Effect of folic acid on animal models, cell cultures, and human oral clefts: a literature review

Background Folate is a naturally occurring, water-soluble B vitamin. The synthetic form of this compound is folic acid (FA), the deficiency of which is linked to neural tube disorders (NTD), which can be prevented by consuming it before, or during the early months of, pregnancy. However, the effect of FA on oral cleft formation remains controversial. The aim of the present study was to review the evidence concerning the effect of FA on the formation of cleft lip and palate (CLP) in both animals and humans, as well as its impact on different cell types. A search was conducted on various databases, including MEDLINE, EMBASE, and Central, for articles published until January 2020. Main body Current systematic reviews indicate that FA, alone or in combination with other vitamins, prevents NTD; however, there is no consensus on whether its consumption can prevent CLP formation. Conversely, the protective effect of FA on palatal cleft (CP) induction has been inferred from animal models; additionally, in vitro studies enumerate a cell-type and dose-dependent effect of FA on cell viability, proliferation, and differentiation, hence bolstering evidence from epidemiological studies. Conclusions Meta-analysis, animal models, and in vitro studies demonstrated the protective effect of FA against isolated CP; however, the heterogeneity of treatment protocols, doses, and FA administration method, as well as the different cell types used in in vitro studies, does not conclusively establish whether FA prevents CLP formation

Geochemical characterization of fluoride in water, table salt, active sediment, rock and soil samples, and its possible relationship with the prevalence of enamel fluorosis in children in four municipalities of the department of Huila (Colombia)

Fluoride is an element that affects teeth and bone formation in animals and humans. Though the use of systemic fluoride is an evidence-based caries preventive measure, excessive ingestion can impair tooth development, mainly the mineralization of tooth enamel, leading to a condition known as enamel fluorosis. In this study, we investigated the geochemical characterization of fluoride in water, table salt, active sediment, rock and soil samples in four endemic enamel fluorosis sentinel municipalities of the department of Huila, Colombia (Pitalito, Altamira, El Agrado and Rivera), and its possible relationship with the prevalence of enamel fluorosis in children. The concentration of fluoride in drinking water, table salt, active sediment, rock, and soil was evaluated by means of an ion selective electrode and the geochemical analyses were performed using X-ray fluorescence. Geochemical analysis revealed fluoride concentrations under 15 mg/kg in active sediment, rock and soil samples, not indicative of a significant delivery to the watersheds studied. The concentration of fluoride in table salt was found to be under the inferior limit (less than 180 μg/g) established by the Colombian regulations. Likewise, exposure doses for fluoride water intake did not exceed the recommended total dose for all ages from 6 months. Although the evidence does not point out at rocks, soils, fluoride-bearing minerals, fluoridated salt and water, the hypothesis of these elements as responsible of the current prevalence of enamel fluorosis cannot be discarded since, aqueducts might have undergone significant changes overtime

Subcutaneous anti-COVID-19 hyperimmune immunoglobulin for prevention of disease in asymptomatic individuals with SARS-CoV-2 infection : a double-blind, placebo-controlled, randomised clinical trial

Anti-COVID-19 hyperimmune immunoglobulin (hIG) can provide standardized and controlled antibody content. Data from controlled clinical trials using hIG for the prevention or treatment of COVID-19 outpatients have not been reported. We assessed the safety and efficacy of subcutaneous anti-COVID-19 hyperimmune immunoglobulin 20% (C19-IG20%) compared to placebo in preventing development of symptomatic COVID-19 in asymptomatic individuals with SARS-CoV-2 infection. We did a multicentre, randomized, double-blind, placebo-controlled trial, in asymptomatic unvaccinated adults (≥18 years of age) with confirmed SARS-CoV-2 infection within 5 days between April 28 and December 27, 2021. Participants were randomly assigned (1:1:1) to receive a blinded subcutaneous infusion of 10 mL with 1 g or 2 g of C19-IG20%, or an equivalent volume of saline as placebo. The primary endpoint was the proportion of participants who remained asymptomatic through day 14 after infusion. Secondary endpoints included the proportion of individuals who required oxygen supplementation, any medically attended visit, hospitalisation, or ICU, and viral load reduction and viral clearance in nasopharyngeal swabs. Safety was assessed as the proportion of patients with adverse events. The trial was terminated early due to a lack of potential benefit in the target population in a planned interim analysis conducted in December 2021. registry: . 461 individuals (mean age 39.6 years [SD 12.8]) were randomized and received the intervention within a mean of 3.1 (SD 1.27) days from a positive SARS-CoV-2 test. In the prespecified modified intention-to-treat analysis that included only participants who received a subcutaneous infusion, the primary outcome occurred in 59.9% (91/152) of participants receiving 1 g C19-IG20%, 64.7% (99/153) receiving 2 g, and 63.5% (99/156) receiving placebo (difference in proportions 1 g C19-IG20% vs. placebo, −3.6%; 95% CI -14.6% to 7.3%, p = 0.53; 2 g C19-IG20% vs placebo, 1.1%; −9.6% to 11.9%, p = 0.85). None of the secondary clinical efficacy endpoints or virological endpoints were significantly different between study groups. Adverse event rate was similar between groups, and no severe or life-threatening adverse events related to investigational product infusion were reported. Our findings suggested that administration of subcutaneous human hyperimmune immunoglobulin C19-IG20% to asymptomatic individuals with SARS-CoV-2 infection was safe but did not prevent development of symptomatic COVID-19.

Nutrición parenteral domiciliaria en España, 2019: informe del Grupo de Nutrición Artificial Domiciliaria y Ambulatoria NADYA

RESUMEN Objetivo: comunicar los datos de nutrición parenteral domiciliaria (NPD) obtenidos del registro del grupo NADYA-SENPE (www.nadyasenpe.com) del año 2019. Material y métodos: análisis descriptivo de los datos recogidos de pacientes adultos y pediátricos con NPD en el registro NADYA-SENPE desde el 1 de enero al 31 de diciembre de 2019. Resultados: se registraron 283 pacientes (51,9 %, mujeres), 31 niños y 252 adultos procedentes de 47 hospitales españoles, lo que representa una tasa de prevalencia de 6,01 pacientes/millón de habitantes/año 2019. El diagnóstico más frecuente en los adultos fue “oncológico paliativo” y “otros” (21,0 %). En los niños fue la enfermedad de Hirschsprung junto a la enterocolitis necrotizante, las alteraciones de la motilidad intestinal y la pseudoobstrucción intestinal crónica, con 4 casos cada uno (12,9 %). El primer motivo de indicación fue el síndrome del intestino corto tanto en los niños (51,6 %) como en los adultos (37,3 %). El tipo de catéter más utilizado fue el tunelizado tanto en los niños (75,9 %) como en los adultos (40,8 %). Finalizaron 68 episodios, todos en adultos: la causa más frecuente fue el fallecimiento (54,4 %). Pasaron a la vía oral el 38,2 %. Conclusiones: el número de centros y profesionales colaboradores con el registro NADYA va incrementándose. Se mantienen estables las principales indicaciones y los motivos de finalización de la NPD

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Mutations, Genes, and Phenotypes Related to Movement Disorders and Ataxias

26 páginas, 4 figuras, 3 tablasOur clinical series comprises 124 patients with movement disorders (MDs) and/or ataxia with cerebellar atrophy (CA), many of them showing signs of neurodegeneration with brain iron accumulation (NBIA). Ten NBIA genes are accepted, although isolated cases compatible with abnormal brain iron deposits are known. The patients were evaluated using standardised clinical assessments of ataxia and MDs. First, NBIA genes were analysed by Sanger sequencing and 59 patients achieved a diagnosis, including the detection of the founder mutation PANK2 p.T528M in Romani people. Then, we used a custom panel MovDisord and/or exome sequencing; 29 cases were solved with a great genetic heterogeneity (34 different mutations in 23 genes). Three patients presented brain iron deposits with Fe-sensitive MRI sequences and mutations in FBXO7, GLB1, and KIF1A, suggesting an NBIA-like phenotype. Eleven patients showed very early-onset ataxia and CA with cortical hyperintensities caused by mutations in ITPR1, KIF1A, SPTBN2, PLA2G6, PMPCA, and PRDX3. The novel variants were investigated by structural modelling, luciferase analysis, transcript/minigenes studies, or immunofluorescence assays. Our findings expand the phenotypes and the genetics of MDs and ataxias with early-onset CA and cortical hyperintensities and highlight that the abnormal brain iron accumulation or early cerebellar gliosis may resembling an NBIA phenotype.This work was supported by the Instituto de Salud Carlos III (ISCIII)—Subdirección General de Evaluación y Fomento de la Investigación within the framework of the National R + D+I Plan co-funded with European Regional Development Funds (ERDF) [Grants PI18/00147 and PI21/00103 to CE]; the Fundació La Marató TV3 [Grants 20143130 and 20143131 to BPD and CE]; and by the Generalitat Valenciana [Grant PROMETEO/2018/135 to CE]. Part of the equipment employed in this work was funded by Generalitat Valenciana and co-financed with ERDF (OP ERDF of Comunitat Valenciana 2014–2020). PS had an FPU-PhD fellowship funded by the Spanish Ministry of Education, Culture and Sport [FPU15/00964]. IH has a PFIS-PhD fellowship [FI19/00072]. ASM has a contract funded by the Spanish Foundation Per Amor a l’Art (FPAA)Peer reviewe

Nutrición parenteral domiciliaria en España 2018. Informe del Grupo de Nutrición Artificial Domiciliaria y Ambulatoria NADYA

Aim: to communicate home parenteral nutrition (HPN) data obtained from the HPN registry of the NADYA-SENPE group (www.nadya-senpe. com) for the year 2018. Material and methods: descriptive analysis of the data collected from adult and pediatric patients with HPN in the NADYA-SENPE group registry from January 1st, 2018 to December 31st, 2018. Results: there were 278 patients from 45 Spanish hospitals (54.7 % women), 23 children and 255 adults, which represent a prevalence rate of 5.95 patients/million inhabitants/year 2018. The most frequent diagnosis in adults was " palliative cancer" (22.0 %), followed by "others". In children it was Hirschsprung's disease together with necrotizing enterocolitis, with four cases (17.4 %). The first indication was short bowel syndrome in both children (60.9 %) and adults (35.7 %). The most frequently used type of catheter was tunneled in both children (81.0 %) and adults (41.1 %). Ending 75 episodes, the most frequent cause was death (52.0 %) and change to oral feeding (33.3 %). Conclusions: the number of centers and collaborating professionals in the registry of patients receiving HPN remains stable, as well as the main indications and reasons for termination of HPN

Nutrición parenteral domiciliaria en España 2018. Informe del Grupo de Nutrición Artificial Domiciliaria y Ambulatoria NADYA

Aim: To communicate home parenteral nutrition (HPN) data obtained from the HPN registry of the NADYA-SENPE group (www.nadya-senpe.  com) for the year 2018. Material and methods: Descriptive analysis of the data collected from adult and pediatric patients with HPN in the NADYA-SENPE group registry from January 1st, 2018 to December 31st, 2018.  Results: There were 278 patients from 45 Spanish hospitals (54.7% women), 23 children and 255 adults, which represent a prevalence rate of 5.95 patients/million inhabitants/year 2018. The most frequent diagnosis in adults was “palliative cancer” (22.0%), followed by “others”. In children it was Hirschsprung’s disease together with necrotizing enterocolitis, with four cases (17.4%). The first indication was short bowel syndrome in both children (60.9%) and adults (35.7%). The most frequently used type of catheter was tunneled in both children (81.0%) and adults (41.1%). Ending 75 episodes, the most frequent cause was death (52.0%) and change to oral feeding (33.3%). Conclusions: The number of centers and collaborating professionals in the registry of patients receiving HPN remains stable, as well as the main indications and reasons for termination of HPN.Objetivo: comunicar los datos de nutrición parenteral domiciliaria (NPD) obtenidos del registro del grupo NADYA-SENPE (www.nadyasenpe. com) del año 2018. Material y métodos: análisis descriptivo de los datos recogidos de pacientes adultos y pediátricos con NPD en el registro NADYA-SENPE del 1 de enero al 31 de diciembre de 2018. Resultados: se registraron 278 pacientes (54,7% mujeres), 23 niños y 255 adultos, procedentes de 45 hospitales españoles, lo que representa una tasa de prevalencia de 5,95 pacientes/millón de habitantes/año 2018. El diagnóstico más frecuente en adultos fue “oncológico paliativo” (22,0%), seguido de “otros”. En niños fue la enfermedad de Hirschsprung junto con la enterocolitis necrotizante, con cuatro casos (17,4%). El primer motivo de indicación fue síndrome de intestino corto tanto en niños (60,9%) como en adultos (35,7%). El tipo de catéter más utilizado fue el tunelizado tanto en niños (81,0%) como en adultos (41,1%). Finalizaron 75 episodios, la causa más frecuente fue el fallecimiento (52,0%) y el paso a vía oral (33,3%). Conclusiones: el número de centros y profesionales colaboradores en el registro de pacientes que reciben NPD se mantiene estable, así como las principales indicaciones y los motivos de finalización de la NPD

Measurement of b jet shapes in proton-proton collisions at root s=5.02 TeV

We present the first study of charged-hadron production associated with jets originating from b quarks in proton-proton collisions at a center-of-mass energy of 5.02 TeV. The data sample used in this study was collected with the CMS detector at the CERN LHC and corresponds to an integrated luminosity of 27.4 pb(-1). To characterize the jet substructure, the differential jet shapes, defined as the normalized transverse momentum distribution of charged hadrons as a function of angular distance from the jet axis, are measured for b jets. In addition to the jet shapes, the per-jet yields of charged particles associated with b jets are also quantified, again as a function of the angular distance with respect to the jet axis. Extracted jet shape and particle yield distributions for b jets are compared with results for inclusive jets, as well as with the predictions from the pythia and herwig++ event generators.Peer reviewe