Neuregulin-1 attenuates mortality associated with experimental cerebral malaria.

BackgroundCerebral Malaria (CM) is a diffuse encephalopathy caused by Plasmodium falciparum infection. Despite availability of antimalarial drugs, CM-associated mortality remains high at approximately 30% and a subset of survivors develop neurological and cognitive disabilities. While antimalarials are effective at clearing Plasmodium parasites they do little to protect against CM pathophysiology and parasite-induced brain inflammation that leads to seizures, coma and long-term neurological sequelae in CM patients. Thus, there is urgent need to explore therapeutics that can reduce or prevent CM pathogenesis and associated brain inflammation to improve survival. Neuregulin-1 (NRG-1) is a neurotrophic growth factor shown to protect against brain injury associated with acute ischemic stroke (AIS) and neurotoxin exposure. However, this drug has not been tested against CM-associated brain injury. Since CM-associated brain injuries and AIS share similar pathophysiological features, we hypothesized that NRG-1 will reduce or prevent neuroinflammation and brain damage as well as improve survival in mice with late-stage experimental cerebral malaria (ECM).MethodsWe tested the effects of NRG-1 on ECM-associated brain inflammation and mortality in P. berghei ANKA (PbA)-infected mice and compared to artemether (ARM) treatment; an antimalarial currently used in various combination therapies against malaria.ResultsTreatment with ARM (25 mg/kg/day) effectively cleared parasites and reduced mortality in PbA-infected mice by 82%. Remarkably, NRG-1 therapy (1.25 ng/kg/day) significantly improved survival against ECM by 73% despite increase in parasite burden within NRG-1-treated mice. Additionally, NRG-1 therapy reduced systemic and brain pro-inflammatory factors TNFalpha, IL-6, IL-1alpha and CXCL10 and enhanced anti-inflammatory factors, IL-5 and IL-13 while decreasing leukocyte accumulation in brain microvessels.ConclusionsThis study suggests that NRG-1 attenuates ECM-associated brain inflammation and injuries and may represent a novel supportive therapy for the management of CM

Clinical Trials in Head Injury

Traumatic brain injury (TBI) remains a major public health problem globally. In the United States the incidence of closed head injuries admitted to hospitals is conservatively estimated to be 200 per 100,000 population, and the incidence of penetrating head injury is estimated to be 12 per 100,000, the highest of any developed country in the world. This yields an approximate number of 500,000 new cases each year, a sizeable proportion of which demonstrate signficant long-term disabilities. Unfortunately, there is a paucity of proven therapies for this disease. For a variety of reasons, clinical trials for this condition have been difficult to design and perform. Despite promising pre-clinical data, most of the trials that have been performed in recent years have failed to demonstrate any significant improvement in outcomes. The reasons for these failures have not always been apparent and any insights gained were not always shared. It was therefore feared that we were running the risk of repeating our mistakes. Recognizing the importance of TBI, the National Institute of Neurological Disorders and Stroke (NINDS) sponsored a workshop that brought together experts from clinical, research, and pharmaceutical backgrounds. This workshop proved to be very informative and yielded many insights into previous and future TBI trials. This paper is an attempt to summarize the key points made at the workshop. It is hoped that these lessons will enhance the planning and design of future efforts in this important field of research.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63185/1/089771502753754037.pd

Writers Talk Featuring Byron Pitts

Interview featuring Byron PittsOhio State University. Center for the Study and Teaching of Writin

Religious Programs, Institutional Adjustment, and Recidivism among Former Inmates in Prison Fellowship Programs

This study examines the impact of religious programs on institutional adjustment and recidivism rates in two matched groups of inmates from four adult male prisons in New York State. One group had participated in programs sponsored by Prison Fellowship (PF); the other had no involvement with PF. PF and non-PF inmates are similar on measures of institutional adjustment, as measured by both general and serious prison infractions, and recidivism, as measured by arrests during a one-year follow-up period. However, after controlling for level of involvement in PF-sponsored programs, inmates who were most active in Bible studies were significantly less likely to be rearrested during the follow-up period

Prevalence and correlates of a diagnosis of sexually transmitted infection among young aboriginal and Torres strait islander people: A national survey

Background: Young Aboriginal and Torres Strait Islander (Aboriginal) people are recognized as a priority population for the control of sexually transmissible infections (STIs) in Australia. This article reports the prevalence of self-reported STI diagnoses and their correlates among Aboriginal people aged 16 to 29 years. Methods: Results were analyzed from a survey conducted between 2011 and 2013 at regular community events. Univariate and multivariate logistic regression models were used to identify the correlates of a history of STI diagnosis among participants who reported being sexually active and ever having been tested for STIs. All analyses were stratified by sex. Results: Of the 2877 participants in this study, 2320, comprising 60% females, self-reported ever having had vaginal or anal sex, and a further subset of 1589 (68%) reported ever being tested for any of the following STIs: chlamydia, gonorrhea, syphilis, or trichomonas. Within this latter group, the proportion who reported that they had had a positive STI diagnosis was 25%. In multivariate analysis, women who reported sexual debut before the age of 16 years (prevalence ratio [PR], 1.53; 95% confidence interval, 1.16-2.81; P < 0.05), ever having had oral sex (PR, 2.66; 1.47-4.82; P < 0.001), inconsistent condom use in the past 12 months (PR, 1.71; 1.13-2.58; P < 0.012), having had sex with someone they had just met (adjusted odds ratio, 1.74; 1.21-2.50; P < 0.003), and using ecstasy (PR, 1.81; 1.16-2.81; P < 0.009) were significantly associated with a selfreported history of an STI diagnosis. For men, being older (25-29 years; PR, 2.10; 1.10-3.96; P < 0.023), being gay or bisexual (PR, 2.22; 1.16-4.27; P < 0.016), not using a condom during last sex, (PR, 1.74; 1.10-2.76; P < 0.019), past ecstasy use (PR, 1.88; 1.11-3.20; P < 0.019), and injecting drug use (PR, 2.81; 1.35-5.88); P < 0.006) were independent predictors of ever reporting being diagnosed as having an STI. Discussion: In the first community-based survey of this population, a self-reported history of ever being diagnosed as having prevalent STIs was common in sexually active young Aboriginal people who reported STI testing in the past. This population requires targeted education and health service interventions to address the high burden of STIs

Illicit and injecting drug use among Indigenous young people in urban, regional and remote Australia

Introduction and Aims: To examine patterns of illicit drug use among Australian Indigenous young people, identify correlates of frequent use separately in urban, regional and remote settings and characterise those who inject. Design and Method: Cross-sectional design at 40 Indigenous events. Self-complete surveys were administered to Indigenous people aged 16–29 years using mobile devices. Results: 2,877 participants completed the survey. One in five reported using cannabis at least weekly in the previous year, but the use of other drugs was less prevalent. Patterns of drug use were largely similar across regions, although more participants in urban and regional areas reported using ecstasy (12% vs 11% vs 5%) and cocaine (6% vs 3% vs 1%) and more reported weekly cannabis use (18% vs 22% vs 14%). Injecting was rare (3%) but those who did inject reported a high incidence of needle sharing (37%). Methamphetamine (37%), heroin (36%) and methadone (26%) were the most commonly injected drugs, and injecting was related to prison experience (AOR 5.3 95% CI 2.8–10.0). Discussion and Conclusion: Attention is needed in relation to cannabis use, particularly among those Indigenous young people living in regional and urban settings. Also, although injecting is uncommon, it is associated with prison involvement. Priority must be given to reducing the numbers of Indigenous youth entering justice settings, delaying the age at first entry to justice settings, and reducing the risk of BBV acquisition while in custody through, for example, prison-based NSP, BBV education, and Indigenous-specific treatment that emphasises connection to country and culture. [Bryant J, Ward J, Wand H, Byron K, Bamblett A, Waples-Crowe P, Betts S, Coburn T, Delaney-Thiele D, Worth H, Kaldor J, Pitts M. Illicit and injecting drug use among Indigenous young people in urban, regional and remote Australia. Drug Alcohol Rev 2016;35:447–455]