Health-related quality of life with rivaroxaban plus aspirin vs. aspirin alone in chronic stable cardiovascular disease: Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) trial

AIMS: This study aimed to compare the effects of the combination of rivaroxaban and aspirin with aspirin alone on health-related quality of life in the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) trial. METHODS and results: Health-related quality of life assessed using the EQ-5D-3L. The treatment effects on health utility and EQ visual analogue scale (EQ VAS) scores were compared between rivaroxaban plus aspirin and aspirin alone in terms of adjusted mean difference in change from baseline and odds ratio of having deterioration events. Nine thousand forty-nine (98.9%) and 6916 (75.5%) completed the EQ-5D-3L at baseline and at final visit, respectively. Nine thousand twenty-eight (98.9%) and 6887 (76.3%) completed the EQ-5D-3L at baseline and final visit, respectively. Mean (standard deviation) health utility and EQ VAS scores at baseline were 0.871 (0.141) and 76.0 (15.3), respectively, for the rivaroxaban plus aspirin group, compared with 0.873 (0.139) and 75.8 (15.1) for the aspirin group. Adjusted mean difference in change from baseline utility was -0.002 [95% confidence interval (CI), -0.006, 0.002, P = 0.30] between the combination therapy group and the aspirin group. The odds ratio (95% CI) of experiencing deterioration in health utility was 1.01 (95% CI, 0.93, 1.10, P = 0.81) between the two groups. Adjusted mean difference in change from baseline EQ VAS was 0.02 (95% CI, -0.43, 0.47, P = 0.93) between the two groups. CONCLUSION: This analysis of the COMPASS trial demonstrated that the quality of life of patients was similar between the rivaroxaban plus aspirin group and the aspirin alone group. REGISTRATION: Trial registration number: ClinicalTrials.gov number (NCT01776424). Trial protocol and statistical analysis plan: https://www.nejm.org/doi/full/10.1056/NEJMoa1709118#APPNEJMoa1709118PRO.

Exploration of the mechanism underlying the therapeutic effect of electroacupuncture at chengshan acupoint on post-hemorrhoidectomy anal pain: Insights from the mAChRs/IP3-Ca2+-CaM signaling pathway.

OBJECTIVE: In the context of postoperative anal pain, understanding the intricate mechanisms and effective interventions is paramount. This study investigates the role of Muscarinic Acetylcholine Receptors (mAChRs) and the IP3-Ca2+-CaM signaling pathway in a rat model of postoperative anal pain, exploring the potential analgesic effects of electroacupuncture. METHODS: Comprehensive approaches involving mechanical sensitivity assays, Western blotting, immunohistochemistry, and intracellular calcium concentration measurement were used. RESULTS: The authors found elevated mAChRs expression in the postoperative pain model. Antagonizing mAChRs reduced pain sensitivity and attenuated the IP3-Ca2+-CaM pathway. Remarkably, electroacupuncture treatment further mitigated pain, potentially by suppressing this signaling cascade. INTERPRETATION: These findings reveal a novel connection between mAChRs and the IP3-Ca2+-CaM pathway in postoperative anal pain and suggest electroacupuncture as a promising avenue for pain relief through these mechanisms, offering insights into innovative strategies for postoperative pain management.

Significance of concurrent evaluation of HER2 gene amplification and p53 and Ki67 expression in gastric cancer tissues.

OBJECTIVE: The primary objective of this study is to explore the significance of concurrent evaluation of HER2 gene amplification and p53 and Ki67 expression in gastric cancer tissues. METHODS: Fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) methodologies were used to detect HER2 gene amplification, as well as the expression levels of HER2, p53, and Ki67 proteins, across a group of 78 gastric cancer cases. RESULTS: The expression rate of the HER2 protein was determined to be 43.6% (34/78), with 17.9% (14/78) categorized as HER2 protein 3 + , 14.1% (11/78) as HER2 protein 2 + , and 11.5% (9/78) as HER2 protein 1 + . Using FISH technology, the HER2 gene amplification rate was identified as 19.2% (15/78), including 3 cases of HER2 gene cluster amplification, 5 cases of large granular amplification, 4 cases of punctate amplification, and 3 cases of high polysomy. The positive rate of p53 in gastric cancer cells was 52.6% (41/78), with 62.8% (49/78) of patients exhibiting a ki67 proliferation index ≤ 30, and 37.2% (29/78) accounting for a ki67 proliferation index > 30. The expression rates of the HER2 gene, p53, and ki67 in gastric cancer tissues were significantly associated with both gastric cancer staging and lymph node metastasis (P < 0.05). CONCLUSION: The HER2 gene amplification rate and gene copy number exhibit a positive correlation with the expression rates of p53 and ki67. Combining these assessments can provide crucial insights into the assessment of metastatic potential, disease progression, and prognosis of gastric tumor cells. This holds paramount importance in steering the formulation of individualized treatment strategies.

Assessing clinical pathological characteristics and gene expression patterns associated with hepatoid adenocarcinoma of the stomach.

OBJECTIVE: The objective of this study is to assess the clinical pathological attributes of Hepatoid Adenocarcinoma of the Stomach (HAS) and to delineate the differential diagnostic considerations about it. METHOD: The investigation involved analyzing 31 HAS cases using histomorphological assessment, immunohistochemical profiling, and relevant gene detection methodologies. RESULTS: Among the 31 HAS cases, 9 (29.0%) were of trabecular hepatoid adenocarcinoma of the stomach, 7 (22.6%) were of glandular hepatoid adenocarcinoma of the stomach, 4 (12.9%) were of nesting hepatoid adenocarcinoma of the stomach, 3 (9.7%) were of clear cell hepatoid adenocarcinoma of the stomach, and 8 (25.8%) were of diverse hepatoid adenocarcinoma of the stomach. Of these 31 cases, 24 were male, accounting for 77.4% of the cases. Serum alpha-fetoprotein (AFP) levels were notably elevated, with radioimmunoassay results reaching 1240 ng/ml; 28 out of 31 cases had AFP levels below 25 µg/l, accounting for 90.3%. Related genes: HER2 protein indicated positive expression on the cell membrane in 35.5% (11/31) of the cases; HER2 gene amplification detected by the FISH technique was 12.9% (4/31). Tumoral stromal lymphocytes exhibited a PD-1 positive expression rate of 58.1% (18/31). In gastric cancer tissues, the PD-L1 positive rate was 45.1% (14/31). CONCLUSION: HAS represents a distinctive subtype of gastric cancer with a propensity for mimicking other forms of tumors, underscoring the significance of discerning its unique histopathological attributes for accurate differential diagnosis and tailored therapeutic interventions.

A real-world observational study of dupilumab treatment in adult patients with prurigo nodularis

Abstract Background: Prurigo nodularis (PN) is a chronic inflammatory skin condition that has a significant unmet needs for effective treatment options. Objective: To assess the efficacy and safety of dupilumab in adult patients with PN refractory to traditional therapies. Methods: This ongoing, real-life study examined dupilumab treatment in 8 adult patients diagnosed with PN for at least 6 months. The included patients were prescribed 300 mg dupilumab biweekly for at least 16 weeks. Efficacy was the primary outcome by means of multiple standardized scale measurements while safety was also reported. Results: PN patients treated with dupilumab showed notable clinical improvement. After 16 weeks of dupilumab treatment, the mean Investigator Global Assessment (IGA) score reduced from 3.75 to 1.50. Patients mean Numerical Rating Scale Itch Intensity (NRSI), Dermatology Life Quality Index (DLQI), and Hospital Anxiety and Depression Scale (HADS) ratings reduced from 8.625, 15.13, and 14.50 to 1.563, 4.625, and 1.000 respectively. The majority of the patients (87.5%) reported dupilumab as effective while no adverse events have been reported. Study limitations: This study was limited to a small cohort of adult PN patients and a short-time observation period. Conclusions: Dupilumab is effective and tolerable in adult PN patients with significant improvement in skin lesions, itching, and quality of life.

A real-world observational study of dupilumab treatment in adult patients with prurigo nodularis.

BACKGROUND: Prurigo nodularis (PN) is a chronic inflammatory skin condition that has a significant unmet needs for effective treatment options. OBJECTIVE: To assess the efficacy and safety of dupilumab in adult patients with PN refractory to traditional therapies. METHODS: This ongoing, real-life study examined dupilumab treatment in 8 adult patients diagnosed with PN for at least 6 months. The included patients were prescribed 300 mg dupilumab biweekly for at least 16 weeks. Efficacy was the primary outcome by means of multiple standardized scale measurements while safety was also reported. RESULTS: PN patients treated with dupilumab showed notable clinical improvement. After 16 weeks of dupilumab treatment, the mean Investigator Global Assessment (IGA) score reduced from 3.75 to 1.50. Patients mean Numerical Rating Scale Itch Intensity (NRSI), Dermatology Life Quality Index (DLQI), and Hospital Anxiety and Depression Scale (HADS) ratings reduced from 8.625, 15.13, and 14.50 to 1.563, 4.625, and 1.000 respectively. The majority of the patients (87.5%) reported dupilumab as effective while no adverse events have been reported. STUDY LIMITATIONS: This study was limited to a small cohort of adult PN patients and a short-time observation period. CONCLUSIONS: Dupilumab is effective and tolerable in adult PN patients with significant improvement in skin lesions, itching, and quality of life.

Quercetin alleviates ferroptosis accompanied by reducing M1 macrophage polarization during neutrophilic airway inflammation.

Ferroptosis is a kind of regulated cell death, supporting the pathological process of lung inflammation, including asthma. Quercetin (QCT), a kind of natural dietary flavonoid, exerts anti-inflammatory and anti-ferroptosis effects in various diseases. However, the role of QCT in ferroptosis-associated airway inflammation of neutrophilic asthma remains to be described. Our study aimed to investigate the therapeutic effects of QCT on neutrophilic airway inflammation of asthma. Ferrostatin-1 (Fer-1), as a kind of ferroptosis inhibitor, was used to demonstrate whether neutrophilic airway inflammation of asthma relied on ferroptosis. In our study, the alleviation effect of QCT on neutrophilic airway inflammation was similar to Fer-1. Moreover, the significantly decreased levels of ferroptosis anti-oxidant protein (GPX4 and SLC7A11), increased malondialdehyde (MDA) levels, upregulated levels of 4-hydroxynonenal (4-HNE) expression by immunohistochemistry, and distorted mitochondria morphological changes in the lung tissues suggested lung ferroptosis in neutrophilic airway inflammation, which could be reversed by QCT treatment. In vitro experiments showed that QCT reduced LPS-induced ferroptosis through upregulating cell viability and levels of ferroptosis anti-oxidant protein (SLC7A11 and GPX4), reducing inflammatory cytokines, and decreasing the levels of MDA. Furthermore, ferroptosis was accompanied by enhancing M1 phenotype in neutrophilic airway inflammation, and QCT suppressed ferroptosis by inhibiting the pro-inflammatory M1 profile in vitro and in vivo, just as Fer-1 did. In conclusion, our study found that QCT ameliorated ferroptosis-associated neutrophilic airway inflammation accompanied by inhibiting M1 macrophage polarization. QCT may be a promising ferroptosis inhibitor for neutrophilic airway inflammation.

HIPEC with CRS versus cytoreductive surgery (CRS) for the gastric cancer metastasis to peritoneum.

BACKGROUND: Peritoneal metastases (PM) have a poor prognosis in gastric cancer (GC). Cytoreductive surgery (CRS) gives favorable outcomes, but the influence of hyperthermic intraperitoneal chemotherapy (HIPEC) remains contentious. We designed to distinguish results between CRS versus HIPEC-CRS in patients with peritoneal metastases from gastric cancer. MATERIALS AND METHODS: PubMed, Scopus, Embase and Cochrane library accessed to collect data and language is restricted to English. RevMan 5.4 was used to perform statistical analysis. The outcomes for categorical variables are mentioned in the risk ratio. RESULTS: Ten trials involving 1367 patients in which 707 were CRS-HIPEC, while 660 CRS. We got significant results in 3rd year survival (P < 0.05), while 1st and 5th years are not statistically significant P > 0.05. CONCLUSION: To compare with CRS, CRS-HIPEC has improved survival rate in deprived of further morbidity or mortality.

FOXD2-AS1 acts an oncogene in esophageal squamous cell carcinoma through sponging miR-204-3p.

PURPOSE: A growing number of evidences has revealed that long non-coding RNAs (lncRNAs) have vital effect in the pathogenesis of esophageal squamous cell carcinoma (ESCC). In our work, we found that lncRNA FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1) was significantly increased in clinical ESCC samples and cell lines. METHODS: The biological effect of FOXD2-AS1 on EC109 and KYSE150 cells showed that the low expression of FOXD2-AS1 inhibited the proliferation through CCK8 and colony formation assays, invasion by transwell chamber test, migration abilities by wound healing assay, and enhance apoptosis rates by flow cytometry assay. RESULTS: Through bioinformatics analysis and luciferase reporter assays, microRNA (miR)-204-3p was proved to be a target of FOXD2-AS1. We further confirmed that FOXD2-AS1 was the upstream inhibitor of miR-204-3p and the down-regulation of miR-204-3p reversed the repressive effects of low expression of FOXD2-AS1 on ESCC progression. In addition, inhibition of FOXD2-AS1 effectively suppressed the tumor growth. CONCLUSIONS: In general, our results suggested that FOXD2-AS1 may be of vital therapeutic importance for the treatment of ESCC patients.

Comparison of different local analgesia protocols in postoperative pain management after total knee arthroplasty.

OBJECTIVES: This study was to compare the effects of different local analgesia protocols on osteoarthritis patients undergoing total knee arthroplasty (TKA). METHODS: Medical records of 148 osteoarthritis patients who underwent unilateral TKA between October 2016 and October 2017 in our hospital were retrospectively analyzed. All these patients were divided into three groups according to the pain management protocol (morphine, morphine + cocktail [100 mg ropivacaine, 10 mg morphine, and 30 mL 0.9% sodium chloride solution containing 2 mL betamethasone (4 mg)], or cocktail). The postoperative visual analog scale (VAS) score, muscle strength, and complications were compared between the groups. RESULTS: At 6 and 12 hours post-operation, the VAS score in group C was significantly higher than that in group A or group B. In addition, the muscle (quadriceps femoris) strength score of group C (3.7 ± 2.8) was significantly higher than that in groups A and B at 6 and 12 hours post-operation. The VAS score and muscle strength score showed no significant differences among the three groups at 24 and 36 hours post-operation. The time of postoperative first void of group C was significantly shorter than that of groups A and B. Groups A or B had a significantly higher incidence of nausea and emesis compared with group C. The incidence of pruritus was higher in groups A or B than that in group C. CONCLUSION: Epidural anesthesia combined with local analgesic cocktail injection is a preferable effective multimodal analgesia for TKA.

Xuezhikang alleviates lipid accumulation via AMPK activation in hepatocellular steatosis model

Abstract Xuezhikang (XZK) is an extract of Chinese red yeast rice. It has multiple protective effects in cardiovascular systems. However, the underlying mechanism by which XZK affects free fatty acid (FFA)-induced lipogenesis in hepatocellular steatosis model is still unknown. Herein, we investigated this mechanism in HepG2 cells. The HepG2 cells were treated with palmitate acid (PA) to induce lipogenesis. Then the PA-induced HepG2 cells were subsequently treated with XZK. After 24 h of treatment, we determined the intracellular triglyceride (TG) contents and average areas of lipid droplets. To study the involvement of AMPK signaling pathway, we pre-treated the PA-induced HepG2 cells with Compound C, an AMPK inhibitor, before XZK treatment. Expressions of p-AMPK and AMPK were determined by Western blot. The results showed that XZK decreased TG content and lipid accumulation in hepatocellular steatosis model. Compound C abolished the effects of XZK. These results demonstrated for the first time that XZK protects hepatocytes against lipid accumulation induced by free fatty acids. Its effects may be mediated by the activation of AMPK pathway.

CD4+ T cells in the lungs of acute sarcoidosis patients recognize an Aspergillus nidulans epitope.

Löfgren's syndrome (LS) is an acute form of sarcoidosis characterized by a genetic association with HLA-DRB1*03 (HLA-DR3) and an accumulation of CD4+ T cells of unknown specificity in the bronchoalveolar lavage (BAL). Here, we screened related LS-specific TCRs for antigen specificity and identified a peptide derived from NAD-dependent histone deacetylase hst4 (NDPD) of Aspergillus nidulans that stimulated these CD4+ T cells in an HLA-DR3-restricted manner. Using ELISPOT analysis, a greater number of IFN-γ- and IL-2-secreting T cells in the BAL of DR3+ LS subjects compared with DR3+ control subjects was observed in response to the NDPD peptide. Finally, increased IgG antibody responses to A. nidulans NDPD were detected in the serum of DR3+ LS subjects. Thus, our findings identify a ligand for CD4+ T cells derived from the lungs of LS patients and suggest a role of A. nidulans in the etiology of LS.

Sirolimus Can Increase the Disappearance Rate of Cardiac Rhabdomyomas Associated with Tuberous Sclerosis: A Prospective Cohort and Self-Controlled Case Series Study.

OBJECTIVES: To investigate the efficacy and safety of sirolimus in the treatment of cardiac rhabdomyomas associated with tuberous sclerosis complex and the specific benefits in different subgroups. STUDY DESIGN: The study was a prospective cohort and self-controlled case series study. Based on the prevalence of cardiac rhabdomyoma at different ages, we estimated the natural tumor disappearance rate. The subgroup analysis was done by Cox regression. Self-controlled case series method was used to assess the magnitude and duration of the drug effect. Adverse events were described. RESULTS: A total of 217 patients were included in the cohort study. Tumor disappearance rate was higher in younger age groups (hazard ratio = 0.99, P = .027) and female patients (hazard ratio = 2.08, P = .015). The age-adjusted incidence ratio showed that the disappearance of rhabdomyomas between 3 and 6 months was more related to sirolimus. Adverse events were observed 60 times in 42 of 217 children, mainly stomatitis. CONCLUSIONS: Sirolimus can increase the disappearance rate of cardiac rhabdomyoma in the tuberous sclerosis complex population. Efficacy varies by sex and age: female and younger patients have higher tumor disappearance rate. Sirolimus is well-tolerated.

Feasibility of using deep learning to detect coronary artery disease based on facial photo.

AIMS: Facial features were associated with increased risk of coronary artery disease (CAD). We developed and validated a deep learning algorithm for detecting CAD based on facial photos. METHODS AND RESULTS: We conducted a multicentre cross-sectional study of patients undergoing coronary angiography or computed tomography angiography at nine Chinese sites to train and validate a deep convolutional neural network for the detection of CAD (at least one ≥50% stenosis) from patient facial photos. Between July 2017 and March 2019, 5796 patients from eight sites were consecutively enrolled and randomly divided into training (90%, n = 5216) and validation (10%, n = 580) groups for algorithm development. Between April 2019 and July 2019, 1013 patients from nine sites were enrolled in test group for algorithm test. Sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were calculated using radiologist diagnosis as the reference standard. Using an operating cut point with high sensitivity, the CAD detection algorithm had sensitivity of 0.80 and specificity of 0.54 in the test group; the AUC was 0.730 (95% confidence interval, 0.699-0.761). The AUC for the algorithm was higher than that for the Diamond-Forrester model (0.730 vs. 0.623, P < 0.001) and the CAD consortium clinical score (0.730 vs. 0.652, P < 0.001). CONCLUSION: Our results suggested that a deep learning algorithm based on facial photos can assist in CAD detection in this Chinese cohort. This technique may hold promise for pre-test CAD probability assessment in outpatient clinics or CAD screening in community. Further studies to develop a clinical available tool are warranted.

Body Mass Index Trajectories in Early Life Is Predictive of Cardiometabolic Risk.

OBJECTIVE: To identify distinct body mass index (BMI) trajectories across the life-course and explore the effects of BMI trajectories on the adult cardiovascular disease outcomes using a dataset with 30 years of follow-up in northern China. STUDY DESIGN: A total of 2839 participants aged 6-18 years whose BMIs were measured 3-6 times during the Hanzhong Adolescent Hypertension Study were included in our analysis. Latent mixture modeling was used to clarify distinct BMI trajectories in longitudinal analyses. RESULTS: Three groups with distinct trajectories in BMI were identified by the latent mixed models: a low-increasing group (n = 1324 [36.64%]), a moderate-increasing group (n = 1178 [16.89%]), and a high-increasing group (n = 337 [39.46%]). Compared with the participants in the low-increasing group, the risk ratios of hypertension, type 2 diabetes mellitus, high-risk triglycerides, and high-risk high-density lipoprotein cholesterol were more than 3.0 in the high-increasing group (all P < .001) after being fully adjusted. Increased risks existed in high brachial-ankle pulse wave velocity for the high-increasing group compared with the low-increasing group (RR, 2.75; 95% CI, 1.94-3.91; P < .001). Additionally, participants in the moderate-increasing group had a 2.31-fold increased risks of left ventricular hypertrophy (95% CI, 1.25-4.30; P = .008). CONCLUSIONS: Our study indicates that BMI trajectories from childhood to adulthood vary and that an elevated BMI trajectory in early life is predictive of an increased the risk of developing cardiovascular disease risks. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02734472.

The Relationship Between Postpartum Depression and Lower Maternal Confidence in Mothers with a History of Depression During Pregnancy.

The objective of the present study is to evaluate the association of postpartum depression and low maternal confidence in a sample of women who had depression during pregnancy. Cross-sectional study performed from 2013 to 2015 with 346 postpartum women who had participated in an intervention to treat their depression during pregnancy. This study used the Maternal Confidence Questionnaire and the Patient Health Questionnaire 9-item scale. The prevalence ratio, adjusted and non-adjusted, and the 95% CI were calculated using Poisson regression with robust variance. Multivariate models estimated the Prevalence Ratios between postpartum depression and low maternal confidence adjusted for socio-demographic variables and maternal characteristics. Statistical analysis was performed with the STATA12. Among a sample of women who were depressed during pregnancy, only 19% had probably moderate to severe depression and nearly half, 48%, reported high maternal confidence in the postpartum period. In the fully adjusted model, women with moderate/severe probable depression showed increased risk of lower maternal confidence in comparison to women without probable depression Prevalence Ratio = 1.37 (95% CI 1.10-1.71). The results reinforce the importance of the evaluation of maternal confidence feelings in primary care particularly for women with more severe forms of depression.

Socioeconomic status and risk of cardiovascular disease in 20 low-income, middle-income, and high-income countries: the Prospective Urban Rural Epidemiologic (PURE) study

Background Socioeconomic status is associated with differences in risk factors for cardiovascular disease incidence and outcomes, including mortality. However, it is unclear whether the associations between cardiovascular disease and common measures of socioeconomic status­wealth and education­differ among high-income, middle-income, and low-income countries, and, if so, why these differences exist. We explored the association between education and household wealth and cardiovascular disease and mortality to assess which marker is the stronger predictor of outcomes, and examined whether any differences in cardiovascular disease by socioeconomic status parallel differences in risk factor levels or differences in management. Methods In this large-scale prospective cohort study, we recruited adults aged between 35 years and 70 years from 367 urban and 302 rural communities in 20 countries. We collected data on families and households in two questionnaires, and data on cardiovascular risk factors in a third questionnaire, which was supplemented with physical examination. We assessed socioeconomic status using education and a household wealth index. Education was categorized as no or primary school education only, secondary school education, or higher education, defined as completion of trade school, college, or university. Household wealth, calculated at the household level and with household data, was defined by an index on the basis of ownership of assets and housing characteristics. Primary outcomes were major cardiovascular disease (a composite of cardiovascular deaths, strokes, myocardial infarction, and heart failure), cardiovascular mortality, and all-cause mortality. Information on specific events was obtained from participants or their family. (AU)

Intimate Partner Violence Is Associated with Suicidality Among Low-Income Postpartum Women.

BACKGROUND: Although intimate partner violence (IPV) during perinatal period is more common than during other maternal health conditions, it receives less attention within research on maternal mortality rates. Given the risks for maternal mortality because of suicidality, the purpose of this investigation is to examine the risk of suicidal ideation (SI) among postpartum women exposed to IPV. MATERIALS AND METHODS: In this cross-sectional study, participants were recruited between May 2005 and March 2007 from primary care clinics in São Paulo, Brazil. A total of 701 postpartum women were included in the analysis. Postpartum SI was assessed using the clinical interview schedule-revised. IPV was assessed using a structured questionnaire previously validated in Brazilian populations. Crude and adjusted risk ratios with 95% confidence intervals (95% CI) were estimated using Poisson regression with robust variance to examine the association between IPV and the risk for postpartum SI. RESULTS: The prevalence of postpartum SI was 4%. Among those with postpartum SI, 70% reported IPV during the postpartum period. Compared with non-IPV counterparts, postpartum women who reported IPV had an increased risk for SI (relative risk [RR] 7.25, 95% CI: 3.23-16.27). In the fully adjusted model, the risk for SI remained significantly higher for women who experienced IPV than for those who did not (RR 3.02, 95% CI: 1.29-7.07). CONCLUSIONS: Postpartum women exposed to violence had a threefold greater risk of having suicidal thoughts.

The Enzymatic and Structural Basis for Inhibition of Echinococcus granulosus Thioredoxin Glutathione Reductase by Gold(I).

AIMS: New drugs are needed to treat flatworm infections that cause severe human diseases such as schistosomiasis. The unique flatworm enzyme thioredoxin glutathione reductase (TGR), structurally different from the human enzyme, is a key drug target. Structural studies of the flatworm Echinococcus granulosus TGR, free and complexed with AuI-MPO, a novel gold inhibitor, together with inhibition assays were performed. RESULTS: AuI-MPO is a potent TGR inhibitor that achieves 75% inhibition at a 1:1 TGR:Au ratio and efficiently kills E. granulosus in vitro. The structures revealed salient insights: (i) unique monomer-monomer interactions, (ii) distinct binding sites for thioredoxin and the glutaredoxin (Grx) domain, (iii) a single glutathione disulfide reduction site in the Grx domain, (iv) rotation of the Grx domain toward the Sec-containing redox active site, and (v) a single gold atom bound to Cys519 and Cys573 in the AuI-TGR complex. Structural modeling suggests that these residues are involved in the stabilization of the Sec-containing C-terminus. Consistently, Cys→Ser mutations in these residues decreased TGR activities. Mass spectroscopy confirmed these cysteines are the primary binding site. INNOVATION: The identification of a primary site for gold binding and the structural model provide a basis for gold compound optimization through scaffold adjustments. CONCLUSIONS: The structural study revealed that TGR functions are achieved not only through a mobile Sec-containing redox center but also by rotation of the Grx domain and distinct binding sites for Grx domain and thioredoxin. The conserved Cys519 and Cys573 residues targeted by gold assist catalysis through stabilization of the Sec-containing redox center. Antioxid. Redox Signal. 27, 1491-1504.