Cognitive mediators of the effect of peer victimization on loneliness

The impact of stress on psychological adjustment may be mediated by cognitive interpretations (i.e., appraisals) of events for individuals. Defining characteristics of loneliness suggest that appraisals of blame, threat, and perceived control may be particularly important in this domain. AIMS: To evaluate the extent to which cognitive appraisals (perceived control, threat, and blame) can mediate the effect of peer victimization on loneliness. SAMPLE: One hundred and ten children (54 boys, 56 girls) aged 8-12 years attending mainstream schools in Scotland. METHOD: Self-report measures of peer victimization, appraisal, and loneliness. RESULTS: Perceived control partially mediated the effects of peer victimization on loneliness, but neither blame nor threat were mediators. All three measures of control were significantly associated with loneliness at the bivariate level, but only perceived control was significant when the appraisals were entered as predictors in a hierarchical multiple linear regression. CONCLUSIONS: The results highlight the importance of research designs assessing multiple categories of appraisal. Furthermore, they suggest that intervention efforts aiming to combat feelings of loneliness within a peer victimization context should address children's appraisals of perceived control

Neurosteroids and Self-Reported Pain in Veterans Who Served in the U.S. Military after September 11, 2001

Nearly half of Operation Enduring Freedom / Operation Iraqi Freedom (OEF/OIF) veterans experience continued pain post-deployment. Several investigations report analgesic effects of allopregnanolone and other neurosteroids in animal models, but few data are currently available focusing on neurosteroids in clinical populations. Allopregnanolone positively modulates GABAA receptors and demonstrates pronounced analgesic and anxiolytic effects in rodents, yet studies examining the relationship between pain and allopregnanolone in humans are limited. We thus hypothesized that endogenous allopregnanolone and other neurosteroid levels may be negatively correlated with self-reported pain symptoms in humans

Quantitative High-Resolution Genomic Analysis of Single Cancer Cells

During cancer progression, specific genomic aberrations arise that can determine the scope of the disease and can be used as predictive or prognostic markers. The detection of specific gene amplifications or deletions in single blood-borne or disseminated tumour cells that may give rise to the development of metastases is of great clinical interest but technically challenging. In this study, we present a method for quantitative high-resolution genomic analysis of single cells. Cells were isolated under permanent microscopic control followed by high-fidelity whole genome amplification and subsequent analyses by fine tiling array-CGH and qPCR. The assay was applied to single breast cancer cells to analyze the chromosomal region centred by the therapeutical relevant EGFR gene. This method allows precise quantitative analysis of copy number variations in single cell diagnostics

Proof-of-Concept Trial with the Neurosteroid Pregnenolone Targeting Cognitive and Negative Symptoms in Schizophrenia

The neurosteroid pregnenolone and its sulfated derivative enhance learning and memory in rodents. Pregnenolone sulfate also positively modulates NMDA receptors and could thus ameliorate hypothesized NMDA receptor hypofunction in schizophrenia. Furthermore, clozapine increases pregnenolone in rodent hippocampus, possibly contributing to its superior efficacy. We therefore investigated adjunctive pregnenolone for cognitive and negative symptoms in patients with schizophrenia or schizoaffective disorder receiving stable doses of second-generation antipsychotics in a pilot randomized, placebo-controlled, double-blind trial. Following a 2-week single-blind placebo lead-in, patients were randomized to pregnenolone (fixed escalating doses to 500 mg/day) or placebo, for 8 weeks. Primary end points were changes in BACS and MCCB composite and total SANS scores. Of 21 patients randomized, 18 completed at least 4 weeks of treatment (n = 9/group). Pregnenolone was well tolerated. Patients receiving pregnenolone demonstrated significantly greater improvements in SANS scores (mean change = 10.38) compared with patients receiving placebo (mean change = 2.33), p = 0.048. Mean composite changes in BACS and MCCB scores were not significantly different in patients randomized to pregnenolone compared with placebo. However, serum pregnenolone increases predicted BACS composite scores at 8 weeks in the pregnenolone group (rs = 0.81, p = 0.022). Increases in allopregnanolone, a GABAergic pregnenolone metabolite, also predicted BACS composite scores (rs = 0.74, p = 0.046). In addition, baseline pregnenolone (rs = −0.76, p = 0.037), pregnenolone sulfate (rs = − 0.83, p = 0.015), and allopregnanolone levels (rs = −0.83, p = 0.015) were inversely correlated with improvements in MCCB composite scores, further supporting a possible role for neurosteroids in cognition. Mean BACS and MCCB composite scores were correlated (rs = 0.74, p <0.0001). Pregnenolone may be a promising therapeutic agent for negative symptoms and merits further investigation for cognitive symptoms in schizophrenia

Decrease in Incidence of Colorectal Cancer Among Individuals 50 Years or Older After Recommendations for Population-based Screening

BACKGROUND & AIMS: The incidence of colorectal cancer (CRC) in the United States is increasing among adults younger than 50 years, but incidence has decreased among older populations after population-based screening was recommended in the late 1980s. Blacks have higher incidence than whites. These patterns have prompted suggestions to lower the screening age for average-risk populations or in blacks. At the same time, there has been controversy over whether reductions in CRC incidence can be attributed to screening. We examined age-related and race-related differences in CRC incidence during a 40-year time period. METHODS: We determined the age-standardized incidence of CRC from 1975 through 2013 by using the population-based Surveillance, Epidemiology, and End Results (SEER) program of cancer registries. We calculated incidence for 5-year age categories (20-24 years through 80-84 years and 85 years or older) for different time periods (1975-1979, 1980-1984, 1985-1989, 1990-1994, 1995-1999, 2000-2004, 2005-2009, and 2010-2013), tumor subsite (proximal colon, descending colon, and rectum), and stages at diagnosis (localized, regional, and distant). Analyses were stratified by race (white vs black). RESULTS: There were 450,682 incident cases of CRC reported to the SEER registries during the entire period (1975-2013). Overall incidence was 75.5/100,000 white persons and 83.6/100,000 black persons. CRC incidence peaked during 1980 through 1989 and began to decrease in 1990. In whites and blacks, the decreases in incidence between the time periods of 1980-1984 and 2010-2013 were limited to the screening-age population (ages 50 years or older). Between these time periods, there was 40% decrease in incidence among whites compared with 26% decrease in incidence among blacks. Decreases in incidence were greater for cancers of the distal colon and rectum, and reductions in these cancers were greater among whites than blacks. CRC incidence among persons younger than 50 years decreased slightly between 1975-1979 and 1990. However, among persons 20-49 years old, CRC incidence increased from 8.3/100,000 persons in 1990-1994 to 11.4/100,000 persons in 2010-2013; incidence rates in younger adults were similar for whites and blacks. CONCLUSIONS: On the basis of an analysis of the SEER cancer registries from 1975 through 2013, CRC incidence decreased only among individuals 50 years or older between the time periods of 1980-1984 and 2010-2013. Incidence increased modestly among individuals 20-49 years old between the time periods of 1990-1994 and 2010-2013. The decision of whether to recommend screening for younger populations requires a formal analysis of risks and benefits. Our observed trends provide compelling evidence that screening has had an important role in reducing CRC incidence

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Functional Variant in Complement C3 Gene Promoter and Genetic Susceptibility to Temporal Lobe Epilepsy and Febrile Seizures

BACKGROUND: Human mesial temporal lobe epilepsies (MTLE) represent the most frequent form of partial epilepsies and are frequently preceded by febrile seizures (FS) in infancy and early childhood. Genetic associations of several complement genes including its central component C3 with disorders of the central nervous system, and the existence of C3 dysregulation in the epilepsies and in the MTLE particularly, make it the C3 gene a good candidate for human MTLE. METHODOLOGY/PRINCIPAL FINDINGS: A case-control association study of the C3 gene was performed in a first series of 122 patients with MTLE and 196 controls. Four haplotypes (HAP1 to 4) comprising GF100472, a newly discovered dinucleotide repeat polymorphism [(CA)8 to (CA)15] in the C3 promoter region showed significant association after Bonferroni correction, in the subgroup of MTLE patients having a personal history of FS (MTLE-FS+). Replication analysis in independent patients and controls confirmed that the rare HAP4 haplotype comprising the minimal length allele of GF100472 [(CA)8], protected against MTLE-FS+. A fifth haplotype (HAP5) with medium-size (CA)11 allele of GF100472 displayed four times higher frequency in controls than in the first cohort of MTLE-FS+ and showed a protective effect against FS through a high statistical significance in an independent population of 97 pure FS. Consistently, (CA)11 allele by its own protected against pure FS in a second group of 148 FS patients. Reporter gene assays showed that GF100472 significantly influenced C3 promoter activity (the higher the number of repeats, the lower the transcriptional activity). Taken together, the consistent genetic data and the functional analysis presented here indicate that a newly-identified and functional polymorphism in the promoter of the complement C3 gene might participate in the genetic susceptibility to human MTLE with a history of FS, and to pure FS. CONCLUSIONS/SIGNIFICANCE: The present study provides important data suggesting for the first time the involvement of the complement system in the genetic susceptibility to epileptic seizures and to epilepsy

Resolving taxonomic uncertainty in vulnerable elasmobranchs : are the Madeira skate (Raja maderensis) and the thornback ray (Raja clavata) distinct species?

Skates and rays constitute the most speciose group of chondrichthyan fishes, yet are characterised by remarkable levels of morphological and ecological conservatism. They can be challenging to identify, which makes monitoring species compositions for fisheries management purposes problematic. Owing to their slow growth and low fecundity, skates are vulnerable to exploitation and species exhibiting endemism or limited ranges are considered to be the most at risk. The Madeira skate Raja maderensis is endemic and classified as ‘Data Deficient’ by the IUCN, yet its taxonomic distinctiveness from the morphologically similar and more wide-ranging thornback ray Raja clavate is unresolved. This study evaluated the sequence divergence of both the variable control region and cytochrome oxidase I ‘DNA barcode’ gene of the mitochondrial genome to elucidate the genetic differentiation of specimens identified as R. maderensis and R. clavate collected across much of their geographic ranges. Genetic evidence was insufficient to support the different species designations. However regardless of putative species identification, individuals occupying waters around the Azores and North African Seamounts represent an evolutionarily significant unit worthy of special consideration for conservation management