In Vitro Recombination Catalyzed by Bacterial Class 1 Integron Integrase IntI1 Involves Cooperative Binding and Specific Oligomeric Intermediates

Gene transfer via bacterial integrons is a major pathway for facilitating the spread of antibiotic resistance genes across bacteria. Recently the mechanism underlying the recombination catalyzed by class 1 integron recombinase (IntI1) between attC and attI1 was highlighted demonstrating the involvement of a single-stranded intermediary on the attC site. However, the process allowing the generation of this single-stranded substrate has not been determined, nor have the active IntI1•DNA complexes been identified. Using the in vitro strand transfer assay and a crosslink strategy we previously described we demonstrated that the single-stranded attC sequences could be generated in the absence of other bacterial proteins in addition to IntI. This suggests a possible role for this protein in stabilizing and/or generating this structure. The mechanism of folding of the active IntI•DNA complexes was further analyzed and we show here that it involves a cooperative binding of the protein to each recombination site and the emergence of different oligomeric species specific for each DNA substrate. These findings provide further insight into the recombination reaction catalyzed by IntI1

A statistical network analysis of the HIV/AIDS epidemics in Cuba

The Cuban contact-tracing detection system set up in 1986 allowed the reconstruction and analysis of the sexual network underlying the epidemic (5,389 vertices and 4,073 edges, giant component of 2,386 nodes and 3,168 edges), shedding light onto the spread of HIV and the role of contact-tracing. Clustering based on modularity optimization provides a better visualization and understanding of the network, in combination with the study of covariates. The graph has a globally low but heterogeneous density, with clusters of high intraconnectivity but low interconnectivity. Though descriptive, our results pave the way for incorporating structure when studying stochastic SIR epidemics spreading on social networks

Comparison of Short-Term Estrogenicity Tests for Identification of Hormone-Disrupting Chemicals

The aim of this study was to compare results obtained by eight different short-term assays of estrogenlike actions of chemicals conducted in 10 different laboratories in five countries. Twenty chemicals were selected to represent direct-acting estrogens, compounds with estrogenic metabolites, estrogenic antagonists, and a known cytotoxic agent. Also included in the test panel were 17β-estradiol as a positive control and ethanol as solvent control. The test compounds were coded before distribution. Test methods included direct binding to the estrogen receptor (ER), proliferation of MCF-7 cells, transient reporter gene expression in MCF-7 cells, reporter gene expression in yeast strains stably transfected with the human ER and an estrogen-responsive reporter gene, and vitellogenin production in juvenile rainbow trout. 17β-Estradiol, 17α-ethynyl estradiol, and diethylstilbestrol induced a strong estrogenic response in all test systems. Colchicine caused cytotoxicity only. Bisphenol A induced an estrogenic response in all assays. The results obtained for the remaining test compounds—tamoxifen, ICI 182.780, testosterone, bisphenol A dimethacrylate, 4-n-octylphenol, 4-n-nonylphenol, nonylphenol dodecylethoxylate, butylbenzylphthalate, dibutylphthalate, methoxychlor, o,p′-DDT, p,p′-DDE, endosulfan, chlomequat chloride, and ethanol—varied among the assays. The results demonstrate that careful standardization is necessary to obtain a reasonable degree of reproducibility. Also, similar methods vary in their sensitivity to estrogenic compounds. Thus, short-term tests are useful for screening purposes, but the methods must be further validated by additional interlaboratory and interassay comparisons to document the reliability of the methods

The empirical basis for modelling glacial erosion rates

Glaciers are highly effective agents of erosion that have profoundly shaped Earth’s surface, but there is uncertainty about how glacial erosion should be parameterised in landscape evolution models. Glacial erosion rate is usually modelled as a function of glacier sliding velocity, but the empirical basis for this relationship is weak. In turn, climate is assumed to control sliding velocity and hence erosion, but this too lacks empirical scrutiny. Here, we present statistically robust relationships between erosion rates, sliding velocities, and climate from a global compilation of 38 glaciers. We show that sliding is positively and significantly correlated with erosion, and derive a relationship for use in erosion models. Our dataset further demonstrates that the most rapid erosion is achieved at temperate glaciers with high mean annual precipitation, which serve to promote rapid sliding. Precipitation has received little attention in glacial erosion studies, but our data illustrate its importance

Comparing international coverage of 9/11 : towards an interdisciplinary explanation of the construction of news

This article presents an interdisciplinary model attempting to explain how news is constructed by relying on the contributions of different fields of study: News Sociology, Political Communications, International Communications, International Relations. It is a first step towards developing a holistic theoretical approach to what shapes the news, which bridges current micro to macro approaches. More precisely the model explains news variation across different media organization and countries by focusing on the different way the sense of newsworthiness of journalists is affected by three main variables: national interest, national journalistic culture, and editorial policy of each media organization. The model is developed on the basis of an investigation into what shaped the media coverage of 9/11 in eight elite newspapers across the US, France, Italy and Pakistan

Inequitable access to substance abuse treatment services in Cape Town, South Africa

BACKGROUND:Despite high levels of substance use disorders in Cape Town, substance abuse treatment utilization is low among people from disadvantaged communities in Cape Town, South Africa. To improve substance abuse treatment utilization, it is important to identify any potential barriers to treatment initiation so that interventions to reduce these barriers can be implemented. To date, substance abuse research has not examined the factors associated with substance abuse treatment utilization within developing countries. Using the Behavioural Model of Health Services Utilization as an analytic framework, this study aimed to redress this gap by examining whether access to substance abuse treatment is equitable and the profile of variables associated with treatment utilization for people from poor communities in Cape Town, South Africa. METHODS: This study used a case-control design to compare 434 individuals with substance use disorders from disadvantaged communities who had accessed treatment with 555 controls who had not accessed treatment on a range of predisposing, treatment need and enabling/restricting variables thought to be associated with treatment utilization. A hierarchical logistic regression was conducted to assess the unique contribution that the need for treatment, predisposing and enabling/restricting variable blocks made on substance abuse treatment utilization. RESULTS: Findings revealed that non-need enabling/restricting variables accounted for almost equal proportions of the variance in service utilization as the need for treatment variables. These enabling/restricting variables also attenuated the influence of the treatment need and predisposing variables domains on chances of treatment utilization. Several enabling/restricting variables emerged as powerful partial predictors of utilization including competing financial priorities, geographic access barriers and awareness of treatment services. Perceived severity of drug use, a need for treatment variable) was also a partial predictor of utilization. CONCLUSIONS: Findings point to inequitable access to substance abuse treatment services among people from poor South African communities, with non-need factors being significant determinants of treatment utilization. In these communities, treatment utilization can be enhanced by (i) expanding the existing repertoire of services to include low threshold services that target individuals with less severe problems; (ii) providing food and transport vouchers as part of contingency management efforts, thereby reducing some of the financial and geographic access barriers; (iii) introducing community-based mobile outpatient treatment services that are geographically accessible; and (iv) employing community-based outreach workers that focus on improving awareness of where, when and how to access existing treatment services

Torsades de pointes during laparoscopic adrenalectomy of a pheochromocytoma: a case report

<p>Abstract</p> <p>Introduction</p> <p>Torsades de pointes is a rare but potentially lethal arrhythmia. The amount of literature available on Torsades de pointes occurring in patients with pheochromocytoma is limited, and we found no literature describing this dysrhythmia in a patient with pheochromocytoma under anesthesia.</p> <p>Case presentation</p> <p>We describe the case of a 42-year-old Caucasian woman without QT prolongation preoperatively with recurrent Torsades de pointes during laparoscopic removal of a pheochromocytoma. Torsades de pointes mainly occurs in the setting of a prolonged QT interval. This patient neither had a prolonged QT preoperatively nor was her family history suspect for a congenital long QT syndrome. Most likely, our patient had an acquired long QT syndrome, elicited by the combination of flecainide, hypomagnesemia and adrenergic stimulation during manipulation of the tumor.</p> <p>Conclusion</p> <p>We show that in the case of a surgical pheochromocytoma removal, perioperative conditions can elicit an acquired or previously unknown congenital long QT syndrome. Therefore, preoperative α- and β-blockade is advised, QT-prolonging drugs should be avoided and potassium and magnesium plasma levels should be kept at normal to high levels.</p

Extent and structure of health insurance expenditures for complementary and alternative medicine in Swiss primary care

BACKGROUND: The study is part of a nationwide evaluation of complementary and alternative medicine (CAM) in primary care in Switzerland. The goal was to evaluate the extent and structure of basic health insurance expenditures for complementary and alternative medicine in Swiss primary care. METHODS: The study was designed as a cross-sectional evaluation of Swiss primary care providers and included 262 certified CAM physicians, 151 noncertified CAM physicians and 172 conventional physicians. The study was based on data from a mailed questionnaire and on reimbursement information obtained from health insurers. It was therefore purely observational, without interference into diagnostic and therapeutic procedures applied or prescribed by physicians. Main outcome measures included average reimbursed costs per patient, structured into consultation- and medication-related costs, and referred costs. RESULTS: Total average reimbursed cost per patient did not differ between CAM physicians and conventional practitioners, but considerable differences were observed in cost structure. The proportions of reimbursed costs for consultation time were 56% for certified CAM, 41% for noncertified CAM physicians and 40% for conventional physicians; medication costs – including expenditures for prescriptions and directly dispensed drugs – respectively accounted for 35%, 18%, and 51% of costs. CONCLUSION: The results indicate no significant difference for overall treatment cost per patient between CAM and COM primary care in Switzerland. However, CAM physicians treat lower numbers of patients and a more cost-favourable patient population than conventional physicians. Differences in cost structure reflect more patient-centred and individualized treatment modalities of CAM physicians

The role of parental achievement goals in predicting autonomy-supportive and controlling parenting

Although autonomy-supportive and controlling parenting are linked to numerous positive and negative child outcomes respectively, fewer studies have focused on their determinants. Drawing on achievement goal theory and self-determination theory, we propose that parental achievement goals (i.e., achievement goals that parents have for their children) can be mastery, performance-approach or performance-avoidance oriented and that types of goals predict mothers' tendency to adopt autonomy-supportive and controlling behaviors. A total of 67 mothers (aged 30-53 years) reported their goals for their adolescent (aged 13-16 years; 19.4 % girls), while their adolescent evaluated their mothers' behaviors. Hierarchical regression analyses showed that parental performance-approach goals predict more controlling parenting and prevent acknowledgement of feelings, one autonomy-supportive behavior. In addition, mothers who have mastery goals and who endorse performance-avoidance goals are less likely to use guilt-inducing criticisms. These findings were observed while controlling for the effect of maternal anxiety

Negative Feedback Regulation following Administration of Chronic Exogenous Corticosterone

Administration of exogenous glucocorticoids is known to suppress the HPA axis and has been reported to occupy brain glucocorticoid receptors, eventually leading to down-regulation. To determine the effects of chronic corticosterone administration on HPA axis function, corticosterone was administered as both 25% and 50% corticosteronekholesterol pellets. Rats were sacrificed 6 days after corticosterone pellet implantation. The 25% corticosterone pellets produced a small increase in morning corticosterone concentrations but no change in evening ACTH or corticosterone secretion. The 50% corticosterone pellets produced constant corticosterone concentrations of 5–6 pg/dl, with no circadian variation in corticosterone, indicating inhibition of evening ACTH and corticosterone secretion. The 25% corticosterone pellets produced no significant decrease in thymus weight or in adrenal weight; 50% corticosterone pellets produced significant decreases in thymus weight and adrenal weight. Neither 25% nor 50% corticosterone pellets produced significant decreases in GR in hippocampus and cortex. The 50% corticosterone pellets treatment resulted in a decrease in anterior pituitary POMC mRNA levels, a decrease in baseline and oCRH stimulated ACTH release from the anterior pituitary, and a near complete inhibition of the AM and PM response to restraint stress. These results suggest that: 1) the HPA axis was able to adjust to the small increase in glucocorticoids produced by the 25% cort pellets with minimal disturbances in function and 2) 50% corticosterone pellets exert a significant inhibitory effect on stress and diurnal ACTH secretion which appears to be exerted at the pituitary as well as possible inhibitory effects on brain.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72571/1/j.1365-2826.1995.tb00665.x.pd