Facies, depositional environment, and palaeoecology of the Middle Triassic Cassina Beds (Meride Limestone, Monte San Giorgio, Switzerland).

The Ladinian Cassina beds belong to the fossiliferous levels of the world-famous Middle Triassic Monte San Giorgio Lagerstatte (UNESCO World Heritage List, Canton Ticino, Southern Alps). Although they are a rich archive for the depositional environment of an important thanatocoenosis, previous excavations focused on vertebrates and particularly on marine reptiles. In 2006, the Museo Cantonale di Storia Naturale (Lugano) started a new research project focusing for the first time on microfacies, micropalaeontological, palaeoecological and taphonomic analyses. So far, the upper third of the sequence has been excavated on a surface of around 40 m(2), and these new data complete those derived from new vertebrate finds (mainly fishes belonging to Saurichthys, Archaeosemionotus, Eosemionotus and Peltopleurus), allowing a better characterization of the basin. Background sedimentation on an anoxic to episodically suboxic seafloor resulted in a finely laminated succession of black shales and limestones, bearing a quasi-anaerobic biofacies, which is characterized by a monotypic benthic foraminiferal meiofauna and has been documented for the first time from the whole Monte San Giorgio sequence. Event deposition, testified by turbidites and volcaniclastic layers, is related to sediment input from basin margins and to distant volcanic eruptions, respectively. Fossil nekton points to an environment with only limited connection to the open sea. Terrestrial macroflora remains document the presence of emerged areas covered with vegetation and probably located relatively far away. Proliferation of benthic microbial mats is inferred on the basis of microfabrics, ecological considerations and taphonomic (both biostratinomic and diagenetic) features of the new vertebrate finds, whose excellent preservation is ascribed to sealing by biofilms. The occurrence of allochthonous elements allows an insight into the shallow-waters of the adjoining time-equivalent Salvatore platform. Finally, the available biostratigraphic data are critically reviewed.

A review of achievements of the national schistosomiasis control program in middle and upper Egypt areas

In Egypt the "national schistosomiasis control program" was formulated to control transmission by reduction of prevalence and intensity of current infections, and thereby achieve an acceptable level of schistosomiasis disease control. The program was implemented foremost in Middle Egypt (1977) and Upper Egypt (1980), collectively extending 800 km alongside of the River Nile and accommodate about 10.5 million people. Schistosoma haematobium has been essentially the prevailing species infection in both areas. The strategy of control entailed both area-wide mollusciciding with niclosamide, and selective population chemotherapy with metrifonate. Evaluation in 1986 showed that prevalence dropped from pre-control 29.4% in Middle Egypt and 26.3% in Upper Egypt to 6% and 7.8% respectively, together with a remarkable drop of infections among children. Also mean intensity attained low levels consistent of low grade infections. It is evident therefore that in these areas where an enhancement of schistosomiasis infections had been anticipated the employment of the twofold strategy effected a state of low-prevalence/low-intensity signifying a lowered reservoir of infection and a substantial interference with the potentials of transmission.

Vaniprevir with pegylated interferon alpha-2a and ribavirin in treatment-naïve patients with chronic hepatitis C: a randomized phase II study.

Vaniprevir (MK-7009) is a macrocyclic hepatitis C virus (HCV) nonstructural protein 3/4A protease inhibitor. The aim of the present phase II study was to examine virologic response rates with vaniprevir in combination with pegylated interferon alpha-2a (Peg-IFN-α-2a) plus ribavirin (RBV). In this double-blind, placebo-controlled, dose-ranging study, treatment-naïve patients with HCV genotype 1 infection (n = 94) were randomized to receive open-label Peg-IFN-α-2a (180 μg/week) and RBV (1,000-1,200 mg/day) in combination with blinded placebo or vaniprevir (300 mg twice-daily [BID], 600 mg BID, 600 mg once-daily [QD], or 800 mg QD) for 28 days, then open-label Peg-IFN-α-2a and RBV for an additional 44 weeks. The primary efficacy endpoint was rapid viral response (RVR), defined as undetectable plasma HCV RNA at week 4. Across all doses, vaniprevir was associated with a rapid two-phase decline in viral load, with HCV RNA levels approximately 3 log(10) IU/mL lower in vaniprevir-treated patients, compared to placebo recipients. Rates of RVR were significantly higher in each of the vaniprevir dose groups, compared to the control regimen (68.8%-83.3% versus 5.6%; P < 0.001 for all comparisons). There were numerically higher, but not statistically significant, early and sustained virologic response rates with vaniprevir, as compared to placebo. Resistance profile was predictable, with variants at R155 and D168 detected in a small number of patients. No relationship between interleukin-28B genotype and treatment outcomes was demonstrated in this study. The incidence of adverse events was generally comparable between vaniprevir and placebo recipients; however, vomiting appeared to be more common at higher vaniprevir doses. CONCLUSION: Vaniprevir is a potent HCV protease inhibitor with a predictable resistance profile and favorable safety profile that is suitable for QD or BID administration.

HCV infection after liver transplantation is associated with lower levels of alloreactive CD4+CD25+CD45RO+IL-7R+high+ T cells

Aim: Expression of IL-7R discriminates alloreactive CD4 T cells (Foxp3 negative), from IL-7Rlow regulatory CD4 T cells (Foxp3 positive). Chronic hepatitis C virus infection (HCV) reduces expression of IL-7R on T cells thus promoting persistence of infection. The aim of this study was to analyze the effect of HCV infection on the expression of IL-7R of activated CD4+ T cells in liver transplant patients. Patients and methods: We analyzed PBMC from liver transplant recipients for the expression of CD4, CD25, FoxP3, IL-7R (24 HCV negative and 29 HCV-chronically infected). We compared these data with non-transplanted individuals (52 HCV-chronically infected patients and 38 healthy donors). Results: In HCV-infected liver transplant recipients, levels of CD4+CD25+CD45RO+IL-7R+ T cells were significantly reduced (10.5+/-0.9%) when compared to non-HCV-infected liver transplant recipients (17.6+/-1.4%) (P<0.001), while both groups (HCV-infected and negative transplant recipients) had significantly higher levels than healthy individuals (6.6+/-0.9%) (P<0.0001). After successful antiviral therapy (sustained antiviral response), 6 HCV-infected transplant recipients showed an increase of CD4+CD25+CD45RO+IL-7R+ T cells, reaching levels similar to that of non-HCVinfected recipients (10.73+/-2.63% prior therapy versus 21.7+/-6.3% after clearance of HCV). (P<0.05) In 4 non-responders (i.e. HCVRNA remaining present in serum), levels of CD4+CD25+CD45RO+IL-7R+ T cells remained unmodified during and after antiviral treatment (11.8+/- 3.3% versus 11.3+/-3.3% respectively). Conclusions: Overall, these data indicate that CD4+CD25+CD45RO+IL-7R+ T cells appear to be modulated by chronic HCV infection after liver transplantation. Whether lower levels of alloreactive T cells in HCV-infected liver transplant recipients are associated with a tolerogenic profile remains to be studied.

Association between conventional risk factors and different ultrasound-based markers of atherosclerosis at carotid and femoral levels in a middle-aged population.

Ultrasound detection of sub-clinical atherosclerosis (ATS) may help identify individuals at high cardiovascular risk. Most studies evaluated intima-media thickness (IMT) at carotid level. We compared the relationships between main cardiovascular risk factors (CVRF) and five indicators of ATS (IMT, mean and maximal plaque thickness, mean and maximal plaque area) at both carotid and femoral levels. Ultrasound was performed on 496 participants aged 45-64 years randomly selected from the general population of the Republic of Seychelles. 73.4 % participants had ≥ 1 plaque (IMT thickening ≥ 1.2 mm) at carotid level and 67.5 % at femoral level. Variance (adjusted R2) contributed by age, sex and CVRF (smoking, LDL-cholesterol, HDL-cholesterol, blood pressure, diabetes) in predicting any of the ATS markers was larger at femoral than carotid level. At both carotid and femoral levels, the association between CVRF and ATS was stronger based on plaque-based markers than IMT. Our findings show that the associations between CVRF and ATS markers were stronger at femoral than carotid level, and with plaque-based markers rather than IMT. Pending comparison of these markers using harder cardiovascular endpoints, our findings suggest that markers based on plaque morphology assessed at femoral artery level might be useful cardiovascular risk predictors.

Prevalence and factors associated with difficulty and intention to quit smoking in Switzerland.

ABSTRACT: BACKGROUND: Recent data indicate a slight decrease in the prevalence of smoking in Switzerland, but little is known regarding the intention and difficulty to quit smoking among current smokers. Hence, we aimed to quantify the difficulty and intention to quit smoking among current smokers in Switzerland. METHODS: Cross-sectional study including 607 female and 658 male smokers. Difficulty, intention and motivation to quit smoking were assessed by questionnaire. RESULTS: 90% of women and 85% of men reported being "very difficult" or "difficult" to quit smoking. Almost three quarters of smokers (73% of women and 71% of men) intended to quit; however, less than 20% of them were in the preparation stage and 40% were in the precontemplation stage. On multivariate analysis, difficulty to quit was lower among men (Odds ratio and 95% [confidence interval]: 0.51 [0.35-0.74]) and increased with nicotine dependence and number of previous quitting attempts (OR=3.14 [1.75-5.63] for 6+ attempts compared to none). Intention to quit decreased with increasing age (OR=0.48 [0.30-0.75] for [greater than or equal to]65 years compared to <45 years) and increased with nicotine dependence, the number of previous quitting attempts (OR=4.35 [2.76-6.83] for 6+ attempts compared to none) and among non-cigarette smokers (OR=0.51 [0.28-0.92]). Motivation to quit was inversely associated with nicotine dependence and positively associated with the number of previous quitting attempts and personal history of lung disease. CONCLUSION: Over two thirds of Swiss smokers want to quit. However, only a small fraction wishes to do so in the short term. Nicotine dependence, previous attempts to quit or previous history of lung disease are independently associated with difficulty and intention to quit.

Cellular schwannomas of the intracranial and intraspinal compartment: morphological and immunological characteristics compared with classical benign schwannomas.

The concept of cellular schwannoma as an unusual benign tumor is well established for peripheral nerves but has never been tested in neurosurgical series. In order to test the validity of this concept in cranial nerves and spinal roots we performed an analysis of the clinical and morphological characteristics of 12 cellular and 166 classical benign schwannomas. Immunohistochemical detection of antigen expression in Schwann cells including proliferating cell nuclear antigen (PCNA) was also performed. This study shows that cellular schwannomas in neurosurgical series manifest at a lower age than the classical benign variant and occur mainly in the spinal roots. Mitotic activity and sinusoidal vessels appear more frequently in cellular schwannomas and constitute with high cellularity, the most valuable criteria separating both entities. The postoperative course in both types of tumors was free of metastases or sarcomatous changes. Immunoexpression of S-100 protein, vimentin, epithelial membrane antigen and glial fibrillary acidic protein is not statistically different between the two variants. In contrast, PCNA is more highly expressed in cellular schwannomas. These These results confirm the concept that cellular schwannomas are a clinico-pathological variant of benign schwannomas and provide significant support for the introduction of this entity in neurosurgical oncology.

IV thrombolysis and renal function.

OBJECTIVE: To investigate the association of renal impairment on functional outcome and complications in stroke patients treated with IV thrombolysis (IVT). METHODS: In this observational study, we compared the estimated glomerular filtration rate (GFR) with poor 3-month outcome (modified Rankin Scale scores 3-6), death, and symptomatic intracranial hemorrhage (sICH) based on the criteria of the European Cooperative Acute Stroke Study II trial. Unadjusted and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Patients without IVT treatment served as a comparison group. RESULTS: Among 4,780 IVT-treated patients, 1,217 (25.5%) had a low GFR (<60 mL/min/1.73 m(2)). A GFR decrease by 10 mL/min/1.73 m(2) increased the risk of poor outcome (OR [95% CI]): (ORunadjusted 1.20 [1.17-1.24]; ORadjusted 1.05 [1.01-1.09]), death (ORunadjusted 1.33 [1.28-1.38]; ORadjusted 1.18 [1.11-1.249]), and sICH (ORunadjusted 1.15 [1.01-1.22]; ORadjusted 1.11 [1.04-1.20]). Low GFR was independently associated with poor 3-month outcome (ORadjusted 1.32 [1.10-1.58]), death (ORadjusted 1.73 [1.39-2.14]), and sICH (ORadjusted 1.64 [1.21-2.23]) compared with normal GFR (60-120 mL/min/1.73 m(2)). Low GFR (ORadjusted 1.64 [1.21-2.23]) and stroke severity (ORadjusted 1.05 [1.03-1.07]) independently determined sICH. Compared with patients who did not receive IVT, treatment with IVT in patients with low GFR was associated with poor outcome (ORadjusted 1.79 [1.41-2.25]), and with favorable outcome in those with normal GFR (ORadjusted 0.77 [0.63-0.94]). CONCLUSION: Renal function significantly modified outcome and complication rates in IVT-treated stroke patients. Lower GFR might be a better risk indicator for sICH than age. A decrease of GFR by 10 mL/min/1.73 m(2) seems to have a similar impact on the risk of death or sICH as a 1-point-higher NIH Stroke Scale score measuring stroke severity.

Associations between alcohol consumption and selected cytokines in a Swiss population-based sample (CoLaus study).

To assess the associations between alcohol consumption and cytokine levels (interleukin-1beta - IL-1β; interleukin-6 - IL-6 and tumor necrosis factor-α - TNF-α) in a Caucasian population. Population sample of 2884 men and 3201 women aged 35-75. Alcohol consumption was categorized as nondrinkers, low (1-6 drinks/week), moderate (7-13/week) and high (14+/week). No difference in IL-1β levels was found between alcohol consumption categories. Low and moderate alcohol consumption led to lower IL-6 levels: median (interquartile range) 1.47 (0.70-3.51), 1.41 (0.70-3.32), 1.42 (0.66-3.19) and 1.70 (0.83-4.39) pg/ml for nondrinkers, low, moderate and high drinkers, respectively, p<0.01, but this association was no longer significant after multivariate adjustment. Compared to nondrinkers, moderate drinkers had the lowest odds (Odds ratio=0.86 (0.71-1.03)) of being in the highest quartile of IL-6, with a significant (p<0.05) quadratic trend. Low and moderate alcohol consumption led to lower TNF-α levels: 2.92 (1.79-4.63), 2.83 (1.84-4.48), 2.82 (1.76-4.34) and 3.15 (1.91-4.73) pg/ml for nondrinkers, low, moderate and high drinkers, respectively, p<0.02, and this difference remained borderline significant (p=0.06) after multivariate adjustment. Moderate drinkers had a lower odds (0.81 [0.68-0.98]) of being in the highest quartile of TNF-α. No specific alcoholic beverage (wine, beer or spirits) effect was found. Moderate alcohol consumption is associated with lower levels of IL-6 and (to a lesser degree) of TNF-α, irrespective of the type of alcohol consumed. No association was found between IL-1β levels and alcohol consumption.

Methylation profile of TP53 regulatory pathway and mtDNA alterations in breast cancer patients lacking TP53 mutations.

The present study investigated promoter hypermethylation of TP53 regulatory pathways providing a potential link between epigenetic changes and mitochondrial DNA (mtDNA) alterations in breast cancer patients lacking a TP53 mutation. The possibility of using the cancer-specific alterations in serum samples as a blood-based test was also explored. Triple-matched samples (cancerous tissues, matched adjacent normal tissues and serum samples) from breast cancer patients were screened for TP53 mutations, and the promoter methylation profile of P14(ARF), MDM2, TP53 and PTEN genes was analyzed as well as mtDNA alterations, including D-loop mutations and mtDNA content. In the studied cohort, no mutation was found in TP53 (DNA-binding domain). Comparison of P14(ARF) and PTEN methylation patterns showed significant hypermethylation levels in tumor tissues (P < 0.05 and <0.01, respectively) whereas the TP53 tumor suppressor gene was not hypermethylated (P < 0.511). The proportion of PTEN methylation was significantly higher in serum than in the normal tissues and it has a significant correlation to tumor tissues (P < 0.05). mtDNA analysis revealed 36.36% somatic and 90.91% germline mutations in the D-loop region and also significant mtDNA depletion in tumor tissues (P < 0.01). In addition, the mtDNA content in matched serum was significantly lower than in the normal tissues (P < 0.05). These data can provide an insight into the management of a therapeutic approach based on the reversal of epigenetic silencing of the crucial genes involved in regulatory pathways of the tumor suppressor TP53. Additionally, release of significant aberrant methylated PTEN in matched serum samples might represent a promising biomarker for breast cancer.

Subclinical hyperthyroidism and the risk of coronary heart disease and mortality.

BACKGROUND: Data from prospective cohort studies regarding the association between subclinical hyperthyroidism and cardiovascular outcomes are conflicting.We aimed to assess the risks of total and coronary heart disease (CHD) mortality, CHD events, and atrial fibrillation (AF) associated with endogenous subclinical hyperthyroidism among all available large prospective cohorts. METHODS: Individual data on 52 674 participants were pooled from 10 cohorts. Coronary heart disease events were analyzed in 22 437 participants from 6 cohorts with available data, and incident AF was analyzed in 8711 participants from 5 cohorts. Euthyroidism was defined as thyrotropin level between 0.45 and 4.49 mIU/L and endogenous subclinical hyperthyroidism as thyrotropin level lower than 0.45 mIU/L with normal free thyroxine levels, after excluding those receiving thyroid-altering medications. RESULTS: Of 52 674 participants, 2188 (4.2%) had subclinical hyperthyroidism. During follow-up, 8527 participants died (including 1896 from CHD), 3653 of 22 437 had CHD events, and 785 of 8711 developed AF. In age- and sex-adjusted analyses, subclinical hyperthyroidism was associated with increased total mortality (hazard ratio[HR], 1.24, 95% CI, 1.06-1.46), CHD mortality (HR,1.29; 95% CI, 1.02-1.62), CHD events (HR, 1.21; 95%CI, 0.99-1.46), and AF (HR, 1.68; 95% CI, 1.16-2.43).Risks did not differ significantly by age, sex, or preexisting cardiovascular disease and were similar after further adjustment for cardiovascular risk factors, with attributable risk of 14.5% for total mortality to 41.5% forAF in those with subclinical hyperthyroidism. Risks for CHD mortality and AF (but not other outcomes) were higher for thyrotropin level lower than 0.10 mIU/L compared with thyrotropin level between 0.10 and 0.44 mIU/L(for both, P value for trend, .03). CONCLUSION: Endogenous subclinical hyperthyroidism is associated with increased risks of total, CHD mortality, and incident AF, with highest risks of CHD mortality and AF when thyrotropin level is lower than 0.10 mIU/L.

Increased clozapine plasma concentrations and side effects induced by smoking cessation in 2 CYP1A2 genotyped patients.

Clozapine, an atypical antipsychotic, depends mainly on cytochrome P4501A2 (CYP1A2) for its metabolic clearance. CYP1A2 is inducible by smoking, and lower plasma concentrations of clozapine are measured in smokers than in nonsmokers. Case reports have been published on the effects of discontinuing smoking in patients receiving clozapine, which might lead to elevated plasma concentrations and severe side effects. We present 2 cases on the consequences of smoking cessation in patients receiving this drug. In the first patient, smoking cessation resulted, within 2 weeks, in severe sedation and fatigue, with an approximately 3-fold increase of plasma clozapine concentrations. In the second patient, a very high plasma concentration of clozapine (3004 ng/mL) was measured 6 days following a 16-day stay in a general hospital, during which smoking was prohibited. In the latter patient, the replacement of omeprazole, a strong CYP1A2 inducer, by pantoprazole, a weaker CYP1A2 inducer, could have contributed, in addition to smoking cessation, to the observed strong increase of plasma clozapine concentrations. Genotyping of the 2 patients revealed that they were carriers of the AA genotype for the -164C>A polymorphism (CYP1A2*1F) in intron 1 of CYP1A2 gene, which has previously been shown to confer a high inducibility of CYP1A2 by smoking. Thus, at the initiation of clozapine treatment, smoking patients should be informed that, if they decide to stop smoking, they are encouraged to do so but must inform their prescriber beforehand. Also, because of the increased use of no-smoking policies in many hospitals, studies examining the consequences of such policies on the pharmacokinetics/pharmacodynamics of drugs metabolized by CYP1A2, taking into account different CYP1A2 genotypes, are needed.

Improving Students’ Learning Aspirations Beyond Post-Primary Education: A First Account of Two Non-Formal Education Programmes in Middle-Income

Non-formal education programmes are active in a number of developing countries. These programmes offer vulnerable students an opportunity to pursue their education although they were excluded for various reasons from the formal education systems. This paper examines the impact of two programmes (one in Mauritius, and one in Thailand) on their participants’ aspirations towards learning. We develop a methodology to measure the perception of students regarding their learning experience. More than a third of them, for example, believe that there is no barrier to their education. Most acknowledge the role of their teachers in raising their aspirations towards their educational achievement. When compared to male students, female students seem to value more the role of their education.

Kaposi sarcoma herpes virus antibody response and viremia following highly active antiretroviral therapy in the Swiss HIV Cohort study.

OBJECTIVE: To describe the effect of HAART on Kaposi sarcoma herpes virus (KSHV) antibody response and viremia among HIV-positive MSM. DESIGN: A follow-up study of 272 HIV-positive MSM (including 22 with Kaposi sarcoma) who first initiated HAART between January 1996 and July 2004 in the Swiss HIV Cohort Study. METHODS: For each individual, two serum samples, one at HAART initiation and another 24 months later, were tested for latent and lytic KSHV antibodies using immunofluorescence assays, and for KSHV viremia using PCR. Factors associated with changes in KSHV antibody titers and viremia were evaluated. RESULTS: At HAART initiation, 69.1 and 75.0% of patients were seropositive to latent and lytic KSHV antibodies, respectively. Seropositivity was associated with the presence of Kaposi sarcoma, older age, lower CD8 cell count and higher CD4/CD8 ratio. Prevalence of KSHV viremia at HAART initiation was 6.4%, being significantly higher among patients with Kaposi sarcoma (35.0%), and those with HIV viral loads 100 000 copies/ml (11.7%) or higher. At 24-month follow-up, geometric mean titers (GMTs) among KSHV seropositive patients increased and antibody seroprevalence was higher. Having Kaposi sarcoma and/or CD4 cell counts less than 50 cells/microl at HAART initiation was associated both with higher probability for antibody titers to increase (including seroconversion) and larger increases in GMTs. Only one of 17 viremic patients at HAART initiation had viremia at 24-month follow-up. CONCLUSION: HAART increases KSHV-specific humoral immune response and clearance of viremia among HIV-infected MSM, consistent with the dramatic protection offered by HAART against Kaposi sarcoma.