The effect of rapamycin treatment on cerebral ischemia: A systematic review and meta-analysis of animal model studies

Background:Amplifying endogenous neuroprotective mechanisms is a promising avenue for stroke therapy. One target is mammalian target of rapamycin (mTOR), a serine/threonine kinase regulating cell proliferation, cell survival, protein synthesis, and autophagy. Animal studies investigating the effect of rapamycin on mTOR inhibition following cerebral ischemia have shown conflicting results.Aim:To conduct a systematic review and meta-analysis evaluating the effectiveness of rapamycin in reducing infarct volume in animal models of ischemic stroke.Summary of review:Our search identified 328 publications. Seventeen publications met inclusion criteria (52 comparisons: 30 reported infarct size and 22 reported neurobehavioral score). Study quality was modest (median 4 of 9) with no evidence of publication bias. The point estimate for the effect of rapamycin was a 21.6% (95% CI, 7.6%–35.7% p Conclusion:Low-dose rapamycin treatment may be an effective therapeutic option for stroke. Modest study quality means there is a potential risk of bias. We recommend further high-quality preclinical studies on rapamycin in stroke before progressing to clinical trials

Food insecurity, school absenteeism and educational attainment of adolescents in Jimma Zone Southwest Ethiopia: a longitudinal study

<p>Abstract</p> <p>Background</p> <p>Food insecurity not only affects physical growth and health of children but also their intellectual development, school attendance and academic performance. However, most evidences are based on studies in high income countries. Although food insecurity is common in Ethiopia, to what extent it affects school attendance and educational attainment of adolescents is not explored. We hypothesized that food insecure adolescents would be more likely to be absent from school and have lower grades attained after 1 year compared to their food secure peers.</p> <p>Methods</p> <p>We used data from 2009 adolescents in the age group of 13-17 years from two consecutive surveys of a five year longitudinal family study in Southwest Ethiopia. A stratified random sampling was used to select participants. Regression analyses were used to compare school absenteeism and the highest grade attained after 1 year of follow-up in food secure and insecure adolescents. The analysis was adjusted for demographic factors, reported illness and workload.</p> <p>Results</p> <p>Significantly more (33.0%) food insecure adolescents were absent from school compared with their food secure peers (17.8%, P < 0.001). Multivariable logistic regression analyses showed that after adjusting for gender, place of residence and gender of the household head, adolescent food insecurity [OR 1.77 (1.34-2.33)], severe household food insecurity [OR 1.62 (1.27-2.06)], illness during the past one month before the survey [OR 2.26 (1.68-3.06)], the highest grade aspired to be completed by the adolescent [OR 0.92 (0.88-0.96)], and the number of days that the adolescent had to work per week [OR 1.16 (1.07-1.26)] were independent predictors of school absenteeism. Similarly after controlling for household income and gender of the household head, adolescent food insecurity(P < 0.001), severe household food insecurity(P < 0.001), illness during the last month(P < 0.001) and rural residence(P < 0.001) were inversely associated with highest grade attained, while age of the adolescent(P < 0.001), the highest grade intended to be completed(P < 0.001) and residence in semi urban area(P < 0.001) were positively associated with the highest grade attained.</p> <p>Conclusions</p> <p>Adolescent and household food insecurity are positively associated with school absenteeism and a lower educational attainment. Programs aiming to achieve universal access to primary education in food insecure environments should integrate interventions to ensure food security of adolescents.</p

English Language Proficiency and Geographical Proximity to a Safety Net Clinic as a Predictor of Health Care Access

Studies suggest that proximity to a safety net clinic (SNC) promotes access to care among the uninsured. Distance-based barriers to care may be greater for people with limited English proficiency (LEP), compared to those who are English proficient (EP), but this has not been explored. We assessed the relationship between distance to the nearest SNC and access in non-rural uninsured adults in California, and examined whether this relationship differs by language proficiency. Using the 2005 California Health Interview Survey and a list we compiled of California’s SNCs, we calculated distance between uninsured interviewee residence and the exact address of the nearest SNC. Using multivariate regression to adjust for other relevant characteristics, we examined associations between this distance and interviewee’s probability of having a usual source of health care (USOC) and having visited a physician in the prior 12 months. To examine differences by language proficiency, we included interactions between distance and language proficiency. Uninsured LEP adults living within 2 miles of a SNC were 9.3% less likely than their EP counterparts to have a USOC (P = 0.046). Further, distance to the nearest SNC was inversely associated with the probability of having a USOC among LEP, but not among EP; consequently, the difference between LEP and EP in the probability of having a USOC widened with increasing distance to the nearest SNC. There was no difference between LEP and EP adults living within 2 miles of a SNC in likelihood of having a physician visit; however, as with USOC, distance to the nearest SNC was inversely associated with the probability of having a physician visit among LEP but not EP. The effect sizes diminished, but remained significant, when we included county fixed effects in the models. Having LEP is a barrier to health care access, which compounds when combined with increased distance to the nearest SNC, among uninsured adults. Future studies should explore potential mechanisms so that appropriate interventions can be implemented

A study of tuberculosis in road traffic-killed badgers on the edge of the British bovine TB epidemic area

The role of badgers in the geographic expansion of the bovine tuberculosis (bTB) epidemic in England is unknown: indeed there have been few published studies of bTB in badgers outside of the Southwest of England where the infection is now endemic in cattle. Cheshire is now on the edge of the expanding area of England in which bTB is considered endemic in cattle. Previous studies, over a decade ago when bovine infection was rare in Cheshire, found no or only few infected badgers in the south eastern area of the county. In this study, carried out in 2014, road-killed badgers were collected through a network of local stakeholders (farmers, veterinarians, wildlife groups, government agencies), and Mycobacterium bovis was isolated from 21% (20/94) badger carcasses. Furthermore, there was strong evidence for co-localisation of M. bovis SB0129 (genotype 25) infection in both badgers and cattle herds at a county scale. While these findings suggest that both badgers and cattle are part of the same geographically expanding epidemic, the direction of any cross-species transmission and the drivers of this expansion cannot be determined. The study also demonstrated the utility of using road-killed badgers collected by stakeholders as a means of wildlife TB surveillance

Lynch syndrome: barriers to and facilitators of screening and disease management

Background Lynch syndrome is a hereditary cancer with confirmed carriers at high risk for colorectal (CRC) and extracolonic cancers. The purpose of the current study was to develop a greater understanding of the factors influencing decisions about disease management post-genetic testing. Methods The study used a grounded theory approach to data collection and analysis as part of a multiphase project examining the psychosocial and behavioral impact of predictive DNA testing for Lynch syndrome. Individual and small group interviews were conducted with individuals from 10 families with the MSH2 intron 5 splice site mutation or exon 8 deletion. The data from confirmed carriers (n = 23) were subjected to re-analysis to identify key barriers to and/or facilitators of screening and disease management. Results Thematic analysis identified personal, health care provider and health care system factors as dominant barriers to and/or facilitators of managing Lynch syndrome. Person-centered factors reflect risk perceptions and decision-making, and enduring screening/disease management. The perceived knowledge and clinical management skills of health care providers also influenced participation in recommended protocols. The health care system barriers/facilitators are defined in terms of continuity of care and coordination of services among providers. Conclusions Individuals with Lynch syndrome often encounter multiple barriers to and facilitators of disease management that go beyond the individual to the provider and health care system levels. The current organization and implementation of health care services are inadequate. A coordinated system of local services capable of providing integrated, efficient health care and follow-up, populated by providers with knowledge of hereditary cancer, is necessary to maintain optimal health

Culling-Induced Changes in Badger (Meles meles) Behaviour, Social Organisation and the Epidemiology of Bovine Tuberculosis

In the UK, attempts since the 1970s to control the incidence of bovine tuberculosis (bTB) in cattle by culling a wildlife host, the European badger (Meles meles), have produced equivocal results. Culling-induced social perturbation of badger populations may lead to unexpected outcomes. We test predictions from the ‘perturbation hypothesis’, determining the impact of culling operations on badger populations, movement of surviving individuals and the influence on the epidemiology of bTB in badgers using data dervied from two study areas within the UK Government's Randomised Badger Culling Trial (RBCT). Culling operations did not remove all individuals from setts, with between 34–43% of badgers removed from targeted social groups. After culling, bTB prevalence increased in badger social groups neighbouring removals, particularly amongst cubs. Seventy individual adult badgers were fitted with radio-collars, yielding 8,311 locational fixes from both sites between November 2001 and December 2003. Home range areas of animals surviving within removed groups increased by 43.5% in response to culling. Overlap between summer ranges of individuals from Neighbouring social groups in the treatment population increased by 73.3% in response to culling. The movement rate of individuals between social groups was low, but increased after culling, in Removed and Neighbouring social groups. Increased bTB prevalence in Neighbouring groups was associated with badger movements both into and out of these groups, although none of the moving individuals themselves tested positive for bTB. Significant increases in both the frequency of individual badger movements between groups and the emergence of bTB were observed in response to culling. However, no direct evidence was found to link the two phenomena. We hypothesise that the social disruption caused by culling may not only increase direct contact and thus disease transmission between surviving badgers, but may also increase social stress within the surviving population, causing immunosuppression and enhancing the expression of disease

Uptake of genetic testing by the children of Lynch syndrome variant carriers across three generations

Many Lynch syndrome (LS) carriers remain unidentified, thus missing early cancer detection and prevention opportunities. Tested probands should inform their relatives about cancer risk and options for genetic counselling and predictive gene testing, but many fail to undergo testing. To assess predictive testing uptake and demographic factors influencing this decision in LS families, a cross-sectional registry-based cohort study utilizing the Finnish Lynch syndrome registry was undertaken. Tested LS variant probands (1184) had 2068 children divided among three generations: 660 parents and 1324 children (first), 445 and 667 (second), and 79 and 77 (third). Of children aged 418 years, 801 (67.4%), 146 (43.2%), and 5 (23.8%), respectively, were genetically tested. Together, 539 first-generation LS variant carriers had 2068 children and grandchildren (3.84 per carrier). Of the 1548 (2.87 per carrier) eligible children, 952 (61.5%) were tested (1.77 per carrier). In multivariate models, age (OR 1.08 per year; 95% CI 1.06-1.10), family gene (OR 2.83; 1.75-4.57 for MLH1 and 2.59; 1.47-4.56 for MSH2 compared with MSH6), one or more tested siblings (OR 6.60; 4.82-9.03), no siblings (OR 4.63; 2.64-8.10), and parent under endoscopic surveillance (OR 5.22; 2.41-11.31) were independent predictors of having genetic testing. Examples of parental adherence to regular surveillance and genetically tested siblings strongly influenced children at 50% risk of LS to undergo predictive gene testing. High numbers of untested, adult at-risk individuals exist even among well-established cohorts of known LS families with good adherence to endoscopic surveillance.Peer reviewe

Effectiveness of Biosecurity Measures in Preventing Badger Visits to Farm Buildings

This is the final version of the article. Available from Public Library of Science via the DOI in this record.BACKGROUND: Bovine tuberculosis caused by Mycobacterium bovis is a serious and economically important disease of cattle. Badgers have been implicated in the transmission and maintenance of the disease in the UK since the 1970s. Recent studies have provided substantial evidence of widespread and frequent visits by badgers to farm buildings during which there is the potential for close direct contact with cattle and contamination of cattle feed. METHODOLOGY: Here we evaluated the effectiveness of simple exclusion measures in improving farm biosecurity and preventing badger visits to farm buildings. In the first phase of the study, 32 farms were surveyed using motion-triggered infrared cameras on potential entrances to farm buildings to determine the background level of badger visits experienced by each farm. In the second phase, they were divided into four treatment groups; "Control", "Feed Storage", "Cattle Housing" and "Both", whereby no exclusion measures were installed, exclusion measures were installed on feed storage areas only, cattle housing only or both feed storage and cattle housing, respectively. Badger exclusion measures included sheet metal gates, adjustable metal panels for gates, sheet metal fencing, feed bins and electric fencing. Cameras were deployed for at least 365 nights in each phase on each farm. RESULTS: Badger visits to farm buildings occurred on 19 of the 32 farms in phase one. In phase two, the simple exclusion measures were 100% effective in preventing badger entry into farm buildings, as long as they were appropriately deployed. Furthermore, the installation of exclusion measures also reduced the level of badger visits to the rest of the farmyard. The findings of the present study clearly demonstrate how relatively simple practical measures can substantially reduce the likelihood of badger visits to buildings and reduce some of the potential for contact and disease transmission between badgers and cattle.This work was funded by Defra project number SE3119, http://www.defra.gov.uk/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript