Meta-analysis of diffusion tensor imaging studies shows altered fractional anisotropy occurring in distinct brain areas in association with depression

Fractional anisotropy anomalies occurring in the white matter tracts in the brains of depressed patients may reflect microstructural changes underlying the pathophysiology of this disorder. We conducted a meta-analysis of fractional anisotropy abnormalities occurring in major depressive disorder using voxel-based diffusion tensor imaging studies. Using the Embase, PubMed and Google Scholar databases, 89 relevant data sets were identified, of which 7 (including 188 patients with major depressive disorder and 221 healthy controls) met our inclusion criteria. Authors were contacted to retrieve any additional data required. Coordinates were extracted from clusters of significant white matter fractional anisotropy differences between patients and controls. Relevant demographic, clinical and methodological variables were extracted from each study or obtained directly from authors. The meta-analysis was carried out using Signed Differential Mapping. Patients with depression showed decreased white matter fractional anisotropy values in the superior longitudinal fasciculus and increased fractional anisotropy values in the fronto-occipital fasciculus compared to controls. Using quartile and jackknife sensitivity analysis, we found that reduced fractional anisotropy in the left superior longitudinal fasciculus was very stable, with increases in the right fronto-occipital fasciculus driven by just one study. In conclusion, our meta-analysis revealed a significant reduction in fractional anisotropy values in the left superior longitudinal fasciculus, which may ultimately play an important role in the pathology of depression

Illegal immigration and media exposure: evidence on individual attitudes

Illegal immigration has been the focus of much debate in receiving countries, but little is known about the drivers of individual attitudes towards illegal immigrants. To study this question, we use the CCES survey, which was carried out in 2006 in the USA. We find evidence that—in addition to standard labor market and welfare state considerations—media exposure is significantly correlated with public opinion on illegal immigration. Controlling for education, income, ideology, and other socio-demographic characteristics, individuals watching Fox News are 9 percentage points more likely than CBS viewers to oppose the legalization of undocumented immigrants. We find an effect of the same size and direction for CNN viewers, whereas individuals watching PBS are instead more likely to support legalization. Ideological self-selection into different news programs plays an important role, but cannot entirely explain the correlation between media exposure and attitudes about illegal immigration

L-arginine Supplementation Improves Responses to Injury and Inflammation in Dextran Sulfate Sodium Colitis

Inflammatory bowel disease (IBD), consisting of Crohn's disease and ulcerative colitis (UC), results in substantial morbidity and is difficult to treat. New strategies for adjunct therapies are needed. One candidate is the semi-essential amino acid, L-arginine (L-Arg), a complementary medicine purported to be an enhancer of immunity and vitality in the lay media. Using dextran sulfate sodium (DSS) as a murine colonic injury and repair model with similarities to human UC, we assessed the effect of L-Arg, as DSS induced increases in colonic expression of the y+ cationic amino acid transporter 2 (CAT2) and L-Arg uptake. L-Arg supplementation improved the clinical parameters of survival, body weight loss, and colon weight, and reduced colonic permeability and the number of myeloperoxidase-positive neutrophils in DSS colitis. Luminex-based multi-analyte profiling demonstrated that there was a marked reduction in proinflammatory cytokine and chemokine expression with L-Arg treatment. Genomic analysis by microarray demonstrated that DSS-treated mice supplemented with L-Arg clustered more closely with mice not exposed to DSS than to those receiving DSS alone, and revealed that multiple genes that were upregulated or downregulated with DSS alone exhibited normalization of expression with L-Arg supplementation. Additionally, L-Arg treatment of mice with DSS colitis resulted in increased ex vivo migration of colonic epithelial cells, suggestive of increased capacity for wound repair. Because CAT2 induction was sustained during L-Arg treatment and inducible nitric oxide (NO) synthase (iNOS) requires uptake of L-Arg for generation of NO, we tested the effect of L-Arg in iNOS−/− mice and found that its benefits in DSS colitis were eliminated. These preclinical studies indicate that L-Arg supplementation could be a potential therapy for IBD, and that one mechanism of action may be functional enhancement of iNOS activity

Measuring kinetic drivers of pneumolysin pore structure

Most membrane attack complex-perforin/cholesterol-dependent cytolysin (MACPF/CDC) proteins are thought to form pores in target membranes by assembling into pre-pore oligomers before undergoing a pre-pore to pore transition. Assembly during pore formation is into both full rings of subunits and incomplete rings (arcs). The balance between arcs and full rings is determined by a mechanism dependent on protein concentration in which arc pores arise due to kinetic trapping of the pre-pore forms by the depletion of free protein subunits during oligomerisation. Here we describe the use of a kinetic assay to study pore formation in red blood cells by the MACPF/CDC pneumolysin from Streptococcus pneumoniae. We show that cell lysis displays two kinds of dependence on protein concentration. At lower concentrations it is dependent on the pre-pore topore transition of arc oligomers, which we show to be a cooperative process. At higher concentrations it is dependent on the amount of pneumolysin bound to the membrane and reflects the affinity of the protein for its receptor, cholesterol. A lag occurs before cell lysis begins; this is dependent on oligomerisation of pneumolysin. Kinetic dissection of cell lysis by pneumolysin demonstrates the capacity of MACPF/CDCs to generate pore-forming oligomericstructures of variable size with, most likely, different functional roles in biology

Regulation of BRCA1 expression and its relationship to sporadic breast cancer

Germ-line mutations in the BRCA1 tumour suppressor gene contribute to familial breast tumour formation, but there is no evidence for direct mutation of the BRCA1 gene in the sporadic form of the disease. In contrast, decreased expression of the BRCA1 gene has been shown to be common in sporadic tumours, and the magnitude of the decrease correlates with disease progression. BRCA1 expression is also tightly regulated during normal breast development. Determining how these developmental regulators of BRCA1 expression are co-opted during breast tumourigenesis could lead to a better understanding of sporadic breast cancer aetiology and the generation of novel therapeutic strategies aimed at preventing sporadic breast tumour progression

Prevalence and impact of alcohol and other drug use disorders on sedation and mechanical ventilation: a retrospective study

BACKGROUND: Experience suggests that patients with alcohol and other drug use disorders (AOD) are commonly cared for in our intensive care units (ICU's) and require more sedation. We sought to determine the impact of AOD on sedation requirement and mechanical ventilation (MV) duration. METHODS: Retrospective review of randomly selected records of adult patients undergoing MV in the medical ICU. Diagnoses of AOD were identified using strict criteria in Diagnostic and Statistical Manual of Mental Disorders, and through review of medical records and toxicology results. RESULTS: Of the 70 MV patients reviewed, 27 had AOD (39%). Implicated substances were alcohol in 22 patients, cocaine in 5, heroin in 2, opioids in 2, marijuana in 2. There was no difference between AOD and non-AOD patients in age, race, or reason for MV, but patients with AOD were more likely to be male (21 versus 15, p < 0.0001) and had a lower mean Acute Physiology and Chronic Health Evaluation II (22 versus 26, p = 0.048). While AOD patients received more lorazepam equivalents (0.5 versus 0.2 mg/kg.day, p = 0.004), morphine equivalents (0.5 versus 0.1 mg/kg.day, p = 0.03) and longer duration of infusions (16 versus 10 hours/day. medication, p = 0.002), they had similar sedation levels (Richmond Agitation-Sedation Scale (RASS) -2 versus -2, p = 0.83), incidence of agitation (RASS ≥ 3: 3.0% versus 2.4% of observations, p = 0.33), and duration of MV (3.6 versus 3.9 days, p = 0.89) as those without AOD. CONCLUSION: The prevalence of AOD among medical ICU patients undergoing MV is high. Patients with AOD receive higher doses of sedation than their non-AOD counterparts to achieve similar RASS scores but do not undergo longer duration of MV

Early identification of first-year students at risk of dropping out of high-school entry medical school: the usefulness of teachers' ratings of class participation

Dropping out from undergraduate medical education is costly for students, medical schools, and society in general. Therefore, the early identification of potential dropout students is important. The contribution of personal features to dropout rates has merited exploration. However, there is a paucity of research on aspects of student experience that may lead to dropping out. In this study, underpinned by theoretical models of student commitment, involvement, and engagement, we explored the hypothesis of using inferior participation as an indicator of a higher probability of dropping out in year 1. Class participation was calculated as an aggregate score based on teachers' daily observations in class. The study used a longitudinal dataset of six cohorts of high-school entry students (N = 709, 67% females) in one medical school with an annual intake of 120 students. The findings confirmed the initial hypothesis and showed that lower scores of class participation in year 1 added predictive ability to pre-entry characteristics (Pseudo-R2 raised from 0.22 to 0.28). Even though the inclusion of course failure in year 1 resulted in higher explanatory power than participation in class (Pseudo-R2 raised from 0.28 to 0.63), ratings of class participation may be advantageous to anticipate dropout identification, as those can be collected prior to course failure. The implications for practice are that teachers' ratings of class participation can play a role in indicating medical students who may eventually drop out. We conclude that the scores of class participation can contribute to flagging systems for the early detection of student dropouts.(undefined)info:eu-repo/semantics/acceptedVersio