Construction of mice ex vivo spinal cord slice model of neuromyelitis optica induced by NMO-immunoglobulin G

Objective:Using neuromyelitis optica immunoglobulin G(NMO-IgG)to induced ex vivo mice spinal cord slice model.Methods:Vibratome-cut transverse spinal cord slices from 7-day-old C57BL/6Jmouse pups were cultured on transwell porous supports for 7days,then randomly divided into the control group and NMO model group.Slices of the control group were further cultured with human serum complement,while slices from NMO model group were exposed to complement and NMO-IgG.After 24-hour incubation,slices of both groups were measured for aquaporin-4(AQP4),glial fibrillary acidic protein(GFAP),myelin basic protein(MBP)and neurofilament light chain(NFL)by immunofluorescence.Results:Slices exposed to NMO-IgG showed astrocyte swelling,and a significant loss of AQP4and GFAP staining.Ratios of the loss of AQP4and GFAP staining were 77.74%±6.75%and 75.62%±5.76%respectively in the model group,and NMO-like injury score was 3.11±0.60.But there were no obvious losses of AQP4and GFAP staining in the control group,and NMO-like lesion score was 0.00.There were significant differences between the two groups with regards to the above indexes(P<0.01).Ratios of the loss of MBP and NFL staining in the model group were 37.60%±4.88%and46.29%±4.98%respectively,while the corresponding figures in the control group were 9.10%±1.63%and 5.80%±0.81%,and the differences between the two groups were statistically significant(P<0.01).Conclusion:These results suggested that NMO-IgG-induced ex vivo spinal cord slice model possesses typical features of NMO,and this model might be useful for relevant fundamental studies.

Emergency department use among patients from residential aged care facilities under a Hospital in the Nursing Home scheme in public hospitals in Queensland Australia

BACKGROUND: Hospital emergency department(ED) use by patients from residential aged care facilities(RACFs) is not always appropriate, and this calls for interventions to avoid some unnecessary uses. This study aims to compare patterns of ED use by RACF patients with and without a Hospital in the Nursing Home(Hi NH) program.METHODS: RACF patients presenting to EDs of a hospital with and a hospital without this program during pre- and post-intervention periods were included. Data on patient demographics and ED presentation characteristics were obtained from the Emergency Department Information System database, and were analysed by descriptive and comparative statistics.RESULTS: In both hospitals, most RACF residents presenting to EDs were aged between 75–94 years, female, triaged at scale 3 to 5, and transferred on weekdays and during working hours. Almost half of them were subsequently admitted to hospitals. In accordance with the ICD-10-AM diagnostic coding system, diagnoses that consistently ranked among the top three reasons for visiting the two hospitals before and after intervention included Chapter XIX: injury and poisoning and Chapter X: respiratory diseases. Associated with the intervention, significant decreases in the numbers of presentations per 1 000 RACF beds were identified among patients diagnosed with Chapter XI: digestive diseases [rate ratio(95%CI): 0.09(0.04, 0.22); P<0.0001] and Chapter XXI: factors influencing health status and contact with health services [rate ratio(95%CI): 0.22(0.07, 0.66); P=0.007].CONCLUSION: The Hi NH program may reduce the incidence of RACF residents visiting EDs for diagnoses of Chapter XI and Chapter XXI.

Assessment of total and extreme precipitation over central Asia via statistical downscaling: Added value and multi-model ensemble projection

Central Asia(CA)is highly sensitive and vulnerable to changes in precipitation due to global warming,so the projection of precipitation extremes is essential for local climate risk assessment.However,global and regional climate models often fail to reproduce the observed daily precipitation distribution and hence extremes,especially in areas with complex terrain.In this study,we proposed a statistical downscaling(SD)model based on quantile delta mapping to assess and project eight precipitation indices at 73 meteorological stations across CA driven by ERA5 reanalysis data and simulations of 10 global climate models(GCMs)for present and future(2081-2100)periods under two shared socioeconomic pathways(SSP245 and SSP585).The reanalysis data and raw GCM outputs clearly underestimate mean precipitation intensity(SDII)and maximum 1-day precipitation(RX1DAY)and overestimate the number of wet days(R1MM)and maximum consecutive wet days(CWD)at stations across CA.However,the SD model effectively reduces the biases and RMSEs of the modeled precipitation indices compared to the observations.Also it effectively adjusts the distributional biases in the downscaled daily precipitation and indices at the stations across CA.In addition,it is skilled in capturing the spatial patterns of the observed precipitation indices.Obviously,SDII and RX1DAY are improved by the SD model,especially in the southeastern mountainous area.Under the intermediate scenario(SSP245),our SD multi-model ensemble projections project significant and robust increases in SDII and total extreme precipitation(R95PTOT)of 0.5 mm d^(-1) and 19.7 mm,respectively,over CA at the end of the 21st century(2081-2100)compared to the present values(1995-2014).More pronounced increases in indices R95PTOT,SDII,number of very wet days(R10MM),and RX1DAY are projected under the higher emission scenario(SSP585),particularly in the mountainous southeastern region.The SD model suggested that SDII and RX1DAY will likely rise more rapidly than those projected by previous model simulations over CA during the period 2081-2100.The SD projection of the possible future changes in precipitation and extremes improves the knowledge base for local risk management and climate change adaptation in CA.

Genotype-phenotype correlations,surgical selections,and postoperative complications of 5α-reductase 2 deficiency in 69 children with hypospadias

5α-reductase 2 deficiency prevents testosterone from being converted to dihydrotestosterone,which causes abnormal urogenital sinus development.The aim of this study was to analyze the relationship between genotype–phenotype,surgical selections,and postoperative complications of 5α-reductase 2-deficient patients with hypospadias.We retrospectively evaluated the medical records of patients who were diagnosed with 5α-reductase 2 deficiency after genetic testing in the Department of Endocrinology and underwent initial hypospadias surgery in the Department of Urology in Beijing Children’s Hospital,Capital Medical University(Beijing,China),from April 2007 to December 2021.A total of 69 patients were included in this study;the mean age at surgery was 34.1 months,and the average follow-up time was 54.1 months.Sixty children were treated with preoperative hormone stimulation(PHS)to promote penile growth.The average penis length and glans width were increased by 1.46 cm and 0.62 cm,respectively.The most frequent mutations were p.R227Q(39.1%,54/138),p.Q6^(*)(15.2%,21/138),p.G203S(12.3%,17/138),and p.R246Q(11.6%,16/138).In 64 patients who were followed up,43 had a one-stage operation and 21 had a staged operation,and there were significant differences in external masculinization score(EMS)(P=0.008)and the average number of operation required to cure(P<0.001)between one-stage and staged operations.PHS had a positive effect(P<0.001)on penile development.The p.R227Q mutation was associated with higher EMS and less severe hypospadias.One-stage surgery can be selected if conditions permit.The growth and development of children are acceptable in the long term,but penis growth remains unsatisfactory.Longterm complications of hypospadias should be considered during puberty.

Efficacy and safety of human chorionic gonadotropin combined with human menopausal gonadotropin and a gonadotropin-releasing hormone pump for male adolescents with congenital hypogonadotropic hypogonadism

Background:Compared to adult studies,studies which involve the treatment of pediatric congenital hypogonadotropic hypogonadism(CHH)are limited and no universal treatment regimen is available.The aim of this study was to evaluate the feasibility of human chorionic gonadotropin(hCG)/human menopausal gonadotropin(hMG)therapy for treating male adolescents with CHH.Methods:Male adolescent CHH patients were treated with hCG/hMG(n=20)or a gonadotropin-releasing hormone(GnRH)pump(n=21).The treatment was divided into a study phase(0-3 months)and a follow-up phase(3-12 months).The testicular volume(TV),penile length(PL),penis diameter(PD),and sex hormone levels were compared between the two groups.The TV and other indicators between the groups were analyzed using a t-test(equal variance)or a rank sum test(unequal variance).Results:Before treatment,there was no statistical difference between the two groups in terms of the biochemistry,hormones,and other demographic indicators.After 3 months of treatment,the TV of the hCG/hMG and GnRH groups increased to 5.1±2.3 mL and 4.1±1.8 mL,respectively;however,the difference was not statistically significant(P>0.05,t=1.394).The PL reached 6.9±1.8 cm and 5.1±1.6 cm(P<0.05,t=3.083),the PD reached 2.4±0.5 cm and 2.0±0.6 cm(P<0.05,t=2.224),respectively,in the two groups.At the end of 6 months of treatment,biomarkers were in normal range in the two groups.Compared with the GnRH group,the testosterone(T)level and growth of PL and PD were significantly greater in the hCG/hMG group(all P<0.05).While the TV of both groups increased,the difference was not statistically significant(P>0.05,t=0.314).After 9 to 12 months of treatment,the T level was higher in the hCG/hMG group.Other parameters did not exhibit a statistical difference.Conclusions:The hCG/hMG regimen is feasible and effective for treating male adolescents with CHH.The initial 3 months of treatment may be a window to optimally observe the strongest effects of therapy.Furthermore,results from the extended time-period showed positive outcomes at the 1-year mark;however,the long-term effectiveness,strengths,and weaknesses of the hCG/hMG regimen require further research.Trial Registration:ClinicalTrials.gov,NCT02880280;https://clinicaltrials.gov/ct2/show/NCT02880280.

Assessment of Central Asian heat extremes by statistical downscaling:Validation and future projection for 2015-2100

Increasing heatwaves and extreme temperatures have recently been observed across Central Asia(CA).Accurately assessing and projecting the changing climate extremes at the local(station)scale required for climate risk management are therefore highly important.However,global and regional climate models often fail to represent the statistical distributions of observed daily extreme variables and hence extremes in complex terrain.In this work,we developed a statistical downscaling(SD)model to project summer daily maximum temperature(Tmax)and heatwave indices for 65 meteorological stations in CA toward 2100.The SD model involves first-order autoregression and multiple linear regression using large-scale Tmax and circulation indices(Cis)as predictors,and the model is cross-validated against historical observations.The local Tmax and heatwave indices are then projected for 2015-2100 driven by the output of a global climate model(CNRM-CM6-1)under four Shared Socioeconomic Pathways(SSP126,SSP245,SSP370,and SSP585).The application of the SD model significantly improves forecasting of the probability distribution(10th/90th percentiles)of Tmax at stations,particularly across mountainous regions.The model also captures interannual variability and the long-term trend in Tmax,consistent with synoptic-scale inputs.SD projections demonstrate strong warming trends of summer Tmax in CA toward 2100 with rates between 0.35-0.64℃ per decade based on the SSP245 and SSP370 seenarios.Consequently,heatwave occurrence is projected to rise by 1.0-5.0 and 2.0-7.0 d per decade under the SSP245 and SSP370 scenarios,respectively,by 2100.Duration,intensity,and amplitude of heatwaves rise at greater rates under higher-emission scenarios,particularly in southeastern CA.The proposed SD model serves as a useful tool for assessing local climate extremes,which are needed for regional risk management and policymaking for adaption to climate change.