An investigation into accidents in laboratories in universities in China caused by human error: A study based on improved CREAM and SPAR-H.

Although considerable research has been devoted to improving safety in university laboratories, accidents, in that environment, have still occurred frequently at the cost of serious injury or even death of laboratory personnel. Currently, few Human Reliability Analyses (HRA) have been conducted with respect to a university laboratory. The aim of the research was to conduct a reliability study relating to human behaviour in a university laboratory to explore quantitatively the causes and influencing factors relating to the frequency of laboratory accidents. Improved Cognitive Reliability and Error Analysis Method (CREAM) and improved Standardized Plant Analysis Risk HRA (SPAR-H) were employed to assess Human Error Probability (HEP) of 23 subjects. The HEP calculated through improved CREAM proved more accurate than results obtained through improved SPAR-H. Unexpectedly, the results demonstrated that under similar environmental conditions, the HEP of subjects did not decrease with an increase in educational background, including additional experimental time and experience. Moreover, environmental conditions exerted greater impact on personnel reliability than Human Inherent Factors (HIFs) in laboratories. It is anticipated that the study would provide valuable insights, in respect of research methods, and to serve as a practical basis for lowering the accident rate in university laboratories.

Higher Risk of Psychiatric Disorders in Children With Febrile Seizures: A Nationwide Cohort Study in Taiwan.

BACKGROUND: Febrile seizures occur commonly in children aged between six months and six years. A previous Danish study found a positive correlation between febrile seizures and the overall incidence of psychiatric disorders. This population-based nationwide observational study was conducted to investigate the association between febrile seizures and different psychiatric disorders in Taiwan and the associated risk factors. METHODS: This cohort study used data from the National Health Insurance Research Database in Taiwan-a nationwide claims database covering >99% of the Taiwanese population. The study period was from January 2000 to December 2015; the overall median follow-up time was 11.04 ± 10.95 years. Overall, 2464 children with febrile seizures diagnosed between 2000 and 2015 met the inclusion criteria, and 7392 children without febrile seizures matched by index year, age, and sex were included in the control cohorts. Febrile seizures and psychiatric disorders were measured as the exposure and main outcomes, respectively. RESULTS: Children with febrile seizures (n = 2463) were at a high risk of psychiatric disorders (adjusted hazard ratio, 4.70; 95% confidence interval [CI], 2.44 to 7.30; P < 0.001). The risk for anxiety was the highest (adjusted hazard ratio, 21.92; 95% CI, 11.40 to 34.05; P < 0.001). CONCLUSIONS: When treating children with febrile seizures, particular attention should be paid to the symptoms of psychiatric disorders, as early referral may be beneficial for these children.

Increased risk of acute stress disorder and post-traumatic stress disorder in children and adolescents with autism spectrum disorder: a nation-wide cohort study in Taiwan.

Introduction: Children and adolescents with autism spectrum disorder (ASD) may be particularly vulnerable to the impact of traumatic events, yet the association between ASD and the risk of developing acute stress disorder and post-traumatic stress disorder (PTSD) remains uncertain. This study aims to investigate this association, addressing the gap in large-scale evidence on the subject. Methods: Conducted as a retrospective and matched cohort study, data was sourced from the National Health Insurance Research Database (NHIRD) in Taiwan, spanning from January 1, 2000, to December 31, 2015. The study included patients aged 18 years or under newly diagnosed with ASD (n=15,200) and compared them with a matched control group (n=45,600). The Cox proportional regression model was employed to assess the risk of acute stress disorder and PTSD. Results: Over the 15-year follow-up period, a total of 132 participants developed either acute stress disorder or PTSD. Among them, 105 cases (0.691% or 64.90 per 100,000 person-years) were in the ASD group, while 27 cases (0.059% or 5.38 per 100,000 person-years) were in the control group. The adjusted hazard ratio for the ASD group was significantly higher compared to the control group (25.661 with 95% CI = 15.913-41.232; P < .001). Discussion: This study provides compelling evidence that individuals with ASD face an elevated risk of developing acute stress disorder and PTSD. The findings underscore the importance of clinicians recognizing and addressing this vulnerability in ASD individuals exposed to traumatic events. This emphasizes the need for heightened attention to the risk of PTSD and acute stress disorder in the ASD population.

Treatment resistant depression in elderly.

Treatment refractory depression (TRD) in the elderly is a common psychiatric disorder with high comorbidity and mortality. Older adults with TRD often have complicated comorbidities and several predisposing risk factors, which may lead to neuropsychiatric dysfunction and poor response to treatment. Several hypotheses suggest the underlying mechanisms, including vascular, immunological, senescence, or abnormal protein deposition. Treatment strategies for TRD include optimization of current medication dose, augmentation, switching to an alternative agent or class, and combination of different antidepressant classes, as well as nonpharmacological adjuvant interventions such as biophysical stimulation and psychotherapy. In summary, treatment recommendations for TRD in the elderly favor a multimodal approach, combining pharmacological and nonpharmacological treatments.

Bayesian semiparametric joint model of multivariate longitudinal and survival data with dependent censoring.

We consider a novel class of semiparametric joint models for multivariate longitudinal and survival data with dependent censoring. In these models, unknown-fashion cumulative baseline hazard functions are fitted by a novel class of penalized-splines (P-splines) with linear constraints. The dependence between the failure time of interest and censoring time is accommodated by a normal transformation model, where both nonparametric marginal survival function and censoring function are transformed to standard normal random variables with bivariate normal joint distribution. Based on a hybrid algorithm together with the Metropolis-Hastings algorithm within the Gibbs sampler, we propose a feasible Bayesian method to simultaneously estimate unknown parameters of interest, and to fit baseline survival and censoring functions. Intensive simulation studies are conducted to assess the performance of the proposed method. The use of the proposed method is also illustrated in the analysis of a data set from the International Breast Cancer Study Group.

DL-3-n-butylphthalide improves the endothelium-dependent vasodilation in high-fat diet-fed ApoE-/- mice via suppressing inflammation, endothelial necroptosis and apoptosis.

Impaired endothelium-dependent vasodilation in atherosclerosis is a high-risk factor for myocardial infarction and ischemic stroke, and inflammation, necroptosis and apoptosis contribute to endothelial dysfunction in atherosclerosis. Although DL-3-n-butylphthalide (NBP) has been widely used in treating ischemic stroke, its effect on endothelium-dependent vasodilation remains unknown. This study aims to explore whether NBP is able to improve endothelium-dependent vasodilation in atherosclerosis and the underlying mechanisms. Male ApoE-/- mice were fed with a high-fat diet (HFD) for 9-16 weeks to establish a model of atherosclerosis. NBP were given to the mice after eating HFD for 6 weeks and atorvastatin served as a positive control. The endothelium-dependent vasodilation, the blood flow velocity, the atherosclerotic lesion area, the serum levels of lipids, inflammatory cytokines and necroptosis-relevant proteins (RIPK1, RIPK3 and MLKL), and the endothelial necroptosis and apoptosis within the aorta were measured. Human umbilical vein endothelial cells (HUVECs) were incubated with oxidized low-density lipoprotein (ox-LDL) for 48 h to mimic endothelial injury in atherosclerosis, lactate dehydrogenase release, the ratio of necroptosis and apoptosis and the expression of necroptosis-relevant proteins were examined. Similar to atorvastatin, NBP improves endothelium-dependent vasodilation, decreases aortic flow velocity and reduces atherosclerotic lesion area in HFD-fed ApoE-/- mice, concomitant with a reduction in serum lipids, inflammatory cytokines and necroptosis-relevant proteins, and endothelial necroptosis and apoptosis. Consistently, NBP inhibited necroptosis and apoptosis in ox-LDL-treated HUVECs. Based on these observations, we conclude that NBP exerts beneficial effects on improving the endothelium-dependent vasodilation in atherosclerosis via suppressing inflammation, endothelial necroptosis and apoptosis.

Inhibition of MALT1 reduces ferroptosis in rat hearts following ischemia/reperfusion via enhancing the Nrf2/SLC7A11 pathway.

The dysregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and/or solute carrier family 7 member 11 (SLC7A11) is believed to contribute to ferroptosis in the hearts suffered ischemia/reperfusion (I/R), but the mechanisms behind the dysregulation of them are not fully elucidated. Mucosa associated lymphoid tissue lymphoma translocation gene 1 (MALT1) can function as a paracaspase to cleave specified substrates and it is predicted to interact with Nrf2. This study aims to explore whether targeting MALT1 can reduce I/R-induced ferroptosis via enhancing the Nrf2/SLC7A11 pathway. The SD rat hearts were subjected to 1h-ischemia plus 3h-reperfusion to establish the I/R injury model, which showed myocardial injuries (increase in infarct size and creatine kinase release) and up-regulation of MALT1 while downregulation of Nrf2 and SLC7A11 concomitant with the increased ferroptosis, reflecting by an increase in glutathione peroxidase 4 (GPX4) level while decreases in the levels of acyl-CoA synthetase long chain family member 4 (ACSL4), total iron, Fe2+ and lipid peroxidation (LPO); these phenomena were reversed in the presence of MI-2, a specific inhibitor of MALT1. Consistently, similar results were achieved in the cultured cardiomyocytes subjected to 8h-hypoxia plus 12h-reoxygenation. Furthermore, micafungin, an antifungal drug, could also exert beneficial effect on mitigating myocardial I/R injury via inhibition of MALT1. Based on these observations, we conclud that inhibition of MALT1 can reduce I/R-induced myocardial ferroptosis through enhancing the Nrf2/SLC7A11 pathway; and MALT1 may be used as a potential target to seek novel or existing drugs (such as micafungin) for treating myocardial infarction.

Resting-State EEG Connectivity at High-Frequency Bands and Attentional Performance Dysfunction in Stabilized Schizophrenia Patients.

Background and Objectives: Attentional dysfunction has long been viewed as one of the fundamental underlying cognitive deficits in schizophrenia. There is an urgent need to understand its neural underpinning and develop effective treatments. In the process of attention, neural oscillation has a central role in filtering information and allocating resources to either stimulus-driven or goal-relevant objects. Here, we asked if resting-state EEG connectivity correlated with attentional performance in schizophrenia patients. Materials and Methods: Resting-state EEG recordings were obtained from 72 stabilized patients with schizophrenia. Lagged phase synchronization (LPS) was used to measure whole-brain source-based functional connectivity between 84 intra-cortical current sources determined by eLORETA (exact low-resolution brain electromagnetic tomography) for five frequencies. The Conners' Continuous Performance Test-II (CPT-II) was administered for evaluating attentional performance. Linear regression with a non-parametric permutation randomization procedure was used to examine the correlations between the whole-brain functional connectivity and the CPT-II measures. Results: Greater beta-band right hemispheric fusiform gyrus (FG)-lingual gyrus (LG) functional connectivity predicted higher CPT-II variability scores (r = 0.44, p < 0.05, corrected), accounting for 19.5% of variance in the CPT-II VAR score. Greater gamma-band right hemispheric functional connectivity between the cuneus (Cu) and transverse temporal gyrus (TTG) and between Cu and the superior temporal gyrus (STG) predicted higher CPT-II hit reaction time (HRT) scores (both r = 0.50, p < 0.05, corrected), accounting for 24.6% and 25.1% of variance in the CPT-II HRT score, respectively. Greater gamma-band right hemispheric Cu-TTG functional connectivity predicted higher CPT-II HRT standard error (HRTSE) scores (r = 0.54, p < 0.05, corrected), accounting for 28.7% of variance in the CPT-II HRTSE score. Conclusions: Our study indicated that increased right hemispheric resting-state EEG functional connectivity at high frequencies was correlated with poorer focused attention in schizophrenia patients. If replicated, novel approaches to modulate these networks may yield selective, potent interventions for improving attention deficits in schizophrenia.

Effects of comorbid alcohol use disorder on bipolar disorder: Focusing on neurocognitive function and inflammatory markers.

BACKGROUND: Alcohol use disorder (AUD) is a highly prevalent comorbid disorder in patients with bipolar disorder (BD). Both BD and AUD were found to be associated with inflammation and cognitive deficits, but few study has been done on BD comorbid with AUD (BD+AUD). We aimed to investigate the impacts of comorbid AUD and BD on cognitive function, inflammatory and neurotrophic markers. METHOD: We recruited 641 BD patients, 150 patients with BD+AUD, and 185 healthy controls (HC). Neuropsychological tests [Wisconsin card sorting test (WCST), continuous performance test (CPT), and Wechsler memory scale - third edition (WMS-III)] and cytokine plasma levels [tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), interleukin-8 (IL-8), transforming growth factor-ß1 (TGF-ß1), and brain-derived neurotrophic factor (BDNF)] were assessed. RESULTS: BD+AUD patients had worse cognitive performance than those without AUD. There was a significant difference in the plasma levels of TNF-α, IL-8, and BDNF (P < 0.001, <0.001, and 0.01, respectively) between the patients and the HC groups. Post hoc analysis showed that BD+AUD patients had higher levels of TNF-α and IL-8 than BD-only patients (P < 0.001). Additionally, plasma IL-8 levels were negatively associated with number of completed categories in WCST (P = 0.02), and TNF-α levels were negatively associated with visual immediate index in WMS-III (P = 0.05). CONCLUSION: Our results suggest that comorbid AUD and BD might worsen cognitive impairments and inflammatory processes. Further longitudinal studies on BD+AUD may be needed.

Pharmacotherapy May Attenuate the Risk of Child Abuse in Attention-Deficit/Hyperactivity Disorder from the Real-World Evidence.

Objective: Psychiatric disorders, including attention-deficit/hyperactivity disorder (ADHD), may serve as a risk factor for child abuse. Methods: This study aimed to evaluate the association between children and adolescents with ADHD diagnosis and the risk of child abuse. The effectiveness of a pharmacological intervention on reducing the risk of child abuse was also assessed. A nationwide, population-based, retrospective with a matched-cohort study design was used. Data were from the National Health Insurance Research Database of Taiwan over a 15-year period (2000-2015). Results: Increased risk of child abuse in the ADHD group was noticed and the adjusted hazard ratio (HR) was 1.797 (95% confidence interval [CI] = 1.245-2.388, p < 0.001). The Kaplan-Meier analysis showed a significantly higher cumulative incidence in the ADHD group over the 15-year period (Log-rank test p < 0.001). ADHD patients with other psychiatric comorbidities had a higher risk of child abuse. Pharmacological treatment of either methylphenidate or atomoxetine was associated with a reduced risk of child abuse. The total adjusted HR was 1.466 (95% CI = 1.077-1.883, p < 0.001) in medicine group compared with the controls. Conclusions: ADHD was associated with a subsequent risk of child abuse in Taiwan. Pharmacological treatment could reduce the risk of child abuse in ADHD patients.

Effects of Early Risperidone Treatment on Metabolic Parameters in Socially Isolated Rats-Implication of Antipsychotic Intervention across Developmental Stages of Schizophrenia.

BACKGROUND: Second-generation antipsychotics (SGAs) is thought responsible for the metabolic abnormalities of schizophrenic patients, however, some untreated schizophrenic patients had already developed problems with glucose metabolism. The present study examined the hypothesis that schizophrenia itself but not risperidone, an extensively employed SGA, is accountable for metabolic abnormalities. METHODS: A 56-day risperidone regimen (1 mg/kg/day) was employed for rats of social isolation rearing (SIR) beginning at different developmental stage (28 or 56 days after weaning, i.e., adolescent and young adulthood, respectively). Metabolic parameters including body weight, systolic blood pressure (SBP), triglyceride, high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol, and plasma glucose were measured at baseline, 28, and 56 days of the regimen. Oral glucose tolerance test (OGTT) was performed at the end of the regimen. Insulin function was evaluated by area under the curve (AUC) of OGTT, homeostasis model assessment-insulin resistance (HOMA-ir), and Matsuda index. RESULTS: Our results demonstrated that: (i) SIR rats presented higher body weight, plasma triglyceride, and HOMA-ir than social controls. (ii) Higher insulin resistance was specifically presented in young adult rather than adolescent SIR rats. (iii) Adolescent drugged rats showed a lower level of LDL in day 28 of the regimen than young adult. Risperidone led to a lower LDL level in only young adult IR rats in day 56 than undrugged rats. (iv) SIR-induced dysregulation of insulin can be reversed by chronic risperidone treatment beginning at adolescence but not young adulthood. CONCLUSIONS: Our findings support the primary role of schizophrenia in metabolic abnormalities and risperidone appear beneficial when administered earlier.

Online Left-Hemispheric In-Phase Frontoparietal Theta tACS Modulates Theta-Band EEG Source-Based Large-Scale Functional Network Connectivity in Patients with Schizophrenia: A Randomized, Double-Blind, Sham-Controlled Clinical Trial.

EEG studies indicated that schizophrenia patients had increased resting-state theta-band functional connectivity, which was associated with negative symptoms. We recently published the first study showing that theta (6 Hz) transcranial alternating current stimulation (tACS) over left prefrontal and parietal cortices during a working memory task for accentuating frontoparietal theta-band synchronization (in-phase theta-tACS) reduced negative symptoms in schizophrenia patients. Here, we hypothesized that in-phase theta-tACS can modulate theta-band large-scale networks connectivity in schizophrenia patients. In this randomized, double-blind, sham-controlled trial, patients received twice-daily, 2 mA, 20-min sessions of in-phase theta-tACS for 5 consecutive weekdays (n = 18) or a sham stimulation (n = 18). Resting-state electroencephalography data were collected at baseline, end of stimulation, and at one-week follow-up. Exact low resolution electromagnetic tomography (eLORETA) was used to compute intra-cortical activity. Lagged phase synchronization (LPS) was used to measure whole-brain source-based functional connectivity across 84 cortical regions at theta frequency (5-7 Hz). EEG data from 35 patients were analyzed. We found that in-phase theta-tACS significantly reduced the LPS between the posterior cingulate (PC) and the parahippocampal gyrus (PHG) in the right hemisphere only at the end of stimulation relative to sham (p = 0.0009, corrected). The reduction in right hemispheric PC-PHG LPS was significantly correlated with negative symptom improvement at the end of the stimulation (r = 0.503, p = 0.039). Our findings suggest that in-phase theta-tACS can modulate theta-band large-scale functional connectivity pertaining to negative symptoms. Considering the failure of right hemispheric PC-PHG functional connectivity to predict improvement in negative symptoms at one-week follow-up, future studies should investigate whether it can serve as a surrogate of treatment response to theta-tACS.

Acute Mountain Sickness and the Risk of Subsequent Psychiatric Disorders-A Nationwide Cohort Study in Taiwan.

We aim to explore if there is a relationship between acute mountain sickness (AMS) and the risk of psychiatric disorders in Taiwan by using the National Health Insurance Research Database for to the rare studies on this topic. We enrolled 127 patients with AMS, and 1270 controls matched for sex, age, monthly insured premiums, comorbidities, seasons for medical help, residences, urbanization level, levels of care, and index dates were chosen from 1 January 2000 to 31 December 2015. There were 49 patients with AMS and 140 controls developed psychiatric disorders within the 16-year follow-up. The Fine-Gray model analyzed that the patients with AMS were prone to have a greater risk for the development of psychiatric disorders with an adjusted sub-distribution hazard ratio (sHRs) of 10.384 (95% confidence interval [CI]: 7.267-14.838, p < 0.001) for psychiatric disorders. The AMS group was associated with anxiety disorders, depressive disorders, bipolar disorder, sleep disorders, posttraumatic stress disorder/acute stress disorder, psychotic disorder, and substance-related disorder (SRD). The relationship between anxiety, depression, sleep disorders, SRD, and AMS still persisted even after we excluded the psychiatric disorders within the first five years after AMS. There was an association between AMS and the rising risk of psychiatric disorders in the 16 years of long-term follow-up research.

The association between hormone therapy and the risk of lung cancer in postmenopausal women: a 16-year nationwide population-based study.

OBJECTIVE: Although an association between hormone therapy (HT) and the risk of developing lung cancer has been reported, the results on the topic are inconsistent. Our study objective was to investigate whether postmenopausal women who undergo HT exhibit a risk of developing lung cancer. METHODS: In this matched cohort study, we obtained the data of 38,104 postmenopausal women older than 45 years who were treated using HT between 2000 and 2015 from Taiwan's National Health Insurance Research Database, and 152,416 matched participants who were not treated using HT were enrolled as controls at a 1:4 ratio. RESULTS: We used a Cox proportional hazards regression model to identify the risk of developing lung cancer during 16 years of follow-up, and the results indicate no significant difference in the proportion of postmenopausal women treated using HT ( P = 0.129) who developed lung cancer and that of those not treated using HT (0.866% [330 of 38,104] vs 0.950% [1,449 of 152,416]). After adjustment for age and other variables, the adjusted hazard ratio was 0.886 (95% CI, 0.666-1.305, P = 0.433), indicating no association between HT and lung cancer development in postmenopausal women. In a subgroup analysis, the risk of lung cancer was significantly lower in the women who were treated using HT when the HT cumulative dosage was ≥401 mg or when the therapy duration was ≥5 years compared with in those not treated using HT; the adjusted hazard ratios were 0.633 (95% CI, 0.475-0.930; P < 0.001) and 0.532 (95% CI, 0.330-0.934; P < 0.001), respectively, after adjustment. CONCLUSIONS: Our results indicate that HT is not associated with the risk of lung cancer development in postmenopausal women; furthermore, a higher cumulative dosage and the long-term effects of HT reduce the risk of developing lung cancer.

The association between abused adults and substance abuse in Taiwan, 2000-2015.

OBJECTIVE: To investigate whether adults suffering from violence were at risk of substance abuse and provides insight into the relationship between male and female abusers and substance abuse from 2000 to 2015 in Taiwan. METHODS: This study used data on outpatient, emergency, and inpatient visits for 2 million people enrolled in universal health insurance from 2000 to 2015. ICD-9 diagnosis codes 995.8 (abused adult) and E960-E969 (homicide and injury purposely inflicted by other persons) were defined in this case study, analyzing first-time violence in adults aged 18-64 (study group). Non-abused patients (control group) were matched in a 1:4 ratio, and the paired variables were gender, age (± 1 year), pre-exposure Charlson Comorbidity Index, and year of medical treatment. SAS 9.4 and Cox regression were used for data analysis. RESULTS: A total of 8,726 people suffered violence (control group: 34,904 people) over 15 years. The prevalence of substance abuse among victims of violence was 78.3/104, 61.9/104, and 51.5/104 for tobacco use disorder, alcoholism, and alcohol abuse, respectively. The risk (adults, overall) of drug abuse, drug dependence, and alcoholism after exposure to violence (average 9 years) was 7.47, 7.15, and 6.86 times (p < 0.01), respectively, compared with those without violence. The risk (adults, males) of drug abuse, drug dependence, and alcohol abuse after exposure to violence (average 9 years) was 6.85, 6.27, and 6.07 times, respectively, higher than those without violence (p < 0.01). Risks of drug dependence, alcohol abuse and alcoholism (adults, females) after exposure to violence (average 9 years) were 14.92, 12.26, and 11.55 times, respectively, higher than non-abused ones (p < 0.01). CONCLUSION: The risks of substance abuse, after adult violence, are higher than in those who have not suffered violent injuries.

Increased incidence of alcohol use disorder and alcohol-related psychiatric disorders in patients with obstructive sleep apnea: A nationwide population-based cohort study.

BACKGROUND: Obstructive sleep apnea (OSA) and alcohol-related diseases (ARDs), including alcohol use disorder, alcohol-related psychiatric disorders, alcoholic liver disease, alcoholic polyneuropathy alcoholic cardiomyopathy, and alcoholic gastritis, are both highly prevalent conditions. Alcohol consumption is associated with a higher risk of sleep apnea. However, whether OSA increases the risk of ARD has not, as yet, been studied comprehensively. Our study aimed to determine whether OSA increases the subsequent risk of ARD. METHODS: This study utilized the data from Taiwan's National Health Insurance Database between 2000 and 2015. We identified 7722 individuals newly diagnosed with OSA and randomly selected sex-, age-, and index date-matched (1:3) 22,166 controls without OSA, with a total of 29,888 subjects. We used the Fine and Gray's survival analysis to estimate the effects of OSA on ARD. RESULTS: The OSA cohort had an adjusted hazard ratio of subsequent ARDs as 1.486 (95% Confidence Interval: 1.301-1.698), when comparing the cohort without OSA. The Kaplan-Meier analysis showed that the cumulative incidence of ARDs was significantly higher in the OSA cohort than in the controls in the first year of follow-up, till the end of the follow-up. A post-hoc analysis showed that OSA was associated with alcohol use disorder, alcohol-related psychiatric disorders, and alcoholic liver disease, but not alcoholic polyneuropathy, alcoholic cardiomyopathy, and alcoholic gastritis. The use of psychoactive medication, including the sedative-hypnotics, antidepressants or antipsychotics were associated with a lower risk of ARDs. CONCLUSIONS: Our study demonstrates that the OSA patients are at a higher risk of developing ARDs.

Role of suPAR in the Pathogenesis of Podocyte Injury of Primary Focal Segmental Glomerulosclerosis / 中山大学学报(医学科学版)

ObjectiveThis study aims to investigate the role of suPAR in the pathogenesis of podocyte injury in FSGS. Methods① The sera of primary FSGS patients （17 cases） were collected. Healthy volunteers （10 cases） and patients with other types of primary nephrotic syndrome （10 cases） were set as normal and disease controls. SuPAR levels were detected by ELISA； ② Podocytes were stimulated by suPAR in vitro， and cells were collected to analyze apoptosis by flow cytometry and for RNAseq analysis； ③ Differentially expressed genes （DEGs） were screened from RNAseq data. Both up-regulated and down-regulated genes were analyzed by KEGG and GO enrichment analysis. Heat map was used to show expression of genes related to podocyte focal adhesion， slit diaphragm and actin dynamics and endocytosis. Differentially expressed genes were verified by qPCR. Results① The level of suPAR in FSGS patients was significantly increased， and that in other nephrotic syndrome（NS） patients was also significantly increased； ② suPAR stimulation significantly altered the transcriptome pattern of human podocytes. A total of 272 up-regulated genes and 288 down-regulated genes were screened； ③ KEGG and GO enrichment analysis of up-regulated and down-regulated genes showed that Focal adhesion and DNA replication and DNA repair related pathways were significantly down-regulated； ④ suPAR did not increase podocyte apoptosis. ConclusionThe level of suPAR is significantly increased in patients with primary FSGS. SuPAR may promote podocyte injury by interfering with genomic homeostasis and disrupting focal adhesion， slit diaphragm， actin dynamics and endocytosis-related functional molecules of podocytes.

High-Frequency Transcranial Random Noise Stimulation Modulates Gamma-Band EEG Source-Based Large-Scale Functional Network Connectivity in Patients with Schizophrenia: A Randomized, Double-Blind, Sham-Controlled Clinical Trial.

Schizophrenia is associated with increased resting-state large-scale functional network connectivity in the gamma frequency. High-frequency transcranial random noise stimulation (hf-tRNS) modulates gamma-band endogenous neural oscillations in healthy individuals through the application of low-amplitude electrical noises. Yet, it is unclear if hf-tRNS can modulate gamma-band functional connectivity in patients with schizophrenia. We performed a randomized, double-blind, sham-controlled clinical trial to contrast hf-tRNS (N = 17) and sham stimulation (N = 18) for treating negative symptoms in 35 schizophrenia patients. Short continuous currents without neuromodulatory effects were applied in the sham group to mimic real-stimulation sensations. We used electroencephalography to investigate if a five-day, twice-daily hf-tRNS protocol modulates gamma-band (33-45 Hz) functional network connectivity in schizophrenia. Exact low resolution electromagnetic tomography (eLORETA) was used to compute intra-cortical activity from regions within the default mode network (DMN) and fronto-parietal network (FPN), and functional connectivity was computed using lagged phase synchronization. We found that hf-tRNS reduced gamma-band within-DMN and within-FPN connectivity at the end of stimulation relative to sham stimulation. A trend was obtained between the change in within-FPN functional connectivity from baseline to the end of stimulation and the improvement of negative symptoms at the one-month follow-up (r = -0.49, p = 0.055). Together, our findings suggest that hf-tRNS has potential as a network-level approach to modulate large-scale functional network connectivity pertaining to negative symptoms of schizophrenia.

High-Frequency Transcranial Random Noise Stimulation over the Left Prefrontal Cortex Increases Resting-State EEG Frontal Alpha Asymmetry in Patients with Schizophrenia.

Reduced left-lateralized electroencephalographic (EEG) frontal alpha asymmetry (FAA), a biomarker for the imbalance of interhemispheric frontal activity and motivational disturbances, represents a neuropathological attribute of negative symptoms of schizophrenia. Unidirectional high-frequency transcranial random noise stimulation (hf-tRNS) can increase the excitability of the cortex beneath the stimulating electrode. Yet, it is unclear if hf-tRNS can modulate electroencephalographic FAA in patients with schizophrenia. We performed a randomized, double-blind, sham-controlled clinical trial to contrast hf-tRNS and sham stimulation for treating negative symptoms in 35 schizophrenia patients. We used electroencephalography to investigate if 10 sessions of hf-tRNS delivered twice-a-day for five consecutive weekdays would modulate electroencephalographic FAA in schizophrenia. EEG data were collected and FAA was expressed as the differences between common-log-transformed absolute power values of frontal right and left hemisphere electrodes in the alpha frequency range (8-12.5 Hz). We found that hf-tRNS significantly increased FAA during the first session of stimulation (p = 0.009) and at the 1-week follow-up (p = 0.004) relative to sham stimulation. However, FAA failed to predict and surrogate the improvement in the severity of negative symptoms with hf-tRNS intervention. Together, our findings suggest that modulating electroencephalographic frontal alpha asymmetry by using unidirectional hf-tRNS may play a key role in reducing negative symptoms in patients with schizophrenia.