Virginia Woolf, I Understand

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Study on the gender dimension of trafficking in human beings

The purpose of this study is to contribute to the identification and understanding of what it means to be ‘taking into account the gender perspective, to strengthen the prevention of this crime and protection of the victims there-of’, as required in Article 1 of European Union (EU) Directive 2011/36/EU on Preventing and Combating Trafficking in Human Beings and Protecting its Victims in the context of the EU Strategy (COM(2012) 286 final) Towards the Eradication of Trafficking in Human Beings. The study contributes to Priority E Action 2 of the Strategy, which states that ‘the Commission will develop knowledge on the gender dimensions of human trafficking, including the gender consequences of the various forms of trafficking and potential differences in the vulnerability of men and women to victimisation and its impact on them.’ Its specific objectives and tasks are to address: the ‘gender dimension of vulnerability, recruitment, and victimisation’; ‘gender issues related to traffickers and to those creating demand’; and ‘an examination of law and policy responses on trafficking in human beings from a gender perspective’. The study addresses the five priorities of the EU Strategy: identifying, protecting, and assisting victims of traf-ficking; stepping up the prevention of trafficking in human beings; better law enforcement; enhanced coordination and cooperation among key actors and policy coherence; and increased knowledge of an effective response to emerging concerns. This study, according to its terms of reference, aims to look specifically at the gender dimension of trafficking for the purpose of sexual exploitation. This follows evidence from statistical data from Eurostat, as well as da-ta from The European Police Office (Europol) and the United Nations Office on Drugs and Crime (UNODC), accord-ing to which the most reported form of exploitation of victims is that of sexual exploitation and its strong gen-der dimension (96 % women and girls). It further addresses recommendations addressed in the Resolution of the European Parliament of 26 February 2014 on sexual exploitation and prostitution and its impact on gender equality (2013/2103(INI)) urging the European Commission to evaluate the impact that the European legal frame-work designed to eliminate trafficking for sexual exploitation has had to date and to undertake further research on patterns of prostitution, on human trafficking for the purpose of sexual exploitation and on the increased lev-el of sex tourism in the EU, with particular reference to minors, and to promote the exchange of best practices among the Member States. The study identifies and draws on EU law and policy competence in gender equality in its identification of the gen-der dimensions of trafficking. The gender dimensions are clustered into five issues: gender specificity and equal treatment; gender expertise, gender balance in decision-making and gender mainstreaming; the relationship be-tween prostitution and trafficking; gendered policy fields and strategic priorities; gendered systems and the the-ory of prevention

multiple pulmonary and multivesicular interatrial septum hydatid cysts in a native italian patient

Multivesicular, pulmonary and cardiac hydatidosis are rarely observed and can give rise to serious complications. Cysts can remain asymptomatic for a long time, until they reveal themselves perforating into cardiac chambers and/or pulmonary arteries or the systemic circulation. A rare case of multivesicular interatrial septum hydatid cyst with multiple pulmonary involvement in a native Italian farm labourer is reported. Clinical, radiological, serological and histological findings are described. MR imaging showed the exact anatomic location and the multivesicular nature of the cardiac cyst and was useful in planning surgical treatment. A successful outcome was achieved with a combination of pre- and post-operative albendazole therapy and a three-step surgery procedure. The patient made a rapid recovery and his post-operative period was totally uneventful. This case highlights the importance of an early multidisciplinary surgical approach and long-term chemotherapy treatment of this serious and rare disease. MR Imaging was crucial in the pre-surgical and follow-up observations

Quantifying structural racism in cohort studies to advance prospective evidence

Calls-to-action in health research have described a need to improve research on race, ethnicity, and structural racism. Well-established cohort studies typically lack access to novel structural and social determinants of health (SSDOH) or precise race and ethnicity categorization, contributing to a loss of rigor to conduct informative analyses and a gap in prospective evidence on the role of structural racism in health outcomes. We propose and implement methods that prospective cohort studies can use to begin to rectify this, using the Women's Health Initiative (WHI) cohort as a case study. To do so, we evaluated the quality, precision, and representativeness of race, ethnicity, and SSDOH data compared with the target US population and operationalized methods to quantify structural determinants in cohort studies. Harmonizing racial and ethnic categorization to the current standards set by the Office of Management and Budget improved measurement precision, aligned with published recommendations, disaggregated groups, decreased missing data, and decreased participants reporting “some other race”. Disaggregation revealed sub-group disparities in SSDOH, including a greater proportion of Black-Latina (35.2%) and AIAN-Latina (33.3%) WHI participants with income below the US median compared with White-Latina (42.5%) participants. We found similarities in the racial and ethnic patterning of SSDOH disparities between WHI and US women but less disparity overall in WHI. Despite higher individual-level advantage in WHI, racial disparities in neighborhood resources were similar to the US, reflecting structural racism. Median neighborhood income was comparable between Black WHI ($39,000) and US ($34,700) women. WHI SSDOH-associated outcomes may be generalizable on the basis of comparing across race and ethnicity but may quantitatively (but not qualitatively) underestimate US effect sizes. This paper takes steps towards data justice by implementing methods to make visible hidden health disparity groups and operationalizing structural-level determinants in prospective cohort studies, a first step to establishing causality in health disparities research

Cytoplasmic p53 couples oncogene-driven glucose metabolism to apoptosis and is a therapeutic target in glioblastoma.

Cross-talk among oncogenic signaling and metabolic pathways may create opportunities for new therapeutic strategies in cancer. Here we show that although acute inhibition of EGFR-driven glucose metabolism induces only minimal cell death, it lowers the apoptotic threshold in a subset of patient-derived glioblastoma (GBM) cells. Mechanistic studies revealed that after attenuated glucose consumption, Bcl-xL blocks cytoplasmic p53 from triggering intrinsic apoptosis. Consequently, targeting of EGFR-driven glucose metabolism in combination with pharmacological stabilization of p53 with the brain-penetrant small molecule idasanutlin resulted in synthetic lethality in orthotopic glioblastoma xenograft models. Notably, neither the degree of EGFR-signaling inhibition nor genetic analysis of EGFR was sufficient to predict sensitivity to this therapeutic combination. However, detection of rapid inhibitory effects on [18F]fluorodeoxyglucose uptake, assessed through noninvasive positron emission tomography, was an effective predictive biomarker of response in vivo. Together, these studies identify a crucial link among oncogene signaling, glucose metabolism, and cytoplasmic p53, which may potentially be exploited for combination therapy in GBM and possibly other malignancies

Genome-Wide Interactions with Dairy Intake for Body Mass Index in Adults of European Descent

Scope: Body weight responds variably to the intake of dairy foods. Genetic variation may contribute to inter‐individual variability in associations between body weight and dairy consumption. Methods and results: A genome‐wide interaction study to discover genetic variants that account for variation in BMI in the context of low‐fat, high‐fat and total dairy intake in cross‐sectional analysis was conducted. Data from nine discovery studies (up to 25 513 European descent individuals) were meta‐analyzed. Twenty‐six genetic variants reached the selected significance threshold (p‐interaction \u3c10−7), and six independent variants (LINC01512‐rs7751666, PALM2/AKAP2‐rs914359, ACTA2‐rs1388, PPP1R12A‐rs7961195, LINC00333‐rs9635058, AC098847.1‐rs1791355) were evaluated meta‐analytically for replication of interaction in up to 17 675 individuals. Variant rs9635058 (128 kb 3’ of LINC00333) was replicated (p‐interaction = 0.004). In the discovery cohorts, rs9635058 interacted with dairy (p‐interaction = 7.36 × 10−8) such that each serving of low‐fat dairy was associated with 0.225 kg m−2 lower BMI per each additional copy of the effect allele (A). A second genetic variant (ACTA2‐rs1388) approached interaction replication significance for low‐fat dairy exposure. Conclusion: Body weight responses to dairy intake may be modified by genotype, in that greater dairy intake may protect a genetic subgroup from higher body weight

The Impact of Small Molecule Binding on the Energy Landscape of the Intrinsically Disordered Protein C-Myc

Intrinsically disordered proteins are attractive therapeutic targets owing to their prevalence in several diseases. Yet their lack of well-defined structure renders ligand discovery a challenging task. An intriguing example is provided by the oncoprotein c-Myc, a transcription factor that is over expressed in a broad range of cancers. Transcriptional activity of c-Myc is dependent on heterodimerization with partner protein Max. This protein-protein interaction is disrupted by the small molecule 10058-F4 (1), that binds to monomeric and disordered c-Myc. To rationalize the mechanism of inhibition, structural ensembles for the segment of the c-Myc domain that binds to 1 were computed in the absence and presence of the ligand using classical force fields and explicit solvent metadynamics molecular simulations. The accuracy of the computed structural ensembles was assessed by comparison of predicted and measured NMR chemical shifts. The small molecule 1 was found to perturb the composition of the apo equilibrium ensemble and to bind weakly to multiple distinct c-Myc conformations. Comparison of the apo and holo equilibrium ensembles reveals that the c-Myc conformations binding 1 are already partially formed in the apo ensemble, suggesting that 1 binds to c-Myc through an extended conformational selection mechanism. The present results have important implications for rational ligand design efforts targeting intrinsically disordered proteins

Interactions of dietary whole-grain intake with fasting glucose- and insulin-related genetic loci in individuals of European descent: a meta-analysis of 14 cohort studies.

OBJECTIVE: Whole-grain foods are touted for multiple health benefits, including enhancing insulin sensitivity and reducing type 2 diabetes risk. Recent genome-wide association studies (GWAS) have identified several single nucleotide polymorphisms (SNPs) associated with fasting glucose and insulin concentrations in individuals free of diabetes. We tested the hypothesis that whole-grain food intake and genetic variation interact to influence concentrations of fasting glucose and insulin. RESEARCH DESIGN AND METHODS: Via meta-analysis of data from 14 cohorts comprising ∼ 48,000 participants of European descent, we studied interactions of whole-grain intake with loci previously associated in GWAS with fasting glucose (16 loci) and/or insulin (2 loci) concentrations. For tests of interaction, we considered a P value <0.0028 (0.05 of 18 tests) as statistically significant. RESULTS: Greater whole-grain food intake was associated with lower fasting glucose and insulin concentrations independent of demographics, other dietary and lifestyle factors, and BMI (β [95% CI] per 1-serving-greater whole-grain intake: -0.009 mmol/l glucose [-0.013 to -0.005], P < 0.0001 and -0.011 pmol/l [ln] insulin [-0.015 to -0.007], P = 0.0003). No interactions met our multiple testing-adjusted statistical significance threshold. The strongest SNP interaction with whole-grain intake was rs780094 (GCKR) for fasting insulin (P = 0.006), where greater whole-grain intake was associated with a smaller reduction in fasting insulin concentrations in those with the insulin-raising allele. CONCLUSIONS: Our results support the favorable association of whole-grain intake with fasting glucose and insulin and suggest a potential interaction between variation in GCKR and whole-grain intake in influencing fasting insulin concentrations