Pharmacologically significant constituents collectively responsible for anti-sepsis action of XueBiJing, a Chinese herb-based intravenous formulation.

Sepsis, a life-threatening health issue, lacks effective medicine targeting the septic response. In China, treatment combining the intravenous herbal medicine XueBiJing with conventional procedures reduces the 28-day mortality of critically ill patients by modulating septic response. In this study, we identified the combined active constituents that are responsible for the XueBiJing's anti-sepsis action. Sepsis was induced in rats by cecal ligation and puncture (CLP). The compounds were identified based on their systemic exposure levels and anti-sepsis activities in CLP rats that were given an intravenous bolus dose of XueBiJing. Furthermore, the identified compounds in combination were assessed, by comparing with XueBiJing, for levels of primary therapeutic outcome, pharmacokinetic equivalence, and pharmacokinetic compatibility. We showed that a total of 12 XueBiJing compounds, unchanged or metabolized, circulated with significant systemic exposure in CLP rats that received XueBiJing. Among these compounds, hydroxysafflor yellow A, paeoniflorin, oxypaeoniflorin, albiflorin, senkyunolide I, and tanshinol displayed significant anti-sepsis activities, which involved regulating immune responses, inhibiting excessive inflammation, modulating hemostasis, and improving organ function. A combination of the six compounds, with the same respective doses as in XueBiJing, displayed percentage survival and systemic exposure in CLP rats similar to those by XueBiJing. Both the combination and XueBiJing showed high degrees of pharmacokinetic compatibility regarding interactions among the six active compounds and influences of other circulating XueBiJing compounds. The identification of XueBiJing's pharmacologically significant constituents supports the medicine's anti-sepsis use and provides insights into a polypharmacology-based approach to develop medicines for effective sepsis management.

Neuroprotective Effects of Leptin on the APP/PS1 Alzheimer's Disease Mouse Model: Role of Microglial and Neuroinflammation.

Background: Microglia are closely linked to Alzheimer's disease (AD) many years ago; however, the pathological mechanisms of AD remain unclear. The purpose of this study was to determine whether leptin affected microglia in the hippocampus of young and aged male APP/PS1 mice. Objective: In a transgenic model of AD, we investigated the association between intraperitoneal injection of leptin and microglia. Methods: We intraperitoneal injection of leptin (1mg/kg) every day for one week and analyzed inflammatory markers in microglia in the hippocampus of adult (6 months) and aged (12 months) APP/PS1 mice. Results: In all leptin treatment group, the brain Aß levels were decrease. We found increased levels of IL-1ß, IL-6 and microglial activation in the hippocampus of adult mice. Using aged mice as an experimental model for chronic neuroinflammation and leptin resistance, the number of Iba-1+ microglia and the levels of IL-1ß/IL-6 in the hippocampus were greatly increased as compared to the adult. But between the leptin treatment and un-treatment, there were no difference. Conclusion: Leptin signaling would regulate the activation of microglia and the release of inflammatory factors, but it is not the only underlying mechanism in the neuroprotective effects of AD pathogenesis.

Seasonal flexibility of the gut structure and physiology in Eremias multiocellata.

Although gut seasonal plasticity has been extensively reported, studies on physiological flexibility, such as water-salt transportation and motility in reptiles, are limited. Therefore, this study investigated the intestinal histology and gene expression involved in water-salt transport (AQP1, AQP3, NCC, and NKCC2) and motility regulation (nNOS, CHRM2, and ADRB2) in desert-dwelling Eremias multiocellata during winter (hibernating period) and summer (active period). The results showed that mucosal thickness, the villus width and height, the enterocyte height of the small intestine, and the mucosal and submucosal thicknesses of the large intestine were greater in winter than in summer. However, submucosal thickness of the small intestine and muscularis thickness of the large intestine were lower in winter than in summer. Furthermore, AQP1, AQP3, NCC, nNOS, CHRM2, and ADRB2 expressions in the small intestine were higher in winter than in summer; AQP1, AQP3, and nNOS expressions in the large intestine were lower in winter than in summer, with the upregulation of NCC and CHRM2 expressions; no significant seasonal differences were found in intestinal NKCC2 expression. These results suggest that (i) intestinal water-salt transport activity is flexible during seasonal changes where AQP1, AQP3 and NCC play a vital role, (ii) the intestinal motilities are attenuated through the concerted regulation of nNOS, CHRM2, and ADRB2, and (iii) the physiological flexibility of the small and large intestine may be discrepant due to their functional differences. This study reveals the intestinal regulation and adaptation mechanisms in E. multiocellata in response to the hibernation season.

Bacterial communities during composting cultivation of oyster mushroom Pleurotus floridanus using broken eggs as the nitrogen source and study of agronomic and nutritional properties.

Introduction: Broken eggs are a byproduct of the poultry industry and a potential nitrogen source for mushroom cultivation. However, its feasibility needs to be evaluated experimentally. Methods: In this study, a series of different addition amounts (0, 1.8, 3.6, 5.3 and 8.5%, w/w) of broken egg mixture (BEM) were applied in the composting cultivation process of oyster mushroom. The physicochemical properties and bacterial communities of composting substrate, and agronomic and nutritional properties of fruiting bodies were determined. Results and discussion: The results showed that the BEM addition significantly (P < 0.05) increased the total nitrogen content in the composted substrate, and the contents of crude protein, total amino acids and essential amino acids of mushrooms. The P3 treatment (initial C/N of 26:1) showed the highest biological efficiency (BE) of 100.19% and a low contamination rate (CR) of 7.00%, while the higher dosage of BEM (P4 and P5) led to a sharp decrease in BE and a sharp increase in CR. High throughput sequencing revealed that the addition of BEM significantly (P < 0.05) changed the bacterial communities in the substrate at the beginning of composting. Streptococcus and Lactococcus were predominant bacterial genera in BEM treatments at the beginning stage of composting, while Acinetobacter became predominant at the ending stage. The co-occurrence network analysis showed that the P3 treatment demonstrated a much more complex bacterial community. The structural equation model analysis indicated that the addition of BEM affected the bacterial communities and nitrogen metabolism during composting, which further affected agronomic and nutritional properties of oyster mushrooms. An appropriate amount of BEM combined with composting processes can significantly improve the yield and quality of oyster mushroom, providing a new way for efficient utilization of BEM.

Five-year remission without disease progression in a patient with relapsed/refractory multiple myeloma with extramedullary disease treated with LCAR-B38M chimeric antigen receptor T cells in the LEGEND-2 study: a case report.

BACKGROUND: Multiple myeloma remains incurable despite treatment advancements over the last 20 years. LCAR-B38M Cells in Treating Relapsed/Refractory Multiple Myeloma was a phase 1, first-in-human, investigator-initiated study in relapsed/refractory multiple myeloma conducted at four sites in China. The study used LCAR-B38M chimeric antigen receptor-T cells expressing two B-cell maturation antigen-targeting single-domain antibodies designed to confer avidity, and a CD3ζ signaling domain with a 4-1BB costimulatory domain to optimize T-cell activation and proliferation. This chimeric antigen receptor construct is identical to ciltacabtagene autoleucel. In the LEGEND-2 study (n = 57, Xi'an site), overall response rate was 88%; median (95% CI) progression-free survival and overall survival were 19.9 (9.6-31.0) and 36.1 (26.4-not evaluable) months, respectively; and median follow-up was 25 months. This case study reports on a patient with relapsed/refractory multiple myeloma (λ light chain type) who was treated with LCAR-B38M chimeric antigen receptor T cells in the LEGEND-2 study (Xi'an site); he had received five prior lines of treatment and had extensive extramedullary lesions. CASE PRESENTATION: The patient, a 56-year-old Asian male, received cyclophosphamide (500 mg daily × 3 days) as lymphodepletion therapy and a total dose of 0.5 × 106 chimeric antigen receptor + T cells/kg split into three infusions (days 1, 24, and 84 from June to August 2016). He experienced grade 2 cytokine release syndrome after the first infusion; all symptoms resolved with treatment. No cytokine release syndrome occurred following the second and third infusions. His λ light chain levels decreased and normalized 20 days after the first infusion, and extramedullary lesions were healed as of January 2018. He has sustained remission for 5 years and received no other multiple myeloma treatments after LCAR-B38M chimeric antigen receptor T cell infusion. As of 30 October 2020, the patient is still progression-free and has maintained minimal residual disease-negative (10-4) complete response status for 52 months. CONCLUSIONS: This case provides support that treatment with LCAR-B38M chimeric antigen receptor T cells can result in long-term disease remission of 5 or more years without disease progression in a heavily pretreated patient with extensive extramedullary disease and no other treatment options.

CoNoT: Coupled Nonlinear Transform-Based Low-Rank Tensor Representation for Multidimensional Image Completion.

Recently, the transform-based tensor nuclear norm (TNN) methods have shown promising performance and drawn increasing attention in tensor completion (TC) problems. The main idea of these methods is to exploit the low-rank structure of frontal slices of the tensor under the transform. However, the transforms in TNN methods usually treat all modes equally and do not consider the different traits of different modes (i.e., spatial and spectral/temporal modes). To address this problem, we suggest a new low-rank tensor representation based on the coupled nonlinear transform (called CoNoT) for a better low-rank approximation. Concretely, spatial and spectral/temporal transforms in the CoNoT, respectively, exploit the different traits of different modes and are coupled together to boost the implicit low-rank structure. Here, we use the convolutional neural network (CNN) as the CoNoT, which can be learned solely from an observed multidimensional image in an unsupervised manner. Based on this low-rank tensor representation, we build a new multidimensional image completion model. Moreover, we also propose an enhanced version (called Ms-CoNoT) to further exploit the spatial multiscale nature of real-world data. Extensive experiments on real-world data substantiate the superiority of the proposed models against many state-of-the-art methods both qualitatively and quantitatively.

Preoperative computed tomography-guided localization for multiple lung nodules: a Meta-analysis.

PURPOSE: Approximately 20% of patients with lung nodules (LNs) have multiple LNs (MLNs). This meta-analysis was performed to assess the safety and efficacy of computed tomography (CT)-guided localization of MLNs in comparison with those of single LN (SLN) localization. MATERIAL AND METHODS: The PubMed, Embase, and Cochrane Library were searched to collect relevant articles published till February 2022. The meta-analysis was performed using the RevMan v5.3. RESULTS: In total, seven studies met the inclusion criteria for this meta-analysis. No significant difference was observed between patients with MLNs and SLN in terms of pooled successful localization rate based on LNs (p = 0.64) and patients (p = 0.06). The pooled duration of localization was significantly shorter and the pooled pneumothorax and lung hemorrhage rates were significantly lower in the SLN group than in the MLNs group (p < 0.00001 for all). The pooled duration of hospital stay was comparable between the MLNs and SLN groups (p = 0.96). Significant heterogeneity was observed in the endpoints of duration of localization (I2 = 75%) and pneumothorax (I2 = 53%). CONCLUSIONS: CT-guided simultaneous MLN localization is clinically safe and effective, despite requiring a longer procedural time and having higher incidence of pneumothorax and lung hemorrhage than SLN localization.

Comparison between coil and hook-wire localization before video-assisted thoracoscopic surgery for lung nodules: a systematic review and meta-analysis.

Introduction: Both coil and hook-wire localization techniques are commonly employed prior to video-assisted thoracic surgery (VATS) resection in patients with lung nodules (LNs), but the relative advantages of each remain uncertain. Aim: This meta-analysis was performed to explore the relative safety and efficacy of coil localization (CL) and hook-wire localization (HWL) for patients with LNs. Material and methods: The PubMed, Embase, Cochrane Library, Wanfang, and CINK databases were searched to identify relevant studies published as of February 2022, after which pooled analyses of study outcomes were conducted. Results: In total, 8 studies met the inclusion criteria for the present meta-analysis. Successful localization rates were higher for the CL group relative to the HWL group (p = 0.0001). The CL group additionally exhibited significantly lower pooled total complication, pneumothorax, and lung hemorrhage rates relative to the HWL group (p = 0.01, p = 0.0001, p = 0.0009). Pooled duration of localization, VATS procedure duration, and wedge resection duration values were comparable in both groups (p = 0.69, p = 0.16, p = 0.76), as were chest pain scores (p = 0.06). When specifically analyzing the subset of patients with ground-glass LNs, pooled pneumothorax rates were significantly lower in the CL group relative to the HWL group (p = 0.03). Significant publication bias was detected with respect to rates of lung hemorrhage (Egger test, p = 0.029), but was not evident for other analyzed variables. Conclusions: These results suggest that the coil-based localization of LNs before VATS resection is safer and more effective than hook-wire localization.

Seasonal flexibility of kidney structure and factors regulating water and salt in Eremias multiocellata.

Although sodium and water reabsorption by the kidney plays a major role in maintaining body fluid homeostasis, the seasonal response of renal morphology and the factors involved in water and salt regulation are not well known, especially in reptiles. Eremias multiocellata is a typical desert-dwelling lizard. Here, we compared water and salt regulation of E. multiocellata in winter (hibernation), spring (emerging from hibernation), and summer (active) according to histomorphometry and the expression of genes such as those encoding aquaporins (AQP1, AQP2, AQP3), the Na+-Cl- cotransporter (NCC), the Na+-K+-2Cl- cotransporter (NKCC2), renin (Ren), angiotensin II receptor type 2 (AT2R), and endothelial nitric oxide synthase (eNOS) in the kidneys. The results showed that the area of Bowman's capsule and the glomerular density were lower in winter compared to summer and spring, and the lumen size of the DCT, PCT, and IS was greater in spring than in summer. Compared to summer and spring, the expression of AQP1, AQP3, NCC, NKCC2, Ren, and eNOS was significantly decreased in winter, whereas the expression of AQP2 and AT2R remained high. These results indicate that E. multiocellata balances its water budget via morpho-functional changes in different seasons. Although renal function was temporarily attenuated during winter, the regulation of aquaporins genes was not synchronous, indicating the complexity and particularity of water and salt regulation in desert lizards when facing the constraints of harsh environmental conditions, seasonal variations, and hibernation. These results will enrich the understanding of water and salt regulation mechanisms in desert reptiles.

Four-year follow-up of LCAR-B38M in relapsed or refractory multiple myeloma: a phase 1, single-arm, open-label, multicenter study in China (LEGEND-2).

BACKGROUND: LCAR-B38M is a chimeric antigen receptor T cell product with two binding domains targeting B cell maturation antigen. Our previous reports showed a remarkable efficacy of LCAR-B38M in patients with relapsed/refractory multiple myeloma (RRMM) at a median follow-up of 2 years. Here, we report long-term safety and efficacy data from a median follow-up of 4 years. METHODS: LEGEND-2 was a phase 1, single-arm, open-label study conducted in four registered sites in China. Seventy-four participants with RRMM received LCAR-B38M treatment. Lymphodepletion was performed using cyclophosphamide or cyclophosphamide plus fludarabine. LCAR-B38M, at a median dose of 0.513 × 106 cells/kg, was intravenously administered either in three split infusions or in a single infusion. The primary objective was the safety of LCAR-B38M, and the secondary objective was efficacy. RESULTS: As of May 25, 2021, the median follow-up was 47.8 months. All patients experienced ≥ 1 adverse events (AEs). Grade ≥ 3 AEs were observed in 45/74 (60.8%) patients. Cytokine release syndrome (CRS) occurred in 68/74 (91.9%) cases; 7 (9.5%) had grade ≥ 3 CRS. One patient experienced grade 1 central nervous system toxicity. The overall response rate was 87.8%. Fifty-four out of 74 (73.0%) patients achieved complete response. The median progression-free survival was 18.0 months, and the median overall survival for all patients was not reached. The median duration of response was 23.3 months. Four patients experienced viral infection more than 6 months post-infusion, and four patients developed second primary non-hematological malignancies at a median time of 11.5 months post-CAR-T cell transfer. CONCLUSIONS: The 4-year follow-up data of LCAR-B38M therapy demonstrated a favorable long-term safety profile and a durable response in patients with RRMM. Trial registration Clinicaltrials.gov NCT03090659 (retrospectively registered on March 27, 2017); ChiCTR-ONH-17012285.

Heat shock protein 90α in nipple discharge as a potential tumor marker for breast cancer.

Heat shock protein 90α (HSP90α) has been confirmed to be upregulated in the blood in various types of tumors and may therefore serve as a potential tumor marker. However, whether HSP90α exists in nipple discharge remains unknown, and its expression and diagnostic value in nipple discharge remain unclear. In this study, the expression of HSP90α, carcinoembryonic antigen (CEA), and cancer antigen 153 in nipple discharge and blood from 128 patients was measured. Receiver operating characteristic curve was used to assess the diagnostic value of HSP90α. Further, its relationship with clinicopathological parameters of patients with breast cancer was analyzed. The results showed that the expression of HSP90α in nipple discharge was significantly higher in patients with breast cancer than in those with benign disease, and its diagnostic value was better than that of CEA. Combination of HSP90α and CEA showed better diagnostic efficacy than HSP90α or CEA alone. Moreover, the expression of HSP90α displayed a stepwise increase from benign lesions, followed by carcinoma in situ to invasive ductal carcinoma. HSP90α was positively correlated with Ki67 expression. However, there was no significant difference in the expression of HSP90α in blood between patients with breast cancer and benign disease. Further, the expression of HSP90α was higher in nipple discharge than in blood. In summary, HSP90α was upregulated in the nipple discharge of patients with breast cancer, and it may be related to the occurrence and progression of breast cancer. HSP90α in nipple discharge may serve as a potential diagnostic marker for breast cancer.

Longitudinal association between movement behaviours and depressive symptoms among adolescents using compositional data analysis.

BACKGROUND: Research examining the associations between movement behaviours and mental health indicators within a compositional framework are sparse and limited by their cross-sectional study design. This study has three objectives. First, to describe the change in movement behaviour composition over time. Second, to explore the association between change in movement behaviour composition and change in depressive symptoms. Third, to explore how reallocations of time between movement behaviours are associated with changes in depressive symptoms. METHODS: Longitudinal data of 14,620 students in grades 9-12 (mean age: 14.9 years) attending secondary schools in Canada (Ontario, British Columbia, Alberta, Quebec) were obtained from two waves (2017/18, 2018/19) of the COMPASS study. Moderate-to-vigorous physical activity (MVPA), recreational screen time, and sleep duration were self-reported. Depressive symptoms were measured using the Center for Epidemiologic Studies Depression Scale (Revised)-10 (CESD-R-10). Compositional data analyses using pivot coordinates and compositional isotemporal substitution for longitudinal data were used to analyse the data. Analyses accounted for school clustering, were stratified by gender and age (< or ≥ 15 years), and were adjusted for race/ethnicity, body mass index z-score, baseline movement behaviour composition, and baseline depressive symptoms. RESULTS: There were significant differences in movement behaviour composition over time across all subgroups. For example, the relative contributions of MVPA and sleep duration to the movement behaviour composition decreased over time while screen time increased among younger boys and girls and older girls. Increasing sleep duration relative to the remaining behaviours (i.e. screen time and MVPA) was associated with lower depressive symptoms among all subgroups. Increasing screen time relative to the remaining behaviours (i.e. MVPA and sleep duration) was associated with higher depressive symptoms among all subgroups. Increasing MVPA relative to the remaining behaviours (i.e. screen time and sleep duration) was associated with lower depressive symptoms in older girls only. Isotemporal substitution estimates indicated that decreasing screen time by 60 minutes/day and replacing that time with 60 minutes of additional sleep is associated with the largest change in depressive symptoms across all subgroups. CONCLUSIONS: Findings from this prospective analysis suggest that increased sleep duration and reduced screen time are important determinants of lower depressive symptoms among adolescents.

Comprehensive analysis of the transcriptional expressions and prognostic value of S100A family in pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) remains a treatment-refractory malignancy with poor prognosis. It is urgent to identify novel and valid biomarkers to predict the progress and prognosis of PDAC. The S100A family have been identified as being involved in cell proliferation, migration and differentiation progression of various cancer types. However, the expression patterns and prognostic values of S100As in PDAC remain to be analyzed. METHODS: We investigated the transcriptional expressions, methylation level and prognostic value of S100As in PDAC patients from the Oncomine, GEPIA2, Linkedomics and cBioPortal databases. Real-time PCR was used to detect the expressions of S100A2/4/6/10/14/16 in four pancreatic cancer cell lines and pancreatic cancer tissues from PDAC patients undergoing surgery. To verify the results further, immunohistochemistry was used to measure the expression of S100A2/4/6/10/14/16 in 43 PDAC patients' tissue samples. The drug relations of S100As were analyzed by using the Drugbank database. RESULTS: The results suggested that, the expression levels of S100A2/4/6/10/14/16 were elevated to PDAC tissues than in normal pancreatic tissues, and the promoter methylation levels of S100A S100A2/4/6/10/14/16 in PDAC (n = 10) were lower compared with normal tissue (n = 184) (P < 0.05). In addition, their expressions were negatively correlated with PDAC patient survival. CONCLUSIONS: Taken together, these results suggest that S100A2/4/6/10/14/16 might be served as prognostic biomarkers for survivals of PDAC patients.

The impact of providing personalized depression risk information on self-help and help-seeking behaviors: Results from a mixed methods randomized controlled trial.

OBJECTIVES: To evaluate the impact of providing personalized depression risk information on self-help and help-seeking behaviors among individuals who are at high risk of having a major depressive episode (MDE). MATERIALS AND METHODS: In a mixed methods randomized controlled trial, participants who were at high risk of having a MDE, were recruited from across Canada, and were randomized into intervention (n = 358) and control (n = 354) groups. Participants in the intervention group received their personalized depression risk estimated by sex-specific risk prediction models for MDE. All participants were assessed at baseline, 6 and 12 months. RESULTS: Repeated measure mixed effects modeling showed significant between group differences in self-help scores. In the complete case analysis, the between group difference in mean self-help change score was 1.13 at 12 months (effect size = 0.16). Among participants who reported "fair" or "poor health," the between group difference in mean self-help change score was 2.78 at 12 months (effect size = 0.35). The qualitative data revealed three themes and the findings are consistent with the quantitative results. CONCLUSIONS: Providing personalized depression risk information has a positive impact on self-help in high-risk individuals, particularly in those with poor health.

Multi-Dimensional Visual Data Completion via Low-Rank Tensor Representation Under Coupled Transform.

This paper addresses the tensor completion problem, which aims to recover missing information of multi-dimensional images. How to represent a low-rank structure embedded in the underlying data is the key issue in tensor completion. In this work, we suggest a novel low-rank tensor representation based on coupled transform, which fully exploits the spatial multi-scale nature and redundancy in spatial and spectral/temporal dimensions, leading to a better low tensor multi-rank approximation. More precisely, this representation is achieved by using two-dimensional framelet transform for the two spatial dimensions, one/two-dimensional Fourier transform for the temporal/spectral dimension, and then Karhunen-Loéve transform (via singular value decomposition) for the transformed tensor. Based on this low-rank tensor representation, we formulate a novel low-rank tensor completion model for recovering missing information in multi-dimensional visual data, which leads to a convex optimization problem. To tackle the proposed model, we develop the alternating directional method of multipliers (ADMM) algorithm tailored for the structured optimization problem. Numerical examples on color images, multispectral images, and videos illustrate that the proposed method outperforms many state-of-the-art methods in qualitative and quantitative aspects.

Rationale and Methodology of the 2018 Canadian Armed Forces Members and Veterans Mental Health Follow-up Survey (CAFVMHS): A 16-year Follow-up Survey: Raison D'être Et Méthodologie De L'enquête De Suivi Sur La Santé Mentale Des Membres Des Forces Armées Canadiennes Et Des Anciens Combattants, 2018 (ESSMFACM).

OBJECTIVE: Knowledge is limited regarding the longitudinal course and predictors of mental health problems, suicide, and physical health outcomes among military and veterans. Statistics Canada, in collaboration with researchers at the University of Manitoba and an international team, conducted the Canadian Armed Forces Members and Veterans Mental Health Follow-Up Survey (CAFVMHS). Herein, we describe the rationale and methods of this important survey. METHOD: The CAFVMHS is a longitudinal survey design with 2 time points (2002 and 2018). Regular Force military personnel who participated in the first Canadian Community Health Survey Cycle 1.2-Mental Health and Well-Being, Canadian Forces Supplement (CCHS-CFS) in 2002 (N = 5,155) were reinterviewed in 2018 (n = 2,941). The World Mental Health Survey-Composite International Diagnostic Interview was used with the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) criteria. RESULTS: The CAFVMHS includes 2,941 respondents (66% veterans; 34% active duty) and includes data on mental disorder diagnoses, physical health conditions, substance use, medication use, general health, mental health services, perceived need for care, social support, moral injury, deployment experiences, stress, physical activity, military-related sexual assault, childhood experiences, and military and sociodemographic information. CONCLUSIONS: The CAFVMHS provides a unique opportunity to further understand the health and well-being of military personnel in Canada over time to inform intervention and prevention strategies and improve outcomes. The data are available through the Statistics Canada Research Data Centres across Canada and can be used cross-sectionally or be longitudinally linked to the 2002 CCHS-CFS data.

MicroRNA-145 plays a role in mitochondrial dysfunction in alveolar epithelial cells in lipopolysaccharide-induced acute respiratory distress syndrome.

BACKGROUND: Acute respiratory distress syndrome (ARDS) causes substantial mortalities. Alveolar epithelium is one of the main sites of cell injuries in ARDS. As an important kind of microRNAs (miRNAs), microRNA-145 (miR-145) has been studied in various diseases, while its role in ARDS has not been investigated. METHODS: Lipopolysaccharide (LPS) was intratracheally instilled to establish a rat ARDS model. Cytokines from bronchoalveolar lavage fluid (BALF) were measured using rat tumor necrosis factor-α and interleukin-6 enzyme-linked immunosorbent assay kits (R&D Systems), and the pathological structures were evaluated using hematoxylin and eosin (H&E) staining and transmission electron microscope; the lung miR-145 messenger RNA (mRNA) was detected using quantitative polymerase chain reaction. Bioinformatics focused on the target genes and possible pathways of gene regulation. RESULTS: A rat model of LPS-induced ARDS was successfully established. The miR-145 was down-regulated in the LPS-induced ARDS lung, and mitochondrial dysfunction was observed in alveolar epithelial cells, most obviously at 72 hours after LPS. TargetScan and miRDB databases were used to predict the target genes of miR-145. A total of 428 overlapping genes were identified, seven genes were associated with mitochondrial function, and Ogt, Camk2d, Slc8a3, and Slc25a25 were verified. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were enriched in the mitogen-activated protein kinase (MAPK) signaling pathway, and Gene Ontology (GO) biological process was mainly enriched in signal transduction and transcription regulation. CONCLUSIONS: The miR-145 is down-regulated in LPS-induced ARDS, and affects its downstream genes targeting mitochondrial functions.

Artificial neural network predicts hemorrhagic contusions following decompressive craniotomy in traumatic brain injury.

BACKGROUND: This study aimed to explore relevant factors of hemorrhagic contusions following decompressive craniotomy (DC) in traumatic brain injury (TBI) and create an artificial neural network (ANN) prediction model of the risk factors of hemorrhagic contusions. METHODS: This study analyzed 425 patients with TBI who underwent DC in the Neurosurgery Department of Shaoxing People's Hospital between 2009 and 2014. Patients were divided into two groups according to the first postoperative CT scans: hemorrhage group and non-hemorrhage group. Gender, age, preoperative situations (Initial Rotterdam CT Score, GCS Score, pupillary response, laboratory data and preoperative hematoma), the time gap between trauma and DC, postoperative CT scans, and Glasgow Outcome Scale (GOS) scores were recorded. ANN was used to predict hematoma. Correlation analysis was used to state the relationship between increased hemorrhage volumes and GOS scores. RESULTS: The ANN prediction model was established. This model included 11 parameters: initial Rotterdam CT score, GCS score, C-reactive protein, age, the time gap between trauma and DC, pupillary response, platelet count, bone-flap size, glucose level, hernia magnitude and preoperative hematoma volume. The overall predictive accuracy of the model was 73.0%. CONCLUSIONS: Initial Rotterdam CT scores and GCS scores may predict the risk of expansion contusions following DC. The ANN prediction model has a high accuracy to forecast hemorrhage.

Clinical staging for youth at-risk for serious mental illness: A longitudinal perspective.

OBJECTIVE: The objective of this study was to identify a sample of youth in distinct stages of risk for the development of a serious mental illness (SMI) according to a published clinical staging model and to follow this sample longitudinally to determine clinical changes over time. This article reports the 6- and 12-month follow-up of the cohort. METHODS: This study recruited 243 youth, ages 12 to 25. The sample included (a) 42 healthy controls, (b) 41 nonhelpseeking individuals with no mental illness but some risk of SMI, for example, having a first-degree relative with an SMI (stage 0), (c) 53 youth experiencing distress and mild symptoms of anxiety or depression (stage 1a), and (d) 107 youth with attenuated symptoms of SMIs such as bipolar disorder or psychosis (stage 1b). Participants completed a range of measures assessing depression, anxiety, mania, suicide ideation, attenuated psychotic symptoms, negative symptoms, anhedonia and beliefs about oneself at baseline, 6- and 12-months. RESULTS: There were few changes for healthy controls and stage 0 participants, although approximately 7% did move to a symptomatic stage within 12-months. Of stage 1a participants, 50% remained symptomatic, with 7.5% moving to stage 1b or developing a SMI. Approximately 9% of stage 1byouth developed a SMI within 12-months and approximately one-third had remission of symptoms during the follow-up. CONCLUSIONS: Results suggest that the implementation of a transdiagnostic staging model may be useful in youth mental health and support consideration of clinical stage-based treatment for youth with early features of risk.

Functional imaging in youth at risk for transdiagnostic serious mental illness: Initial results from the PROCAN study.

BACKGROUND: In their early stages, serious mental illnesses (SMIs) are often indistinguishable from one another, suggesting that studying alterations in brain activity in a transdiagnostic fashion could help to understand the neurophysiological origins of different SMI. The purpose of this study was to examine brain activity in youth at varying stages of risk for SMI using functional magnetic resonance imaging tasks (fMRI) that engage brain systems believed to be affected. METHODS: Two hundred and forty three participants at different stages of risk for SMI were recruited to the Canadian Psychiatric Risk and Outcome (PROCAN) study, however only 179 were scanned. Stages included asymptomatic participants at no elevated risk, asymptomatic participants at elevated risk due to family history, participants with undifferentiated general symptoms of mental illness, and those experiencing attenuated versions of diagnosable psychiatric illnesses. The fMRI tasks included: (1) a monetary incentive delay task; (2) an emotional Go-NoGo and (3) an n-back working memory task. RESULTS: Strong main effects with each of the tasks were found in brain regions previously described in the literature. However, there were no significant differences in brain activity between any of the stages of risk for SMI for any of the task contrasts, after accounting for site, sex and age. Furthermore, results indicated no significant differences even when participants were dichotomized as asymptomatic or symptomatic. CONCLUSIONS: These results suggest that univariate BOLD responses during typical fMRI tasks are not sensitive markers of SMI risk and that further study, particularly longitudinal designs, will be necessary to understand brain changes underlying the early stages of SMI.