Pain catastrophising predicts alcohol hangover severity and symptoms

Alcohol hangover is a cause of considerable social and economic burden. Identification of predictors of alcohol hangover severity have the potential to contribute to reductions in costs associated with both absenteeism/presenteeism and health care. Pain catastrophising (PC) is the tendency to ruminate and describe a pain experience in more exaggerated terms. The current study examines the possibility that this cognitive coping strategy may influence experience of alcohol hangover. The aims of the current study were to (1) examine the relationship between hangover severity and PC, (2) explore and identify discreet factors within the Acute Hangover Scale (AHS) and (3) explore whether independent factors/dimensions of acute hangover are differentially predicted by PC. A retrospective survey (n = 86) was conducted in which participants completed the Acute Hangover Scale (AHS); the Pain Catastrophising Scale (PCS); a questionnaire pertaining to the amount of alcohol consumed; and a demographic information questionnaire. Regression analyses showed a significant relationship between PC and hangover severity scores and demonstrated that PC was, in fact, a stronger predictor of perceived hangover severity than estimated peak blood alcohol concentrations (eBACs). Factor analysis of the AHS scale, resulted in the identification of two distinct symptom dimensions; ‘Headache and thirst’, and ‘Gastric and cardiovascular’ symptoms. Regression analyses showed that both eBAC and PCS score were significantly associated with ‘Headache and thirst’. However, only PCS score was associated with ‘Gastric and cardiovascular’ symptoms. These novel findings implicate a role for cognitive coping strategies in self-reports of alcohol hangover severity, and may have implications for understanding behavioural response to hangover, as well as suggesting that hangover and PC may be important factors mediating the motivation to drink and/or abuse alcohol, with potential implications in addiction research. Furthermore, these findings suggest that distinct alcohol hangover symptoms may be associated with different mechanisms underlying the experience of alcohol hangover

In vitro synergy and enhanced murine brain penetration of saquinavir coadministered with mefloquine.

Highly active antiretroviral therapy has substantially improved prognosis in human immunodeficiency virus (HIV). However, the integration of proviral DNA, development of viral resistance, and lack of permeability of drugs into sanctuary sites (e.g., brain and lymphocyte) are major limitations to current regimens. Previous studies have indicated that the antimalarial drug chloroquine (CQ) has antiviral efficacy and a synergism with HIV protease inhibitors. We have screened a panel of antimalarial compounds for activity against HIV-1 in vitro. A limited efficacy was observed for CQ, mefloquine (MQ), and mepacrine (MC). However, marked synergy was observed between MQ and saquinavir (SQV), but not CQ in U937 cells. Furthermore, enhancement of the antiviral activity of SQV and four other protease inhibitors (PIs) by MQ was observed in MT4 cells, indicating a class specific rather than a drug-specific phenomenon. We demonstrate that these observations are a result of inhibition of multiple drug efflux proteins by MQ and that MQ also displaces SQV from orosomucoid in vitro. Finally, coadministration of MQ and SQV in CD-1 mice dramatically altered the tissue distribution of SQV, resulting in a >3-fold and >2-fold increase in the tissue/blood ratio for brain and testis, respectively. This pharmacological enhancement of in vitro antiviral activity of PIs by MQ now warrants further examination in vivo

Protein kinase C epsilon is required for macrophage activation and defense against bacterial infection

Imperial Cancer Research Fund, and grants FEDER 2FD-1997-1432 from Comisión Interministerial de Ciencia y Tecnología (CICYT) and PM98-0120 from Dirección General de Enseñanza Superior e Investigación Científica, Spain. F. Otto was supported by Deutsche Forschungsgemeinschaft grant Ot 134/1-1

Ethnic Differences in Carotid Intima-Media Thickness Between UK Children of Black African-Caribbean and White European Origin.

BACKGROUND AND PURPOSE: UK black African-Caribbean adults have higher risks of stroke than white Europeans and have been shown to have increased carotid intima-media thickness (cIMT). We examined whether corresponding ethnic differences in cIMT were apparent in childhood and, if so, whether these could be explained by ethnic differences in cardiovascular risk markers. METHODS: We conducted a 2-stage survey of 939 children (208 white European, 240 black African-Caribbean, 258 South Asian, 63 other Asian, 170 other ethnicity), who had a cardiovascular risk assessment and measurements of cIMT at mean ages of 9.8 and 10.8 years, respectively. RESULTS: Black African-Caribbean children had a higher cIMT than white Europeans (mean difference, 0.014 mm; 95% CI, 0.008-0.021 mm; P<0.0001). cIMT levels in South Asian and other Asian children were however similar to those of white Europeans. Among all children, cIMT was positively associated with age, systolic and diastolic blood pressure and inversely with combined skinfold thickness and serum triglyceride. Mean triglyceride was lower among black African-Caribbeans than white Europeans; blood pressure and skinfold thickness did not differ appreciably. However, adjustment for these risk factors had little effect on the cIMT difference between black African-Caribbeans and white Europeans. CONCLUSIONS: UK black African-Caribbean children have higher cIMT levels in childhood; the difference is not explained by conventional cardiovascular risk markers. There may be important opportunities for early cardiovascular prevention, particularly in black African-Caribbean children

Empirical likelihood estimation of the spatial quantile regression

The spatial quantile regression model is a useful and flexible model for analysis of empirical problems with spatial dimension. This paper introduces an alternative estimator for this model. The properties of the proposed estimator are discussed in a comparative perspective with regard to the other available estimators. Simulation evidence on the small sample properties of the proposed estimator is provided. The proposed estimator is feasible and preferable when the model contains multiple spatial weighting matrices. Furthermore, a version of the proposed estimator based on the exponentially tilted empirical likelihood could be beneficial if model misspecification is suspect

Utilising proteomic approaches to understand oncogenic human herpesviruses

The γ‑herpesviruses Epstein-Barr virus and Kaposi's sarcoma‑associated herpesvirus are successful pathogens, each infecting a large proportion of the human population. These viruses persist for the life of the host and may each contribute to a number of malignancies, for which there are currently no cures. Large‑scale proteomic-based approaches provide an excellent means of increasing the collective understanding of the proteomes of these complex viruses and elucidating their numerous interactions within the infected host cell. These large‑scale studies are important for the identification of the intricacies of viral infection and the development of novel therapeutics against these two important pathogens

Multi-color Molecular Visualization of Signaling Proteins Reveals How C-Terminal Src Kinase Nanoclusters Regulate T Cell Receptor Activation

Elucidating the mechanisms that controlled T cell activation requires visualization of the spatial organization of multiple proteins on the submicron scale. Here, we use stoichiometrically accurate, multiplexed, singlemolecule super-resolution microscopy (DNA-PAINT) to image the nanoscale spatial architecture of the primary inhibitor of the T cell signaling pathway, Csk, and two binding partners implicated in its membrane association, PAG and TRAF3. Combined with a newly developed co-clustering analysis framework, we find that Csk forms nanoscale clusters proximal to the plasma membrane that are lost post-stimulation and are re-recruited at later time points. Unexpectedly, these clusters do not co-localize with PAG at the membrane but instead provide a ready pool of monomers to downregulate signaling. By generating CRISPR-Cas9 knockout T cells, our data also identify that a major risk factor for autoimmune diseases, the protein tyrosine phosphatase non-receptor type 22 (PTPN22) locus, is essential for Csk nanocluster re-recruitment and for maintenance of the synaptic PAG population