Human Immunodeficiency Virus (HIV) types Western blot (WB) band profiles as potential surrogate markers of HIV disease progression and predictors of vertical transmission in a cohort of infected but antiretroviral therapy naïve pregnant women in Harare, Zimbabwe

<p>Abstract</p> <p>Background</p> <p>Expensive CD4 count and viral load tests have failed the intended objective of enabling access to HIV therapy in poor resource settings. It is imperative to develop simple, affordable and non-subjective disease monitoring tools to complement clinical staging efforts of inexperienced health personnel currently manning most healthcare centres because of brain drain. Besides accurately predicting HIV infection, sequential appearance of specific bands of WB test offers a window of opportunity to develop a less subjective tool for monitoring disease progression.</p> <p>Methods</p> <p>HIV type characterization was done in a cohort of infected pregnant women at 36 gestational weeks using WB test. Student-t test was used to determine maternal differences in mean full blood counts and viral load of mothers with and those without HIV <it>gag </it>antigen bands. Pearson Chi-square test was used to assess differences in lack of bands appearance with vertical transmission and lymphadenopathy.</p> <p>Results</p> <p>Among the 64 HIV infected pregnant women, 98.4% had pure HIV-1 infection and one woman (1.7%) had dual HIV-1/HIV-2 infections. Absence of HIV pol antigen bands was associated with acute infection, p = 0.002. All women with chronic HIV-1 infection had antibody reactivity to both the HIV-1 envelope and polymerase antigens. However, antibody reactivity to gag antigens varied among the women, being 100%, 90%, 70% and 63% for p24, p17, p39 and p55, respectively. Lack of antibody reactivity to gag p39 antigen was associated with disease progression as confirmed by the presence of lymphadenopathy, anemia, higher viral load, p = 0.010, 0.025 and 0.016, respectively. Although not statistically significant, women with p39 band missing were 1.4 times more likely to transmit HIV-1 to their infants.</p> <p>Conclusion</p> <p>Absence of antibody reactivity to pol and gag p39 antigens was associated with acute infection and disease progression, respectively. Apart from its use in HIV disease diagnosis, WB test could also be used in conjunction with simpler tests like full blood counts and patient clinical assessment as a relatively cheaper disease monitoring tool required prior to accessing antiretroviral therapy for poor resource settings. However, there is also need to factor in the role of host-parasite genetics and interactions in disease progression.</p

Chronic kidney disease and use of dental services in a united states public healthcare system: a retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>As several studies have shown an association between periodontal disease and chronic kidney disease (CKD), regular dental care may be an important strategy for reducing the burden of CKD. Access to dental care may be limited in the US public health system.</p> <p>Methods</p> <p>In this retrospective cohort study of 6,498 adult patients with (n = 2,235) and without (n = 4,263) CKD and at least 12 months of follow-up within the San Francisco Department of Public Health Community Health Network clinical databases, we examined the likelihood of having a dental visit within the observation period (2005-2010) using Cox proportional hazards models. To determine whether dental visits reflected a uniform approach to preventive service use in this setting, we similarly examined the likelihood of having an eye visit among those with diabetes, for whom regular retinopathy screening is recommended. We defined CKD status by average estimated glomerular filtration rate based on two or more creatinine measurements ≥ 3 months apart (no CKD, ≥ 60 ml/min/1.73 m²; CKD, < 60 ml/min/1.73 m²).</p> <p>Results</p> <p>Only 11.0% and 17.4% of patients with and without CKD, respectively, had at least one dental visit. Those with CKD had a 25% lower likelihood of having a dental visit [HR = 0.75, 95% CI (0.64-0.88)] than those without CKD after adjustment for confounders. Among the subgroup of patients with diabetes, 11.8% vs. 17.2% of those with and without CKD had a dental visit, while 58.8% vs. 57.8% had an eye visit.</p> <p>Conclusions</p> <p>Dental visits, but not eye visits, in a US public healthcare setting are extremely low, particularly among patients with CKD. Given the emerging association between oral health and CKD, addressing factors that impede dental access may be important for reducing the disparate burden of CKD in this population.</p

The Role of Oligomerization and Cooperative Regulation in Protein Function: The Case of Tryptophan Synthase

The oligomerization/co-localization of protein complexes and their cooperative regulation in protein function is a key feature in many biological systems. The synergistic regulation in different subunits often enhances the functional properties of the multi-enzyme complex. The present study used molecular dynamics and Brownian dynamics simulations to study the effects of allostery, oligomerization and intermediate channeling on enhancing the protein function of tryptophan synthase (TRPS). TRPS uses a set of α/β–dimeric units to catalyze the last two steps of L-tryptophan biosynthesis, and the rate is remarkably slower in the isolated monomers. Our work shows that without their binding partner, the isolated monomers are stable and more rigid. The substrates can form fairly stable interactions with the protein in both forms when the protein reaches the final ligand–bound conformations. Our simulations also revealed that the α/β–dimeric unit stabilizes the substrate–protein conformation in the ligand binding process, which lowers the conformation transition barrier and helps the protein conformations shift from an open/inactive form to a closed/active form. Brownian dynamics simulations with a coarse-grained model illustrate how protein conformations affect substrate channeling. The results highlight the complex roles of protein oligomerization and the fine balance between rigidity and dynamics in protein function

Globular cluster systems and galaxy formation

Globular clusters are compact, gravitationally bound systems of up to a million stars. The GCs in the Milky Way contain some of the oldest stars known, and provide important clues to the early formation and continuing evolution of our Galaxy. More generally, GCs are associated with galaxies of all types and masses, from low-mass dwarf galaxies to the most massive early-type galaxies which lie in the centres of massive galaxy clusters. GC systems show several properties which connect tightly with properties of their host galaxies. For example, the total mass of GCs in a system scales linearly with the dark matter halo mass of its host galaxy. Numerical simulations are at the point of being able to resolve globular cluster formation within a cosmological framework. Therefore, GCs link a range of scales, from the physics of star formation in turbulent gas clouds, to the large-scale properties of galaxies and their dark matter. In this Chapter we review some of the basic observational approaches for GC systems, some of their key observational properties, and describe how GCs provide important clues to the formation of their parent galaxies.Comment: 32 pages, 6 figures. Accepted for publication in the book "Reviews in Frontiers of Modern Astrophysics: From Space Debris to Cosmology" (eds Kabath, Jones and Skarka; publisher Springer Nature) funded by the European Union Erasmus+ Strategic Partnership grant "Per Aspera Ad Astra Simul" 2017-1-CZ01-KA203-03556

Systematic review of methods used in meta-analyses where a primary outcome is an adverse or unintended event

addresses: Peninsula College of Medicine and Dentistry, St Luke's Campus, University of Exeter, Exeter, UK. [email protected]: PMCID: PMC3528446types: Journal Article; Research Support, Non-U.S. Gov't© 2012 Warren et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Adverse consequences of medical interventions are a source of concern, but clinical trials may lack power to detect elevated rates of such events, while observational studies have inherent limitations. Meta-analysis allows the combination of individual studies, which can increase power and provide stronger evidence relating to adverse events. However, meta-analysis of adverse events has associated methodological challenges. The aim of this study was to systematically identify and review the methodology used in meta-analyses where a primary outcome is an adverse or unintended event, following a therapeutic intervention