Fluorescent Double Network Hydrogels with Ionic Responsiveness and High Mechanical Properties for Visual Detection

We developed a fluorescent double network hydrogel with ionic responsiveness and high mechanical properties for visual detection.The nanocomposite hydrogel of laponite and polyacrylamide serves as the first network,while the ionic cross-linked hydrogel of terbium ions and sodium alginate serves as the second network.The double-network structure,the introduction of nanoparticles and the reversible ionic crosslinked interactions confer high mechanical properties to the hydrogel.Terbium ions are not only used as the ionic cross-linked points,but also used as green emitters to endow hydrogels with fluorescent properties.On the basis of the “antenna effect” of terbium ions and the ion exchange interaction,the fluorescence of the hydrogels can make selective responses to various ions(such as organic acid radical ions,transition metal ions) in aqueous solutions,which enables a convenient strategy for visual detection toward ions.Consequently,the fluorescent double network hydrogel fabricated in this study is promising for use in the field of visual sensor detection.

Rosmarinic acid improves tracheal smooth muscle responsiveness and lung pathological changes in ovalbumin-sensitized rats

Objective:To evaluate the effect of rosmarinic acid on tracheal smooth muscle responsiveness and lung pathological changes in ovalbumin-sensitized rats.Methods:Rats were randomly divided into six groups:the control group,the asthmatic group,and the asthmatic groups treated with dexamethasone(1 mg/kg;oral gavage)or three doses of rosmarinic acid(0.5,1,and 2 mg/kg;oral gavage).For induction of asthma,rats received intraperitoneal injections and inhalation of ovalbumin.After 21 days,bronchoalveolar lavage fluid and lung samples were collected for histopathological analyses.Moreover,total and differential white blood cell counts were determined.Results:The rosmarinic acid-treated group had significantly lower tracheal smooth muscle responses to methacholine than the asthmatic group.In addition,rosmarinic acid reduced white blood cell count and the percentages of eosinophils,monocytes,and neutrophils while increasing the percentage of lymphocytes.Ovalbumin-induced lung pathological changes were significantly improved by treatment with rosmarinic acid.Conclusions:Rosmarinic acid improves tracheal smooth muscle responsiveness and lung pathological changes in ovalbumin-sensitized rats.

Maternal obesity exacerbates the responsiveness of offspring BALB/c mice to cow's milk protein-induced food allergy

Food allergy has become a significant public health problem affecting a large number of people worldwide.Maternal obesity causes inflammation and alters the immune system of offspring,which may exacerbate their food allergy.The aim of this study was to determine whether offspring mice born to obese mothers would have more serve reactions to cow's milk protein-induced food allergy,and further investigate the underlying mechanisms.Female offspring BALB/c mice of mothers with normal and high-fat diets were sensitized withβ-lactoglobulin(BLG),respectively.Maternal obesity increased the serum immunoglobulin E and mouse mast cell protease levels,though did not have significant influence on anaphylactic symptom score,core temperature and diarrhea rate of offspring mice after BLG sensitization.Furthermore,maternal obesity led to a lower level of occludin mRNA expression in BLG-sensitized mice.The mice born to obese mothers exhibited increased mRNA expression levels of GATA-3,interleukin(IL)-4 and IL-10 in jejunum after BLG sensitization,indicating maternal obesity intensified Th2-type biased immune responses.In conclusion,maternal obesity exerted exacerbating effects on the responsiveness of their offspring to cow's milk protein sensitization.

Responsiveness and minimal clinically important difference of the Chinese version of the Low Vision Quality of Life Questionnaire after cataract surgery

AIM: To investigate the Chinese version of the Low Vision Quality of Life Questionnaire(CLVQOL) as an instrument for obtaining clinically important changes after cataract surgery.METHODS: Patients underwent cataract surgery in Shanghai General Hospital, Shanghai Jiao Tong University, who fit the inclusion criteria were recruited. Two CLVQOLs were administered, including a preoperative CLVQOL and a CLVQOL at the end of the 3 mo follow-up period, and were completed using face-to-face interviews or phone interviews conducted by trained investigators. The minimal clinically important difference(MCID) was calculated using an anchor-based method and a distribution method. In addition, the responsiveness of the questionnaire was measured.RESULTS: A total of 155 residents were enrolled. The average visual acuity(VA) preoperatively was 0.08(SD=0.05), and it increased to 0.47(SD=0.28) at the end of followup. Statistically significant positive changes in the CLVQOL scores indicated significant improvement of vision related quality of life after cataract surgery. With the larger value between the two results as the final value, the MCID values of the CLVQOL(scores of the four scales as well as the total score) were 8.94, 2.61, 4.34, 3.10 and 17.63, respectively. The CLVQOL has both good internal and external responsiveness.CONCLUSION: CLVQOL scores are appropriate instruments for obtaining clinically important changes after cataract surgery. This study is an effective exploration for establishingcataract surgery efficacy standards, which helps clinical and scientific research workers in ophthalmology to gain a more in-depth understanding when using CLVQOL.

Passive leg raising as an indicator of fluid responsiveness in patients with severe sepsis

BACKGROUND:In the management of critically ill patients,the assessment of volume responsiveness and the decision to administer a fluid bolus constitute a common dilemma for physicians.Static indices of cardiac preload are poor predictors of volume responsiveness.Passive leg raising(PLR) mimics an endogenous volume expansion(VE) that can be used to predict fluid responsiveness.This study was to assess the changes in stroke volume index(SVI) induced by PLR as an indicator of fluid responsiveness in mechanically ventilated patients with severe sepsis.METHODS:This was a prospective study.Thirty-two mechanically ventilated patients with severe sepsis were admitted for VE in ICU of the First Affiliated Hospital,Zhejiang University School of Medicine and Ningbo Medical Treatment Center Lihuili Hospital from May 2010 to December 2011.Patients with non-sinus rhythm or arrhythmia,parturients,and amputation of the lower limbs were excluded.Measurements of SVI were obtained in a semi-recumbent position(baseline) and during PLR by the technique of pulse indicator continuous cardiac output(PiCCO) system prior to VE.Measurements were repeated after VE(500 mL 6%hydroxyethyl starch infusion within 30 minutes)to classify patients as either volume responders or non-responders based on their changes in stroke volume index(ASVI) over 15%.Heart rate(HR),systolic artery blood pressure(ABPs),diastolic artery blood pressure(ABPd),mean arterial blood pressure(ABPm),mean central venous pressure(CVPm)and cardiac index(CI) were compared between the two groups.The changes of ABPs,ABPm,CVPm,and SVI after PLR and VE were compared with the indices at the baseline.The ROC curve was drawn to evaluate the value of ASVI and the change of CVPm(ACVPm) in predicting volume responsiveness.SPSS 17.0 software was used for statistical analysis.RESULTS:Among the 32 patients,22 were responders and 10 were non-responders.After PLR among the responders,some hemodynamic variables(including ABPs,ABPd,ABPm and CVPm)were significantly elevated(101.2±17.6 vs.118.6±23.7,P=0.03;52.8±10.7 vs.64.8±10.7,P=0.006;68.3+11.7 vs.81.9±14.4,P=0.008;6.8±3.2 vs.11.9±4.0,P=0.001).After PLR,the area under curve(AUC) and the ROC curve of △SV1 and ACVPm for predicting the responsiveness after VE were0.882±0.061(95%CI 0.759-1.000) and 0.805±0.079(95%CI 0.650-0.959) when the cut-off levels of ASVI and ACVPm were 8.8%and 12.7%,the sensitivities were 72.7%and 72.7%,and the specificities were 80%and 80%.CONCLUSION:Changes in ASVI and ACVPm induced by PLR are accurate indices for predicting fluid responsiveness in mechanically ventilated patients with severe sepsis.

Meta-Analysis of Ventilated versus Spontaneously Breathing Patients in Predicting Fluid Responsiveness by Inferior Vena Cava Variation

Purpose: Respiratory variation in inferior vena cava (ΔIVC) has been extensively studied in predicting fluid responsiveness, but the results are conflicting. We performed a systemic review and meta-analysis of studies aiming at investigating the diagnostic accuracy of ΔIVC in predicting fluid responsiveness. Methods: MEDLINE, EMBASE, Cochrane Database and Web of Science were screened for relevant original and review articles from inception to July 2016. The meta-analysis determined the pooled sensitivity, specificity, diagnostic odds ratio (DOR) and area under the ROC curve (AUROC). In addition, subgroup analyses were performed in mechanically ventilated patients and spontaneously breathing patients. Results: A total of 20 studies involving 635 patients were included. Cutoff values of ΔIVC varied from 12% to 42%, the pooled sensitivity and specificity was 0.68 (0.62 - 0.75) and 0.80 (0.75 - 0.85), respectively. The DOR was 14.2 (6.0 - 33.6) and the AUROC was 0.86 (0.78 - 0.93). Subgroup analysis showed better diagnostic performance in patients on mechanical ventilation than in spontaneously breathing patients with higher sensitivity (0.75 vs. 0.56), specificity (0.82 vs. 0.78), DOR (22.9 vs. 7.9) and AUROC (0.90 vs. 0.80). The best threshold of ΔIVC in patients on mechanical ventilation was IVC distensibility index (ΔIVC ≥17% ±4%), compared to IVC collapsibility index (ΔcIVC ≥33% ±12%) in spontaneously breathing patients. Conclusion: ΔIVC is not an accurate predictor of fluid responsiveness in patients with acute circulatory failure. In patients on mechanical ventilation, the predicting ability of ΔIVC was moderate with acceptable sensitivity and specificity;in spontaneously breathing patients, the specificity remains acceptable but its sensitivity is poor.

Arterial Pulse Pressure Variation versus Central Venous Pressure as a Predictor for Fluid Responsiveness during Open Major Abdominal Operations

Introduction: Fluid resuscitation is the cornerstone in the management of hemodynamically unstable patients. Dynamic parameters of fluid responsiveness, like pulse pressure variation, have the advantage of being more reliable index for fluid management. Objective: The aim of our study was to compare between arterial pulse pressure variation (PPV) versus central venous pressure (CVP) as a predictor for fluid responsiveness during major open abdominal operations. Patients and Methods: 60 adult patients under general anesthesia with mechanical ventilation underwent open major abdominal surgical procedures were included in our prospective randomized controlled study. Intravenous fluid was infused and monitored by CVP in control group or by PPV in the other group. Hemodynamic variables (heart rate, invasive blood pressure, PPV and CVP) were measured at baseline after anesthesia induction and every 10 min, during first hour of operation, and then every 15 min, till end of surgery. Blood loss and total i.v. fluid & blood transfusion given to patients were recorded and compared between two groups intraoperatively. Results: Patients in the PPV group required more intraoperative fluid and blood transfusion than patients in CVP group to achieve more stable hemodynamic parameters. The fall in blood pressure (>20% of baseline) and increase in heart rate are more common in CVP group (p Conclusion: PPV is a better predictor and a good guide for fluid responsiveness. More stable hemodynamic variables are observed in PPV group.

Remodeled structure and reduced contractile responsiveness of ocular ciliary artery in spontaneously hypertensive rats

AIM: To investigate the alterations in both structure and contractile responsiveness of ocular ciliary artery(OCA) in spontaneously hypertensive rat(SHR).METHODS: In this experiment, 20-week-old male SHR and Wistar Kyoto rat(WKY) were studied. The heart rate(HR), the blood pressure(BP; the systolic BP and the diastolic BP) of rats with an electronic sphygmomanometer were measured. Vascular morphometry and isometric tension measurement were used to investigate the alterations in structure and contractility of OCA.RESULTS: A general narrowing of OCAs was observed in SHR compared to the control WYK. In SHR, the media of OCAs were thicker, the luminal diameters were smaller, and the media-to-lumen ratios were higher when compared with WKY(P<0.05). The contractions of OCAs evoked by norepinephrine were smaller in SHR compared to control(P<0.05). Then, OCAs were pretreated with iberiotoxin, L-NAME, or indomethacin 30 min before norepinephrineinduced contraction. Iberiotoxin(0.1 μmol/L) has not changed the norepinephrine-induced contractions in OCAs from both groups. However, L-NAME(100 μmol/L) increased the vasoconstrictions, the increased extents were similar in SHR and WKY(P>0.05). Indomethacin(10 μmol/L) decreased the contractions induced by norepinephrine in OCAs from WKY(P<0.05), but did not change those contractions in vessels from SHR(P>0.05).CONCLUSION: Our results demonstrate that the structure and function of OCAs are altered in hypertension. OCAs from SHR are remodeled with decreased lumen diameter and increased media-to-lumen ratio. Moreover, the contractile responsiveness of OCAs from SHR is diminished due to the disruption of vasoconstrictive effect of prostaglandins.

Individual Differences in Stress Responsiveness of the Hypothalamic-Pituitary-Adrenal Axis and Its Vasopressinergic Regulation in Old Monkeys

Stress adaptation is fundamental for health, and the hypothalamic-pituitary-adrenal axis (HPA) is one of its main mechanisms. Considerable data indicate that arginine vasopressin (AVP) related disturbances of stress adaptation can occur with aging. However, most studies of such kind have been performed on rodents, give contradictory results and fail to consider individual characteristics of the animals. The purpose of this study was to investigate individual HPA responsiveness to acute stress and its vasopressinergic regulation in old female rhesus monkeys that differ in their behavioral responses to stress. Animals with depression-like or anxiety-like behavior (DAB) responded with higher plasma levels of ACTH and AVP, lower levels of corticosteroids and higher cortisol/DHEAS molar ratios to restraint stress and to insulin-induced hypoglycemia compared with animals with healthy adaptive behavior. AVP and ACTH dynamics were closely correlated in most animals. AVP treatment produced differences in HPA responses similar to those produced by the stressors. The ACTH response to hypoglycemic stress in the DAB animal with highest HPA responsiveness was dramatically reduced by prior administration of a V1b receptor antagonist. These results suggest that the dysfunctions of HPA observed in old animals with DAB are caused by increased tone of the vasopressinergic system in regulation of HPA stress reactivity.

MONTE CARLO SIMULATION FOR MODELING THE EFFECT OF GROUND SEGMENT LOCATION ON IN-ORBIT RESPONSIVENESS OF LEO SUNSYNCHRONOUS SATELLITES

Responsiveness is a challenge for space systems to sustain competitive advantage over al-ternate non-spaceborne technologies.For a satellite in its operational orbit,in-orbit responsiveness is defined as the capability of the satellite to respond to a given demand in a timely manner.In this paper,it is shown that Average Wait Time(AWT) to pick up user demand from ground segment is the ap-propriate metric to evaluate the effect of ground segment location on in-orbit responsiveness of Low Earth Orbit(LEO) sunsynchronous satellites.This metric depends on pattern of ground segment access to satellite and distribution of user demands in time domain.A mathematical model is presented to determine pattern of ground segment access to satellite and concept of cumulative distribution function is used to simulate distribution of user demands for markets with different total demand scenarios.Monte Carlo simulations are employed to take account of uncertainty in distribution and total volume of user demands.Sampling error and standard deviation are used to ensure validity of AWT metric obtained from Monte Carlo simulations.Incorporation of the proposed metric in the ground segment site location process results in more responsive satellite systems which,in turn,lead to greater customer satisfaction levels and attractiveness of spaceborne systems for different applications.Finally,simula-tion results for a case study are presented.

Dynamic-Distributed Load Balancing for Highly-Performance and Responsiveness Distributed-GIS (D-GIS)

In recent years, several results have been introduced to enhance distributed GIS performance. While much more efforts have focused on tile map and simple symbologies on dynamic map, load balancing GIS servers have not been addressed by the GIS community so far. This paper, therefore, proposed dynamic distributed load balancing for D-GIS in order to quickly render information to client interface by involving a set of GIS servers which process clients’ requests depending of an algorithm. In the model, several concepts were introduced and defined: Virtual Server within physical machine which constitutes a setup environment for a single GIS server, Load Hash Table which contains information about virtual server’s capacity, real-time load and other mandatory elements, Request Split Table which splits requests depending of the input area’s Quantity of Information and stores request tasks composition for later reconstitution. At last we have Distributed Failover Callback Function Table level one (respectively level two) which determines whether or not the request had been successfully processed by the chosen virtual server (respectively physical machine). This table allows sending back the same request to another virtual server (respectively physical node). Two load handlers (primary and secondary) are defined in case of failure. Our Model achieves efficient load balancing by: providing efficient node selection;optimizing request routing;managing node failover;involving client’s request partitioning and introducing method type decomposition. A simulation of the algorithm shows a low response time when performing GIS operations.

Achieving Responsiveness through Supply Chain Integration:A Moderating Effect of Industry-4.0

This article is aiming to investigate the emerging impact of industry-4.0 on supply chain integration and responsiveness in the electronics industry in China.Specifically,it is to investigate the moderating effect of industry-4.0 as a strategic factor on the causal relationship from operational integration to supply chain responsiveness.This study develops hypotheses based the on selected literature reviews in the relevant research areas,and tests the hypotheses in the empirical sample data set collected from 76 electronics firms by using hierarchical multiple regression method.The results of this study shows that industry-4.0 as an emerging strategic factor has not only directly helped the level of market responsiveness of the firms,but also has significantly strengthens the already proven positive causal relationship from operational integration within the supply chain to the overall market responsiveness as part of supply chain performance.To improve the supply chain responsiveness in the electronics industry,managers can now make more confident and informed decisions to channel their resources towards the initiatives of industry-4.0 by up-grading perhaps their current information systems and business processes,knowing full well the dual benefits offered by the Industry 4.0 initiatives.The study extends the concurrent literature by conceptualising the moderating effect of industry-4.0 on the causal relationship between supply chain integration and business responsiveness.

Diagnostic Accuracy of Transthoracic Echocardiography to Predict Fluid Responsiveness by Passive Leg Raising in the Critically Ill: A Meta-Analysis

Background: Hemodynamic instability is common in critical patients and not all patients respond to fluid challenge, so we need accurate and rapid hemodynamic techniques to help the clinicians to guide fluid treatment. Numerous hemodynamic techniques have been used to predict fluid responsiveness till now. Transthoracic echocardiography (TTE) appears to have the ability to predict fluid responsiveness, but there is no consensus on whether it can be used by passive leg raising (PLR). Methods: We performed a literature search using MEDLINE (source PubMed, from 1947), EMBASE (from 1974) and the Cochrane Database of Systematic Reviews for prospective studies with no restrictions. Pooled effect estimates were obtained by using random-effects meta-analysis. Results: 7 prospective studies involving 261 patients and 285 boluses were identified. The pooled sensitivity and specificity of TTE are 86% (79% - 91%) and 90% (83% - 94%), respectively. The summary receiver operating characteristic (sROC) curve shows an optimum joint sensitivity and specificity of 0.88, with area under the sROC curve (AUC) of 0.94. The result of diagnostic odds ratio (DOR) is 50.62 (95% confidence interval [CI]: 23.70 - 108.12). The results of positive likelihood ratio (+LR) and negative likelihood ratio (?LR) are 7.07 (95% CI: 4.39 - 11.38) and 0.19 (95% CI: 0.13 - 0.28), which indicated strong diagnostic evidence. Conclusions: TTE is a repeatable and reliable noninvasive tool to predict fluid responsiveness in the critically ill during PLR with good test performance. This meta-analysis brings evidence to employ well-trained clinician-echocardiographers to assess patients’ volume statue via TTE to benefit daily work in intensive care units (ICUs).

Meta-Analysis of Invasive versus Non-Invasive Techniques to Predict Fluid Responsiveness by Passive Leg Raising in the Critically Ill

Objective: To analyze the accuracy and specificity of recent studies to compare the ability of predicting fluid responsiveness with Passive Leg Raising (PLR) by using invasive or non-invasive techniques during passive leg raising. Data Sources: MEDLINE, EMBASE and the Cochrane Database of Systematic Reviews were systematically searched. Study Selection: Clinical trials that reported the sensitivity, specificity and area under the receiver operating characteristic curve (AUC) between the responder and non-responder induced by passive leg raising and Volume Expansion (VE) in critical ill patients were selected. 246 studies were screened, 14 studies were included for data extraction, which met our inclusion criteria. Data Extraction: Data were abstracted on study characteristics, patient population, type and amount of VE, time of VE, definition of responders, position, techniques used for measuring hemodynamic change, number and percentage of responders, the correlation coefficient, sensitivity, specificity, best threshold and area under the ROC curve (AUC). Meta-analytic techniques were used to summarize the data. Data Synthesis: A total of 524 critical ill patients from 14 studies were analyzed. Data are reported as point estimate (95% confidence intervals). The pooled sensitivity and specificity of invasive techniques were 80% (73% - 85%) and 89% (84% - 93%) respectively with the area under the sROC of 0.94. While, the pooled sensitivity and specificity of non-invasive techniques were 88% (84% - 92%) and 91% (86% - 94%) respectively with the area under the sROC of 0.95. The pooled DOR of invasive techniques was 32.2 (13.6 - 76.8), which was much lower than that of non-invasive techniques with the value of 64.3 (33.9 - 121.7). Conclusions: The hemodynamic indexes changes induced by PLR could reliably predict fluid responsiveness. Non-invasive hemodynamic techniques with their accuracy and safety can benefit the daily work in ICUs. Because the number of patients included in the present trials was small, further studies should be undertaken to confirm these findings.

Immune regulation of the gut-brain axis and lung-brain axis involved in ischemic stroke

Local ischemia often causes a series of inflammatory reactions when both brain immune cells and the peripheral immune response are activated.In the human body,the gut and lung are regarded as the key reactional targets that are initiated by brain ischemic attacks.Mucosal microorganisms play an important role in immune regulation and metabolism and affect blood-brain barrier permeability.In addition to the relationship between peripheral organs and central areas and the intestine and lung also interact among each other.Here,we review the molecular and cellular immune mechanisms involved in the pathways of inflammation across the gut-brain axis and lung-brain axis.We found that abnormal intestinal flora,the intestinal microenvironment,lung infection,chronic diseases,and mechanical ventilation can worsen the outcome of ischemic stroke.This review also introduces the influence of the brain on the gut and lungs after stroke,highlighting the bidirectional feedback effect among the gut,lungs,and brain.

Transcriptomic analysis in Anemone flaccida rhizomes reveals ancillary pathway for triterpene saponins biosynthesis and differential responsiveness to phytohormones

Anemone flaccida Fr. Schmidt is a perennial medicinal herb that contains pentacyclic triterpenoid saponins as the major bioactive constituents. In China, the rhizomes are used as treatments for a variety of ailments including arthritis. However, yields of the saponins are low, and little is known about the plant's genetic background or phytohormonal responsiveness. Using one-quarter of the 454 pyrosequencing information from the Roche GS FLX Titanium platform, we performed a transcriptomic analysis to identify 157 genes putatively encoding 26 enzymes involved in the synthesis of the bioactive compounds. It was revealed that there are two biosynthetic pathways of triterpene saponins in A. flaccida. One pathway depends on β-amyrin synthase and is similar to that found in other plants. The second, subsidiary("backburner") pathway is catalyzed by camelliol C synthase and yields β-amyrin as minor byproduct. Both pathways used cytochrome P450-dependent monooxygenases(CYPs) and family 1 uridine diphosphate glycosyltransferases(UGTs) to modify the triterpenoid backbone. The expression of CYPs and UGTs were quite different in roots treated with the phytohormones methyl jasmonate, salicylic acid and indole-3-acetic acid. This study provides the first large-scale transcriptional dataset for the biosynthetic pathways of triterpene saponins and their phytohormonal responsiveness in the genus Anemone.

Performance of the Autism Spectrum Rating Scale and Social Responsiveness Scale in Identifying Autism Spectrum Disorder Among Cases of Intellectual Disability

The Autism Spectrum Rating Scale(ASRS) and the Social Responsiveness Scale(SRS) have been widely used for screening autism spectrum disorder(ASD) in the general population during epidemiological studies, but studies of individuals with intellectual disability(ID) are quite limited. Therefore, we recruited the parents/caregivers of 204 ASD cases, 71 ID cases aged 6–18 years from special education schools, and 402 typically developing(TD) children in the same age span from a communitybased population to complete the ASRS and SRS. The results showed that the ID group scored significantly lower on total and subscale scores than the ASD group on both scales(P \ 0.05) but higher than TD children(P \ 0.05).Receiver operating characteristic analyses demonstrated a similar fair performance in discriminating ASD from ID with the ASRS(area under the curve(AUC) = 0.709,sensitivity = 77.0%, specificity = 52.1%, positive predictive value(PPV) = 82.2%) and the SRS(AUC = 0.742,sensitivity = 59.8%, specificity = 77.5%, PPV = 88.4%).The results showed that individuals with ID had clear autistic traits and discriminating ASD from ID cases was quite challenging, while assessment tools such as ASRS and SRS, help to some degree.

Assessing the Accuracy of the Modified Chinese Autism Spectrum Rating Scale and Social Responsiveness Scale for Screening Autism Spectrum Disorder in Chinese Children

The reported prevalence of autism spectrum disorder(ASD) has been increasing rapidly in many parts of the world. However, data on its prevalence in China are largely missing. Here, we assessed the suitability of the modi?ed Chinese version of a newly-developed ASD screening tool, the Modi?ed Chinese Autism Spectrum Rating Scales(MC-ASRS) in screening for ASD in Chi nese children aged 6–12 years, through comparison with the Social Responsiveness Scale(SRS) that has been widely used for ASD screening. We recruited the par ents/caregivers of 1588 typically-developing children and190 children with ASD aged 6–12 years to complete the MC-ASRS and SRS, and evaluated the validity of both scales in discriminating children with ASD from those developing typically. The results showed that MC-ASRSperformed as well as SRS in sensitivity, speci?city, and area-under-the-curve(both [0.95) in receiver operating characteristic analysis, with a fair false-negative rate.These results suggest that MC-ASRS is a promising tool for screening for children with ASD in the general Chinese population.

Immune consequences of exercise in hypoxia:A narrative review

Immune outcomes are key mediators of many health benefits of exercise and are determined by exercise type,dose(frequency/duration,intensity),and individual characteristics.Similarly,reduced availability of ambient oxygen(hypoxia)modulates immune functions depending on the hypoxic dose and the individual capacity to respond to hypoxia.How combined exercise and hypoxia(e.g.,high-altitude training)sculpts immune responses is not well understood,although such combinations are becoming increasingly popular.Therefore,in this paper,we summarize the impact on immune responses of exercise and of hypoxia,both independently and together,with a focus on specialized cells in the innate and adaptive immune system.We review the regulation of the immune system by tissue oxygen levels and the overlapping and distinct immune responses related to exercise and hypoxia,then we discuss how they may be modulated by nutritional strategies.Mitochondrial,antioxidant,and anti-inflammatory mechanisms underlie many of the adaptations that can lead to improved cellular metabolism,resilience,and overall immune functions by regulating the survival,differentiation,activation,and migration of immune cells.This review shows that exercise and hypoxia can impair or complement/synergize with each other while regulating immune system functions.Appropriate acclimatization,training,and nutritional strategies can be used to avoid risks and tap into the synergistic potentials of the poorly studied immune consequences of exercising in a hypoxic state.

Prediction of treatment response to antipsychotic drugs for precision medicine approach to schizophrenia:randomized trials and multiomics analysis

Background:Choosing the appropriate antipsychotic drug(APD)treatment for patients with schizophrenia(SCZ)can be challenging,as the treatment response to APD is highly variable and difficult to predict due to the lack of effective biomarkers.Previous studies have indicated the association between treatment response and genetic and epigenetic factors,but no effective biomarkers have been identified.Hence,further research is imperative to enhance precision medicine in SCZ treatment.Methods:Participants with SCZ were recruited from two randomized trials.The discovery cohort was recruited from the CAPOC trial(n=2307)involved 6 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,Quetiapine,Aripiprazole,Ziprasidone,and Haloperidol/Perphenazine(subsequently equally assigned to one or the other)groups.The external validation cohort was recruited from the CAPEC trial(n=1379),which involved 8 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,and Aripiprazole groups.Additionally,healthy controls(n=275)from the local community were utilized as a genetic/epigenetic reference.The genetic and epigenetic(DNA methylation)risks of SCZ were assessed using the polygenic risk score(PRS)and polymethylation score,respectively.The study also examined the genetic-epigenetic interactions with treatment response through differential methylation analysis,methylation quantitative trait loci,colocalization,and promoteranchored chromatin interaction.Machine learning was used to develop a prediction model for treatment response,which was evaluated for accuracy and clinical benefit using the area under curve(AUC)for classification,R^(2) for regression,and decision curve analysis.Results:Six risk genes for SCZ(LINC01795,DDHD2,SBNO1,KCNG2,SEMA7A,and RUFY1)involved in cortical morphology were identified as having a genetic-epigenetic interaction associated with treatment response.The developed and externally validated prediction model,which incorporated clinical information,PRS,genetic risk score(GRS),and proxy methylation level(proxyDNAm),demonstrated positive benefits for a wide range of patients receiving different APDs,regardless of sex[discovery cohort:AUC=0.874(95%CI 0.867-0.881),R^(2)=0.478;external validation cohort:AUC=0.851(95%CI 0.841-0.861),R^(2)=0.507].Conclusions:This study presents a promising precision medicine approach to evaluate treatment response,which has the potential to aid clinicians in making informed decisions about APD treatment for patients with SCZ.Trial registration Chinese Clinical Trial Registry(https://www.chictr.org.cn/),18 Aug 2009 retrospectively registered:CAPOC-ChiCTR-RNC-09000521(https://www.chictr.org.cn/showproj.aspx?proj=9014),CAPEC-ChiCTRRNC-09000522(https://www.chictr.org.cn/showproj.aspx?proj=9013).