Estimated Risk of HIV Acquisition and Practice for Preventing Occupational Exposure: A Study of Healthcare Workers at Tumbi and Dodoma Hospitals, Tanzania.

Health care workers (HCWs) are at risk of acquiring human immuno-deficiency virus (HIV) and other infections via exposure to infectious patients' blood and body fluids. The main objective of this study was to estimate the risk of HIV transmission and examine the practices for preventing occupational exposures among HCWs at Tumbi and Dodoma Hospitals in Tanzania. This study was carried out in two hospitals, namely, Tumbi in Coast Region and Dodoma in Dodoma Region. In each facility, hospital records of occupational exposure to HIV infection and its management were reviewed. In addition, practices to prevent occupational exposure to HIV infection among HCWs were observed. The estimated risk of HIV transmission due to needle stick injuries was calculated to be 7 cases per 1,000,000 HCWs-years. Over half of the observed hospital departments did not have guidelines for prevention and management of occupational exposure to HIV infections and lacked well displayed health and safety instructions. Approximately, one-fifth of the hospital departments visited failed to adhere to the instructions pertaining to correlation between waste materials and the corresponding colour coded bag/container/safety box. Seventy four percent of the hospital departments observed did not display instructions for handling infectious materials. Inappropriate use of gloves, lack of health and safety instructions, and lack of use of eye protective glasses were more frequently observed at Dodoma Hospital than at Tumbi Hospital. The poor quality of the hospital records at the two hospitals hampered our effort to characterise the risk of HIV infection acquisition by HCWs. Greater data completeness in hospital records is needed to allow the determination of the actual risk of HIV transmission for HCWs. To further reduce the risk of HIV infection due to occupational exposure, hospitals should be equipped with sufficient personal protective equipment (PPE) and HCWs should be reminded of the importance of adhering to universal precautions

Low-level regulatory T-cell activity is essential for functional type-2 effector immunity to expel gastrointestinal helminths

Helminth infection is frequently associated with the expansion of regulatory T cells (Tregs) and suppression of immune responses to bystander antigens. We show that infection of mice with the chronic gastrointestinal helminth Heligmosomoides polygyrus drives rapid polyclonal expansion of Foxp3(+)Helios(+)CD4(+) thymic (t)Tregs in the lamina propria and mesenteric lymph nodes while Foxp3(+)Helios(-)CD4(+) peripheral (p)Treg expand more slowly. Notably, in partially resistant BALB/c mice parasite survival positively correlates with Foxp3(+)Helios(+)CD4(+) tTreg numbers. Boosting of Foxp3(+)Helios(+)CD4(+) tTreg populations by administration of recombinant interleukin-2 (rIL-2):anti-IL-2 (IL-2C) complex increased worm persistence by diminishing type-2 responsiveness in vivo, including suppression of alternatively activated macrophage and granulomatous responses at the sites of infection. IL-2C also increased innate lymphoid cell (ILC) numbers, indicating that Treg functions dominate over ILC effects in this setting. Surprisingly, complete removal of Tregs in transgenic Foxp3-DTR mice also resulted in increased worm burdens, with "immunological chaos" evident in high levels of the pro-inflammatory cytokines IL-6 and interferon-γ. In contrast, worm clearance could be induced by anti-CD25 antibody-mediated partial depletion of early Treg, alongside increased T helper type 2 responses and without incurring pathology. These findings highlight the overarching importance of the early Treg response to infection and the non-linear association between inflammation and the prevailing Treg frequency

At the coalface and the cutting edge: general practitioners’ accounts of the rewards of engaging with HIV medicine

The interviews we conducted with GPs suggest that an engagement with HIV medicine enables clinicians to develop strong and long-term relationships with and expertise about the care needs of people living with HIV ‘at the coalface’, while also feeling connected with a broader network of medical practitioners and other professionals concerned with and contributing to the ever-changing world of science: ‘the cutting edge’. The general practice HIV prescriber is being modelled here as the interface between these two worlds, offering a rewarding opportunity for general practitioners to feel intimately connected to both community needs and scientific change

Experimental Microbial Evolution of Extremophiles

Experimental microbial evolutions (EME) involves studying closely a microbial population after it has been through a large number of generations under controlled conditions (Kussell 2013). Adaptive laboratory evolution (ALE) selects for fitness under experimentally imposed conditions (Bennett and Hughes 2009; Dragosits and Mattanovich 2013). However, experimental evolution studies focusing on the contributions of genetic drift and natural mutation rates to evolution are conducted under non-selective conditions to avoid changes imposed by selection (Hindré et al. 2012). To understand the application of experimental evolutionary methods to extremophiles it is essential to consider the recent growth in this field over the last decade using model non-extremophilic microorganisms. This growth reflects both a greater appreciation of the power of experimental evolution for testing evolutionary hypotheses and, especially recently, the new power of genomic methods for analyzing changes in experimentally evolved lineages. Since many crucial processes are driven by microorganisms in nature, it is essential to understand and appreciate how microbial communities function, particularly with relevance to selection. However, many theories developed to understand microbial ecological patterns focus on the distribution and the structure of diversity within a microbial population comprised of single species (Prosser et al. 2007). Therefore an understanding of the concept of species is needed. A common definition of species using a genetic concept is a group of interbreeding individuals that is isolated from other such groups by barriers of recombination (Prosser et al. 2007). An alternative ecological species concept defines a species as set of individuals that can be considered identical in all relevant ecological traits (Cohan 2001). This is particularly important because of the abundance and deep phylogenetic complexity of microbial communities. Cohan postulated that “bacteria occupy discrete niches and that periodic selection will purge genetic variation within each niche without preventing divergence between the inhabitants of different niches”. The importance of gene exchange mechanisms likely in bacteria and archaea and therefore extremophiles, arises from the fact that their genomes are divided into two distinct parts, the core genome and the accessory genome (Cohan 2001). The core genome consists of genes that are crucial for the functioning of an organism and the accessory genome consists of genes that are capable of adapting to the changing ecosystem through gain and loss of function. Strains that belong to the same species can differ in the composition of accessory genes and therefore their capability to adapt to changing ecosystems (Cohan 2001; Tettelin et al. 2005; Gill et al. 2005). Additional ecological diversity exists in plasmids, transposons and pathogenicity islands as they can be easily shared in a favorable environment but still be absent in the same species found elsewhere (Wertz et al. 2003). This poses a major challenge for studying ALE and community microbial ecology indicating a continued need to develop a fitting theory that connects the fluid nature of microbial communities to their ecology (Wertz et al. 2003; Coleman et al. 2006). Understanding the nature and contribution of different processes that determine the frequencies of genes in any population is the biggest concern in population and evolutionary genetics (Prosser et al. 2007) and it is critical for an understanding of experimental evolution

Hazardous drinking among young adults seeking outpatient mental health services

BACKGROUND: Alcohol use can have a significant negative impact on young adults in mental health treatment. This cross-sectional study examined prevalence and factors associated with hazardous drinking among young adults seeking outpatient mental health services, rate of alcohol use disorders (AUDs), and the relationship between hazardous drinking and other types of substance use. METHODS: Participants were 487 young adults ages 18–25 who completed self-administered computerized screening questions for alcohol and drug use. Alcohol use patterns were assessed and predictors of hazardous drinking (≥5 drinks on one or more occasions in the past year) were identified using logistic regression. RESULTS: Of the 487 participants, 79.8 % endorsed prior-year alcohol use, 52.3 % reported one or more episodes of hazardous drinking in the prior year and 8.2 % were diagnosed with an AUD. Rates of recent and lifetime alcohol, tobacco and marijuana use were significantly greater in those with prior-year hazardous drinking. In logistic regression, prior-year hazardous drinking was associated with lifetime marijuana use (OR 3.30, p < 0.001; 95 % CI 2.05, 5.28), lifetime tobacco use (OR 1.88, p = 0.004; 95 % CI 1.22, 2.90) and older age (OR 1.18 per year, p < 0.001; 95 % CI 1.08, 1.29). CONCLUSIONS: In an outpatient mental health setting, high rates of hazardous drinking were identified, and drinking was associated with history of other substance use. Results highlight patient characteristics associated with hazardous drinking that mental health providers should be aware of in treating young adults, especially older age and greater use of tobacco and marijuana

Screening out irrelevant cell-based models of disease

The common and persistent failures to translate promising preclinical drug candidates into clinical success highlight the limited effectiveness of disease models currently used in drug discovery. An apparent reluctance to explore and adopt alternative cell-and tissue-based model systems, coupled with a detachment from clinical practice during assay validation, contributes to ineffective translational research. To help address these issues and stimulate debate, here we propose a set of principles to facilitate the definition and development of disease-relevant assays, and we discuss new opportunities for exploiting the latest advances in cell-based assay technologies in drug discovery, including induced pluripotent stem cells, three-dimensional (3D) co-culture and organ-on-a-chip systems, complemented by advances in single-cell imaging and gene editing technologies. Funding to support precompetitive, multidisciplinary collaborations to develop novel preclinical models and cell-based screening technologies could have a key role in improving their clinical relevance, and ultimately increase clinical success rates