Evaluation of the effects of a VEGFR-2 inhibitor compound on alanine aminotransferase gene expression and enzymatic activity in the rat liver

Article deposited according to agreement with BMC, December 6, 2010.YesFunding provided by the Open Access Authors Fund

Field Epidemiology and Laboratory Training Programs in sub-Saharan Africa from 2004 to 2010: need, the process, and prospects

As of 2010 sub-Saharan Africa had approximately 865 million inhabitants living with numerous public health challenges. Several public health initiatives [e.g., the United States (US) President’s Emergency Plan for AIDS Relief and the US President’s Malaria Initiative] have been very successful at reducing mortality from priority diseases. A competently trained public health workforce that can operate multi-disease surveillance and response systems is necessary to build upon and sustain these successes and to address other public health problems. Sub-Saharan Africa appears to have weathered the recent global economic downturn remarkably well and its increasing middle class may soon demand stronger public health systems to protect communities. The Epidemic Intelligence Service (EIS) program of the US Centers for Disease Control and Prevention (CDC) has been the backbone of public health surveillance and response in the US during its 60 years of existence. EIS has been adapted internationally to create the Field Epidemiology Training Program (FETP) in several countries. In the 1990s CDC and the Rockefeller Foundation collaborated with the Uganda and Zimbabwe ministries of health and local universities to create 2-year Public Health Schools Without Walls (PHSWOWs) which were based on the FETP model. In 2004 the FETP model was further adapted to create the Field Epidemiology and Laboratory Training Program (FELTP) in Kenya to conduct joint competencybased training for field epidemiologists and public health laboratory scientists providing a master’s degree to participants upon completion. The FELTP model has been implemented in several additional countries in sub-Saharan Africa. By the end of 2010 these 10 FELTPs and two PHSWOWs covered 613 million of the 865 million people in sub-Saharan Africa and had enrolled 743 public health professionals. We describe the process that we used to develop 10 FELTPs covering 15 countries in sub-Saharan Africa from 2004 to 2010 as a strategy to develop a locally trained public health workforce that can operate multi-disease surveillance and response systems.Key words: Field epidemiology, laboratory management, multi-disease surveillance and response systems, public health workforce capacity buildin

Metallothionein – overexpression as a highly significant prognostic factor in melanoma: a prospective study on 1270 patients

Metallothioneins (MT) are ubiquitous, intracellular small proteins with high affinity for heavy metal ions. In the last decades, it was shown that MT overexpression in a variety of cancers is associated with resistance to anticancer drugs and is combined with a poor prognosis. In this prospective study, we examined the role of MT overexpression in melanoma patients as a prognostic factor for progression and survival. Between 1993 and 2004, 3386 patients with primary cutaneous melanoma were investigated by using a monoclonal antibody against MT on routinely fixed, paraffin-embedded tissues. In all, 1270 patients could be followed up for further statistical analysis (Fisher's exact test, Mantel–Haenszel χ2 test, Kaplan–Meier curves). The MT data of disease-free interval and overall survival were compared univariately and multivariately in Cox regression analysis. Immunohistochemical overexpression of MT in tumour cells of patients with primary melanoma (310 of 1270; 24.4%) was associated with a higher risk for progression (117 of 167; 70.1%) and reduced survival (80 of 110; 72.7%) of the disease (P<0.0001). Similarly, Kaplan–Meier curves gave highly significant disadvantages for the MT-positive group. Univariate analysis (relative risk 7.4; 95% confidence interval (CI) 5.2–10.2; P<0.0001 for progression; relative risk 7.1; 95% CI 4.7–10.9; P<0.0001 for survival), as well as multivariate analysis with other prognostic markers resulted in MT overexpression as a highly significant and independent factor for prognosis in primary melanoma

HIV-1 Residual Viremia Correlates with Persistent T-Cell Activation in Poor Immunological Responders to Combination Antiretroviral Therapy

BACKGROUND:The clinical significance and cellular sources of residual human immunodeficiency virus type 1 (HIV-1) production despite suppressive combination antiretroviral therapy (cART) remain unclear and the effect of low-level viremia on T-cell homeostasis is still debated. METHODOLOGY/PRINCIPAL FINDINGS:We characterized the recently produced residual viruses in the plasma and short-lived blood monocytes of 23 patients with various immunological responses to sustained suppressive cART. We quantified the residual HIV-1 in the plasma below 50 copies/ml, and in the CD14(high) CD16(-) and CD16+ monocyte subsets sorted by flow cytometry, and predicted coreceptor usage by genotyping V3 env sequences. We detected residual viremia in the plasma of 8 of 10 patients with poor CD4+ T-cell reconstitution in response to cART and in only 5 of 13 patients with good CD4+ T-cell reconstitution. CXCR4-using viruses were frequent among the recently produced viruses in the plasma and in the main CD14(high) CD16(-) monocyte subset. Finally, the residual viremia was correlated with persistent CD4+ and CD8+ T-cell activation in patients with poor immune reconstitution. CONCLUSIONS:Low-level viremia could result from the release of archived viruses from cellular reservoirs and/or from ongoing virus replication in some patients. The compartmentalization of the viruses between the plasma and the blood monocytes suggests at least two origins of residual virus production during effective cART. CXCR4-using viruses might be produced preferentially in patients on cART. Our results also suggest that low-level HIV-1 production in some patients may contribute to persistent immune dysfunction despite cART

Mapping Game Preferences Of Older Adults: A Field Study Towards Tailored Gamified Applications

Digital applications are a valuable addition to traditional healthcare. An opportunity in retaining motivation to use these applications lies in gamification. To design a gamified healthcare application for a specific target group, such as the older adult, detailed insight in their game preferences is needed. This insight enables us to tailor gamification to the user to make applications more engaging and usable, which is thought to better facilitate underlying healthcare goals. This raises the need for methods to assess these game preferences. Towards such a method, we deploy a classification for game content based on the five domains of play theory. In this study, 12 older adults played five off-the-shelf tablet games for one week. Preferences were assessed through a questionnaire, log data and semi-structured interview. The resulting overview of preferences was used to make recommendations for future gamification as well as a refinement of the classification