TEAD4 is a master regulator of high-risk nasopharyngeal carcinoma.

The molecular basis underlying nasopharyngeal carcinoma (NPC) remains unclear. Recent progress in transcriptional regulatory network analysis helps identify the master regulator (MR) proteins that transcriptionally define malignant tumor phenotypes. Here, we investigated transcription factor-target interactions and identified TEA domain transcription factor 4 (TEAD4) as an MR of high-risk NPC. Precisely, TEAD4 promoted NPC migration, invasion and cisplatin resistance, depending on its autopalmitoylation. Mechanistically, YTHDF2 (YTH domain family 2) recognized WTAP (Wilms tumor 1-associating protein)-mediated TEAD4 m6A methylation to facilitate its stability and led to aberrant up-regulation of TEAD4. Up-regulated TEAD4 further drove NPC progression by transcriptionally activating BZW2 (basic leucine zipper and W2 domains 2) to induce the oncogenic AKT pathway. Moreover, the transcriptional activity of TEAD4 was independent of its canonical coactivators YAP/TAZ. Clinically, TEAD4 serves as an independent predictor of unfavorable prognosis and cisplatin response in NPC. Our data revealed the crucial role of TEAD4 in driving tumor malignancy, thus, may provide therapeutic vulnerability in NPC.

Association of birth weight with cancer risk: a dose-response meta-analysis and Mendelian randomization study.

BACKGROUND: Several articles have shown that birth weight is associated with the risk of many types of cancers. However, the results are inconsistent, and whether the relationship has a causal effect remains unknown. METHODS: We searched the PubMed and Embase libraries up to March 2021 and selected observational studies reporting the relationship between birth weight and adult-onset cancer risk. Dose-response meta-analysis and two-sample Mendelian randomization (MR) analysis were used to estimate the effect. RESULT: In our dose-response meta-analysis, six cancers from 46 studies were found to have significant associations with birth weight. (Ovarian cancer: RR: 1.21, 95% CI 1.01-1.44; breast cancer: RR: 1.12, 95% CI 1.08-1.16; colorectal cancer: RR: 1.20, 95% CI 1.01-1.43; endometrial cancer: RR: 0.85, 95% CI 0.78-0.93; prostate cancer: RR: 1.27, 95% CI 1.01-1.61; testicular cancer: RR: 1.21, 95% CI 1.03-1.43). As birth weight increased, the slope of the dose-response curve of breast cancer increased continuously, and the curve of testicular cancer was U-shaped. In the MR study, seven cancers were included. Only invasive mucinous ovarian cancer was found to have a causal effect on birth weight (OR: 0.62; 95% CI 0.39-0.97), while other cancers did not. CONCLUSIONS: Our findings suggest that birth weight are unlikely to have a casual effect on risk of cancers via the MR analysis, although the dose-response meta-analysis shows that there is a nonlinear relationship between birth weight and breast cancer and testicular cancer. More relevant researches are needed to further investigate their effect.

The association between dairy products consumption and prostate cancer risk: a systematic review and meta-analysis.

In this study, we conducted a meta-analysis to estimate the relationship between the consumption of dairy products and the risk of prostate cancer. We searched PubMed, Embase and Cochrane databases for relevant articles and identified a total of thirty-three cohort studies between 1989 and 2020. The qualities of included studies were assessed using Newcastle-Ottawa scale. Pooled adjusted relative risks (RR) with 95 % CI were calculated. We performed subgroup analyses stratified by dairy type, prostate cancer type, follow-up years, treatment era, collection times, adjustment for confounders and geographic location. In the subgroup analysis stratified by prostate cancer type, the pooled RR were 0·98 (95 % CI 0·94, 1·03) in the advanced group, 1·10 (95 % CI 0·98, 1·24) in the non-advanced group and 0·92 (95 % CI 0·84, 1·00) in the fatal group. In the dose-response analysis, a positive association for the risk of prostate cancer was observed for total dairy products 400 g/d (RR: 1·02; 95 % CI 1·00, 1·03), total milk 200 g/d (RR: 1·02; 95 % CI 1·01, 1·03), cheese 40 g/d (RR: 1·01; 95 % CI 1·00, 1·03) and butter 50 g/d (RR: 1·03; 95 % CI 1·01, 1·05). A decreased risk was observed for the intake of whole milk 100 g/d (RR: 0·97; 95 % CI 0·96, 0·99). Our meta-analysis suggests that high intakes of dairy products may be associated with an increased risk of prostate cancer; however, since many of the studies were affected by prostate-specific antigen (PSA) screening bias, additional studies with an adjustment of PSA screening are needed.

Impact of obstructive sleep apnea on cancer risk: a systematic review and meta-analysis.

PURPOSE: We aimed to study the effect of obstructive sleep apnea (OSA) on cancer risk. METHODS: We searched PubMed, Embase, and Cochrane databases for relevant studies. The qualities of included studies were assessed using Newcastle-Ottawa Scale (NOS). Unadjusted and adjusted analyses were performed. We also conducted subgroup analyses stratified by gender, severity of OSA, study design, and cancer type. RESULTS: After literatures search, 18 studies were included in the present study. In the unadjusted analysis, we discovered an increased cancer risk in patients with OSA with a pooled relative risk (RR) in the OSA group of 1.49 (95% confidence interval (CI): 1.32-1.69, I2 = 32%, P = 0.15). In adjusted analysis, OSA correlated with cancer risk (RR: 1.36, 95% CI: 1.18-1.56, I2 = 54%, P < 0.01). In subgroup stratified by gender and OSA severity, OSA statistically with cancer risk in females (RR: 1.27, 95% CI: 1.06-1.51) and moderate to severe OSA groups (RR: 2.62, 95% CI: 1.64; 4.19). In subgroup stratified by study design, a trend toward statistically significant differences was observed in prospective studies (RR: 1.21, 95% CI: 0.99-1.48) and cross-sectional studies (RR: 1.81, 95% CI: 0.96-3.41). Patients with OSA in the retrospective study group had a statistically higher chance of developing cancer (RR: 1.41, 95% CI: 1.11-1.79). When stratified by cancer group, statistically significant differences was observed in many types of cancer (breast cancer: RR: 1.32, 95% CI: 1.03-1.70; central nervous system cancer: RR: 1.71, 95% CI: 1.06-2.75; kidney cancer: RR: 1.81, 95% CI: 1.20-2.74; liver cancer: RR: 1.19, 95% CI: 1.10-1.29; and pancreatic cancer: RR: 1.23, 95% CI: 1.14-1.33). CONCLUSIONS: This systematic review and meta-analysis suggests that obstructive sleep apnea may increase risk of cancer.

Uncovering the Genetic of Cadmium Accumulation in the Rice 3K Panel.

Because Cadmium (Cd) is harmful to humans, and most non-smokers are exposed to Cd mainly through rice consumption, low-Cd rice breeding is urgently needed. It might not be possible to apply variation created using gene editing technology to breeding directly, so it is important to explore genetic variation in this trait in a natural population. In this study, variation in 4 genes was identified among 3024 accessions from the International Rice Research Institute 3000 Rice Genome Project (IRRI 3K-RGP) and 71 other important varieties, and the relationships between the variants and plant Cd accumulation were validated with hydroponic and pot experiments. Variants in OsNRAMP1, OsNRAMP5, OsLCD, and OsHMA3 were grouped into two, four, three, and two haplotypes, respectively. Fourteen combinations of these haplotypes, which were referred to as Cd-mobile types, were found in the collection. Of these, type 14 was shown to have the greatest potential for low-Cd accumulation, and functional markers for this type were designed. The results of this study provide an important resource for low-Cd rice breeding and highlight an effective strategy for pre-breeding programs.

Insufficient S-adenosylhomocysteine hydrolase compromises the beneficial effect of diabetic BMSCs on diabetic cardiomyopathy.

BACKGROUND: Autologous stem cell therapy is a promising strategy for cardiovascular diseases including diabetic cardiomyopathy (DCM), but conclusions from clinical trials were compromised. We assumed that diabetes might induce the dysfunction of stem cells and thus limit its therapeutic effect. This study aimed to compare the effect of diabetes and nondiabetes-derived bone marrow mesenchymal stem cells (BMSCs) transplantation on DCM and explored the potential mechanism. METHODS: Rats with diabetes were induced using high-fat diets and streptozotocin (STZ) injection. BMSCs harvested from diabetic and nondiabetic rats were infused into DCM rats, and the effects on the heart were identified by echocardiography and histopathology. The inhibition or overexpression of SAHH in nondiabetic and diabetic BMSCs was used to confirm its key role in stem cell activity and cardiac therapy. RESULTS: Compared with normal BMSCs, the therapeutic effects of diabetic rat-derived stem cells on improving cardiac function and adverse remodeling were significantly attenuated. In vitro, diabetic BMSCs had lower cell viability and paracrine function than nondiabetic BMSCs. It was further found that diabetic BMSCs had obvious mitochondrial oxidative stress damage and S-adenosylhomocysteine (SAH) accumulation due to S-adenosylhomocysteine hydrolase (SAHH) deficiency. SAHH inhibition by adenosine dialdehyde (ADA) or shSAHH plasmid in normal BMSCs significantly reduced the favorable effects on endothelial cell proliferation and tube-forming capacity. In contrast, SAHH overexpression in diabetic BMSCs significantly improved cellular activity and paracrine function. Transplantation of BMSCs with SAHH overexpression improved cardiac adverse remodeling and angiogenesis. Activation of the Nrf2 signaling pathway may be one of the key mechanisms of SAHH-mediated improvement of stem cell viability and cardiac repair. CONCLUSIONS: Diabetes leads to compromised bioactivity and repair capacity of BMSCs. Our study suggests that SAHH activation may improve the cardioprotective effect of autologous transplantation of diabetes-derived BMSCs on patients with DCM. Diabetes induced the inhibition of S-adenosylhomocysteine (SAH) expression and aging phenotype in BMSCs and thus decreased the cell viability and paracrine function. Compared with normal BMSCs, the therapeutic effects of diabetic rat-derived BMSCs on improving cardiac function and adverse remodeling were significantly attenuated. SAHH overexpression in diabetic BMSCs significantly rescued cellular function partly via activating Nrf2/HO-1 signal. Transplantation of diabetic BMSCs with SAHH overexpression improved angiogenesis and cardiac adverse remodeling in rats.

Spontaneous Ventilation Video-Assisted Thoracoscopic Surgery for Geriatric Patients With Non-Small-Cell Lung Cancer.

OBJECTIVES: The aim of the present study was to compare the short-term outcomes between spontaneous ventilation video-assisted thoracic surgery (SV-VATS) and mechanical ventilation video-assisted thoracic surgery (MV-VATS) in the elderly. All patients included in the present study underwent lobectomy, segmentectomy, or wedge resection and lymph node dissection. DESIGN: A retrospective cohor. SETTING: The first affiliated hospital of Guangzhou Medical University, Guangzhou, China. PARTICIPANTS: The present study included 799 elderly patients diagnosed with non-small-cell lung cancer undergoing SV-VATS or MV-VATS. After propensity score matching, 80 patients in the SV-VATS group and 80 patients in the MV-VATS group were analyzed. INTERVENTIONS: Patients in the SV-VATS group received spontaneous-ventilation anesthesia, which was administered as follows: intravenous anesthesia + laryngeal mask airway + thoracic paravertebral block + visceral pleural surface anesthesia + thoracic vagus nerve block. Patients in the MV-VATS group received general endotracheal anesthesia. SV-VATS or MV-VATS was performed according to the preference of the patients. MEASUREMENTS AND MAIN RESULTS: There were no significant differences in anesthesia time (226.3 ± 79.8 v 238.5 ± 66.2 min; p = 0.44), surgery time (166.2 ± 102.6 v 170.1 ± 83.4 min; p = 0.66), and number of dissected lymph nodes (5.3 ± 7.5 v 4.4 ± 7.4; p = 0.23) between the two groups. There were significant differences in intraoperative bleeding (61.5 ± 165.1 v 82.2 ± 116.9 mL; p < 0.001). After surgery, the two groups were statistically comparable in terms of hospitalization (17.6 ± 7.6 v 17.2 ± 6.9 days; p = 0.95) and incidence of complications (7.5% v 13.8%; p = 0.20), while there were significant differences in chest tube duration (6.1 ± 3.3 v 4.5 ± 1.2 days; p < 0.001). CONCLUSIONS: SV-VATS is feasible and as safe as MV-VATS, and it could be considered as an alternative treatment for the elderly.

Exosomal-mediated transfer of APCDD1L-AS1 induces 5-fluorouracil resistance in oral squamous cell carcinoma via miR-1224-5p/nuclear receptor binding SET domain protein 2 (NSD2) axis.

Oral squamous cell carcinoma (OSCC) poses a threat to public health worldwide. LncRNA APCDD1L-AS1 has been reported to participate in tumorigenesis and development of acquired chemoresistance. However, the role of APCDD1L-AS1 in 5-fluorouracil (5-FU) resistance regulation within OSCC is still obscure. In this study, 5-FU-resistant cell models were established with OSCC cell lines (HSC-3 and HN-4). Gene expressions and protein levels were detected by RT-qPCR and Western blotting, respectively. CCK-8, colony forming, and flow cytometry were utilized to measure IC50 value, cell viability, and cell apoptosis of 5-FU-resistant OSCC cells. Dual-luciferase reporter assay and RIP assay were applied to identify the associations between miR-1224-5p and APCDD1L-AS1 or NSD2. Herein, high APCDD1L-AS1 expression was shown in OSCC tissues and cells resistant to 5-FU and related to the worse prognosis of OSCC patients. APCDD1L-AS1 knockdown impaired 5-FU resistance in 5-FU-resistant OSCC cells by reducing IC50 value, suppressing cell viability, and accelerating cell apoptosis. Besides, extracellular APCDD1L-AS1 could be transferred to sensitive cells via exosome incorporation, thereby transmitting 5-FU resistance in OSCC cells. Besides, miR-1224-5p was a molecular target of APCDD1L-AS1 and directly targeted NSD2 in 5-FU-resistant cells. MiR-1224-5p exhibited a much lower level in 5-FU-resistant tissues and increased 5-FU sensitivity in 5-FU-resistant OSCC cells. Moreover, NSD2 upregulation neutralized the influence of blocking APCDD1L-AS1 in HSC-3/5-FU and HN-4/5-FU cells on 5-FU resistance. To sum up, our study demonstrated that exosomal APCDD1L-AS1 conferred resistance to 5-FU in HSC-3/5-FU and HN-4/5-FU cells via the miR-1224-5p/NSD2 axis, thus providing a novel target for OSCC chemoresistance.

Diagnostic value of ultrasound-guided needle biopsy in undiagnosed pleural effusions: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Undiagnosed pleural effusions (UPEs) are a common problem of respiratory medicine, leading to an increased diagnostic burden globally. However, the most efficient and cost-effective approaches to UPEs remain controversial. This study aimed to assess the diagnostic value of ultrasound-guided needle biopsy (UGNB) in UPEs. METHODS: We conducted a search of PubMed, Embase, the Cochrane Library and reference lists of retrieved studies with no publication data limitation. Articles that investigated the diagnostic accuracy of UGNB in UPEs were included. The quality of eligible studies was assessed using Quality Assessment of Diagnostic Accuracy Studies-2. The diagnostic value of UGNB was evaluated by calculating the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds rate, and the area under the curve for the summary receiver operating characteristic curve using a random effects model. RESULTS: Seven studies comprising 165 patients with UPEs met the inclusion criteria. UGNB had a pooled sensitivity of 83% (95% confidence intervals [CI], 75% - 89%), a specificity of 100% (95% CI, 90% - 100%), a positive likelihood ratio of 8.89 (95% CI, 3.29 - 24.02), a negative likelihood ratio of 0.23 (95% CI, 0.16 - 0.33), a diagnostic odds rate of 51.47 (95% CI, 14.70 - 180.16), and an area under the curve of 0.94. Six pneumothorax cases (3.6%), 5 local wound infections (3.0%), and 1 empyema case (less than 1%) were observed. There was no significant heterogeneity or publication bias in this study. CONCLUSIONS: Based on current evidence, UGNB is a safe and convenient procedure with a high accuracy for diagnosing UPEs. However, physicians should still be cautious in interpreting negative UGNB results.

Spontaneous ventilation video-assisted thoracoscopic surgery for patients with non-small-cell lung cancer with excess body weight.

OBJECTIVES: The feasibility and safety of spontaneous ventilation (SV) video-assisted thoracoscopic surgery (VATS) for non-small-cell lung cancer (NSCLC) in patients with excess body weight [defined as body mass index (BMI) ≥ 25 kg/m2] remain unclear. METHODS: Patients with NSCLC with excess body weight who underwent SV-VATS or mechanical ventilation (MV) VATS (MV-VATS) between April 2012 and July 2018 were analysed retrospectively. Propensity score matching was applied to balance the distribution of demographic characteristics. The short-term outcomes between the SV-VATS group and MV-VATS group were compared. RESULTS: From April 2012 to July 2018, a total of 703 patients with excess body weight were included, 68 of whom underwent SV-VATS and 635 of whom underwent MV-VATS. After propensity score matching, the distribution of demographic characteristics was well balanced. BMIs (26.65 ± 1.74 vs 27.18 ± 2.36 kg/m2; P = 0.29) were similar between the groups. Patients who underwent SV-VATS had similar anaesthesia times (213 ± 57 vs 233 ± 67 min; P = 0.16) and similar operative times (122 ± 44 vs 142 ± 56 min; P = 0.086). The intraoperative bleeding volume, postoperative chest tube duration, volume of pleural drainage, number of dissected N1 and N2 station lymph nodes, length of hospitalization and incidence of complications were comparable between the 2 groups. CONCLUSIONS: Primary lung cancer resection is feasible and not associated with safety issues under SV-VATS in selected patients with NSCLC with excess body weight.

Volunteerism and Cardiovascular Health: The HCHS/SOL Sociocultural Ancillary Study.

OBJECTIVES: The objective of this study was to examine the association between volunteerism and favorable cardiovascular health (CVH) among Hispanics/Latinos living in the US. METHODS: Data from the Hispanic Community Health Study/Study of Latinos (2008-2011) Sociocultural Ancillary Study were used (N = 4,926; ages 18-74 years). Favorable CVH was defined as positive profiles of all major CVD risk factors: low total serum cholesterol, blood pressure, and body mass index; not having diabetes; and not smoking. Survey-weighted logistic regression models were adjusted for sociodemographic, lifestyle, and psychological factors. In secondary analyses, we tested whether the volunteerism-CVH association was modified by sex, age, or years lived in the US (<10 vs. ≥10 years; a proxy acculturation measure). RESULTS: Prevalence of volunteerism was 14.5%. Compared to non-volunteers, volunteers had 1.67 higher odds of favorable CVH in the fully-adjusted model (Odds Ratio [OR] = 1.67, 95% Confidence Interval [CI] = 1.11, 2.52). There was evidence of effect modification by acculturation; only volunteers who had lived in the US ≥10 years had 2.41 higher odds of favorable CVH (OR = 2.41, 95% CI=1.53, 3.80). There was no evidence of effect modification by sex or age. CONCLUSIONS: Volunteerism was associated with favorable CVH among US Hispanics/Latinos.

The Association Between Family Social Network Size and Healthy Lifestyle Factors: Results from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

We examined associations of central family (i.e., children, parents, in-laws) social network size with healthy lifestyle factors (i.e., favorable body mass index, physical activity, diet, alcohol use, smoking). Using data on 15,511 Hispanics/Latinos 18-74 years old from the Hispanic Community Health Study/Study of Latinos, multivariable adjusted survey logistic regression was used to compute associations of social network size with healthy lifestyle factors. A one-unit higher total of central family size was associated with lower odds of healthy body mass index (OR 0.90; 95% CI 0.86-0.93) and having all five healthy lifestyle factors (OR 0.90; 95% CI 0.85-0.96). Findings suggest familial structural social support may contribute to healthy lifestyle factors and differ based on the type of relationship among Hispanics/Latinos.

Rapid effect of bisphenol A on glutamate-induced Ca2+ influx in hippocampal neurons of rats.

Intracellular Ca2+ signaling plays an essential role in synaptic plasticity. This study examined the effect of BPA on concentration of intracellular Ca2+ ([Ca2+]i) by measuring fluorescence intensity of Ca2+ in hippocampal neurons in vitro. The results showed that BPA for 30 min exerted dose-dependently dual effects on glutamate-elevated [Ca2+]i: BPA at 1-10 µM suppressed but at 1-100 nM enhanced glutamate-raised [Ca2+]i. BPA-potentiated [Ca2+]i was blocked by the antagonist of NMDA receptor and was eliminated by an estrogen-related receptor gamma (ERRγ) antagonist rather than an AR antagonist. Both inhibitors of MAPK/ERKs and MAPK/p38 blocked BPA-enhanced [Ca2+]i. Co-treatment of BPA with 17ß-E2 or DHT eliminated the enhancement of 17ß-E2, DHT, and BPA in glutamate-elevated [Ca2+]i. These results suggest that BPA at nanomole level rapidly enhances Ca2+ influx through NMDA receptor by ERRγ-mediated MAPK/ERKs and MAPK/p38 signaling pathways. However, BPA antagonizes both estrogen and androgen enhancing NMDA receptor-mediated Ca2+ influx in hippocampal neurons.

Association of dispositional optimism with Life's Simple 7's Cardiovascular Health Index: results from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) Sociocultural Ancillary Study (SCAS).

OBJECTIVES: Mounting evidence links positive psychological functioning to restorative health processes and favourable medical outcomes. However, very little is known about the relationship between optimism, an indicator of psychological functioning and the American Heart Association (AHA)-defined concept of cardiovascular health (CVH), particularly in Hispanics/Latinos of diverse backgrounds. To address limitations of existing literature, this study investigated the association between dispositional optimism and CVH in a heterogeneous sample of Hispanics/Latinos residing in the USA. DESIGN: Cross-sectional study. PARTICIPANTS AND SETTING: Data were analysed from 4919 adults ages 18-75 of the Hispanic Community Health Study/Study of Latinos parent study and the Sociocultural Ancillary Study. MAIN OUTCOME MEASURES: Optimism was assessed using the 6-item Life Orientation Test-Revised (range from 6 to 30). AHA classification standards were used to derive an additive CVH score with operationalisation of indicators as Ideal, Intermediate and Poor. The overall CVH score included indicators of diet, body mass index, physical activity, cholesterol, blood pressure, fasting glucose and smoking status. Multivariate linear and logistic regressions were used to examine associations of optimism with CVH (Life's Simple 7), after adjusting for sociodemographic factors and depressive symptoms. RESULTS: Each increase in the optimism total score was associated with a greater CVH score (ß=0.03 per unit increase, 95% CI 0.01 to 0.05). When modelling tertiles of optimism, participants with moderate (ß=0.24 to 95% CI 0.06 to 0.42) and high (ß=0.12, 95% CI 0.01 to 0.24) levels of optimism displayed greater CVH scores when compared with their least optimistic peers. CONCLUSION: This study offers preliminary evidence for an association between optimism and CVH in a large heterogeneous group of Hispanic/Latino adults. Our study adds scientific knowledge of psychological assets that may promote CVH and suggests a novel therapeutic target for consideration. Future studies are needed to explore causality and potential mechanism underlying the relationship between positive emotion and heart health.

Bisphenol-A antagonizes the rapidly modulating effect of DHT on spinogenesis and long-term potentiation of hippocampal neurons.

Bisphenol A (BPA), a common environmental endocrine disruptor, modulates estrogenic, antiestrogenic, and antiandrogenic effects throughout the lifespan. Recent studies found more obvious adverse effect of BPA on some neurobehavior in males than that in females. In this study, BPA at 10-100 nM rapidly increased the densities of the dendrite spine and synapse in cultured hippocampal neurons of rats in vitro within 1 h. Co-treatment of BPA (100 nM) with dihydrotestosterone (DHT, 10 nM) or with 17ß-E2 (10 nM) completely eliminated the promotion of DHT or 17ß-E2 in the densities of the dendritic spine and synapse. Pretreatment of estrogen receptors (ERs) antagonist ICI182,780 but not of androgen receptors (ARs) antagonist flutamide (Flu) for 30min completely blocked BPA-enhanced densities of the dendritic spine and synapse. Pretreatment of flutamide for 30min before BPA and DHT completely rescued BPA-enhanced densities of the dendritic spine and synapse. Furthermore, pretreatment of ERK1/2 inhibitor U0126 or p38 inhibitor SB203580 entirely eliminated BPA-induced increases in the densities of the dendritic spine and synapse. Meanwhile, BPA (100 nM) enhanced long-term potentiation (LTP) induction of dentate gyrus in hippocampal slices of younger male rats, which was not blocked by co-incubation of flutamide but was inhibited by pretreatment of an P38 inhibitor SB203580. Co-application of BPA with DHT inhibited DHT-suppressed LTP. These results are the first demonstrating the antagonism of BPA to the rapid modification of DHT in synaptic plasticity. However, BPA alone rapidly promotes spinogenesis and synaptic activity through ER instead of AR, and both ERKs and p38 signaling pathways are involved in these processes.

Structural social support and cardiovascular disease risk factors in Hispanic/Latino adults with diabetes: results from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

OBJECTIVE(S): Cross-sectional and longitudinal studies have yielded inconsistent findings on the associations of social support networks with cardiovascular health in Hispanic/Latino adults with diabetes. We examined the cross-sectional associations of structural social support and traditional cardiovascular disease (CVD) risk factors in a diverse sample of Hispanic/Latino adults with diabetes. RESEARCH DESIGN AND METHODS: This analysis included 2994 adult participants ages 18-74 with diabetes from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL - 2008-2011). Select items from the Social Network Inventory (SNI) were used to assess indices of structural social support, i.e. network size (number of children, parents, and in-laws) and frequency of familial contact. Standardized methods were used to measure abdominal obesity, BMI, hypertension, hypercholesterolemia, and smoking status. Multivariate regression was used to examine associations of structural support with individual CVD risk factors with demographics, acculturation, physical health, and psychological ill-being (depressive symptoms and anxiety) included as covariates. RESULTS: There were no significant cross-sectional associations of structural support indices with abdominal obesity, hypertension, hypercholesterolemia, or smoking status. There was a marginally significant (OR: 1.05; 95%CI 0.99-1.11) trend toward higher odds of obesity in participants reporting a larger family unit (including children, parents, and in-laws) and those with closer ties with extended family relatives (OR: 1.04; 95%CI 0.99-1.09). CONCLUSIONS: Structural social support was marginally associated with higher odds of obesity in Hispanic/Latino adults with diabetes. Alternate forms of social support (e.g. healthcare professionals, friends, peers) should be further explored as potential markers of cardiac risk in Hispanics/Latinos with diabetes.

Association of Serum Lipids and Obstructive Lung Disease in Hispanic/Latino Adults of Diverse Backgrounds.

RATIONALE: Substantial variation in the prevalences of obstructive lung disease exist between Hispanic/Latino heritage groups. Experimental studies have posited biological mechanisms linking serum lipids and lipid-lowering medications with obstructive lung disease. The aim of this study is to examine the associations of serum lipid levels with the prevalences of asthma and chronic obstructive pulmonary disease in the Hispanic Community Health Study/Study of Latinos and how these associations vary by Hispanic/Latino heritage group. METHODS: The Hispanic Community Health Study/Study of Latinos is a population-based probability sample of 16,415 self-identified Hispanic/Latino persons aged 18-74 years recruited between 2008 and 2011 from randomly selected households in four US field centers. The baseline clinical examination included comprehensive biological testing (fasting serum lipid levels), behavioral and socio-demographic assessments, medication inventory including inhalers, and respiratory data including questionnaires for asthma and standardized spirometry with post-bronchodilator measures for identification of obstructive lung disease. MEASUREMENTS AND MAIN RESULTS: Hispanic/Latinos with current asthma had lower age- and statin-use-adjusted mean serum total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels than their non-asthmatic counterparts. In analysis adjusted for age plus gender, ethnicity, cigarette smoking, alcohol intake, body mass index, lipid/cholesterol-lowering medications, age at immigration, health insurance status, and use of oral corticosteroids, increasing serum levels of total cholesterol and low-density lipoprotein cholesterol were associated with lower odds of current asthma in the estimated population. Unlike asthma, Hispanic/Latinos with chronic obstructive pulmonary disease had lower mean high-density lipoprotein than their non- chronic obstructive pulmonary disease counterparts. In the fully adjusted analysis no significant associations were found between lipid levels and prevalent chronic obstructive pulmonary disease. CONCLUSIONS: We showed a modest inverse relationship between serum lipid levels and current asthma. These results highlight some important differences in Hispanics/Latinos and certain serum lipids may be factors or markers of obstructive lung disease.

Relationships of nativity and length of residence in the U.S. with favorable cardiovascular health among Hispanics/Latinos: The Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

Individuals with favorable levels of all readily measured major CVD risk factors (low CV risk) during middle age incur lower cardiovascular morbidity and mortality, lower all-cause mortality, and lower Medicare costs at older ages compared to adults with one or more unfavorable CVD risk factors. Studies on predictors of low CV risk in Hispanics/Latinos have focused solely on Mexican-Americans. The objective of this study was to use data from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL; enrolled 2008 to 2011) to assess relationships of nativity and length of residence in the US, a commonly used proxy for acculturation, with low CV risk (not currently smoking; no diabetes; untreated total cholesterol <200mg/dL; untreated blood pressure<120/<80; body mass index <25kg/m(2); and no major ECG abnormalities) in 15,047 Central American, South American, Cuban, Dominican, Mexican, Puerto Rican men and women, and Hispanic/Latino men and women identifying as other or >1 heritage. We also tested whether associations varied by Hispanic/Latino background. Women living in the US<10years were 1.96 (95% confidence interval: 1.37, 2.80) times more likely to be low CV risk than US-born women after adjusting for sociodemographic characteristics, diet, physical activity, and self-reported experiences of ethnic discrimination. Findings varied in men by Hispanic/Latino background, but length of residence was largely unrelated to low CV risk. These findings highlight the role acculturative processes play in shaping cardiovascular health in Hispanics/Latinos.

Reduction in multi-lineage and erythroid progenitors distinguishes myelodysplastic syndromes from non-malignant cytopenias.

We studied the diagnostic role of CFC assays in myelodysplastic syndromes (MDS) using CFC data from bone marrow (BM) and peripheral blood (PB) of 221 MDS patients, 51 patients with non-malignant causes of cytopenia and/or dysplasia and 50 normal controls. A consistent decrease in BM but not PB multi-lineage and erythroid progenitor frequencies was seen in patients with MDS compared to controls (P<0.05). Automated distinction showed a sensitivity of 87+/-6% and a specificity of 71+/-11% in classifying MDS patients. In conclusion, a defect in early hematopoietic progenitor activity, in particular erythroid activity, distinguishes MDS from non-MDS.

[Relationship between interleukin-6 gene-572C/G polymorphism and chronic periodontitis].

OBJECTIVE: To investigate the relationship between interleukin-6 (IL-6) gene -572C/G polymorphism and the risk of chronic periodontitis disease. METHODS: IL-6-572C/G genotype polymorphism was examined in 93 patients with chronic periodontitis and 96 control subjects by PCR restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: IL-6-572GG genotype and G allele were more frequent in chronic periodontitis patients than that in control subjects (P<0.05). -572CC, CG and GG genotype frequency were 52.7 % , 40.9 %, 6.4 % in chronic periodontitis patients and 67.7 %, 31.3%, 1.0 % in control subjects, respectively. -572CG + GG genotype and G allele were more frequent in patients than that in control subjects (P<0.05). Compared with CC genotype,the odds ratio for chronic periodontitis was 1.88 (95% CI: 1.04-3.40, P<0.05) for CG + GG genotype. CONCLUSIONS: The frequency of -572CG + GG genotype was higher in patients with chronic periodontitis compared with the control subjects. IL-6-572C/G polymorphism may be a genetic susceptibility factor for chronic periodontitis in Chinese Hans population.