c) associations of cognition and caregiving with biomarkers of iron, Vitamin A, B-vitamin, and fatty acid status. In a randomized controlled trial (n = 869), pregnant women daily received either multiple micronutrients (MMN), 20 g/day lipid-based nutrient supplements (LNS), or a control iron/folic acid (IFA) tablet. After delivery, supplementation continued in the MMN and LNS arms, and the IFA control group received placebo until 6 months post-partum, when cognition (n = 712), caregiving behaviour (n = 669), and biomarkers of nutritional status (n = 283) were assessed. In the full group, only one difference was significant: the IFA arm scored 0.22 SD (95% CI [0.01, 0.39], p = .03) higher than the LNS arm in mental rotation. Among subgroups of women with baseline low hemoglobin, poor iron status, or malaria, those who received LNS scored 0.4 to 0.7 SD higher than the IFA arm in verbal fluency. Breastmilk docosahexaenoic acid and Vitamin B12 concentrations were positively associated with verbal fluency and digit span forward (adjusting for covariates ps < .05). In this population in Malawi, maternal supplementation with MMN or LNS did not positively affect maternal cognition or caregiving. Maternal docosahexaenoic acid and B12 status may be important for post-partum attention and executive function.

During maturation, pancreatic islets achieve their full capacity to secrete insulin in response to glucose, undergo morphological changes in which alpha-cells decrease and beta-cell mass increases, and they acquire the normal alpha- and beta-cell proportion changes that are important for islet functions later in life. In rodents, the first week of postweaning is critical for islet maturation. Multiple studies have documented the detrimental effects of several conditions on pancreatic maturation; however, few studies have addressed the use of pharmacological agents to enhance islet maturation. Biotin might have a potential action on islet maturation. Pharmacological concentrations of biotin have been found to modify islet morphology and function. In a previous study, we found that mice fed a biotin-supplemented diet for 8 weeks after weaning showed an increase in basal and glucose stimulated insulin secretion, enlarged islet size, and modified islet structure. In the present study, we investigated the effect of biotin on maturation features during the first week postweaning. Female BALB/cAnN Hsd mice were fed a control or a biotin-supplemented diet for 1 week after weaning. Compared with the control, biotin-supplemented mice showed an increase in pancreatic islet number and area in addition to an augmented proportion of beta-cells in the islet. These effects were related to an increase in beta-cell proliferation. No differences were found in insulin secretion, blood glucose concentrations, or serum insulin levels. These results indicate that biotin supplementation is capable of affecting beta-cell proliferation and might be a therapeutic agent for establishing strategies for regenerative medicine.

This report on vitamin B-12 (B12) is part of the Biomarkers of Nutrition for Development (BOND) Project, which provides state-of-the art information and advice on the selection, use, and interpretation of biomarkers of nutrient exposure, status, and function. As with the other 5 reports in this series, which focused on iodine, folate, zinc, iron, and vitamin A, this B12 report was developed with the assistance of an expert panel (BOND B12 EP) and other experts who provided information during a consultation. The experts reviewed the existing literature in depth in order to consolidate existing relevant information on the biology of B12, including known and possible effects of insufficiency, and available and potential biomarkers of status. Unlike the situation for the other 5 nutrients reviewed during the BOND project, there has been relatively little previous attention paid to B12 status and its biomarkers, so this report is a landmark in terms of the consolidation and interpretation of the available information on B12 nutrition. Historically, most focus has been on diagnosis and treatment of clinical symptoms of B12 deficiency, which result primarily from pernicious anemia or strict vegetarianism. More recently, we have become aware of the high prevalence of B12 insufficiency in populations consuming low amounts of animal-source foods, which can be detected with ≥1 serum biomarker but presents the new challenge of identifying functional consequences that may require public health interventions.

ImportanceNeural tube defects are among the most common major congenital anomalies in the United States and may lead to a range of disabilities or death. Daily folic acid supplementation in the periconceptional period can prevent neural tube defects. However, most women do not receive the recommended daily intake of folate from diet alone.ObjectiveTo update the 2009 US Preventive Services Task Force (USPSTF) recommendation on folic acid supplementation in women of childbearing age.Evidence reviewIn 2009, the USPSTF reviewed the effectiveness of folic acid supplementation in women of childbearing age for the prevention of neural tube defects in infants. The current review assessed new evidence on the benefits and harms of folic acid supplementation.FindingsThe USPSTF assessed the balance of the benefits and harms of folic acid supplementation in women of childbearing age and determined that the net benefit is substantial. Evidence is adequate that the harms to the mother or infant from folic acid supplementation taken at the usual doses are no greater than small. Therefore, the USPSTF reaffirms its 2009 recommendation.Conclusions and recommendationThe USPSTF recommends that all women who are planning or capable of pregnancy take a daily supplement containing 0.4 to 0.8 mg (400-800 µg) of folic acid. (A recommendation).

Insects with restricted diets rely on obligate microbes to fulfil nutritional requirements essential for biological function. Tsetse flies, vectors of African trypanosome parasites, feed exclusively on vertebrate blood and harbour the obligate endosymbiont Wigglesworthia glossinidia. Without Wigglesworthia, tsetse are unable to reproduce. These symbionts are sheltered within specialized cells (bacteriocytes) that form the midgut-associated bacteriome organ. To decipher the core functions of this symbiosis essential for tsetse's survival, we performed dual-RNA-seq analysis of the bacteriome, coupled with metabolomic analysis of bacteriome and haemolymph collected from normal and symbiont-cured (sterile) females. Bacteriocytes produce immune regulatory peptidoglycan recognition protein (pgrp-lb) that protects Wigglesworthia, and a multivitamin transporter (smvt) that can aid in nutrient dissemination. Wigglesworthia overexpress a molecular chaperone (GroEL) to augment their translational/transport machinery and biosynthesize an abundance of B vitamins (specifically B1-, B2-, B3- and B6-associated metabolites) to supplement the host's nutritionally deficient diet. The absence of Wigglesworthia's contributions disrupts multiple metabolic pathways impacting carbohydrate and amino acid metabolism. These disruptions affect the dependent downstream processes of nucleotide biosynthesis and metabolism and biosynthesis of S-adenosyl methionine (SAM), an essential cofactor. This holistic fundamental knowledge of the symbiotic dialogue highlights new biological targets for the development of innovative vector control methods.

Insects with restricted diets rely on obligate microbes to fulfil nutritional requirements essential for biological function. Tsetse flies, vectors of African trypanosome parasites, feed exclusively on vertebrate blood and harbour the obligate endosymbiont Wigglesworthia glossinidia. Without Wigglesworthia, tsetse are unable to reproduce. These symbionts are sheltered within specialized cells (bacteriocytes) that form the midgut-associated bacteriome organ. To decipher the core functions of this symbiosis essential for tsetse's survival, we performed dual-RNA-seq analysis of the bacteriome, coupled with metabolomic analysis of bacteriome and haemolymph collected from normal and symbiont-cured (sterile) females. Bacteriocytes produce immune regulatory peptidoglycan recognition protein (pgrp-lb) that protects Wigglesworthia, and a multivitamin transporter (smvt) that can aid in nutrient dissemination. Wigglesworthia overexpress a molecular chaperone (GroEL) to augment their translational/transport machinery and biosynthesize an abundance of B vitamins (specifically B1-, B2-, B3- and B6-associated metabolites) to supplement the host's nutritionally deficient diet. The absence of Wigglesworthia's contributions disrupts multiple metabolic pathways impacting carbohydrate and amino acid metabolism. These disruptions affect the dependent downstream processes of nucleotide biosynthesis and metabolism and biosynthesis of S-adenosyl methionine (SAM), an essential cofactor. This holistic fundamental knowledge of the symbiotic dialogue highlights new biological targets for the development of innovative vector control methods.

ImportanceNeural tube defects are among the most common major congenital anomalies in the United States and may lead to a range of disabilities or death. Daily folic acid supplementation in the periconceptional period can prevent neural tube defects. However, most women do not receive the recommended daily intake of folate from diet alone.ObjectiveTo update the 2009 US Preventive Services Task Force (USPSTF) recommendation on folic acid supplementation in women of childbearing age.Evidence reviewIn 2009, the USPSTF reviewed the effectiveness of folic acid supplementation in women of childbearing age for the prevention of neural tube defects in infants. The current review assessed new evidence on the benefits and harms of folic acid supplementation.FindingsThe USPSTF assessed the balance of the benefits and harms of folic acid supplementation in women of childbearing age and determined that the net benefit is substantial. Evidence is adequate that the harms to the mother or infant from folic acid supplementation taken at the usual doses are no greater than small. Therefore, the USPSTF reaffirms its 2009 recommendation.Conclusions and recommendationThe USPSTF recommends that all women who are planning or capable of pregnancy take a daily supplement containing 0.4 to 0.8 mg (400-800 µg) of folic acid. (A recommendation).

Hydrogen sulfide (H2 S) is a highly neurotoxic gas. Acute exposure can lead to neurological sequelae among survivors. A drug for treating neurological sequelae in survivors of acute H2 S intoxication is needed. Using a novel mouse model we evaluated the efficacy of cobinamide (Cob) for increasing survival of, and reducing neurological sequalae in, mice exposed to sublethal doses of H2 S. There were two objectives: (1) to determine the dose-response efficacy of Cob and (2) to determine the effective therapeutic time window of Cob. To explore objective 1, mice were injected intramuscularly with Cob at 0, 50, or 100 mg/kg at 2 min after H2 S exposure. For objective 2, mice were injected intramuscularly with 100 mg/kg Cob at 2, 15, and 30 min after H2 S exposure. For both objectives, mice were exposed to 765 ppm of H2 S gas. Cob significantly reduced H2 S-induced lethality in a dose-dependent manner (P < 0.05). Cob-treated mice exhibited significantly fewer seizures and knockdowns compared with the H2 S-exposed group. Cob also reversed H2 S-induced weight loss, behavioral deficits, neurochemical changes, cytochrome c oxidase enzyme inhibition, and neurodegeneration in a dose- and time-dependent manner (P < 0.01). Overall, these findings show that Cob increases survival and is neuroprotective in a mouse model of H2 S-induced neurological sequelae.

BackgroundHyperhomocysteinemia (HHcy) is associated with inflammation and a rise in the expression of matrix metalloproteinase-9 (MMP-9) in the vascular wall. However, the role of HHcy in the growth and rupture of cerebral aneurysms remains unclear.MethodsThirteen-week-old female Sprague-Dawley rats were subject to bilateral ovariectomy and ligation of the right common carotid artery and fed an 8 % high-salt diet to induce cerebral aneurysms. Two weeks later, they underwent ligation of the bilateral posterior renal arteries. They were divided into two groups and methionine (MET) was or was not added to their drinking water. In another set of experiments, the role of folic acid (FA) against cerebral aneurysms was assessed.ResultsDuring a 12-week observation period, subarachnoid hemorrhage due to aneurysm rupture was observed at the anterior communicating artery (AcomA) or the posterior half of the circle of Willis. HHcy induced by excessive MET intake significantly increased the incidence of ruptured aneurysms at 6-8 weeks. At the AcomA of rats treated with MET, we observed the promotion of aneurysmal growth and infiltration by M1 macrophages. Furthermore, the mRNA level of MMP-9, the ratio of MMP-9 to the tissue inhibitor of metalloproteinase-2, and the level of interleukin-6 were higher in these rats. Treatment with FA abolished the effect of MET, suggesting that the inflammatory response and vascular degradation at the AcomA is attributable to HHcy due to excessive MET intake.ConclusionsWe first demonstrate that in hypertensive ovariectomized rats, HHcy induced by excessive MET intake may be associated with the propensity of the aneurysm wall to rupture.

BackgroundHyperhomocysteinemia (HHcy) is associated with inflammation and a rise in the expression of matrix metalloproteinase-9 (MMP-9) in the vascular wall. However, the role of HHcy in the growth and rupture of cerebral aneurysms remains unclear.MethodsThirteen-week-old female Sprague-Dawley rats were subject to bilateral ovariectomy and ligation of the right common carotid artery and fed an 8 % high-salt diet to induce cerebral aneurysms. Two weeks later, they underwent ligation of the bilateral posterior renal arteries. They were divided into two groups and methionine (MET) was or was not added to their drinking water. In another set of experiments, the role of folic acid (FA) against cerebral aneurysms was assessed.ResultsDuring a 12-week observation period, subarachnoid hemorrhage due to aneurysm rupture was observed at the anterior communicating artery (AcomA) or the posterior half of the circle of Willis. HHcy induced by excessive MET intake significantly increased the incidence of ruptured aneurysms at 6-8 weeks. At the AcomA of rats treated with MET, we observed the promotion of aneurysmal growth and infiltration by M1 macrophages. Furthermore, the mRNA level of MMP-9, the ratio of MMP-9 to the tissue inhibitor of metalloproteinase-2, and the level of interleukin-6 were higher in these rats. Treatment with FA abolished the effect of MET, suggesting that the inflammatory response and vascular degradation at the AcomA is attributable to HHcy due to excessive MET intake.ConclusionsWe first demonstrate that in hypertensive ovariectomized rats, HHcy induced by excessive MET intake may be associated with the propensity of the aneurysm wall to rupture.

The human genome actively transcribes a large amount of non-coding genes, including microRNA and long noncoding RNAs (lncRNAs). Compared to well-known microRNAs, lncRNAs are poorly characterized. However, emerging evidence suggests that lncRNAs may be dysregulated in prostate cancer, but their role in prostate cancer remains elusive. We hypothesize that prostate cancer may exploit this mechanism to promote tumor progression and metastasis, and therapy resistance. Thus, overall goal of this application is to determine whether lncRNAs function as competitive endogenous RNAs (CeRNAs) which are capable of sequestering microRNAs to regulate RNA transcripts. A better understanding of how microRNAs are dysregulated in prostate cancer may help biomarker discovery, ultimately developing a better strategy for prostate cancer treatment., The original document contains color images.

ObjectiveRecurrence risk of congenital heart disease (CHD) in families with an affected first-degree relative is increased as compared with the general population. Advances in genetic testing and evidence that preconceptual folic acid supplementation may decrease risk of CHD warrant preventative counseling for at-risk families. Our goal was to document patterns of preconceptual folic acid supplementation and recurrence risk counseling in at-risk families in order to identify opportunities for improved preventative care.DesignMothers referred for a fetal echocardiogram were prospectively enrolled. Cases were defined as mothers deemed to be at higher risk of having an affected fetus with CHD given an affected parent or affected previous pregnancy with CHD. Controls were defined as mothers with no prenatal risk factors. Mothers completed a validated questionnaire assessing use of folic acid supplementation and receipt of recurrence risk counseling. Chi-square analyses were performed to analyze questionnaire responses and demographic data.ResultsA total of 314 subjects participated (controls = 216, cases = 98). Cases took preconceptual folic acid supplementation more often than controls (P < .001), but only 55% started preconceptually. Maternal advanced education and counseling (P < .001) were associated with preconceptual supplementation, whereas complexity of CHD in the relative was not. While 70% of cases received some recurrence risk counseling, those with advanced education and complex CHD in the affected relative were more likely to receive counseling. Few at-risk cases interacted with genetic services (19%).ConclusionsAt-risk mothers with lower education are less likely to take preconceptual folic acid supplementation or receive recurrence risk counseling. Health care providers should proactively provide this information to all at-risk patients and develop collaborations with genetic services.

BACKGROUND: Little information is available on B vitamin concentrations in human milk or on how they are affected by maternal B vitamin deficiencies, antiretroviral therapy, or maternal supplementation. OBJECTIVE: The objective was to evaluate the effects of antiretroviral therapy and/or lipid-based nutrient supplements (LNSs) on B vitamin concentrations in breast milk from HIV-infected women in Malawi. DESIGN: Breast milk was collected from 537 women recruited within the Breastfeeding, Antiretrovirals, and Nutrition study at 2 or 6 wk and 24 wk postpartum. Women were assigned to receive antiretrovirals and LNSs, antiretrovirals only, LNSs only, or a control. Antiretrovirals and LNSs were given to the mothers from weeks 0 to 28. The antiretrovirals were zidovudine/lamivudine and nelfinavir or lopinavir/ritonavir. LNSs provided 93-118% of the Recommended Dietary Allowances of thiamin, riboflavin, niacin, pyridoxine, and vitamin B-12. Infants were exclusively breastfed. RESULTS: LNSs increased milk concentrations of all vitamins except thiamin, whereas antiretrovirals lowered concentrations of nicotinamide, pyridoxal, and vitamin B-12. Although antiretrovirals alone had no significant effect on riboflavin concentrations, they negatively affected the LNS-induced increase in this vitamin. Thiamin was not influenced by the study interventions. Concentrations of all B vitamins were much lower than usually accepted values. CONCLUSIONS: All B vitamins were low in milk, and all but thiamin were increased by maternal supplementation with LNSs. Antiretrovirals alone decreased concentrations of some B vitamins in milk. When LNS was given in addition to antiretrovirals, the negative effect of antiretrovirals offset the positive effect of LNSs for all vitamins except thiamin. This trial was registered at clinicaltrials.gov as NCT00164762.

INTRODUCTION: Approximately 60-70 pregnancies are affected by neural tube defects (NTD) in Denmark annually. Folic acid (FA) deficiency can cause NTD. Periconceptional FA supplementation reduces the risk of NTD by up to 70-80%. Danish women planning pregnancy are recommended 0.4 mg of FA daily from at least one month before planned conception and continuing throughout the first 12 weeks of pregnancy. The aim of the present study was to examine the knowledge about and use of FA supplementation among Danish pregnant women.METHODS: From 11 October 2012 to 15 November 2012, all women attending for a routine nuchal translucency scan were given a questionnaire regarding their knowledge and use of FA supplementation during their current pregnancy.RESULTS: A total of 462 women answered the questionnaire. 95% had taken FA supplements at some point during their pregnancy, but only 10.4% as recommended. More than 80% stated knowledge about recommendations before the current pregnancy. Positive predictors of knowledge were: age > 30 years, multiparity, Danish origin and education > 3 years.CONCLUSION: Despite national recommendations on periconceptional FA supplementation, our study showed that women do not follow these recommendations. Especially women with a low socio-economic status were likely to lack knowledge about FA supplementation in relation to pregnancy. There is a need for revision of the existing national recommendations and for other initiatives aiming to improve women's intake of FA, including FA fortification of flour and/or other food products.FUNDING: not relevant.TRIAL REGISTRATION: The study was approved by the Danish Data Protection Agency (No.: 01855 HVH-2012-044).

Increasing reports of antibiotic resistance involving S. aureus and K. pneumoniae and the resulting high mortality rates in the battlefields have emphasized a critical need for the development of antimicrobial compounds with novel modes of action. Fatty acids are known to serve many critical roles in the cell, including energy storage, integrity and dynamics of biological membranes, cellular metabolism, and cellular signaling, and interference with fatty acid metabolism has been proved to be an effective strategy for inhibition of bacterial growth. N-substituted pantothenate analogs have been developed and shown to inhibit the growth of S. aureus and E. coli (and probably also K. pneumoniae) but have not been tested in preclinical and clinical set-ups, primarily because of their possible interference with human cells. We propose to elucidate differences in the architecture of the compound-pantothenate kinase-binding site between humans and bacteria using x-ray crystallographic techniques and exploit these differences to develop new compounds specific for the drug-resistant bacterial strains. These new compounds will have the potential to control infections caused by S. aureus and K. pneumoniae, thus improving the survival rate of military personnel wounded in combat. Candidate compounds identified in this study should first be tested in animal models to determine their response to the treatment and subsequently in clinical trials to test the efficacy of this novel approach in humans. Our efficient procedure of the iteration of the computer prediction and experimental verifications with the sufficient feedback will enable us to identify novel drug candidates, which are characterized by fewer side-effects, less likelihood of drug resistance, and will be available to public at costs substantially below industry average., The original document contains color images.

This study investigated the in-vitro digestibility of cold-set whey protein (WP) microgels prepared by two gelation methods (external and internal) containing lipids (0%, 10% or 20% w/w). The incorporation of lipids into these matrices achieved higher entrapment of the bioactive vitamin riboflavin, as well as significant reductions in rates of both the digestion of the protein matrix, and the subsequent diffusion of the water-soluble bioactive. A biexponential model accounted for the contribution of digestion- and diffusion-driven mechanisms in describing the release of riboflavin into enzyme containing simulated gastrointestinal fluids. In particular, for external gelation microgels, as the lipid load within the matrices increased, the contribution of a faster diffusion-driven release was almost completely negated by a slower digestion-assisted release. Lipid loads provided a composite matrix capable of alternating from a burst to a sustained release of bioactive.

This study investigated the in-vitro digestibility of cold-set whey protein (WP) microgels prepared by two gelation methods (external and internal) containing lipids (0%, 10% or 20% w/w). The incorporation of lipids into these matrices achieved higher entrapment of the bioactive vitamin riboflavin, as well as significant reductions in rates of both the digestion of the protein matrix, and the subsequent diffusion of the water-soluble bioactive. A biexponential model accounted for the contribution of digestion- and diffusion-driven mechanisms in describing the release of riboflavin into enzyme containing simulated gastrointestinal fluids. In particular, for external gelation microgels, as the lipid load within the matrices increased, the contribution of a faster diffusion-driven release was almost completely negated by a slower digestion-assisted release. Lipid loads provided a composite matrix capable of alternating from a burst to a sustained release of bioactive.

Patients with psoriasis are increasingly turning to the use of alternative and complementary medicine to manage their psoriasis. Patients often inquire about what dietary supplements may be beneficial, including the use of oral vitamin D, vitamin B12, selenium, and omega-3 fatty acids in fish oils. In this review we examine the extent to which each of these common nutritional interventions has been studied for the treatment of psoriasis. We weighed evidence from both controlled and uncontrolled prospective trials. The evidence of benefit was highest for fish oils. For other supplements, there is need for additional large, randomized clinical trials to establish evidence of efficacy.

BACKGROUND: Whole blood (WB) has been used in combat since World War I as it is readily available and replaces every element of shed blood. Component therapy has become standard; however, recent military successes with WB resuscitation have revived the debate regarding wider WB use. Characterization of optimal WB storage is needed. We hypothesized that refrigeration preserves WB function and that a pathogen reduction technology (PRT) based on riboflavin and ultraviolet light has no deleterious effect over 21 days of storage. STUDY DESIGN AND METHODS: WB units were stored for 21 days either at 4 C or 22 C. Half of each temperature group underwent PRT, yielding four final treatment groups (n = 8 each): CON 4 (WB at 4 C); CON 22 (WB at 22 C); PRT 4 (PRT WB at 4 C); and PRT 22 (PRT WB at 22 C). Testing was at baseline, Days 1-7, 10, 14, and 21. Assays included coagulation factors; platelet activation, aggregation, and adhesion; and thromboelastography (TEG). RESULTS: Prothrombin time (PT) and partial thromboplastin time increased over time; refrigeration attenuated the effects on PT (p /= 0.009). Aggregation decreased over time (p /= 0.001); losses were attenuated by refrigeration (p /= 0.001). Refrigeration preserved TEG parameters (p /= 0.001) and PRT 4 samples remained within normal limits throughout the study. Refrigeration in combination with PRT inhibited fibrinolysis (p /= 0.001) and microparticle formation (p /= 0.031). Cold storage increased shear-induced platelet aggregation and ristocetin-induced platelet agglutination (p /= 0.032), as well as GPIb-expressing platelets (p /= 0.009). CONCLUSION: The in vitro hemostatic function of WB is largely unaffected by PRT treatment and better preserved by cold storage over 21 days. Refrigerated PRT WB may be suitable for trauma resuscitation. Clinical studies are warranted., Published in Transfusion. v53 supp p137S-149S, Jan 2013. Prepared in collaboration with the Department of Biomedical Engineering, University of Texas, San Antonio, and Terumo BCT Biotechnologies, LLC, Lakewood, CO.

Compare time to breathing between 3 groups of swine (11/group) with cyanide(CN) induced apnea; treated with intravenous(IV) hydroxocobalamin(HOC), IV cobinamide(COB), or IV normal saline(NS) control. Method:33 swine(45-55kg) intubated, anesthetized & instrumented (MAP and cardiac output). Isoflurane low to allow breathing; room air(0.21FiO2). CN infused until apnea. Given HOC(65mg/kg), COB(12.5mg/kg) or NS(20ml) & monitored 60min. Results:Weight, time to apnea, & CN dose similar (p0.10). At treatment, blood CN, lactate levels, & decrease in MAP similar (p0.10). 2/11 swine in NS group survived(p0.001), compared to 10/11 in HOC & 10/11 in COB group. Time to breaths post treatment similar(HOC 1:48min, COB 1:49min). Blood CN levels undetectable post HOC or COB infusion. No statistically significant differences were detected between groups for CO, MAP, RR, or min vent at 60min. Lactate, pH, and PCO2 at 60 min were similar (p0.10). Conclusion: IV COB led to similar time to breathing as IV HOC for CN induced apnea and severe toxicity. Cobinamide was 5 times as potent as hydroxocobalamin., The original document contains color images. Abstract only.

The goal of our research is to introduce a novel means to regenerate the articular cartilage and restore normal function of the joint A strategy that can generate durable hyaline articular cartilage, which will be predominantly type II collagen, and is capable of integrating with the surrounding cartilage matrix (without fissures) could improve the long-term outcome of joint surface repair Key findings are 1) Several modifications of photochemically crosslinked gels including a) Adding fibrin to the type I collagen solution and photchemically crosslinking the combination gel using Riboflavin as the photoinitiator and blue light (458 nm) increases the bulk modulus of the gels; b) Performing the photochemical crosslinking under hy[poxic conditions may improve cell survival; c) Cells are uniformly distributed throughout the crosslinked gels and the cells begin producing pericellular matrix by 2 weeks in vitro in the gels; and c) High cell survival and matrix production was noted in the poly( ethylene) glycol thiol-ene gels. 2) Cell tracking was verified in vivo with Oil labeled cells encapsulated in gels placed in nude mice for up to 8 weeks. 3) Formation of new cartilage matrix was demonstrated in vivo in mice using photochemically crosslinked gels and swine articular chondrocytes placed into cartilage rings 4) Bone marrow-derived mesenchymal stem cells from swine were isolated and differentiated into osteogenic, adipogenic, and chondrogenic lineages with commercial differentiation media containing growth factors inducing differentiation. 5) Chondrocytes encapsulated in photochemically crosslinked hydrogels can survive the crosslinking and implantation process as shown in swine., The original document contains color images.

To compare the rerum to baseline of mean arterial blood pressure (MAP) between 2 groups of swine in acute cyanide toxicity and treated with IV HOC or 10 HOC. We also compared blood cyanide, lactate, pH, nitrotyrosine levels, cerebral oxygenation, and inflammatory markers. 24 swine (48-52kg) were intubated, anesthetized, and instrumented (MAP and cardiac output (CO) monitoring). Cyanide was continuously infused until severe hypotension (50 per cent of baseline MAP). Animals were randomly assigned to IV HOC 150mg/kg or 10 HOC 15 0mg/kg and monitored for 60 min after start of antidote. Baseline mean weight, time to hypotension, and cyanide dose at hypotension were similar. At hypotension, mean MAP, blood cyanide, and lactate levels were similar. Both groups had similar return to baseline MAP. Intraosseous hydroxocobalamin led to similar return to baseline of MAP as intravenous. Mortality, heart rate, cardiac output, lactate, nitrotyrosinc, cerebral NTRS , and inflammatory markers were also similar. TO HOC may be as effective as IV HOC in acute, severe cyanide toxicity., The original document contains color images.

This work details a proof of concept study for vapor phase selective sensing using a strategy of biorecognition elements (BRE) integrated into a zinc oxide field effect transistor (ZnO FET). ZnO FETs are highly sensitive to changes to the environment with little to no selectivity. Addition of a biorecognition element retains the sensitivity of the device while adding selectivity. The DNA aptamer designed to bind the small molecule riboflavin was covalently integrated into the ZnO FET and detects the presence of 116 ppb of riboflavin in a nitrogen atmosphere by a change in current. The unfunctionalized ZnO FET shows no response to this same concentrations of riboflavin, showing that the aptamer-binding strategy may be a promising strategy for vapor phase sensing.

Hypothesis / aims of study Vaginal and laparoscopic gynaecological surgery place the urinary tract at risk of injury. Ureteric injury rates as a result of gynecological procedures vary; for vaginal hysterectomy, it is about 0.1-0.5% [1], and after vaginal repair of anterior and/or apical pelvic organ prolapse, this rate may be as high as 5.1% [2]. Cystoscopic examination of the lower urinary tract is an important method for the intra-operative identification of potential ureteric injury [3]. Traditionally, intravenous agents like indigo carmine have been used to color the ureteric jets to aid visualization at cystoscopy. However, indigo carmine has several albeit rare disadvantages - severe anaphylaxis and cardiac arrhythmias. This study aims to determine whether oral Vitamin B, a renally excreted essential vitamin, which is anecdotally known to change the colour of urine to bright yellow, can be used as a marker of ureteric patency at cystoscopy, thereby reducing the need for intra-operative intravenous indigo carmine. Study design, materials and methods Institutional ethical approval was obtained and all patients provided written informed consent. Patients scheduled for cystoscopy, or for an operation likely to require a cystoscopy, were given 3 tablets of vitamin B complex orally 1-4 hours prior to their operation. The time of administration, time of operation and time of cystoscopy were recorded. The time taken for ureteric jets to be visualized was also recorded. The color of the urine was graded by the operator as being clear (negative) or bright yellow (positive), indicating ureteric patency and no indigo carmine was required. Results 69 women in total were given vitamin B prior to their cystoscopy. One case was cancelled because of presumed but unproven aspiration. Of the remaining 68 cases, the mean time from dose to cystoscopy was 161.6 minutes (SD=69.9). Forty-nine (72.1%) of these trials were rated as positive, with a mean time from dose to cystoscopy of

Hypothesis / aims of study Vaginal and laparoscopic gynaecological surgery place the urinary tract at risk of injury. Ureteric injury rates as a result of gynecological procedures vary; for vaginal hysterectomy, it is about 0.1-0.5% [1], and after vaginal repair of anterior and/or apical pelvic organ prolapse, this rate may be as high as 5.1% [2]. Cystoscopic examination of the lower urinary tract is an important method for the intra-operative identification of potential ureteric injury [3]. Traditionally, intravenous agents like indigo carmine have been used to color the ureteric jets to aid visualization at cystoscopy. However, indigo carmine has several albeit rare disadvantages - severe anaphylaxis and cardiac arrhythmias. This study aims to determine whether oral Vitamin B, a renally excreted essential vitamin, which is anecdotally known to change the colour of urine to bright yellow, can be used as a marker of ureteric patency at cystoscopy, thereby reducing the need for intra-operative intravenous indigo carmine. Study design, materials and methods Institutional ethical approval was obtained and all patients provided written informed consent. Patients scheduled for cystoscopy, or for an operation likely to require a cystoscopy, were given 3 tablets of vitamin B complex orally 1-4 hours prior to their operation. The time of administration, time of operation and time of cystoscopy were recorded. The time taken for ureteric jets to be visualized was also recorded. The color of the urine was graded by the operator as being clear (negative) or bright yellow (positive), indicating ureteric patency and no indigo carmine was required. Results 69 women in total were given vitamin B prior to their cystoscopy. One case was cancelled because of presumed but unproven aspiration. Of the remaining 68 cases, the mean time from dose to cystoscopy was 161.6 minutes (SD=69.9). Forty-nine (72.1%) of these trials were rated as positive, with a mean time from dose to cystoscopy of

BackgroundA nutrient-wide approach may be useful to comprehensively test and validate associations between nutrients (derived from foods and supplements) and blood pressure (BP) in an unbiased manner.Methods and resultsData from 4680 participants aged 40 to 59 years in the cross-sectional International Study of Macro/Micronutrients and Blood Pressure (INTERMAP) were stratified randomly into training and testing sets. US National Health and Nutrition Examination Survey (NHANES) four cross-sectional cohorts (1999-2000, 2001-2002, 2003-2004, 2005-2006) were used for external validation. We performed multiple linear regression analyses associating each of 82 nutrients and 3 urine electrolytes with systolic and diastolic BP in the INTERMAP training set. Significant findings were validated in the INTERMAP testing set and further in the NHANES cohorts (false discovery rate <5% in training, P<0.05 for internal and external validation). Among the validated nutrients, alcohol and urinary sodium-to-potassium ratio were directly associated with systolic BP, and dietary phosphorus, magnesium, iron, thiamin, folacin, and riboflavin were inversely associated with systolic BP. In addition, dietary folacin and riboflavin were inversely associated with diastolic BP. The absolute effect sizes in the validation data (NHANES) ranged from 0.97 mm Hg lower systolic BP (phosphorus) to 0.39 mm Hg lower systolic BP (thiamin) per 1-SD difference in nutrient variable. Inclusion of nutrient intake from supplements in addition to foods gave similar results for some nutrients, though it attenuated the associations of folacin, thiamin, and riboflavin intake with BP.ConclusionsWe identified significant inverse associations between B vitamins and BP, relationships hitherto poorly investigated. Our analyses represent a systematic unbiased approach to the evaluation and validation of nutrient-BP associations.

Cobalamin uptake and transport in mammals are mediated by three cobalamin-binding proteins: haptocorrin, intrinsic factor, and transcobalamin. The nature of cobalamin-binding proteins in lower vertebrates remains to be elucidated. The aim of this study was to characterize the cobalamin-binding proteins of the rainbow trout (Oncorhynchus mykiss) and to compare their properties with those of the three human cobalamin-binding proteins. High cobalamin-binding capacity was found in trout stomach (210 pmol/g), roe (400 pmol/g), roe fluid (390 nmol/liter), and plasma (2500 nmol/liter). In all cases, it appeared to be the same protein based on analysis of partial sequences and immunological responses. The trout cobalamin-binding protein was purified from roe fluid, sequenced, and further characterized. Like haptocorrin, the trout cobalamin-binding protein was stable at low pH and had a high binding affinity for the cobalamin analog cobinamide. Like haptocorrin and transcobalamin, the trout cobalamin-binding protein was present in plasma and recognized ligands with altered nucleotide moiety. Like intrinsic factors, the trout cobalamin-binding protein was present in the stomach and resisted degradation by trypsin and chymotrypsin. It also resembled intrinsic factor in the composition of conserved residues in the primary cobalamin-binding site in the C terminus. The trout cobalamin-binding protein was glycosylated and displayed spectral properties comparable with those of haptocorrin and intrinsic factor. In conclusion, only one soluble cobalamin-binding protein was identified in the rainbow trout, a protein that structurally behaves like an intermediate between the three human cobalamin-binding proteins.