Elevated G2 chromosomal radiosensitivity in Irish breast cancer patients: a comparison with other studies

Previous studies have shown that a significant proportion of breast cancer patients exhibit elevated G2 chromosomal radiosensitivity in contrast to controls (approximately 40%). In this study, the G2 assay was applied to a small number of Irish breast cancer patients who were recorded as sporadic cases and they were compared with a control group to compare and contrast with the previous documented studies. Lymphocyte cultures were set up on whole blood samples and stimulated with phytohaemagglutinin. The cultures were irradiated 74?h later with 0.5?Gy gamma-radiation and cells were arrested in metaphase by treating the cultures with colcemid. The chromosomes were harvested and the aberrations scored per 100 metaphases to assign a G2 score. The assay was first carried out on four donor controls to estimate intra-individual variation and then ten controls for inter-individual variation to measure assay reproducibility. The G2 assay was then applied to 27 breast cancer patients. Good intrinsic assay reproducibility was observed in the coefficient of variation (CV) data in three out of four controls. Intra-individual variation was similar in three out of four of the donors (4.6?–?5.1%) with one donor showing a higher CV compared with the others (22.9%). Inter-individual variation was calculated at 30.5% for all controls. No significant difference was observed between intra- and inter-individual variation using the variance ratio F-test. A G2 radiosensitivity cut-off of 110 aberrations/100 metaphases was calculated from the controls, and from this 70.4% of breast cancer patients and 7.7% of controls were calculated as G2 radiosensitive. This proportion of G2-sensitive breast cancer patients is the highest recorded in studies to date. It is thought that the G2 radiosensitivity assay is a biomarker of breast cancer predisposition genes of low penetrance, suggesting the presence of these genes in the Irish breast cancer patients used in this study who were recorded as sporadic cases. A larger number of Irish patients would be required to consolidate these findings and be representative of the Irish breast cancer population.     

Subcutaneous adipose 11 beta-hydroxysteroid dehydrogenase type 1 activity and messenger ribonucleic acid levels are associated with adiposity and insulinemia in Pima Indians and Caucasians

Metabolic effects of cortisol may be critically modulated by glucocorticoid metabolism in tissues. Specifically, active cortisol is regenerated from inactive cortisone by the enzyme 11 beta-hydroxysteroid dehydrogenase type 1 (11-HSD1) in adipose and liver. We examined activity and mRNA levels of 11-HSD1 and tissue cortisol and cortisone levels in sc adipose tissue biopsies from 12 Caucasian (7 males and 5 females) and 19 Pima Indian (10 males and 9 females) nondiabetic subjects aged 28 +/- 7.6 yr (mean +/- SD; range, 18-45). Adipose 11-HSD1 activity and mRNA levels were highly correlated (r = 0.51, P = 0.003). Adipose 11-HSD1 activity was positively related to measures of total (body mass index, percentage body fat) and central (waist circumference) adiposity (P < 0.05 for all) and fasting glucose (r = 0.43, P = 0.02), insulin (r = 0.60, P = 0.0005), and insulin resistance by the homeostasis model (r = 0.70, P < 0.0001) but did not differ between sexes or ethnic groups. Intra-adipose cortisol was positively associated with fasting insulin (r = 0.37, P = 0.04) but was not significantly correlated with 11-HSD1 mRNA or activity or with other metabolic variables. In this cross-sectional study, higher adipose 11-HSD1 activity is associated with features of the metabolic syndrome. Our data support the hypothesis that increased regeneration of cortisol in adipose tissue influences metabolic sequelae of human obesity.     

An evaluation of intravenous immunoglobulin in the treatment of human immunodeficiency virus-associated thrombocytopenia

BACKGROUND: Anecdotal evidence suggests that high-dose intravenous immunoglobulin (IVIG) is useful in the management of human immunodeficiency virus (HIV)-associated thrombocytopenia. STUDY DESIGN AND METHODS: To rigorously evaluate this therapy, a crossover study was designed to compare IVIG, given at 1 g per kg per day for 2 consecutive days each week for 4 weeks, with intravenous saline placebo administered according to the same schedule. Subjects were randomly assigned to receive either IVIG or saline during the first 4 weeks; if IVIG was given, there was a 4-week period of no therapy before beginning placebo administration. Criteria for eligibility were platelet count of less than 50,000 per microL (50 × 10(9)/L), elevated platelet-associated IgG levels, increased megakaryocytes in the bone marrow, and positive HIV antibody test. Twelve patients (11 men, 1 woman) were studied. Seven patients completed the full protocol. Four dropped out: after 2, 5 (2 patients), and 8 weeks that included at least 2 weeks of IVIG. RESULTS: All patients sustained an increase in platelet count in response to IVIG, with increments ranging from 15,000 to 358,000 per microL (15 to 350 × 10(9)/L) (mean, 180,000/microL [180 × 10(9)/L]; median, 174,000/microL [174 × 10(9)/L]). No patient had an increase after placebo infusions. There were no adverse effects of treatment, and weekly chemical analyses showed no new abnormalities except for mild elevations in the serum protein. The duration of responses ranged from 2 to 10 weeks. No patient demonstrated refractoriness to IVIG. CONCLUSION: IVIG consistently raises platelet counts in patients with HIV-associated thrombocytopenia.     

下坡运动对大鼠骨骼肌肌浆网功能的影响

目的：观测研究下坡(离心)运动对大鼠骨骼肌肌浆网Ca2+-ATP酶活性,Ca2+摄取与释放在量与时程上的影响。此外,测定离子载体的刺激作用,即测定在含与不含(Ca2+离子载体)A23187时Ca2+-ATP酶活性的比值,用以评定囊泡的完整性。方法：成年雄性SD大鼠随机分为对照与离心运动组, 离心运动的大鼠分别于运动后即刻, 4, 24, 48, 72 和144h后取样 (n=7). 离心运动方式采用90min持续跑台下坡运动(-16°;15m/min)。取大鼠红股肌制备组织匀浆, 测定肌浆网Ca2+-ATP酶活性,Ca2+摄取与释放。结果：与对照组[19.25±1.38 nmol ·min-1·(mg protein)-1]相比, 肌浆网Ca2+摄取分别于运动后即刻和4h下降了29% and 36% (P<0.05), 24h依然降低(P<0.05). 肌浆网Ca2+释放与对照组[31.06±2.36 nmol·min-1·(mg protein)-1] 相比,也分别于运动后即刻和4h下降了37% and 39% (P<0.05), 24h持续降低(P<0.05). 用含离子载体测定的肌浆网Ca2+-ATP酶活性运动后4h降低了31%(P<0.05), 并于运动后24h仍然降低 (P<0.05)。运动后, 含与不含A23187时测定的Ca2+-ATP酶活性的比值未见显著性改变, 表明该运动没有明显改变肌浆网膜的完整性。结论：一次性低强度，长时间下坡运动导致肌浆网功能长时间降低, 运动后恢复期两天尚未完全恢复, 亦可构成离心运动诱导的骨骼肌某些功能降低的基础。提示这些变化可能产生于离心收缩时肌节长度不匀一性所造成的张力应激。     

Bamboo leaf-based carbon dots for efficient tumor imaging and therapy

In this study, carbon dots synthesized from bamboo leaf cellulose were used simultaneously as a staining agent and for doxorubicin delivery to target cancer cells. Owing to their nontoxic properties, the production of carbon dots from bamboo leaves is a green approach involving optimized application of bamboo tree waste. For multifunctional applications, the carbon dots were modified with 4-carboxybenzylboronic acid and doxorubicin to improve target specificity and drug delivery to HeLa tumor cells. The resulting modified carbon dots were characterized using different analytical techniques, which showed that they were biocompatible, nontoxic, and highly stable over a wide range of pH values and at high ionic strengths. Furthermore, in vitro confocal microscopy studies demonstrated their blue fluorescence and cellular pathway for entering HeLa cells via folate receptor-mediated endocytosis. Cell viability data and flow cytometry results also confirmed the selective uptake of the carbon dots by HeLa cells, which significantly enhanced cell cytotoxicity.

In this study, carbon dots synthesized from bamboo leaf cellulose were used simultaneously as a staining agent and for doxorubicin delivery to target cancer cells.     

Key High‐efficiency Practices of Emergency Department Providers: A Mixed‐methods Study

Objective

The objective of this study was to determine specific provider practices associated with high provider efficiency in community emergency departments (EDs).

Methods

A mixed‐methods study design was utilized to identify key behaviors associated with efficiency. Stage 1 was a convenience sample of 16 participants (ED medical directors, nurses, advanced practice providers, and physicians) identified provider efficiency behaviors during semistructured interviews. Ninety‐nine behaviors were identified and distilled by a group of three ED clinicians into 18 themes. Stage 2 was an observational study of 35 providers was performed in four (30,000‐ to 55,000‐visit) community EDs during two 4‐hour periods and recorded in minute‐by‐minute observation logs. In Stage 3, each behavior or practice from Stage 1 was assigned a score within each observation period. Behaviors were tested for association with provider efficiency (relative value units/hour) using linear univariate generalized estimating equations with an identity link, clustered on ED site.

Results

Five ED provider practices were found to be positively associated with efficiency: average patient load, using name of team member, conversations with health care team, visits to patient rooms, and running the board. Two behaviors, “inefficiency practices,” demonstrated significant negative correlations: non–work‐related tasks and documentation on patients no longer in the ED.

Conclusions

Average patient load, running the board, conversations with team member, and using names of team members are associated with enhanced provider productivity. Identification of behaviors associated with efficiency can be utilized by medical directors, clinicians, and trainees to improve personal efficiency or counsel team members.

     

Choice of Vein‐Harvest Technique for Coronary Artery Bypass Grafting: Rationale and Design of the REGROUP Trial

The Randomized Endo‐vein Graft Prospective (REGROUP) trial ( ClinicalTrials.gov  NCT01850082) is a randomized, intent‐to‐treat, 2‐arm, parallel‐design, multicenter study funded by the Cooperative Studies Program (CSP No. 588) of the US Department of Veterans Affairs. Cardiac surgeons at 16 Veterans Affairs (VA) medical centers with technical expertise in performing both endoscopic vein harvesting (EVH) and open vein harvesting (OVH) were recruited as the REGROUP surgeon participants. Subjects requiring elective or urgent coronary artery bypass grafting using cardiopulmonary bypass with use of ≥1 saphenous vein graft will be screened for enrollment using pre‐established inclusion/exclusion criteria. Enrolled subjects (planned N = 1150) will be randomized to 1 of the 2 arms (EVH or OVH) after an experienced vein harvester has been assigned. The primary outcomes measure is the rate of major adverse cardiac events (MACE), including death, myocardial infarction, or revascularization. Subject assessments will be performed at multiple times, including at baseline, intraoperatively, postoperatively, and at discharge (or 30 days after surgery, if still hospitalized). Assessment of leg‐wound complications will be completed at 6 weeks after surgery. Telephone follow‐ups will occur at 3‐month intervals after surgery until the participating sites are decommissioned after the trial's completion (approximately 4.5 years after the full study startup). To assess long‐term outcomes, centralized follow‐up of MACE for 2 additional years will be centrally performed using VA and non‐VA clinical and administrative databases. The primary MACE outcome will be compared between the 2 arms, EVH and OVH, at the end of the trial duration.     

锡伯族和汉族冠心病患者颈动脉粥样硬化及冠状动脉病变对比分析

目的 对比分析锡伯族、汉族冠心病患者颈动脉粥样硬化及冠状动脉病变情况.方法 对经冠状动脉造影明确的48例锡伯族、57例汉族冠心病患者和50例正常对照者均行颈动脉超声检查,比较各组间颈动脉内膜中膜厚度、斑块的发生率及冠状动脉病变的Gensini积分.结果 锡伯族、汉族冠心病患者内膜中膜厚度及颈动脉斑块的发生率均高于正常对照者(1.1±0.3 mm和1.0±0.1 mm比0.6±0.2 mm、88.3%和77.2%比38.0%,P<0.05),但锡伯族与汉族间比较没有统计学差异(P>0.05);锡伯族患者冠状动脉病变支数少于汉族(1.82±0.24比2.54±0.31, P<0.05),冠状动脉病变的Gensini积分也明显低于汉族(8.23±1.35比15.84±2.68,P<0.05),且冠状动脉病变支数越多,锡伯族、汉族冠心病患者颈动脉粥样硬化程度越重.结论 锡伯族和汉族冠心病患者颈动脉粥样硬化情况均重于正常对照者,但锡伯族和汉族间比较没有统计学意义;锡伯族和汉族冠心病患者冠状动脉病变存在差异,且锡伯族冠心病患者冠状动脉病变严重程度低于汉族;通过颈动脉内膜中膜厚度的程度可预测冠状动脉病变的存在及严重程度.