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  • Norton Crawford posted an update 4 days, 2 hours ago

    Increased awareness, together with a better understanding of the viral structure and identification of new viral targets, has led to the development of newer RSV vaccines and monoclonal antibodies to confer protection to both preterm and term infants who represent the most vulnerable population for severe RSV disease.Suspected neonatal sepsis is one of the most common diagnoses made in newborns (NBs), but very few NBs actually have sepsis. There is no international consensus to clearly define suspected neonatal sepsis, but each time that this suspected diagnosis is assumed, blood samples are taken, venous accesses are used to administer antibiotics, and the mother-child pair is separated, with prolonged hospital stays. X-rays, urine samples, and a lumbar puncture are sometimes taken. This is of concern, as generally less then 10% and no more than 25%-30% of the NBs in whom sepsis is suspected have proven neonatal sepsis. It seems easy to start antibiotics with suspicion of sepsis, but stopping them is difficult, although there is little or no support to maintain them. Unfortunately, the abuse of antibiotics in inpatient and outpatient NBs is foolish. Its negative impact on neonatal health and the economy is a public health problem of epidemiological and even epidemic proportions. This manuscript is a shortened version of the 10th Clinical Consensus of the Ibero-American Society of Neonatology (SIBEN) on suspected neonatal sepsis at the end of 2018, updated with publications from its completion to February 2020. This manuscript describes useful strategies for everyday neonatal practice when neonatal sepsis is suspected, along with important aspects about the indisputable value of clinical evaluation of the NB and about obtaining and interpreting blood cultures, urine cultures, and other cultures. Likewise, the low value of laboratory tests in suspected neonatal sepsis is demonstrated with evidence and clinical recommendations are made on the appropriate use of antibiotics.Neuronal progenitors in the developing forebrain undergo dynamic competence states to ensure timely generation of specific excitatory and inhibitory neuronal subtypes from distinct neurogenic niches of the dorsal and ventral forebrain, respectively. Here we show evidence of progenitor plasticity when Sonic hedgehog (SHH) signaling is left unmodulated in the embryonic neocortex of the mammalian dorsal forebrain. We found that, at early stages of corticogenesis, loss of Suppressor of Fused (Sufu), a potent inhibitor of SHH signaling, in neocortical progenitors, altered the transcriptomic landscape of male mouse embryos. Ectopic activation of SHH signaling occurred, via degradation of Gli3R, resulting in significant upregulation of fibroblast growth factor 15 (FGF15) gene expression in all E12.5 Sufu-cKO neocortex regardless of sex. Consequently, activation of FGF signaling, and its downstream effector the MAPK signaling, facilitated expression of genes characteristic of ventral forebrain progenitors. Our studies identify the importance of modulating extrinsic niche signals such as SHH and FGF15, to maintain the competency and specification program of neocortical progenitors throughout corticogenesis.SIGNIFICANCE STATEMENT Low levels of FGF15 control progenitor proliferation and differentiation during neocortical development, but little is known on how FGF15 expression is maintained. Our studies identified SHH signaling as a critical activator of FGF15 expression during corticogenesis. We found that Sufu, via Gli3R, ensured low levels of FGF15 was expressed to prevent abnormal specification of neocortical progenitors. These studies advance our knowledge on the molecular mechanisms guiding the generation of specific neocortical neuronal lineages, their implications in neurodevelopmental diseases, and may guide future studies on how progenitor cells may be used for brain repair.Despite recognizing aging as a common risk factor of many human diseases, little is known about its molecular traits. BIO-2007817 order To identify age-associated proteins circulating in human blood, we screened 156 individuals aged 50-92 using exploratory and multiplexed affinity proteomics assays. Profiling eight additional study sets (N = 3,987), performing antibody validation, and conducting a meta-analysis revealed a consistent age association (P = 6.61 × 10-6) for circulating histidine-rich glycoprotein (HRG). Sequence variants of HRG influenced how the protein was recognized in the immunoassays. Indeed, only the HRG profiles affected by rs9898 were associated with age and predicted the risk of mortality (HR = 1.25 per SD; 95% CI = 1.12-1.39; P = 6.45 × 10-5) during a follow-up period of 8.5 yr after blood sampling (IQR = 7.7-9.3 yr). Our affinity proteomics analysis found associations between the particular molecular traits of circulating HRG with age and all-cause mortality. The distinct profiles of this multipurpose protein could serve as an accessible and informative indicator of the physiological processes related to biological aging.

    Children with medical complexity (CMC) often require complex medication regimens. Medication education on hospital discharge should provide a critical safety check before medication management transitions from hospital to family. Current discharge processes may not meet the needs of CMC and their families. The objective of this study is to describe parent perspectives and priorities regarding discharge medication education for CMC.

    We performed a qualitative, focus-group-based study, using ethnography. Parents of hospitalized CMC were recruited to participate in 1 of 4 focus groups; 2 were in Spanish. Focus groups were recorded, transcribed, and then coded and organized into themes by using thematic analysis.

    Twenty-four parents participated in focus groups, including 12 native English speakers and 12 native Spanish speakers. Parents reported a range of 0 to 18 medications taken by their children (median 4). Multiple themes emerged regarding parental ideals for discharge medication education (1) informaen once home. These perspectives could inform initiatives to improve discharge medication education for all patients, including CMC.