heatland34
heatland34
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Human-induced pluripotent stem cells (hiPSCs) allow for the establishment of brain cellular models of psychiatric disorders that account for a patient's genetic background. Here, we conducted an RNA-sequencing profiling study of hiPSC-derived cell lines from schizophrenia (SCZ) subjects, most of which are from a multiplex family, from the population isolate of the Central Valley of Costa Rica. hiPSCs, neural precursor cells, and cortical neurons derived from six healthy controls and seven SCZ subjects were generated using standard methodology. Transcriptome from these cells was obtained using Illumina HiSeq 2500, and differential expression analyses were performed using DESeq2 (|fold change|>1.5 and false discovery rate  less then  0.3), in patients compared to controls. We identified 454 differentially expressed genes in hiPSC-derived neurons, enriched in pathways including phosphoinositide 3-kinase/glycogen synthase kinase 3 (PI3K/GSK3) signaling, with serum-glucocorticoid kinase 1 (SGK1), an inhibitor of glycogen synthase kinase 3β, as part of this pathway. We further found that pharmacological inhibition of downstream effectors of the PI3K/GSK3 pathway, SGK1 and GSK3, induced alterations in levels of neurite markers βIII tubulin and fibroblast growth factor 12, with differential effects in patients compared to controls. While demonstrating the utility of hiPSCs derived from multiplex families to identify significant cell-specific gene network alterations in SCZ, these studies support a role for disruption of PI3K/GSK3 signaling as a risk factor for SCZ.Patients hospitalised with COVID-19 have a high mortality. Identification of patients at increased risk of adverse outcome would be important, to allow closer observation and earlier medical intervention for those at risk, and to objectively guide prognosis for friends and family of affected individuals. We conducted a single-centre retrospective cohort study in all-comers with COVID-19 admitted to a large general hospital in the United Kingdom. Clinical characteristics and features on admission, including observations, haematological and biochemical characteristics, were used to develop a score to predict 30-day mortality, using multivariable logistic regression. We identified 316 patients, of whom 46% died within 30-days. We developed a mortality score incorporating age, sex, platelet count, international normalised ratio, and observations on admission including the Glasgow Coma Scale, respiratory rate and blood pressure. see more The score was highly predictive of 30-day mortality with an area under the receiver operating curve of 0.7933 (95% CI 0.745-0.841). The optimal cut-point was a score ≥ 4, which had a sensitivity of 78.36% and a specificity of 67.59%. Patients with a score ≥ 4 had an odds ratio of 7.6 for 30-day mortality compared to those with a score  less then  4 (95% CI 4.56-12.49, p  less then  0.001). This simple, easy-to-use risk score calculator for patients admitted to hospital with COVID-19 is a strong predictor of 30-day mortality. Whilst requiring further external validation, it has the potential to guide prognosis for family and friends, and to identify patients at increased risk, who may require closer observation and more intensive early intervention.Sperm preparation is critical to achieving a successful intrauterine insemination and requires the processing of a semen sample to remove white blood cells, wash away seminal plasma, and reduce sample volume. We present an automated instrument capable of performing a sperm preparation starting with a diluted semen sample. We compare our device against a density gradient centrifugation by processing 0.5 mL portions of patient samples through each treatment. In 5 min of operating time, the instrument recovers an average of 86% of all sperm and 82% of progressively motile sperm from the original sample while removing white blood cells, replacing the seminal plasma, and reducing the volume of the sample to the clinically required level. In 25 min of operating time, density gradient centrifugation recovers an average of 33% of all sperm and 41% of progressively motile sperm. The automated instrument could improve access to IUI as a treatment option by allowing satellite doctor's offices to offer intrauterine insemination as an option for patients without the clinical support required by existing methods.Premature ovarian insufficiency (POI) refers to severe decline of ovary function in females which usually leads to infertility. It has been reported that the TMEM150B gene is mostly associated with age at natural menopause, early menopause and POI, but its role in female reproduction remains unknown. In this study, we found Tmem150b was highly expressed in mouse oocytes, but its deletion had no obvious effect on meiotic maturation of oocytes indicated by first polar body emission and spindle morphology. There were also no obvious differences in follicle development and corpus luteum formation between knockout and wild type mice. Finally, knockout of Tmem150b did not affect female fertility and sexual hormone levels. In summary, our results suggest that TMEM150B is not essential for female fertility in mice.A 71-day study was conducted to explore the effect of increasing dietary levels (0, 250, 500, 1000 mg kg feed-1; D0, D250, D500 and D1000, respectively) of a blend of microencapsulated organic acids (OA, specifically citric and sorbic acid) and nature identical compounds (NIC, specifically thymol and vanillin), on growth, intestinal immune parameters and gut microbiota (GM) of European sea bass juveniles reared under normal and subsequently suboptimal environmental conditions (high temperature, 30.0 ± 0.4 °C and low oxygen, 4.6 ± 0.6 mg L-1). OA and NIC did not promote growth, feed utilisation and feed intake at the inclusion tested but induced a significantly upregulation of IL-8, IL-10 and TGFβ. GM analyzed by next-generation sequencing showed that OA and NIC were able to exert prebiotic properties stimulating the development of beneficial bacteria taxa such as Lactobacillus, Leuconostoc, and Bacillus sp. Picrust analyses displayed a significant potential functional reconfiguration of GM promoting a decrease in inflammation-promoting and homeostatic functions at increasing OA and NIC administration.

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