Factors associated with pre-ART loss-to-follow up in adults in rural KwaZulu-Natal, South Africa:a prospective cohort study

Background: Timely initiation of antiretroviral treatment (ART) requires sustained engagement in HIV care before treatment eligibility. We assessed loss to follow-up (LTFU) correlates in HIV-positive adults accessing HIV treatment and care, not yet ART-eligible (CD4 &gt;500 cells/mm3).Methods: This was a sub-study of a prospective cohort study (focusing on sexual behaviour) in an area of high HIV prevalence and widespread ART availability in rural KwaZulu-Natal, South Africa. Psychosocial, clinical and demographic data were collected at recruitment from individuals with CD4 &gt;500 cells/mm3. LTFU was defined as not attending clinic within 13 months of last visit or before death. Individuals starting ART were censored at ART initiation. Data were collected between January 2009 and January 2013. Analysis used Competing Risks regression.Results: Two hundred forty-seven individuals (212 females) were recruited (median follow-up 2.13 years, total follow-up 520.15 person-years). 86 remained in pre-ART care (34.8 %), 94 were LTFU (38.1 %), 58 initiated ART (23.5 %), 7 died (2.8 %), 2 transferred out (0.8 %). The LTFU rate was 18.07 per 100 person-years (95 % CI 14.76–21.12). LTFU before a competing event was 13.5 % at one and 34.4 % at three years. Lower LTFU rates were significantly associated with age (&gt;37 versus ?37 years: adjusted sub-Hazard ratio (aSHR) 0.51, 95 % CI 0.30–0.87), openness with family/friends (a little versus not at all, aSHR 0.81, 95 % CI 0.45–1.43; a lot versus not at all, aSHR 1.57, 95 % CI 0.94–2.62), children (0 versus 4+, aSHR 0.68, 95 % CI 0.24–1.87; 1 versus 4+, aSHR 2.05 95 % CI 1.14–3.69, 2 versus 4+; aSHR 1.71, 95 % CI 0.94–3.09; 3 versus 4a, aSHR 1.14, 95 % CI 0.57–2.30), previous CD4 counts (1 versus 0, aSHR 0.81, 95 % CI 0.45–1.43; 2+ versus 0, aSHR 0.43, 95 % CI 0.25–0.73), and most recent partner HIV status (not known versus HIV-positive, aSHR 0.77, 95 % CI 0.50–1.19; HIV-negative versus HIV-positive, aSHR 2.40, 95 % CI 1.18–4.88). The interaction between openness with family/friends and HIV partner disclosure was close to significance (p?=?0.06). Those who had neither disclosed to partners nor were open with family/friends had lowest LTFU rates.Conclusions: Strategies to retain younger people in pre-ART care are required. How openness with others, partner HIV status and disclosure, and children relate to LTFU needs further exploration.<br/

The Management of Cardiovascular Abnormalities in Patient With LEOPARD Syndrome

LEOPARD syndrome (LS) is a rare hereditary disorder in Asian countries. This syndrome consists of multiple systemic abnormalities. In particular, characteristic cardiovascular effects in LS may include variable clinical manifestations from benign to life-threatening courses. The cardiac effects of this syndrome consist of left ventricular hypertrophy (LVH), pulmonary stenosis (PS), coronary artery dilatation and electrocardiogram(ECG) abnormalities. Since there are few LS patients who have undergone a complete cardiovascular evaluation, the nature and clinical prognosis of cardiovascular abnormalities in this syndrome remain uncertain. Also, there have been few reports on therapeutic strategies for cardiovascular abnormalities in LS. Here we describe a case of LS who presented with multiple cardiovascular problems and underwent successful surgical and medical treatment

Regulatory potential for concerted modulation of Nrf2- and Nfkb1-mediated gene expression in inflammation and carcinogenesis

Many studies have implicated nuclear factor E2-related factor 2 (Nrf2) and nuclear factor-κB1 (Nfkb1) in inflammation and cancer. However, the regulatory potential for crosstalk between these two important transcription factors in inflammation and carcinogenesis has not been explored. To delineate conserved transcription factor-binding site signatures, we performed bioinformatic analyses on the promoter regions of human and murine Nrf2 and Nfkb1. We performed multiple sequence alignment of Nrf2 and Nfkb1 genes in five mammalian species – human, chimpanzee, dog, mouse and rat – to explore conserved biological features. We constructed a canonical regulatory network for concerted modulation of Nrf2 and Nfkb1 involving several members of the mitogen-activated protein kinase (MAPK) family and present a putative model for concerted modulation of Nrf2 and Nfkb1 in inflammation/carcinogenesis. Our results reflect potential for putative crosstalk between Nrf2 and Nfkb1 modulated through the MAPK cascade that may influence inflammation-associated etiopathogenesis of cancer. Taken together, the elucidation of potential relationships between Nrf2 and Nfkb1 may help to better understand transcriptional regulation, as well as transcription factor networks, associated with the etiopathogenesis of inflammation and cancer

Myosin IIA Modulates T Cell Receptor Transport and CasL Phosphorylation during Early Immunological Synapse Formation

Activation of T cell receptor (TCR) by antigens occurs in concert with an elaborate multi-scale spatial reorganization of proteins at the immunological synapse, the junction between a T cell and an antigen-presenting cell (APC). The directed movement of molecules, which intrinsically requires physical forces, is known to modulate biochemical signaling. It remains unclear, however, if mechanical forces exert any direct influence on the signaling cascades. We use T cells from AND transgenic mice expressing TCRs specific to the moth cytochrome c 88–103 peptide, and replace the APC with a synthetic supported lipid membrane. Through a series of high spatiotemporal molecular tracking studies in live T cells, we demonstrate that the molecular motor, non-muscle myosin IIA, transiently drives TCR transport during the first one to two minutes of immunological synapse formation. Myosin inhibition reduces calcium influx and colocalization of active ZAP-70 (zeta-chain associated protein kinase 70) with TCR, revealing an influence on signaling activity. More tellingly, its inhibition also significantly reduces phosphorylation of the mechanosensing protein CasL (Crk-associated substrate the lymphocyte type), raising the possibility of a direct mechanical mechanism of signal modulation involving CasL

HIV-associated neurocognitive disorders in sub-Saharan Africa: a pilot study in Cameroon

<p>Abstract</p> <p>Background</p> <p>The disease burden of human immunodeficiency virus (HIV) - acquired immunodeficiency syndrome (AIDS) is highest in sub-Saharan Africa but there are few studies on the associated neurocognitive disorders in this region. The objectives of this study were to determine whether Western neuropsychological (NP) methods are appropriate for use in Cameroon, and to evaluate cognitive function in a sample of HIV-infected adults.</p> <p>Methods</p> <p>We used a battery of 19 NP measures in a cross-sectional study with 44 HIV+ adults and 44 demographically matched HIV- controls, to explore the validity of these NP measures in Cameroon, and evaluate the effect of viral infection on seven cognitive ability domains.</p> <p>Results</p> <p>In this pilot study, the global mean z-score on the NP battery showed worse overall cognition in the HIV+ individuals. Significantly lower performance was seen in the HIV+ sample on tests of executive function, speed of information processing, working memory, and psychomotor speed. HIV+ participants with AIDS performed worse than those with less advanced HIV disease.</p> <p>Conclusions</p> <p>Similar to findings in Western cohorts, our results in Cameroon suggest that HIV infection, particularly in advanced stages, is associated with worse performance on standardized, Western neurocognitive tests. The tests used here appear to be promising for studying NeuroAIDS in sub-Saharan Africa.</p

Regulatory potential for concerted modulation of Nrf2- and Nfkb1-mediated gene expression in inflammation and carcinogenesis.

Many studies have implicated nuclear factor E2-related factor 2 (Nrf2) and nuclear factor-kappaB1 (Nfkb1) in inflammation and cancer. However, the regulatory potential for crosstalk between these two important transcription factors in inflammation and carcinogenesis has not been explored. To delineate conserved transcription factor-binding site signatures, we performed bioinformatic analyses on the promoter regions of human and murine Nrf2 and Nfkb1. We performed multiple sequence alignment of Nrf2 and Nfkb1 genes in five mammalian species - human, chimpanzee, dog, mouse and rat - to explore conserved biological features. We constructed a canonical regulatory network for concerted modulation of Nrf2 and Nfkb1 involving several members of the mitogen-activated protein kinase (MAPK) family and present a putative model for concerted modulation of Nrf2 and Nfkb1 in inflammation/carcinogenesis. Our results reflect potential for putative crosstalk between Nrf2 and Nfkb1 modulated through the MAPK cascade that may influence inflammation-associated etiopathogenesis of cancer. Taken together, the elucidation of potential relationships between Nrf2 and Nfkb1 may help to better understand transcriptional regulation, as well as transcription factor networks, associated with the etiopathogenesis of inflammation and cancer