Arsenic methylation capacity is associated with breast cancer in northern Mexico

Exposure to environmental contaminants, dietary factors and lifestyles may explain worldwide different breast cancer (BC) incidence. Inorganic arsenic (iAs) in the drinking water is a concern in many regions, such as northern Mexico. Studies in several countries have associated the proportion of urinary monomethylarsenic (%MMA) with increased risks for many As-related diseases, including cancer. To investigate the potential relationships between the risk of BC and the capacity to methylate iAs, a hospital-based case–control study (1016 cases/1028 controls) was performed in northern Mexico. Women were directly interviewed about their reproductive histories. The profile of As metabolites in urine was determined by HPLC-ICP-MS and methylation capacity was assessed by metabolite percentages and indexes. Total urinary As, excluding arsenobetaine (TAs-AsB), ranged from 0.26 to 303.29 μg/L. Most women (86%) had TAs-AsB levels below As biological exposure index (35 μg/L). Women with higher %MMA and/or primary methylation index (PMI) had an increased BC risk (%MMA OR_Q5vs.Q1 = 2.63; 95%CI 1.89,3.66; p for trend < 0.001; PMI OR_Q5vs.Q1 = 1.90; 95%CI 1.39,2.59, p for trend < 0.001). In contrast, women with higher proportion of urinary dimethylarsenic (%DMA) and/or secondary methylation index (SMI) had a reduced BC risk (%DMA OR_Q5vs.Q1 = 0.63; 95%CI 0.45,0.87, p for trend 0.006; SMI OR_Q5vsQ1 = 0.42, 95%CI 0.31,0.59, p for trend < 0.001). Neither %iAs nor total methylation index was associated to BC risk. Inter-individual variations in iAs metabolism may play a role in BC carcinogenesis. Women with higher capacity to methylate iAs to MMA and/or a lower capacity to further methylate MMA to DMA were at higher BC risk.     

联合应用顺阿曲库铵与维库溴铵后ED50和ED95的改变

目的：观察顺式阿曲库铵联合维库溴铵用药后ED50和ED95的变化。方法将75例择期手术患者（ASAⅠ~Ⅱ级）随机分为3组：顺式阿曲库铵组、维库溴铵组和顺式阿曲库铵＋维库溴铵组,每组各25例。麻醉诱导后,以单次给药法观察起效时间和T1达到最大抑制的时间,描绘3组患者的量-效曲线,求得各自的ED50和ED95值,并运用等效图法和代数法对两药相互作用进行分析。结果单用顺式阿曲库铵组、维库溴铵组ED50值分别为32.35、28.78μg/kg,ED95值分别为52.67、51.20μg/kg。联合用药时ED50值为16.81、12.17μg/kg,ED95值为23.49、22.16μg/kg,与单独用药相比,差异均有统计学意义。联合用药时ED50和ED95的合用代数值分别为0.942、0.879。结论联合使用顺式阿曲库铵和维库溴铵具有协同作用,且量-效曲线产生左移。     

Racial Differences in Discharge Location After a Traumatic Brain Injury Among Older Adults

ObjectiveTo determine if there were racial differences in discharge location among older adults treated for traumatic brain injury (TBI) at a level 1 trauma center.DesignRetrospective cohort study.SettingR Adams Cowley Shock Trauma Center.ParticipantsBlack and white adults aged ≥65 years treated for TBI between 1998 and 2012 and discharged to home without services or inpatient rehabilitation (N=2902).Main Outcome MeasuresWe assessed the association between race and discharge location via logistic regression. Covariates included age, sex, Abbreviated Injury Scale-Head score, insurance type, Glasgow Coma Scale score, and comorbidities.ResultsThere were 2487 (86%) whites and 415 blacks (14%) in the sample. A total of 1513 (52%) were discharged to inpatient rehabilitation and 1389 (48%) were discharged home without services. In adjusted logistic regression, blacks were more likely to be discharged to inpatient rehabilitation than to home without services compared to whites (odds ratio 1.34, 95% confidence interval, 1.06-1.70).ConclusionsIn this group of Medicare-eligible older adults, blacks were more likely to be discharged to inpatient rehabilitation compared to whites.     

电针对血管性痴呆大鼠记忆力及海马BDNF、PSD-95蛋白表达的影响

目的:观察电针对血管性痴呆(VD)大鼠记忆力的影响,以及其对大鼠海马组织脑源性神经生长因子(BDNF)与突触后致密蛋白-95(PSD-95)蛋白表达的影响,探讨电针治疗血管性痴呆的可能分子机制。方法:将Wistar大鼠随机分为假手术组、模型组和电针组,每组8只。假手术组暴露双侧颈总动脉,但不结扎;模型组和电针组采用双侧颈总动脉永久性结扎法建立VD大鼠模型。治疗过程中3组大鼠均采用柔软型大鼠固定器固定。电针组选取百会、足三里穴,接通电流,每天1次,每次留针30min,连续治疗14天;模型组与假手术组只给予固定。治疗前后采用新事物识别实验对3组大鼠进行记忆力的检测。治疗结束后采用免疫印迹法检测大鼠海马组织BDNF与PSD-95的蛋白质表达情况,采用Image J图像分析系统对蛋白表达水平进行分析。结果:经过14天的治疗后,电针组大鼠对新物体的探索指数高于治疗前(P0.05),高于模型组大鼠(P0.05)。电针组大鼠海马组织的BDNF、PSD-95的蛋白质表达均高于模型组,差异有显著性意义(P0.05)。结论:电针血管性痴呆模型大鼠的百会穴、足三里穴能有效改善血管性痴呆大鼠的记忆能力,提高大鼠海马组织中PSD-95、BDNF蛋白的表达,电针对记忆力的改善可能与PSD-95、BDNF表达增加相关,有可能是通过影响BDNFGluA1-PSD95信号传导通路而发挥效用。     

Rates of Help-Seeking in US Adults With Lifetime DSM-5 Eating Disorders: Prevalence Across Diagnoses and Differences by Sex and Ethnicity/Race

ObjectiveTo investigate, in a nationally representative sample of US adults, the prevalence of help-seeking in individuals with Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) eating disorders (EDs) and to examine sex and ethnic/racial differences.Patients and MethodsThe 2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions-III (N=36,309) included respondents who met the criteria for specific lifetime DSM-5 EDs and answered questions regarding help-seeking for their ED symptoms (anorexia nervosa [AN]: n=275; bulimia nervosa [BN]: n=91; and binge-eating disorder [BED]: n=256).ResultsThe prevalence (standard error) estimates of ever seeking any help for AN, BN, and BED were 34.5% (2.80%), 62.6% (5.36%), and 49.0% (3.74%), respectively. Adjusting for sociodemographic characteristics, men and ethnic/racial minorities (non-Hispanic blacks and Hispanics) were statistically significantly less likely to ever seek help for BED than were women or non-Hispanic whites, respectively. Hispanics also were significantly less likely to seek help for AN relative to non-Hispanic whites.ConclusionThis was the first study in a nationally representative sample of US adults to examine rates of help-seeking, including by sex and ethnic/racial differences, across DSM-5–defined EDs. These findings emphasize the need to develop strategies to encourage help-seeking among individuals with EDs, particularly among men and ethnic/racial minorities.     

Health Care Provider in Triage to Improve Outcomes

ProblemEmergency departments throughout the nation are experiencing crowding related to increased patient volumes and decreased hospital inpatient bed capacity. As a result of lengthy wait times, patients are leaving without having medical treatment, and satisfaction is poor. The purpose of this quality improvement initiative was placing a provider in triage to complement the existing split-flow process aimed to decrease wait times to see a provider, length of stay (LOS), left without being seen (LWBS) rates, and improve patient satisfaction.MethodsA multiprofessional team was established. Nurses, advanced practice providers, and physicians collaborated on a project to place a provider in triage to assist in seeing patients as soon as possible and begin care or treatment.ResultsThe outcomes of the initiative were positive for ED LOS metrics and patient satisfaction. Door-to-provider time decreased from a high of 56 minutes to a low of 13 minutes. The percentage of patients LWBS decreased from a high of 12% to a low of 1.62%.DiscussionThe project showed that the evidence-based practice of a combined split-flow and provider-in-triage model resulted in improvements in throughput for patients who were treated and released from the emergency department.     

老年人外周血淋巴细胞CD28及CD95表达变化研究

目的通过对老年人与成年人外周血淋巴细胞CD28及CD95表达水平的比较性研究,观察淋巴细胞凋亡在免疫衰老中的作用。方法采用免疫荧光标记流式细胞术,分析成年组(20~59岁)与老年组(60~90岁)各20例的外周血淋巴细胞表型水平。结果老年组CD28 CD95-[(8.80±4.86)%]及CD28 细胞[(36.32±10.38)%]明显低于成年组[(23.09±3.48)%、(52.29±4.90)%](P<0.01),而CD28-CD95 [(53.23±8.28)%]、CD95 [(80.25±7.19)%]及CD28-细胞[(63.68±10.38)%]明显高于成年组[(33.58±4.72)%、(63.18±4.12)%、(47.71±4.90)%](P<0.01)。结论老年人CD28 表达随年龄增长而下降,CD28-及CD95 表达随年龄增长而上升。提示淋巴细胞凋亡在免疫衰老中可能具有重要作用。     

Overexpression of C-terminal fragment of glutamate receptor 6 prevents neuronal injury in kainate-induced seizure via disassembly of GluR6-PSD95-MLK3 signaling module

Our previous study showed that when glutamate receptor （GluR）6 C terminus-containing peptide conjugated with the human immunodeficiency virus Tat protein （GluR6）-9c is delivered into hippocampal neurons in a brain ischemic model, the activation of mixed lineage kinase 3 （MLK3） and c-Jun NH2-terminal kinase （JNK） is inhibited via GluR6-postsynaptic density protein 95 （PSD95）. In the present study, we investigated whether the recombinant adenovirus （Ad） carrying GluR6c could suppress the assembly of the GluR6-PSD95-MLK3 signaling module and decrease neuronal cell death induced by kainate in hippocampal CA1 subregion. A seizure model in Sprague-Dawley rats was induced by intraperitoneal injections of kainate. The effect of Ad- Glur6-9c on the phosphorylation of INK, MLK3 and mitogen-activated ldnase kinase 7 （MKK7） was observed with western immunoblots and immunohistochemistry. Our findings revealed that overexpression of GluR6c inhibited the interaction of GluR6 with PSD95 and prevented the kainate-induced activation of INK, MLK3 and MKK7. Furthermore, kainate-mediated neuronal cell death was significantly suppressed by GluR6c. Taken together, GluR6 may play a pivotal role in neuronal cell death.     

Plasma 15-F2t-isoprostane in idiopathic pulmonary arterial hypertension

Background

15-F_2t-isoprostane (15-F_2t-IsoP), a prostaglandin F₂-like compound, is widely recognized as a biomarker of chronic heart failure. This study investigated the potential role and prognostic significance of plasma 15-F_2t-IsoP in patients with idiopathic pulmonary arterial hypertension (IPAH).

Methods

Plasma 15-F_2t-IsoP concentrations were determined in 80 consecutive IPAH patients at the time of their first right heart catheterization, and monitored for 30 ± 12 months. The expression of 15-F_2t-IsoP protein in autopsy lung samples was determined by immunohistochemical staining.

Results

Plasma 15-F_2t-IsoP concentrations were significantly increased in patients with IPAH compared with healthy controls (91 pg/ml vs. 30 pg/ml, respectively; P < 0.001). Patients with baseline 15-F_2t-IsoP concentrations ≥ 97 pg/ml had a significantly lower survival rate than those with lower baseline concentrations (P < 0.001). During follow-up, 15-F_2t-IsoP concentrations in survivors decreased, whereas concentrations in non-surviving patients increased further (P < 0.05). Elevated concentrations of 15-F_2t-IsoP were correlated with a severity of WHO functional class, lower 6-minute walking distance and mixed venous oxygen saturation, higher mean right atrial pressure and brain natriuretic peptide. Multivariate analysis revealed that the plasma 15-F_2t-IsoP concentration was an independent factor associated with mortality. Histological studies showed that the expression of 15-F_2t-IsoP was up-regulated in remodeled pulmonary vessels.

Conclusions

An elevated plasma 15-F_2t-IsoP concentration and a further increase during follow-up may be a risk factor for higher mortality in patients with IPAH.