Electrophysiological correlates of cognition improve with nap during sleep deprivation

The efficacy of a 30-min nap as a countermeasure in the reduction of cognitive decline following 24 h of sleep deprivation (SD) on subjective sleepiness scales, event-related potential (ERP) P300, and contingent negative variation (CNV) was evaluated. The experiment was performed in three sessions on different days between 7 and 8 a.m. on nine normal, healthy males, of age 25–30 years: Session 1. Baseline recordings; Session 2, after one night’s total sleep deprivation, and; Session 3, after 1 week of Session 1, following one night’s sleep deprivation along with a 30-min nap opportunity between 1.00 and 3.00 a.m. Subjective sleepiness scores increased after SD as compared to baseline, but reduced significantly after nap (P < 0.05). There was an increase in P3 peak latency of ERP following SD (16%, P < 0.01), which was reduced with nap (10.7%, P < 0.05).There was an increase in CNV M1 peak latency after SD (18%) which decreased with the use of nap (12.5%) (P < 0.01). The CNV reaction time increased following SD (39.3%) and decreased with the use of nap (24%) (P < 0.01). No significant effects on ERP N1, P1, N2 latencies, P2 and P3 amplitudes and CNV N1, P3, M2 peak latencies and M1, and M2 amplitudes were observed. It was concluded that a 30-min nap, between 1.00 and 3.00 a.m. during night SD, reduces the cognitive decline following 24 h of SD in terms of its electro-physiological correlates. The study is of applied value in optimization of cognitive performance in professions demanding night work schedules.     

Repeating cytology at initial colposcopy does not improve detection of high-grade abnormalities: a retrospective cohort study of 6595 women

OBJECTIVE: To determine if repeating a smear improves detection of high-grade pre-invasive or invasive disease of the cervix compared with women who do not have a repeat smear at the time of the initial colposcopic assessment for referral of an abnormal smear. DESIGN: Retrospective cohort study. SETTING: All Wales Colposcopy database. POPULATION: The cohort included women referred for colposcopy with an abnormal smear result, who were seen between 1st January 2002 and 31st December 2002. METHOD: The management of the group of women who had a repeat smear was compared with the group who did not have a repeat smear test at their first visit. Confidence interval analysis was used to compare results between the two groups. MAIN OUTCOME MEASURE: The positive predictive value and sensitivity of the repeat smear to predict outcome, compared to the referral smear in cases where a smear was not repeated at the colposcopy clinic. RESULTS: 3505 cases (54.0%) did not have a repeat smear at initial colposcopy, whereas 2990 (46%) did. There was a significantly higher rate of referral for low-grade dyskaryosis in the group who had repeat smear testing. The median time interval from the referral smear to the first colposcopy was 49 days for both groups. The specificity and positive predictive value for high-grade lesions were significantly higher in the repeat smear results. The sensitivity was significantly lower, and a high-grade lesion would have been missed with the repeat smear in 14.0% of all referrals. CONCLUSIONS: Colposcopists appeared more inclined to repeat smears for low-grade referrals. The time interval from the referral smear to colposcopy did not appear to influence this decision. A repeat smear test at the first colposcopy visit will detect less high-grade pre-invasive or invasive disease than the initial referral smear.     

Mixed-effects Poisson regression analysis of adverse event reports: the relationship between antidepressants and suicide

A new statistical methodology is developed for the analysis of spontaneous adverse event (AE) reports from post-marketing drug surveillance data. The method involves both empirical Bayes (EB) and fully Bayes estimation of rate multipliers for each drug within a class of drugs, for a particular AE, based on a mixed-effects Poisson regression model. Both parametric and semiparametric models for the random-effect distribution are examined. The method is applied to data from Food and Drug Administration (FDA)'s Adverse Event Reporting System (AERS) on the relationship between antidepressants and suicide. We obtain point estimates and 95 per cent confidence (posterior) intervals for the rate multiplier for each drug (e.g. antidepressants), which can be used to determine whether a particular drug has an increased risk of association with a particular AE (e.g. suicide). Confidence (posterior) intervals that do not include 1.0 provide evidence for either significant protective or harmful associations of the drug and the adverse effect. We also examine EB, parametric Bayes, and semiparametric Bayes estimators of the rate multipliers and associated confidence (posterior) intervals. Results of our analysis of the FDA AERS data revealed that newer antidepressants are associated with lower rates of suicide adverse event reports compared with older antidepressants. We recommend improvements to the existing AERS system, which are likely to improve its public health value as an early warning system.     

Human papillomavirus molecular biology and pathogenesis

Human papillomavirus (HPV) infection is the most common sexually transmitted disease in the world and accounts for an estimated 11% of the global cancer incidence in women. HPV-16 is the most prevalent type detected in cervical cancer and along with types 18, 31, 33 and 45 has been classified as a class I carcinogen. In addition to cervical cancer, HPVs are also associated with the malignant transformation of other mucosal and skin cancers. Thus, the combination of the malignant potential of HPV and its high prevalence of infection confers to it an importance of generalized clinical and virological significance. The natural history of HPV infection with or without treatment varies from spontaneous regression to persistence. The most important mechanism for wart regression appears to be cell-mediated immunity. Cytokines released by keratinocytes or cells of the immune system may play a part in the induction of an effective immune response against HPV infection and the subsequent regression of lesions. This review discusses the molecular biology, pathogenesis and immunology of HPV infections.     

Ocular toxicity by latex of Calotropis procera (Sodom apple)

We report the spectrum of ocular toxicity following accidental inoculation of latex of Calotropis procera (Sodom apple) in 29 eyes between January 2003 and December 2006. All patients presented with sudden painless dimness of vision with photophobia. Twenty-five (86%) patients had initial visual acuity of less than 20/60. All eyes had conjunctival congestion and mild to severe corneal edema with Descemet''s folds. Three (10%) eyes had an epithelial defect, nine (31%) had iridocyclitis, and seven (24%) had associated secondary glaucoma. After treatment with topical corticosteroids, antiglaucoma agents, cycloplegics, hypertonic saline and tears supplements, 27 (93%) eyes recovered completely within 3–14 days. After three months, 17 (74%) out of 23 eyes showed a significant low endothelial cell count compared to the normal fellow eye (P < 0.001).The latex of Calotropis procera causes significant ocular morbidity which may be preventable by simple health education. The long-term effect on corneal endothelium has to be studied further.     

Curcumin enhances the effects of 5-fluorouracil and oxaliplatin in mediating growth inhibition of colon cancer cells by modulating EGFR and IGF-1R

Curcumin (diferuloylmethane), which has been shown to inhibit growth of transformed cells, has no discernible toxicity and achieves high levels in colonic mucosa. 5-fluorouracil (5-FU) or 5-FU plus oxaliplatin (FOLFOX) remains the backbone of colorectal cancer chemotherapeutics, but with limited success. The present investigation was, therefore, undertaken to examine whether curcumin in combination with conventional chemotherapeutic agent(s)/regimen will be a superior therapeutic strategy for colorectal cancer. Indeed, results of our in vitro studies demonstrated that curcumin together with FOLFOX produced a significantly greater inhibition (p < 0.01) of growth and stimulated apoptosis (p < 0.001) of colon cancer HCT-116 and HT-29 cells than that caused by curcumin, 5-FU, curcumin + 5-FU or FOLFOX. These changes were associated with decreased expression and activation (tyrosine phosphorylation) of EGFR, HER-2, HER-3 (72-100%) and IGF-1R (67%) as well as their downstream effectors such as Akt and cycloxygenase-2 (51-97%). Furthermore, while these agents produced a 2-3-fold increase in the expression of IGF-binding protein-3 (IGFBP-3), curcumin together with FOLFOX caused a 5-fold increase in the same, when compared to controls. This in turn led to increased sequestration of IGF by IGFBP-3 rendering IGF-1 unavailable for binding to and activation of IGF-1R. We conclude that the superior effects of the combination therapy of curcumin and FOLFOX are due to attenuation of EGFRs and IGF-1R signaling pathways. We also suggest that inclusion of curcumin to the conventional chemotherapeutic agent(s)/regimen could be an effective therapeutic strategy for colorectal cancer.     

The ratio of Matriptase/HAI-1 mRNA is higher in colorectal cancer adenomas and carcinomas than corresponding tissue from control individuals

Background  

It has recently been shown that overexpression of the serine protease, matriptase, in transgenic mice causes a dramatically increased frequency of carcinoma formation. Overexpression of HAI-1 and matriptase together changed the frequency of carcinoma formation to normal. This suggests that the ratio of matriptase to HAI-1 influences the malignant progression. The aim of this study has been to determine the ratio of matriptase to HAI-1 mRNA expression in affected and normal tissue from individuals with colorectal cancer adenomas and carcinomas as well as in healthy individuals, in order to determine at which stages a dysregulated ratio of matriptase/HAI-1 mRNA is present during carcinogenesis.