Risk for stillbirth among pregnant individuals with SARS-CoV-2 infection varied by gestational age.

BACKGROUND: Despite previous research findings on higher risks of stillbirth among pregnant individuals with SARS-CoV-2 infection, it is unclear whether the gestational timing of viral infection modulates this risk. OBJECTIVE: This study aimed to examine the association between timing of SARS-CoV-2 infection during pregnancy and risk of stillbirth. STUDY DESIGN: This retrospective cohort study used multilevel logistic regression analyses of nationwide electronic health records in the United States. Data were from 75 healthcare systems and institutes across 50 states. A total of 191,403 pregnancies of 190,738 individuals of reproductive age (15-49 years) who had childbirth between March 1, 2020 and May 31, 2021 were identified and included. The main outcome was stillbirth at ≥20 weeks of gestation. Exposures were the timing of SARS-CoV-2 infection: early pregnancy (<20 weeks), midpregnancy (21-27 weeks), the third trimester (28-43 weeks), any time before delivery, and never infected (reference). RESULTS: We identified 2342 (1.3%) pregnancies with COVID-19 in early pregnancy, 2075 (1.2%) in midpregnancy, and 12,697 (6.9%) in the third trimester. After adjusting for maternal and clinical characteristics, increased odds of stillbirth were observed among pregnant individuals with SARS-CoV-2 infection only in early pregnancy (odds ratio, 1.75, 95% confidence interval, 1.25-2.46) and midpregnancy (odds ratio, 2.09; 95% confidence interval, 1.49-2.93), as opposed to pregnant individuals who were never infected. Older age, Black race, hypertension, acute respiratory distress syndrome or acute respiratory failure, and placental abruption were found to be consistently associated with stillbirth across different trimesters. CONCLUSION: Increased risk of stillbirth was associated with COVID-19 only when pregnant individuals were infected during early and midpregnancy, and not at any time before the delivery or during the third trimester, suggesting the potential vulnerability of the fetus to SARS-CoV-2 infection in early pregnancy. Our findings underscore the importance of proactive COVID-19 prevention and timely medical intervention for individuals infected with SARS-CoV-2 during early and midpregnancy.

Potential mechanisms of Shenmai injection against POCD based on network pharmacology and molecular docking.

BACKGROUND: As the population ages, the number of patients with postoperative cognitive dysfunction increases. This study aims to investigate the mechanisms of Shenmai injection as a therapeutic strategy for postoperative cognitive dysfunction using a network pharmacology approach. METHODS: Shenmai injection and its targets were retrieved from the Traditional Chinese Medicine Systems Pharmacology database. Postoperative cognitive dysfunction-associated protein targets were identified using the GeneCards and DisGeNET databases. Subsequently, a protein-protein interaction network was constructed using the String database. For treating postoperative cognitive dysfunction, the core targets of Shenmai injection were identified through topological analysis, followed by the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses performed for annotation. Molecular docking was performed on the screened core targets and components. RESULTS: One hundred and eighty-two related targets of Shenmai injection in treating postoperative cognitive dysfunction were identified. Eleven active ingredients in Shenmai injection were detected to have a close connection with postoperative cognitive dysfunction-related targets. Additionally, Gene Ontology analysis revealed 10 biological processes, 10 cellular components and 10 molecular functions. The Kyoto Encyclopedia of Genes and Genomes analysis identified 20 signaling pathways. The docking results indicated five active ingredients from Shenmai injection can fit in the binding pockets of all three candidate targets. CONCLUSIONS: Thus, the present work systematically explored the anti-postoperative cognitive dysfunction mechanism of potential targets and signaling pathways of Shenmai injection. These results provide an important reference for subsequent basic research on postoperative cognitive dysfunction.

Association of ABCG2 polymorphisms with susceptibility to anti-tuberculosis drug-induced hepatotoxicity in the Chinese population.

The accumulation of endogenous hepatotoxin protoporphyrin IX (PPIX) in the liver was proposed to be a novel mechanism of anti-tuberculosis drug-induced hepatotoxicity (ATDH). ATP-binding cassette transporter G2 (ABCG2) plays an important role in modulating PPIX concentrations. This study aimed to explore the role of ABCG2 genetic polymorphisms in the risk of ATDH in Chinese patients.A 1:4 matched case-control study was performed among 202 ATDH cases and 808 controls. Conditional logistic regression model was used to estimate the association between genotypes and the risk of ATDH by odds ratios (ORs) with 95% confidence intervals (CIs).Male patients with CC genotype of rs2622605 had an increased risk of ATDH (adjusted OR = 1.615, 95% CI: 1.119-2.332, p = 0.011). The peak value of alkaline phosphatase (ALP) was significantly higher in male patients with CC genotype of rs2622605 than in those with TT + TC genotype during antituberculosis treatment (102.0 U/L vs. 98.0 U/L, p = 0.029).This is the first attempt to evaluate the association between ABCG2 genetic variants and the risk of ATDH. Based on the 1:4 matched case-control study, the polymorphism at rs2622605 in the ABCG2 gene may be associated with the susceptibility to ATDH in Chinese male patients.

The role of the genetic variant FECH rs11660001 in the occurrence of anti-tuberculosis drug-induced liver injury.

WHAT IS KNOWN AND OBJECTIVE: The pathogenic mechanism of anti-tuberculosis drug-induced liver injury (AT-DILI) is still largely unknown. Recent studies have indicated that rifampicin and isoniazid cotreatment causes the accumulation of endogenous protoporphyrin IX in the liver through the haem biosynthesis pathway. Alanine synthase 1 (ALAS1) and ferrochelatase (FECH) are the rate-limiting enzymes in the production of haem. The present study aimed to investigate the genetic contribution of the ALAS1 and FECH genes to the risk of AT-DILI in an Eastern Chinese Han population. METHODS: A 1:4 matched case-control study was conducted, and eight SNPs in the ALAS1 and FECH genes were detected and assessed. A multivariate conditional logistic regression model was used to estimate the association between genotypes and the risk of AT-DILI by the odds ratios (ORs) with 95% confidence intervals (CIs), with liver disease history, hepatoprotectant use, smoking and drinking history as covariates. RESULTS AND DISCUSSION: Overall, 202 AT-DILI cases and 808 controls were included in this study. The female patients carrying polymorphisms of rs11660001 in FECH had an increased risk of AT-DILI under the dominant and additive models (OR = 1.831, 95% CI: 1.014-3.307, p = 0.045; OR = 1.673, 95% CI: 1.015-2.760, p = 0.044, respectively). The peak aspartate transaminase level was significantly higher in female patients carrying the GA+AA genotype of rs11660001 than in those with the GG genotype during anti-TB treatment (p = 0.032). WHAT IS NEW AND CONCLUSION: Based on this 1:4 individual matched case-control study, SNP rs11660001 in the FECH gene may be associated with susceptibility to AT-DILI in Chinese female anti-TB treatment patients. Further studies in larger varied populations are needed to validate our findings.

A validation study of the UGT1A4 rs2011404 variant and the risk of anti-tuberculosis drug-induced hepatotoxicity in an Eastern Chinese Han population.

WHAT IS KNOWN AND OBJECTIVE: Anti-tuberculosis (anti-TB) drug-induced hepatotoxicity (ATDH) is a serious adverse drug reaction. A recent study found that the rs2011404 variant of uridine 5'-diphospho-glucuronosyl-transferase 1A4 (UGT1A4) is a marker of susceptibility to ATDH. The present study aimed to validate this relationship in an Eastern Chinese Han anti-TB treatment population. METHODS: A 1:4 matched case-control study was conducted among anti-TB treatment patients in four regions of Jiangsu. ATDH was diagnosed based on the criteria from the Chinese Society of Hepatology and the updated Roussel Uclaf Causality Assessment Method. A conditional logistic regression model was used to estimate the association between rs2011404 genotypes and the risk of ATDH using odds ratios (ORs) with 95% confidence intervals (95% CIs) and smoking, drinking, hepatoprotectant use and liver diseases as covariates. RESULTS AND DISCUSSION: A total of 202 ATDH cases and 808 controls were matched according to age, sex and treatment history. After correcting for potential confounding factors, conditional logistic regression analysis indicated no significant differences in genotypes between the two groups (CC vs. TC: OR = 0.933, 95% CI: 0.457-1.905, p = 0.849). Subgroup analysis suggested that patients carrying the CC genotype at rs2011404 in UGT1A4 were at a reduced risk of moderate or severe liver injury (OR = 0.293, 95% CI: 0.093-0.921, p = 0.036). WHAT IS NEW AND CONCLUSION: Based on a 1:4 individual matched case-control study, possessing the CC genotype at rs2011404 of the UGT1A4 gene reduces the risk of moderate or severe liver injury in Eastern Chinese Han patients receiving anti-TB treatment. Further research is warranted to explain the role of the UGT1A4 gene and its contribution to individual differences in susceptibility to ATDH.

Association between early treatment with Qingfei Paidu decoction and favorable clinical outcomes in patients with COVID-19: A retrospective multicenter cohort study.

The coronavirus disease 2019 (COVID-19) epidemic has been almost controlled in China under a series of policies, including "early diagnosis and early treatment". This study aimed to explore the association between early treatment with Qingfei Paidu decoction (QFPDD) and favorable clinical outcomes. In this retrospective multicenter study, we included 782 patients (males, 56 %; median age 46) with confirmed COVID-19 from 54 hospitals in nine provinces of China, who were divided into four groups according to the treatment initiation time from the first date of onset of symptoms to the date of starting treatment with QFPDD. The primary outcome was time to recovery; days of viral shedding, duration of hospital stay, and course of the disease were also analyzed. Compared with treatment initiated after 3 weeks, early treatment with QFPDD after less than 1 week, 1-2 weeks, or 2-3 weeks had a higher likelihood of recovery, with adjusted hazard ratio (HR) (95 % confidence interval [CI]) of 3.81 (2.65-5.48), 2.63 (1.86-3.73), and 1.92 (1.34-2.75), respectively. The median course of the disease decreased from 34 days to 24 days, 21 days, and 18 days when treatment was administered early by a week (P < 0.0001). Treatment within a week was related to a decrease by 1-4 days in the median duration of hospital stay compared with late treatment (P<0.0001). In conclusion, early treatment with QFPDD may serve as an effective strategy in controlling the epidemic, as early treatment with QFPDD was associated with favorable outcomes, including faster recovery, shorter time to viral shedding, and a shorter duration of hospital stay. However, further multicenter, prospective studies with a larger sample size should be conducted to confirm the benefits of early treatment with QFPDD.

Enhancement of toughness of SiC through compositing SiC-Al interpenetrating phase composites.

Silicon carbide has excellent properties such as high hardness and decomposition temperature, but its applications are limited by its poor toughness. Here, we investigate the enhancement of SiC's toughness by compositing silicon carbide-aluminum (SiC-Al) interpenetrating phase composites (IPCs) via molecular dynamics simulations. IPCs are a class of composites consisting of two or more phases that are topologically continuous and three-dimensionally interconnected through the microstructure. The Young's modulus and ultimate strength gradually increases with an increment of the volume fraction of SiC, opposite to the fracture strain. The interface between SiC and Al affects the mechanical properties of SiC-Al IPCs. When the volume fraction of SiC is less than 0.784, the attenuation rate of ultimate strength and fracture strain decreases. The attenuation rate increases when the volume fraction of SiC is more than 0.784. There are a minimum of ultimate strength and fracture strain at the 0.784, 0.7382 and 2.8610, respectively. The hardness of SiC-Al IPCs is about 48% of SiC. The change of SiC-Al IPCs hardness is more stable than that of SiC in the later stage of the nanoindentation test.

Current health status and history of traumatic brain injury among Ohio adults.

INTRODUCTION: Lifetime history of traumatic brain injury (TBI) with loss of consciousness (LOC) is prevalent in 21% of adult, non-institutionalised residents of Ohio. Prior history has been associated with lower incomes, inability to work and disability. The current study sought to evaluate the relationship between lifetime history and adverse health conditions. METHODS: Data came from the 2014 Ohio Behavioral Risk Factors Surveillance System, which included a state-specific module eliciting lifetime history of TBI. RESULTS: Non-institutionalised adults living in Ohio who have had at least one TBI with LOC were more likely to report fair or poor health, more days of poor health, more days when poor health limited activities, being diagnosed with a chronic condition and having less than 7 hours of sleep per night. The relationship with increasing number of TBIs was monotonic, with the likelihood of adverse health increasing as the number increased. A similar relationship was observed for increasing severity of the worst lifetime TBI. Experiencing a first TBI before age 15 was associated with poorer health but was not statistically different than incurring a first after age 15. CONCLUSIONS: Adults who have experienced TBI with LOC in their lifetime are two to three times more likely to experience adverse health conditions when compared with same age-matched, sex-matched and race-matched adults without such history. These findings support re-examining the public health burden of TBI in light of lifetime exposure and not just the consequences of an index injury.

Lifetime History of Traumatic Brain Injury and Behavioral Health Problems in a Population-Based Sample.

OBJECTIVE: To investigate the relationships between indices of lifetime history of traumatic brain injury (TBI) exposure and measures of behavioral health status among Ohioans. PARTICIPANTS: A random sample (n = 6996) of Ohioans contacted to complete the 2014 Ohio Behavioral Risk Factors Surveillance System (BRFSS). DESIGN: A cross-sectional survey. MAIN MEASURES: The Ohio State University TBI Identification Method adapted for BRFSS module and BRFSS behavioral indicators. RESULTS: After demographic adjustment, lifetime history of TBI was found to be associated with increased odds of binge drinking, heavy drinking, smoking, a depressive disorder, or mental health not being good (≥2 days and ≥14 days in last 30 days). Mixed findings across behavioral indicators were observed in regard to number and severity of injury. Age at first injury showed no remarkable associations with the behavioral health indicators. CONCLUSIONS: Ohioans who have sustained at least one TBI with loss of consciousness in their lifetime are at increased risk for poor behavioral health, including alcohol misuse, smoking, and depression. The findings underscore the need for community-based mental health treatment programs to screen for TBI history in their intake evaluations, and to train clinicians on the provisions of accommodations for cognitive and behavioral deficits.

Association of ABO blood group and antituberculosis drug-induced liver injury: A case-control study from a Chinese Han population.

WHAT IS KNOWN AND OBJECTIVE: Antituberculosis drug-induced liver injury (ATLI) is a serious adverse drug reaction, and its pathogenic mechanism is still largely unknown. Rifampin (RIF) has been reported to cause haemolysis due to the production of drug-dependent antibodies, and haemolysis results in an increased level of free haem, which affects the function of hepatocytes. Blood group determinants can act as specific receptor sites for drug-antibody complexes, causing erythrocyte destruction in the presence of RIF. RIF-induced immune haemolysis may be a potential mechanism for ATLI. Thus, the study aimed to explore the role of ABO blood group systems in Chinese ATLI patients. METHODS: A 1:4 matched case-control study was conducted among 146 ATLI cases and 584 controls. Multivariable conditional logistic regression and Cox proportional regression were used to estimate the association between ABO blood group and risk of ATLI by odds ratio (OR), hazards ratio (HR) and 95% confidence intervals (CIs), and liver disease history and taking hepatoprotectant were used as covariates. RESULTS AND DISCUSSION: Patients in the A, B, AB and non-O blood groups had a significantly higher risk of ATLI than those in the O blood group (OR = 1.832, 95% CI: 1.126-2.983, P = .015; OR = 1.751, 95% CI: 1.044-2.937, P = .034; OR = 2.059, 95% CI: 1.077-3.938, P = .029; OR = 1.822, 95% CI: 1.173-2.831, P = .007, respectively). After considering the time of ALTI occurrence, similar results were found in the A, B, AB and non-O blood groups (HR = 1.676, 95% CI: 1.072-2.620, P = .024; HR = 1.620, 95% CI: 1.016-2.584, P = .043; HR = 2.010, 95% CI: 1.130-3.576, P = .018; HR = 1.701, 95% CI: 1.138-2.542, P = .010, respectively). Furthermore, subgroup analysis also detected a significant association between ABO blood group and ATLI in patients taking RIF (P < .05). However, no significant difference was observed in patients not taking RIF (P > .05). WHAT IS NEW AND CONCLUSION: The present study is the first to evaluate the role of ABO blood group systems in Chinese ATLI cases. Based on the present matched case-control study, the ABO blood group may be associated with susceptibility to ATLI in the Chinese antituberculosis population, especially in patients with blood groups A, B and AB who are taking RIF.

Differences in Postinjury Psychological Symptoms Between Collegiate Athletes With Concussions and Orthopedic Injuries.

OBJECTIVE: To describe the differences in postinjury psychological symptoms among Division I collegiate student athletes who sustained concussions versus orthopedic injures and to examine the effects of injury type on postinjury psychological symptoms during the course of recovery. DESIGN: A prospective cohort study with repeated measures. SETTING: Two Big 10 Conference universities. PARTICIPANTS: Student athletes who were at least 18 years old and participated in one of 9 National Collegiate Athletic Association (NCAA) Division I-sponsored sports during the 2007 to 2011 seasons. MAIN OUTCOME MEASURES: Baseline depressive symptoms and anxiety were measured at enrollment. On identification of an eligible injury, follow-up surveys were conducted among injured athletes at multiple intervals until the injured athlete returned to play. Depressive symptoms, anxiety, fear of return-to-play, and fear of reinjury were measured at the postinjury follow-ups. RESULTS: The concussion group had significantly lower scores of fear of return-to-play (B = -0.94, P = 0.0278) and fear of reinjury (B = -1.11, P = 0.0152) compared with the orthopedic injury group. The concussion group scored higher on depressive symptoms than the orthopedic injury group at 1 month after injury (P = 0.0264), although both groups scored similarly at baseline (P = 0.9729) and at 1 week after injury (P = 0.1475). CONCLUSIONS: Patterns of psychological disturbance differ after concussions and orthopedic injures. Further research is warranted to identify the factors contributing to these differences and to develop effective intervention programs to prevent these symptoms.

Association of FAM65B, AGBL4, and CUX2 genetic polymorphisms with susceptibility to antituberculosis drug-induced hepatotoxicity: validation study in a Chinese Han population.

OBJECTIVE: Antituberculosis (anti-TB) drug-induced hepatotoxicity (ATDH) is a serious adverse drug reaction, and its pathogenic mechanism has not been elucidated thoroughly to date. A recent genome-wide association study reported that seven single-nucleotide polymorphisms (SNPs) in the family with sequence similarity 65, member B gene (FAM65B), ATP/GTP-binding protein-like 4 gene (AGBL4), and cut-like homeobox 2 gene (CUX2) were associated strongly with ATDH in Ethiopian patients. We validated this relationship in a Chinese Han anti-TB treatment population. PATIENTS AND METHODS: A 1 : 2 matched case-control study was carried out of 235 ATDH cases and 470 controls. Multivariate conditional logistic regression analysis was used to estimate the association between genotypes and risk of ATDH by odds ratios with 95% confidence intervals, and weight and hepatoprotectant use were used as covariates. RESULTS: Patients with a polymorphism at rs10946737 in the FAM65B gene were at an increased risk of moderate and severe liver injury under the dominant model (adjusted odds ratio=2.147, 95% confidence interval: 1.067-4.323, P=0.032). No other genotypes or genetic risk scores were found to be significantly related to ATDH. CONCLUSION: This is the first study to explore and validate the relationships between seven SNPs in the FAM65B, AGBL4, and CUX2 genes and ATDH in a Chinese population. On the basis of this case-control study, SNP rs10946737 in FAM65B may be associated with susceptibility to ATDH in Chinese Han anti-TB treatment patients. Further research is warranted to explain the role of the FAM65B gene and its contribution toward individual differences in susceptibility to ATDH.

Relevance of NAT2 genotype to anti-tuberculosis drug-induced hepatotoxicity in a Chinese Han population.

BACKGROUND: Anti-tuberculosis drug-induced hepatotoxicity (ATDH) is a serious adverse drug reaction. The slow acetylator status of N-acetyl transferase 2 (NAT2) is a well-established risk factor for ATDH. One novel tagging single nucleotide polymorphism (tagging SNP), rs1495741, in NAT2 has been found to be highly predictive of the NAT2 phenotype. The present study aimed to validate the relationships between tagging SNP rs1495741 and ATDH in a Chinese Han population. METHODS: A 1:2 matched case-control study was conducted using 235 ATDH cases and 470 controls. Conditional or unconditional logistic regression analysis was used to estimate the association between genotypes and the risk of ATDH according to the odds ratio (OR) with a 95% confidence interval (CI). RESULTS: Patients carrying the AA genotype of tagging SNP rs1495741 were at higher risk of ATDH than those carrying the GG genotype (OR = 1.653, 95% CI = 1.050-2.601; p = 0.030). Subgroup analysis suggested that the AA genotype was a risk factor for ATDH in patients aged older than 50 years (OR = 2.486, 95% CI = 1.313-4.706; p = 0.005), weighing over 50 kg (OR = 1.757, 95% CI = 1.016-3.038; p = 0.044) or using a hepatoprotectant (OR = 1.611, 95% CI = 1.009-2.572; p = 0.046). Tagging SNP rs1495741 was not a significant risk factor for moderate and severe hepatotoxicity but appears to be relevant to risk of mild hepatotoxicity specifically. CONCLUSIONS: The present study is the first to validate the relationships between the tagging SNP rs1495741 and ATDH in a Chinese population. Based on this case-control study, the NAT2 rs1495741 polymorphism is a risk factor for mild but not more severe ATDH in Chinese Han patients.

Initial Emergency Department Visit and Follow-Up Care for Concussions among Children with Medicaid.

OBJECTIVE: To describe the rates and patterns of initial emergency department (ED) encounters and follow-up care for concussions among Medicaid-insured children before and after the 2013 enactment of Ohio concussion law. STUDY DESIGN: Using a time-series design, this study analyzed concussion claim data obtained from Partners for Kids, a pediatric accountable-care organization in Ohio. A total of 12 512 concussions and 48 238 associated claims for services between January 1, 2008, and June 30, 2017, with an initial ED encounter among Medicaid-insured children (ages 0-18 years) were analyzed. The effect of the law on the odds of follow-up care were assessed using generalized estimating equations models, adjusted for sex, age group, and residence location. RESULTS: Of the total 12 512 concussions, 63.9% occurred in male patients, 70.1% in patients ages 10-18 years, and 65.2% in patients from urban areas. The rate of initial ED encounters for concussions increased from 2008 to 2014 (2.8 to 4.9 per 10 000 members), followed by a decrease in 2016 (4.2 per 10 000 members). A significant increase in follow-up care after the initial ED encounter was observed from pre-law to post-law (OR 1.73, 95% CI 1.61, 1.86). A shift in follow-up care was observed from radiology and ambulance services in pre-law to primary care providers in post-law. CONCLUSIONS: The Ohio concussion law may have influenced the patterns of initial ED visit and follow-up care for concussions among Medicaid-insured children. Future studies evaluating the impact of the law should analyze the utilization patterns among children with various insurance/payment types.

Impact of CYP2R1, CYP27A1 and CYP27B1 genetic polymorphisms controlling vitamin D metabolism on susceptibility to hepatitis C virus infection in a high-risk Chinese population.

CYP27A1, CYP2R1 and CYP27B1 hydroxylases are involved in the synthesis of 1, 25-hydroxyvitamin D3, which plays a role in the immune regulation and pathogenesis of hepatitis C virus (HCV) infection. The aim of the present study was to investigate the relationships between polymorphisms in vitamin D pathway genes and HCV infection outcomes in a Chinese population. Nine single-nucleotide polymorphisms (SNPs) of CYP27A1, CYP2R1 and CYP27B1 were genotyped in a high-risk Chinese population. The distributions of these SNPs were compared among groups with different outcomes of HCV infection, including 863 cases of persistent HCV infection, 524 cases of spontaneous clearance, and 1079 uninfected controls. The results showed that the CYP2R1 rs12794714-G, rs10741657-A, rs1562902-C, and rs10766197-G alleles were significantly associated with increased susceptibility to HCV infection (all PFDR < 0.05, in additive/dominant models), and the combined effect of the four unfavorable alleles was related to an elevated risk of HCV infection in a locus-dosage manner (Ptrend = 0.008). Moreover, haplotype analysis suggested that, compared with the most frequent haplotype (Ars12794714Grs10741657Trs1562902Ars10766197), the haplotype containing four unfavorable alleles, GACG, was associated with a higher risk of HCV infection. The results of our study suggest that genetic variants in CYP2R1 may be biomarkers for predicting the susceptibility to HCV infection in the Chinese population.

Possible association of HMOX1 and NQO1 polymorphisms with anti-tuberculosis drug-induced liver injury: A matched case-control study.

WHAT IS KNOWN AND OBJECTIVE: Reactive metabolites from anti-tuberculosis (anti-TB) drugs can result in abnormal accumulation of reactive oxygen species (ROS), which plays an important role in anti-TB drug-induced liver injury (ATLI). Liver cells could keep the production of ROS in balance by antioxidant activities. The heme oxygenase 1, encoded by the HMOX1 gene and NADH:quinone oxidoreductase 1, encoded by the NQO1 gene are crucial mediators of cellular defense against ROS. The present study aimed to investigate the associations between HMOX1 and NQO1 polymorphisms and ATLI in Chinese anti-TB treatment population. METHODS: A matched case-control study was conducted using 314 ATLI cases and 628 controls. Multivariate conditional logistic regression analysis was used to estimate the association between genotypes and risk of ATLI by the odds ratios (ORs) with 95% confidence intervals (CIs), with weight and use of hepatoprotectant as covariates. RESULTS AND DISCUSSION: Patients carrying the GG genotype at rs2071748 in HMOX1 were at a higher risk of ATLI than those with the AA genotype (adjusted OR = 1.503, 95% CI: 1.005-2.249, P = 0.047), and significant differences were also found under the recessive (P = 0.015) and additive (P = 0.045) models. Subgroup analysis confirmed the relationship in mild hepatotoxicity cases under the recessive and additive models (adjusted OR = 1.714, 95% CI: 1.169-2.513, P = 0.006; adjusted OR = 1.287, 95% CI: 1.015-1.631, P = 0.037, respectively). WHAT IS NEW AND CONCLUSION: This is the first study to explore the relationship between HMOX1, NQO1 polymorphisms and ATLI in Chinese anti-TB treatment population. Based on a matched case-control study, genetic polymorphisms of HMOX1 may be associated with susceptibility to ATLI in the Chinese population.

Characteristics and Costs of Pediatric Emergency Department Visits for Sports- and Recreation-Related Concussions, 2006-2014.

BACKGROUND: Although concussion-related emergency department (ED) visits increased after the passage of concussion laws, little is known about how the laws may disproportionately impact ED utilization and associated health care costs among children in different demographic groups. OBJECTIVE: Our aim was to examine the patient and clinical characteristics of pediatric ED visits and associated health care costs for sports- and recreation-related concussions (SRRCs) before and after concussion law enactment. METHODS: We retrospectively analyzed ED visits for SRRCs by children ages 5-18 years between 2006 and 2014 in the Pediatric Health Information System database (n = 123,220). ED visits were categorized as "pre-law," "immediate post-law," and "post-law" according to the respective state concussion law's effective date. Multinomial logistic regression models were used to assess the impact of the law on ED utilization. RESULTS: The majority of visits were by males (n = 83,208; 67.6%), children aged 10-14 years (n = 49,863; 40.9%), and privately insured patients (n = 62,376; 50.6%). Female sex, older age, and insured by Medicaid/Medicare were characteristics associated with increased ED visits during the immediate post-law and post-law periods compared to their counterparts. A significant decrease in proportion of imaging use was observed from pre-law to post-law (adjusted odds ratio 0.49; 95% confidence interval 0.47-0.50; p < 0.0001). While annual adjusted costs per ED visits decreased, annual total adjusted costs per hospital for SRRCs increased from pre-law to post-law (p < 0.0001). CONCLUSIONS: Concussion laws might have impacted pediatric concussion-related ED utilization, with increased annual total adjusted costs. These results may have important implications for policy interventions and their effects on health care systems.

Concussion clinic presentation and symptom duration for pediatric sports-related concussions following Ohio concussion law.

In 2013, Ohio enacted a law to mitigate consequences of pediatric sports-related concussions. This study aimed to describe changes in clinic visits and symptom duration for pediatric sports-related concussions before and after this law. 3,133 new visits by 2,861 unique patients (10-18 years) presenting between April 2012 and April 2015 for sports-related concussions within 30 days of injury were included. There were 937 (29.9%), 1,132 (36.1%) and 1,064 (34.0%) concussion visits for pre-law, immediate-post law, and post-law periods, respectively. A greater proportion of concussion visits was observed among females from pre-law to post-law (P < 0.0001). No differences were observed across the three periods in symptom scores at injury (P = 0.5028) or at first clinic visit (P = 0.5686). However, patients presented to concussion clinics significantly earlier (17.6 vs. 22.8 days, P < 0.0001) and had quicker recovery (26.5 vs. 40.6 days, P < 0.0001) post-law than pre-law.

CysLTR1 Blockage Ameliorates Liver Injury Caused by Aluminum-Overload via PI3K/AKT/mTOR-Mediated Autophagy Activation in Vivo and in Vitro.

Aluminum (Al) is a trivalent cation that can accumulate in animal organs, especially in the liver. We previously demonstrated that Al-overload could induce liver morphologic aberrations and dysfunction. However, the molecular mechanism underlying liver injury caused by Al-overload still remains unknown. In the present study, we investigated the relationship between leukotrienes receptors and the PI3K/AKT/mTOR pathway in Al-induced liver injury in vivo and in vitro. We demonstrated that Al-overload significantly increased the protein expression levels of CysLTR1, PI3K, AKT, mTOR, and p62, while significantly decreasing the LC3BII protein levels in rat liver; thus, suggesting that the autophagy process was inhibited in Al-overloaded rat liver. In addition, MK-571, an inhibitor of CysLTR1, effectively protected the human hepatocyte L02 cells against injury caused by Al exposure. Moreover, CysLTR1 blockage could significantly down-regulate the PI3K/AKT/mTOR pathway and activate autophagy. The effect of MK-571 on cell viability was abolished by the treatment with the autophagy inhibitor (wortmannin) but not with the autophagy agonist (rapamycin). Taken together, our results indicated that the blockage of the leukotriene receptor of CysLTR1 promotes autophagy and further reduces hepatocyte death through the PI3K/AKT/mTOR pathway inhibition. CysLTR1 thus could represent a potential target for the new drug development for chronic noninfective liver injury.

Trends in Pediatric Emergency Department Utilization for Mild Traumatic Brain Injury Before and After Legislation.

OBJECTIVE: To examine the effect of state youth traumatic brain injury (TBI) legislation on pediatric emergency department (ED) utilization for sports and recreation-related mild TBIs (mTBIs). PARTICIPANTS: ED visits by children ages 5 to 18 years between 2006 and 2014 in the Pediatric Health Information System database (N = 452 900). DESIGN: Retrospective analysis. MAIN MEASURES: Rates of ED visits, and injury comparison groups (mTBI, moderate to severe TBI, minor head injury, and long bone fracture). RESULTS: Of the 452 900 ED visits, 123 192 (27.2%) were for mTBI, along with visits for moderate to severe TBIs (n = 5190), minor head injuries (n = 54 566), and long bone fractures (n = 269 952). ED visits for mTBIs were more common among males (67.5%), children ages 10-14 years (42.1%), and the privately insured (50.6%). The proportion of mTBI ED visits increased significantly, particularly from 5 years prelegislation to immediately postlegislation (57.8 to 94.8 mTBI visits per 10 000 ED visits). A similar trend was observed for minor head injuries; however, no significant changes were observed for moderate to severe TBIs and long bone fractures. CONCLUSION: Pediatric ED utilization trends for the injury comparison groups differed from each other, and from pre- and post-TBI legislation. Further research assessing effects of TBI legislation on healthcare utilization is warranted.