Hepatic transaminase and alkaline phosphatase enzyme levels in HIV/HBV co‑infected and HIV mono‑infected patients in Maiduguri, Nigeria

Background: Studies have shown that HIV‑HBV co‑infected patients have an increased risk of liver‑related morbidity and mortality compared to their HIV‑mono‑infected counterparts. Furthermore, it has been reported that HIV‑HBV co‑infected patients have a significantly high incidence of drug‑induced hepatotoxicity following commencement of HAART than HIV‑mono‑infected patients.Objectives: To compare the levels of aspartate amino transferase (AST), alanine amino transferase (ALT) and alkaline phosphatase (ALKPO4) enzyme levels between HAART naïve HIV‑HBV co‑infected patients and their HIV‑mono‑infected counterparts.Materials and Methods: A cross‑sectional descriptive study in which 142 newly diagnosed HIV/HBV co‑infected and HIV mono‑infected adults were investigated for alkaline aminotransferase, aspartate aminotransferase and alkaline phosphatase enzyme levels.Results: The study subjects comprised of 80 (56.3%) females and 62 (46.7%) males. The age range of the study population was 15‑65 years. The mean ages of male and female subjects were 45.5 ± 10.5 years and 39.1 ± 7.5 years respectively (P < 0.05). Sixty‑three (44.4%) study subjects were HIV/HBV co‑infected while 79 (55.6%) were HIV mono‑infected. The mean ALT enzyme level of HIV/HBV co‑infected subjects was significantly higher than that of HIV mono‑infected ones i.e., 42.12 IU/l vs. 27.86 IU/l, (P = 0.038). However, there was no statistically significant difference in the mean AST (30.14 IU/l vs. 29.09 IU/l, P = 0.893) and ALKPO4 (55.86 IU/l vs. 60.97 IU/l, P = 0.205) enzyme levels between HIV‑HBV co‑infected and HIV mono‑infected subjects albeit the two enzymes were moderately elevated in both categories of subjects.Conclusion: The significantly elevated ALT enzyme levels amongst HIV‑HBV co‑infected subjects suggest that HIV‑HBV co‑infected patients may have an increased risk of liver‑related morbidity and mortality than their HIV mono‑infected counterparts. Screening for serological markers of chronic HBV infection, as well as hepatic transaminase enzyme levels in all newly diagnosed HIV‑positive patients is therefore recommended before commencement of HAART.Keywords: Alkaline phosphatase enzyme, hepatitis B virus surface antigen, hepatic transaminase enzymes, human immunodeficiency virusNigerian Journal of Clinical Practice • Oct-Dec 2013 • Vol 16 • Issue

Frontonasal dysplasia Sequence : A case report

Frontonasal dysplasia (FND) is a very rare congenital abnormality in which the mid face does not develop normally. It affects mainly the head and face. Cause is unknown but may be sporadic or familial. We report a rare case of a full term baby who presented with classical features of FND in Maiduguri, Nigeria. Management difficulty in resource limited setting is highlighted.Key words: Dysmorphism, Frontonasaldysplasia, Neonate

Shear capacity evaluation of reinforced concrete beams: finite element simulation

The shear performance of reinforced concrete beams with rectangle cross-section and two different continuous rectangular spiral shear reinforcement under monotonous loading is numerically evaluated. Further, the behaviour of two continuous shear reinforcement systems named, “Single Square Spring Shear Resistance System” (SSSSRS) and “Double Square Spring Shear Resistance System” (DSSSRS) as transverse reinforcements are compared with conventional discontinuous system “Stirrups”. The finite element study includes three (3) beams. The results clearly show that the application of continuous shear reinforcement system delivered improved shear behaviour and enhanced bearing capacity in beams. Beams with Single Square Spring Shear Resistance System (SSSSRS) and Double Square Spring Shear Resistance System (DSSSRS) exhibited 14.4% and 19.8% increased shear performance in comparison with conventional control beam. It was concluded that under the same deflection higher forces was achieved for “Single Square Spring Shear Resistance System” (SSSSRS) and “Double Square Spring Shear Resistance System” (DSSSRS) compared to control specimens

Seroprevalence of IgG anti- T. Gondii antibody among HIV-infected patients in Maiduguri, north eastern Nigeria.

Background: Toxoplasma gondii infection is one of the commonest opportunistic infections in HIV-infected patients, with the fatal consequences of toxoplasmic encephalitis particularly in advanced disease. However, data regarding T.gondii infection in the setting of HIV/AIDS are scant in Nigeria. Objective: To determine the seroprevalence of T.gondii amongst HIV-infected patients as well as to determine the correlation between anti-T.gondii IgG titre and the CD4+ cell count/HIV-1 RNA viral load. Method: A cross sectional study in which a total of 190 subjects were involved i.e. 110 newly diagnosed HAART naïve HIV-positive patients and 80 apparently healthy HIV-negative age- and-sex matched controls that were selected by simple random sampling method. Results: The age range of the study population was 20-64 years. The mean ages of male subjects for both HIV-positives and controls were 37.52 ±8.20 years and 35.79 ±12.31years, respectively, (p= 0.462). On the other hand, the mean ages of female subjects for both HIV-positives and controls were 29.90 ±6.98 years and 32.30 ±10.29 years, respectively, (p=0.149). Twenty one subjects (19.1%) among HIV-positives and 1 (1.25%) HIV-negative tested positive for anti-T.gondii IgG, respectively, (p= 0.000). The prevalence rate ration of anti-T. gondii IgG of HIV positives compared to HIVnegatives was 15.28. Significant proportion of anti-T.gondii positive subjects presented with AIDS defining illnesses compared with their anti-T.gondii negative counterparts. Conclusion:The study has shown that anti-T.gondii IgG is about 15 times more prevalent among HIV positive patients compared to controls. Routine screening for T.gondii IgG anti-body is therefore recommended for all HIV-infected subjects at the facility as well as commencement of chemoprophylaxis against Toxoplasmic encephalitis in HIV-infected patients with CD4+ cell count of <100 cells/ml

Recruitment in the sea: bacterial genes required for inducing larval settlement in a polychaete worm

Metamorphically competent larvae of the marine tubeworm Hydroides elegans can be induced to metamorphose by biofilms of the bacterium Pseudoalteromonas luteoviolacea strain HI1. Mutational analysis was used to identify four genes that are necessary for metamorphic induction and encode functions that may be related to cell adhesion and bacterial secretion systems. No major differences in biofilm characteristics, such as biofilm cell density, thickness, biomass and EPS biomass, were seen between biofilms composed of P. luteoviolacea (HI1) and mutants lacking one of the four genes. The analysis indicates that factors other than those relating to physical characteristics of biofilms are critical to the inductive capacity of P. luteoviolacea (HI1), and that essential inductive molecular components are missing in the non-inductive deletion-mutant strains

Obatoclax induces Atg7-dependent autophagy independent of beclin-1 and BAX/BAK

Direct pharmacological targeting of the anti-apoptotic B-cell lymphoma-2 (BCL-2) family is an attractive therapeutic strategy for treating cancer. Obatoclax is a pan-BCL-2 family inhibitor currently in clinical development. Here we show that, although obatoclax can induce mitochondrial apoptosis dependent on BCL-2 associated x protein/BCL-2 antagonist killer (BAX/BAK) consistent with its on-target pharmacodynamics, simultaneous silencing of both BAX and BAK did not abolish acute toxicity or loss of clonogenicity. This is despite complete inhibition of apoptosis. Obatoclax dramatically reduced viability without inducing loss of plasma membrane integrity. This was associated with rapid processing of light chain-3 (LC3) and reduction of S6 kinase phosphorylation, consistent with autophagy. Dramatic ultrastructural vacuolation, not typical of autophagy, was also induced. Silencing of beclin-1 failed to prevent LC3 processing, whereas knockout of autophagy-related (Atg)7 abolished LC3 processing but failed to prevent obatoclax-induced loss of clonogenicity or ultrastructural changes. siRNA silencing of Atg7 in BAX/BAK knockout mouse embryonic fibroblasts did not prevent obatoclax-induced loss of viability. Cells selected for obatoclax resistance evaded apoptosis independent of changes in BCL-2 family expression and displayed reduced LC3 processing. In summary, obatoclax exhibits BAX- and BAK-dependent and -independent mechanisms of toxicity and activation of autophagy. Mechanisms other than autophagy and apoptosis are blocked in obatoclax resistant cells and contribute significantly to obatoclax's anticancer efficacy

Burden of waterpipe smoking and chewing tobacco use among women of reproductive age group using data from the 2012-13 Pakistan Demographic and Health Survey

Background: Despite the general decline in cigarette smoking, use of alternative forms of tobacco has increased particularly in developing countries. Waterpipe (WP) and Chewing Tobacco (CT) are two such alternative forms, finding their way into many populations. However, the burden of these alternative forms of tobacco and their socio demographic determinants are still unclear. We assessed the prevalence of WP and CT use among women of reproductive age group in Pakistan. Methods: Data from the most recent Pakistan Demographic and Health Survey 2012–13 (n = 13,558) was used for this analysis. Information obtained from ever married women, aged between 15 and 49 years were analyzed using two separate data subgroups; exclusive WP smokers (total n = 12,995) and exclusive CT users (total n = 12,771). Univariate and Multivariate logistic regression analyses were conducted and results were reported as crude and adjusted Odds Ratio with 95 % confidence intervals. Results: Prevalence of WP smoking and CT were 4 % and 2 %, respectively. After multivariate adjustments, ever married women who were: older than 35 years (OR; 4.68 95 % CI, 2.62–8.37), were poorest (OR = 4.03, 95 % CI 2.08–7.81), and had no education (OR = 9.19, 95 % CI 5.10–16.54), were more likely to be WP smokers. Similarly, ever married women who were: older than 35 years (OR = 3.19, 95 % CI 1.69–6.00), had no education (OR = 4.94, 95 % CI 2.62–9.33), were poor (OR = 1.64, 95 % CI 1.07–2.48) and had visited health facility in last 12 months (OR = 1.81, 95 % CI 1.22–2.70) were more likely to be CT users as well. Conclusion: Older women with lower socio-economic profile were more likely to use WP and CT. Focused policies aiming towards reducing the burden of alternate forms of tobacco use among women is urgently needed to control the tobacco epidemic in the country

Sponge spicules as blueprints for the biofabrication of inorganic–organic composites and biomaterials

While most forms of multicellular life have developed a calcium-based skeleton, a few specialized organisms complement their body plan with silica. However, of all recent animals, only sponges (phylum Porifera) are able to polymerize silica enzymatically mediated in order to generate massive siliceous skeletal elements (spicules) during a unique reaction, at ambient temperature and pressure. During this biomineralization process (i.e., biosilicification) hydrated, amorphous silica is deposited within highly specialized sponge cells, ultimately resulting in structures that range in size from micrometers to meters. Spicules lend structural stability to the sponge body, deter predators, and transmit light similar to optic fibers. This peculiar phenomenon has been comprehensively studied in recent years and in several approaches, the molecular background was explored to create tools that might be employed for novel bioinspired biotechnological and biomedical applications. Thus, it was discovered that spiculogenesis is mediated by the enzyme silicatein and starts intracellularly. The resulting silica nanoparticles fuse and subsequently form concentric lamellar layers around a central protein filament, consisting of silicatein and the scaffold protein silintaphin-1. Once the growing spicule is extruded into the extracellular space, it obtains final size and shape. Again, this process is mediated by silicatein and silintaphin-1, in combination with other molecules such as galectin and collagen. The molecular toolbox generated so far allows the fabrication of novel micro- and nanostructured composites, contributing to the economical and sustainable synthesis of biomaterials with unique characteristics. In this context, first bioinspired approaches implement recombinant silicatein and silintaphin-1 for applications in the field of biomedicine (biosilica-mediated regeneration of tooth and bone defects) or micro-optics (in vitro synthesis of light waveguides) with promising results

RNA Silencing of Mcl-1 Enhances ABT-737-Mediated Apoptosis in Melanoma: Role for a Caspase-8-Dependent Pathway

BACKGROUND: Malignant melanoma is resistant to almost all conventional forms of chemotherapy. Recent evidence suggests that anti-apoptotic proteins of the Bcl-2 family are overexpressed in melanoma and may contribute to melanoma's striking resistance to apoptosis. ABT-737, a small-molecule inhibitor of Bcl-2, Bcl-xl and Bcl-w, has demonstrated efficacy in several forms of leukemia, lymphoma as well as solid tumors. However, overexpression of Mcl-1, a frequent observance in melanoma, is known to confer ABT-737 resistance. METHODOLOGY/PRINCIPAL FINDINGS: Here we report that knockdown of Mcl-1 greatly reduces cell viability in combination with ABT-737 in six different melanoma cell lines. We demonstrate that the cytotoxic effect of this combination treatment is due to apoptotic cell death involving not only caspase-9 activation but also activation of caspase-8, caspase-10 and Bid, which are normally associated with the extrinsic pathway of apoptosis. Caspase-8 (and caspase-10) activation is abrogated by inhibition of caspase-9 but not by inhibitors of the death receptor pathways. Furthermore, while caspase-8/-10 activity is required for the full induction of cell death with treatment, the death receptor pathways are not. Finally, we demonstrate that basal levels of caspase-8 and Bid correlate with treatment sensitivity. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that the combination of ABT-737 and Mcl-1 knockdown represents a promising, new treatment strategy for malignant melanoma. We also report a death receptor-independent role for extrinsic pathway proteins in treatment response and suggest that caspase-8 and Bid may represent potential markers of treatment sensitivity

The use of race, ethnicity and ancestry in human genetic research

Post-Human Genome Project progress has enabled a new wave of population genetic research, and intensified controversy over the use of race/ethnicity in this work. At the same time, the development of methods for inferring genetic ancestry offers more empirical means of assigning group labels. Here, we provide a systematic analysis of the use of race/ethnicity and ancestry in current genetic research. We base our analysis on key published recommendations for the use and reporting of race/ethnicity which advise that researchers: explain why the terms/categories were used and how they were measured, carefully define them, and apply them consistently. We studied 170 population genetic research articles from high impact journals, published 2008–2009. A comparative perspective was obtained by aligning study metrics with similar research from articles published 2001–2004. Our analysis indicates a marked improvement in compliance with some of the recommendations/guidelines for the use of race/ethnicity over time, while showing that important shortfalls still remain: no article using ‘race’, ‘ethnicity’ or ‘ancestry’ defined or discussed the meaning of these concepts in context; a third of articles still do not provide a rationale for their use, with those using ‘ancestry’ being the least likely to do so. Further, no article discussed potential socio-ethical implications of the reported research. As such, there remains a clear imperative for highlighting the importance of consistent and comprehensive reporting on human populations to the genetics/genomics community globally, to generate explicit guidelines for the uses of ancestry and genetic ancestry, and importantly, to ensure that guidelines are followed