Publications

Poor quality housing is an infringement on the rights of all humans to a standard of living adequate for health. Among the many vulnerabilities of those without adequate shelter is the risk of disease spread by rodents and other pests. One such disease is Lassa fever, an acute and sometimes severe viral hemorrhagic illness endemic in West Africa. Lassa virus is maintained in the rodent Mastomys natalensis, commonly known as the "multimammate rat," which frequently invades the domestic environment, putting humans at risk of Lassa fever. The highest reported incidence of Lassa fever in the world is consistently in the Kenema District of Sierra Leone, a region that was at the center of Sierra Leone's civil war in which tens of thousands of lives were lost and hundreds of thousands of dwellings destroyed. Despite the end of the war in 2002, most of Kenema's population still lives in inadequate housing that puts them at risk of rodent invasion and Lassa fever. Furthermore, despite years of health education and village hygiene campaigns, the incidence of Lassa fever in Kenema District appears to be increasing. We focus on Lassa fever as a matter of human rights, proposing a strategy to improve housing quality, and discuss how housing equity has the potential to improve health equity and ultimately economic productivity in Sierra Leone. The manuscript is designed to spur discussion and action towards provision of housing and prevention of disease in one of the world's most vulnerable populations.

Stimulation of the intermediate and deep layers of superior colliculus (DLSC) in rodents evokes both orienting/pursuit (approach) and avoidance/flight (defense) responses (Dean et al., 1989). These two classes of response are subserved by distinct output projections associated with lateral (approach) and medial (defense) DLSC (Comoli et al., 2012). In non-human primates, DLSC has been examined only with respect to orienting/approach behaviors, especially eye movements, and defense-like behaviors have not been reported. Here we examined the profile of behavioral responses evoked by activation of DLSC by unilateral intracerebral infusions of the GABA(A) receptor antagonist, bicuculline methiodide (BIC), in nine freely moving macaques. Across animals, the most consistently evoked behavior was cowering (all animals), followed by increased vocalization and escape-like behaviors (seven animals), and attack of objects (three animals). The effects of BIC were dose-dependent within the range 2.5-14 nmol (threshold dose of 4.6 nmol). The behaviors and their latencies to onset did not vary across different infusion sites within DLSC. Cowering and escape-like behaviors resembled the defense-like responses reported after DLSC stimulation in rats, but in the macaques these responses were evoked from both medial and lateral sites within DLSC. Our findings are unexpected in the context of an earlier theoretical perspective (Dean et al., 1989) that emphasized a preferential role of the primate DLSC for approach rather than defensive responses. Our data provide the first evidence for induction of defense-like behaviors by activation of DLSC in monkeys, suggesting that the role of DLSC in responding to threats is conserved across species.

Atrial fibrillation (AF) is the most common arrhythmia worldwide; it is a significant risk factor for stroke and embolization, and has an impact on cardiac function. Despite its impact on morbidity and mortality, our understanding of the etiology and pathophysiology of this disease process is still incomplete. Over the past several decades, there has been evidence to suggest that AF has a significant correlation with metabolic syndrome (MetS). Furthermore, AF appears to be more closely related to specific components of MetS compared with others. This article provides an overview of the various components of MetS and their impact on AF.

MicroRNAs modulate tumorigenesis through suppression of specific genes. As many tumour types rely on overlapping oncogenic pathways, a core set of microRNAs may exist, which consistently drives or suppresses tumorigenesis in many cancer types. Here we integrate The Cancer Genome Atlas (TCGA) pan-cancer data set with a microRNA target atlas composed of publicly available Argonaute Crosslinking Immunoprecipitation (AGO-CLIP) data to identify pan-tumour microRNA drivers of cancer. Through this analysis, we show a pan-cancer, coregulated oncogenic microRNA 'superfamily' consisting of the miR-17, miR-19, miR-130, miR-93, miR-18, miR-455 and miR-210 seed families, which cotargets critical tumour suppressors via a central GUGC core motif. We subsequently define mutations in microRNA target sites using the AGO-CLIP microRNA target atlas and TCGA exome-sequencing data. These combined analyses identify pan-cancer oncogenic cotargeting of the phosphoinositide 3-kinase, TGFβ and p53 pathways by the miR-17-19-130 superfamily members.

SETTING

Lesotho national multidrug-resistant tuberculosis (MDR-TB) program.

OBJECTIVE

To determine the prevalence of drug-resistant TB (DR-TB) among patients registered for MDR-TB treatment after failure or suspected failure of the standard 6-month regimen for new TB patients (Category I).

DESIGN

We conducted a retrospective cohort study of patients registered for MDR-TB treatment following failure or suspected failure of Category I.

RESULTS

A total of 76 patients were included in the analysis, including 51 Category I treatment failures and 25 suspected Category I treatment failures. The prevalence of resistance to any drug was 92% among the treatment failures and 72% among the suspected failures. The proportion of MDR-TB was respectively 78% and 28% among the treatment failures and suspected failures. Among the subgroup of human immunodeficiency virus (HIV) positive patients, the proportion of MDR-TB was 84% among failures and 23% among suspected failures.

CONCLUSION

DR-TB and MDR-TB were common among patients in whom Category I failed. Early initiation of empiric second-line anti-tuberculosis treatment while awaiting culture and drug susceptibility testing (DST) results should be considered for HIV-negative and -positive patients who have failed first-line anti-tuberculosis treatment; patients suspected to be failing a first-line regimen should undergo DST at the end of the intensive phase.

BACKGROUND

The fragmentation of HIV-related diagnostic and treatment services, especially for youth, is a significant barrier for transitioning to care. The study identified key elements that affected care linkage efforts.

METHODS

We conducted 64 interviews across 15 clinical sites. The constant comparative method was used.

RESULTS

Primary linkage to care processes are illustrated through three geographically diverse case studies. Factors included: inter-agency relationships, data sharing protocols, and service duplication concerns. Program improvement strategies were discussed.

CONCLUSIONS

A strong, citywide network is helpful in coordinating care linkage services. These partnerships will be critical in effectively realizing the goals of the National HIV/AIDS.