Inhibition of rotavirus ECwt infection in ICR suckling mice by N-acetylcysteine, peroxisome proliferator-activated receptor gamma agonists and cyclooxygenase-2 inhibitors

Live attenuated vaccines have recently been introduced for preventing rotavirus disease in children. However, alternative strategies for prevention and treatment of rotavirus infection are needed mainly in developing countries where low vaccine coverage occurs. In the present work, N-acetylcysteine (NAC), ascorbic acid (AA), some nonsteroidal anti-inflammatory drugs (NSAIDs) and peroxisome proliferator-activated receptor gamma (PPARγ) agonists were tested for their ability to interfere with rotavirus ECwt infectivity as detected by the percentage of viral antigen-positive cells of small intestinal villi isolated from ECwt-infected ICR mice. Administration of 6 mg NAC/kg every 8 h for three days following the first diarrhoeal episode reduced viral infectivity by about 90%. Administration of AA, ibuprofen, diclofenac, pioglitazone or rosiglitazone decreased viral infectivity by about 55%, 90%, 35%, 32% and 25%, respectively. ECwt infection of mice increased expression of cyclooxygenase-2, ERp57, Hsc70, NF-κB, Hsp70, protein disulphide isomerase (PDI) and PPARγ in intestinal villus cells. NAC treatment of ECwt-infected mice reduced Hsc70 and PDI expression to levels similar to those observed in villi from uninfected control mice. The present results suggest that the drugs tested in the present work could be assayed in preventing or treating rotaviral diarrhoea in children and young animals.

Should I go to court?: an assessment of the role of the Judiciary in disputes between cattle raisers and meatpackers in Brazil

The main objective of this perspective paper is to analyze the role of the judiciary in resolving conflicts between cattle raisers and meatpacking firms in Brazil. Looking at the transaction for the acquisition of cattle for slaughter in the state of Mato Grosso do Sul (the central-western region of Brazil), the analysis encompasses three steps. First, the authors describe the transaction pattern between cattle raisers and meatpacking firms, identifying a guarantee vacuum within the supply chain. Secondly, the authors present evidence that the guarantee vacuum may give rise to legal conflicts of non-payment, which are indeed prevalent in disputes that reach the courts. Finally, the role of the judiciary in resolving these conflicts is investigated. Results suggest that, on average, producers have little confidence in the legal system, indicating the potential function that informal mechanisms may play in the supply chain. The paper concludes by suggesting some implications for public and private strategies.

Occurrence, risk factors, diagnosis and treatment of syphilis in the prospective observational Swiss HIV Cohort Study.

BACKGROUND: Annual syphilis testing was reintroduced in the Swiss HIV Cohort Study (SHCS) in 2004. We prospectively studied occurrence, risk factors, clinical manifestations, diagnostic approaches and treatment of syphilis. METHODS: Over a period of 33 months, participants with positive test results for Treponema pallidum hemagglutination assay were studied using the SHCS database and an additional structured case report form. RESULTS: Of 7244 cohort participants, 909 (12.5%) had positive syphilis serology. Among these, 633 had previously been treated and had no current signs or symptoms of syphilis at time of testing. Of 218 patients with newly detected untreated syphilis, 20% reported genitooral contacts as only risk behavior and 60% were asymptomatic. Newly detected syphilis was more frequent among men who have sex with men (MSM) [adjusted odds ratio (OR) 2.8, P < 0.001], in persons reporting casual sexual partners (adjusted OR 2.8, P < 0.001) and in MSM of younger age (P = 0.05). Only 35% of recommended cerebrospinal fluid (CFS) examinations were performed. Neurosyphilis was diagnosed in four neurologically asymptomatic patients; all of them had a Venereal Disease Research Laboratory (VDRL) titer of 1:>or=32. Ninety-one percent of the patients responded to treatment with at least a four-fold decline in VDRL titer. CONCLUSION: Syphilis remains an important coinfection in the SHCS justifying reintroduction of routine screening. Genitooral contact is a significant way of transmission and young MSM are at high risk for syphilis. Current guidelines to rule out neurosyphilis by CSF analysis are inconsistently followed in clinical practice. Serologic treatment response is above 90% in the era of combination antiretroviral therapy.

Blood pressure and cognitive function: a prospective analysis among adolescents in Seychelles.

OBJECTIVE: An inverse relationship between blood pressure (BP) and cognitive function has been found in adults, but limited data are available in adolescents and young adults. We examined the prospective relation between BP and cognitive function in adolescence. METHODS: We examined the association between BP measured at the ages of 12-15 years in school surveys and cognitive endpoints measured in the Seychelles Child Development Study at ages 17 (n = 407) and 19 (n = 429) years, respectively. We evaluated multiple domains of cognition based on subtests of the Cambridge Neurological Test Automated Battery (CANTAB), the Woodcock Johnson Test of Scholastic Achievement (WJTA), the Finger Tapping test (FT) and the Kaufman Brief Intelligence Test (K-BIT). We used age, sex and height-specific z-scores of SBP, DBP and mean arterial pressure (MAP). RESULTS: Six out of the 21 cognitive endpoints tested were associated with BP. However, none of these associations were found to hold for both males and females or for different subtests within the same neurodevelopmental domain or for both SBP and DBP. Most of these associations disappeared when analyses were adjusted for selected potential confounding factors such as socio-economic status, birth weight, gestational age, BMI, alcohol consumption, blood glucose, and total n-3 and n-6 polyunsaturated fats. CONCLUSIONS: Our findings do not support a consistent association between BP and subsequent performance on tests assessing various cognitive domains in adolescents.

Assessing dystrophies and other muscle diseases at the nanometer scale by atomic force microscopy.

AIM: Atomic force microscopy nanoindentation of myofibers was used to assess and quantitatively diagnose muscular dystrophies from human patients. MATERIALS & METHODS: Myofibers were probed from fresh or frozen muscle biopsies from human dystrophic patients and healthy volunteers, as well as mice models, and Young's modulus stiffness values were determined. RESULTS: Fibers displaying abnormally low mechanical stability were detected in biopsies from patients affected by 11 distinct muscle diseases, and Young's modulus values were commensurate to the severity of the disease. Abnormal myofiber resistance was also observed from consulting patients whose muscle condition could not be detected or unambiguously diagnosed otherwise. DISCUSSION & CONCLUSION: This study provides a proof-of-concept that atomic force microscopy yields a quantitative read-out of human muscle function from clinical biopsies, and that it may thereby complement current muscular dystrophy diagnosis.

Beliefs about and attitudes toward gambling in French-speaking Switzerland.

The present study aims to analyze attitudes and beliefs of the French-speaking general Swiss population (n = 2500; female n = 1280; mean age = 43 years) as regards gambling, which are to date almost exclusively studied in the North American and Australian contexts. Beliefs related to gambling include the perception of the effectiveness of preventive measures toward gambling, the comparative risk assessment of different addictive behaviors, the perceived risks of different types of gambling and attitudes are related to the gambler's personality. The general population perceived gambling rather negatively and was conscious of the potential risks of gambling; indeed, 59.0% of the sample identified gambling as an addictive practice. Slot machines were estimated to bear the highest risk. Compared with women and older people, men and young people indicated more positive beliefs about gambling; they perceived gambling as less addictive, supported structural preventive measures less often, and perceived gambling as a less serious problem for society. Gamblers were more likely to put their practices into perspective, perceiving gambling more positively than non-gamblers. General population surveys on such beliefs can deliver insights into preventive actions that should be targeted to young men who showed more favorable views of gambling, which have been shown to be associated with increased risk for problematic gambling.

Blood pressure and cognitive function: a prospective analysis among adolescents in Seychelles

Objective: An inverse relationship between blood pressure and cognitive function has been found in adults, but limited data are available in adolescents and young adults. We prospectively examined the relation between blood pressure and cognitive function in adolescence. Methods: We examined the association between BP measured at the ages of 12-15 years in school surveys and cognitive endpoints measured in the Seychelles Child Development Study at ages 17 (n=407) and 19 (n=429) years respectively. We evaluated multiple domains of cognition based on subtests of the Cambridge Neurological Test Automated Battery (CANTAB), the Woodcock Johnson Test of Scholastic Achievement (WJTA), the Finger Tapping test (FT) and the Kaufman Brief Intelligence Test (K-BIT). We used age-, sex- and height-specific z-scores of systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP). Results: Six out of the 21 cognitive endpoints tested were associated with BP. However, none of these associations were found to hold for both males and females or for different subtests within the same neurodevelopmental domain or for both SBP and DBP. Most of these associations disappeared when analyses were adjusted for selected potential confounding factors such as socio-economic status, birth weight, gestational age, body mass index, alcohol consumption, blood glucose, and total n-3 and n-6 polyunsaturated fats. Conclusions: Our findings do not support a consistent association between BP and subsequent performance on tests assessing various cognitive domains in adolescents.

Starting a Family at Your Parent's House: Multigenerational Households and Below Replacement Fertility in urban Bulgaria

In societies with strong multigenerational links, economic uncertainty results in choosing to stay with one child, sometimes in association with postponement of first births (i.e. Italy) and sometimes in early childbearing (i.e. Bulgaria). The interaction between intergenerational family practices in lowest-low fertility contexts is likely to play a role on differences timing to parenthood. In this paper, we focus on the phenomenon of women who have one child in their early twenties in Bulgaria and do not intend to have a second child. We argue that the key to this process is the persistence of extended multigenerational households in the Bulgarian context and their effect on young couples' fertility decision making. We use semi-structured interview data from the project Fertility Choices in Central and Eastern Europe and ethnographic fieldnotes. The interviews were collected from a sample of 22 couples resident in Sofia and representing different permutations of educational level, marital status and number of children (0 or 1). The four-year ethnographic fieldwork was conducted in both rural and urban Bulgaria between 1997 and 2009. Results suggest that as long as the economic situation remains dire, and young Bulgarians hopes for the future remain cynical, multigenerational households represent the accepted practice of entering into parenthood for young families.

Long-term outcome after cognitive and behavioral regression in non-lesional epilepsy with CSWS

Purpose: To present the long-term outcome (LTO) of 10 adolescents and young adults with documented cognitive and behavioral regression as children due to non-lesional focal, mainly frontal epilepsy with continuous spike-waves during slow wave sleep (CSWS). Method: Past medical and EEG data of all patients were reviewed and neuropsychological tests exploring main cognitive functions were administered. Result: After a mean duration of follow-up of 15.6 years (range 8-23 years), none of the 10 patients had recovered fully, but four regained borderline to normal intelligence and were almost independent. Patients with prolonged global intellectual regression had the worst outcome, whereas those with more specific and short-lived deficits recovered best. The marked behavioral disorders that were so disturbing during the active period (AP) resolved in all but one patient. Executive functions were neither severely nor homogenously affected. Three patients with a frontal syndrome during the AP disclosed only mild residual executive and social cognition deficits. The main cognitive gains occurred shortly after the AP, but qualitative improvements continued to occur. LTO correlated best with duration of CSWS. Conclusion: Our findings emphasize that cognitive recovery after cessation of CSWS depends on the severity and duration of the initial regression. None of our patients had major executive and social cognition deficits with preserved intelligence as reported in adults with destructive lesions of the frontal lobes during childhood. Early recognition of epilepsy with CSWS and rapid introduction of effective therapy are crucial for a best possible outcome.

Regional cortical volumes and congenital heart disease: a MRI study in 22q11.2 deletion syndrome.

Children with congenital heart disease (CHD) who survive surgery often present impaired neurodevelopment and qualitative brain anomalies. However, the impact of CHD on total or regional brain volumes only received little attention. We address this question in a sample of patients with 22q11.2 deletion syndrome (22q11DS), a neurogenetic condition frequently associated with CHD. Sixty-one children, adolescents, and young adults with confirmed 22q11.2 deletion were included, as well as 80 healthy participants matched for age and gender. Subsequent subdivision of the patients group according to CHD yielded a subgroup of 27 patients with normal cardiac status and a subgroup of 26 patients who underwent cardiac surgery during their first years of life (eight patients with unclear status were excluded). Regional cortical volumes were extracted using an automated method and the association between regional cortical volumes, and CHD was examined within a three-condition fixed factor. Robust protection against type I error used Bonferroni correction. Smaller total cerebral volumes were observed in patients with CHD compared to both patients without CHD and controls. The pattern of bilateral regional reductions associated with CHD encompassed the superior parietal region, the precuneus, the fusiform gyrus, and the anterior cingulate cortex. Within patients, a significant reduction in the left parahippocampal, the right middle temporal, and the left superior frontal gyri was associated with CHD. The present results of global and regional volumetric reductions suggest a role for disturbed hemodynamic in the pathophysiology of brain alterations in patients with neurodevelopmental disease and cardiac malformations.

Expression of foraging and Gp-9 are associated with social organization in the fire ant Solenopsis invicta.

The aim of this study was to investigate levels of expression of two major genes, the odorant binding protein Gp-9 (general protein-9) and foraging, that have been shown to be associated with behavioural polymorphisms in ants. We analysed workers and young nonreproductive queens collected from nests of the monogyne (single reproductive queen per nest) and polygyne (multiple reproductive queens) social forms of Solenopsis invicta. In workers but not young queens, the level of foraging expression was significantly associated with social form and the task performed (ie localization in the nest or foraging area). The level of expression of Gp-9 was also associated with social form and worker localization. In addition there was a higher level of expression of the Gp-9(b) allele compared with the Gp-9(B) allele in the heterozygote workers and the young nonreproductive queens. Finally, in the polygyne colonies the level of expression of foraging was not significantly associated with the Gp-9 genotype for either workers or young nonreproductive queens, suggesting that both genes have independent non-epistatic effects on behaviour in S. invicta.

Biomechanical characterization and in vitro mechanical injury of elderly human femoral head cartilage: comparison to adult bovine humeral head cartilage.

OBJECTIVES: In vitro mechanical injury of articular cartilage is useful to identify events associated with development of post-traumatic osteoarthritis (OA). To date, many in vitro injury models have used animal cartilage despite the greater clinical relevance of human cartilage. We aimed to characterize a new in vitro injury model using elderly human femoral head cartilage and compare its behavior to that of an existing model with adult bovine humeral head cartilage. DESIGN: Mechanical properties of human and bovine cartilage disks were characterized by elastic modulus and hydraulic permeability in radially confined axial compression, and by Young's modulus, Poisson's ratio, and direction-dependent radial strain in unconfined compression. Biochemical composition was assessed in terms of tissue water, solid, and glycosaminoglycan (GAG) contents. Responses to mechanical injury were assessed by observation of macroscopic superficial tissue cracks and histological measurements of cell viability following single injurious ramp loads at 7 or 70%/s strain rate to 3 or 14 MPa peak stress. RESULTS: Confined compression moduli and Young's moduli were greater in elderly human femoral cartilage vs adult bovine humeral cartilage whereas hydraulic permeability was less. Radial deformations of axially compressed explant disks were more anisotropic (direction-dependent) for the human cartilage. In both cartilage sources, tissue cracking and associated cell death during injurious loading was common for 14 MPa peak stress at both strain rates. CONCLUSION: Despite differences in mechanical properties, acute damage induced by injurious loading was similar in both elderly human femoral cartilage and adult bovine humeral cartilage, supporting the clinical relevance of animal-based cartilage injury models. However, inherent structural differences such as cell density may influence subsequent cell-mediated responses to injurious loading and affect the development of OA.

Exact and approximate stepdown methods for multiple hypothesis testing

Consider the problem of testing k hypotheses simultaneously. In this paper,we discuss finite and large sample theory of stepdown methods that providecontrol of the familywise error rate (FWE). In order to improve upon theBonferroni method or Holm's (1979) stepdown method, Westfall and Young(1993) make eective use of resampling to construct stepdown methods thatimplicitly estimate the dependence structure of the test statistics. However,their methods depend on an assumption called subset pivotality. The goalof this paper is to construct general stepdown methods that do not requiresuch an assumption. In order to accomplish this, we take a close look atwhat makes stepdown procedures work, and a key component is a monotonicityrequirement of critical values. By imposing such monotonicity on estimatedcritical values (which is not an assumption on the model but an assumptionon the method), it is demonstrated that the problem of constructing a validmultiple test procedure which controls the FWE can be reduced to the problemof contructing a single test which controls the usual probability of a Type 1error. This reduction allows us to draw upon an enormous resamplingliterature as a general means of test contruction.

Drivers and sources of supply flexibility: An exploratory study

Purpose - There has been much research on manufacturing flexibility, but supply chain flexibility is still an under-investigated area. This paper focuses on supply flexibility, the aspects of flexibility related to the upstream supply chain. Our purpose is to investigate why and how firms increase supply flexibility.Methodology/Approach An exploratory multiple case study was conducted. We analyzed seven Spanish manufacturers from different sectors (automotive, apparel, electronics and electrical equipment).Findings - The results show that there are some major reasons why firms need supply flexibility (manufacturing schedule fluctuations, JIT purchasing, manufacturing slack capacity, low level of parts commonality, demand volatility, demand seasonality and forecast accuracy), and that companies increase this type of flexibility by implementing two main strategies: to increase suppliers responsiveness capability and flexible sourcing . The results also suggest that the supply flexibility strategy selected depends on two factors: the supplier searching and switching costs and the type of uncertainty (mix, volume or delivery).Research limitations - This paper has some limitations common to all case studies, such as the subjectivity of the analysis, and the questionable generalizability of results (since the sample of firms is not statistically significant).Implications - Our study contributes to the existing literature by empirically investigating which are the main reasons for companies needing to increase supply flexibility, how they increase this flexibility, and suggesting some factors that could influence the selection of a particular supply flexibility strategy.

Drug use and suicide attempts: the role of personality factors.

This study on suicide attempts is part of a large research project on dependent behavior in adolescents and young adults. 228 subjects aged 14-25 (107 "drug abusers," 121 controls) from the French speaking part of Switzerland were evaluated on the basis of a semi-structured interview (Mini International Neuropsychiatric Interview), enabling a DSM-IV diagnosis, and self-reports (SSS by Zuckermann, MMPI-2, IDI by Hirschfeld). 31.5% of "drug abuser" males and 41.2% of "drug abuser" females committed one or more suicide attempts. The results of a logistic regression show that the significant factor explaining suicide attempts in drug users is emotional reliance for males and experience-seeking for females.