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Abstract: Mitochondria regulate multiple aspects of neuronal development, physiology, plasticity, and pathology through their regulatory roles in bioenergetic, calcium, redox, and cell survival/death signalling. While several reviews have addressed these different aspects, a comprehensive discussion focussing on the relevance of isolated brain mitochondria and their utilities in neuroscience research has been lacking. This is relevant because the employment of isolated mitochondria rather than their in situ functional evaluation, offers definitive evidence of organelle-specificity, negating the interference from extra mitochondrial cellular factors/signals. This mini-review was designed primarily to explore the commonly employed in organello analytical assays for the assessment of mitochondrial physiology and its dysfunction, with a particular focus on neuroscience research. The authors briefly discuss the methodologies for biochemical isolation of mitochondria, their quality assessment, and cryopreservation. Further, the review attempts to accumulate the key biochemical protocols for in organello assessment of a multitude of mitochondrial functions critical for neurophysiology, including assays for bioenergetic activity, calcium and redox homeostasis, and mitochondrial protein translation. The purpose of this review is not to examine each and every method or study related to the functional assessment of isolated brain mitochondria, but rather to assemble the commonly used protocols of in organello mitochondrial research in a single publication. The hope is that this review will provide a suitable platform aiding neuroscientists to choose and apply the required protocols and tools to address their particular mechanistic, diagnostic, or therapeutic question dealing within the confines of the research area of mitochondrial patho-physiology in the neuronal perspective.

Zinc oxide has several industrial applications due to its versatile properties, which lead to its continuously increasing demand in different industrial sectors. Further, ZnO nanostructures possess unique photocatalytic activity, and because of this, they are being applied to degrade organic dyes through photocatalysis for waste water treatment. Nevertheless, chemical synthesis methods to develop ZnO nanostructures have raised concerns related to environmental issues, while these methods are found to be costly and tedious. As a result, the synthesis of ZnO nanostructures using green methods is gaining popularity due to its low cost and eco-friendly mode, while avoiding the use of toxic chemicals. Green synthesis of ZnO nanostructures using different biological approaches involving plants, algae, and different microorganism-derived bioactive compounds has been well reported for diverse applications. Among different applications, ZnO nanostructures that enable photocatalysis to degrade dye have been found to be imperative for waste water treatments. Therefore, the current review explores recent studies on green synthesis approaches to prepare ZnO nanostructures via adopting different biological methods that rely on plants, algae, and bacterial microorganisms. The properties of ZnO nanostructures, along with their green synthesis routes and feasible mechanisms, have also been discussed in this review. This review focuses on the use and efficiency of green route synthesized ZnO nanostructures as nanophotocatalysts for the degradation of organic dyes in waste water treatment. Additionally, existing challenges in green synthesis methods and the efficiency of ZnO nanostructures to degrade organic dyes following photocatalysis has been discussed.

IntroductionThe role of interferon gamma (IFN-γ) +874 A>T (rs2430561) gene polymorphism has been evaluated in different ethnicities with pulmonary tuberculosis (PTB) infection, and inconsistent results have been reported. In this study, a meta-analysis was performed to determine the precise association between IFN-γ +874 A>T gene polymorphism and PTB susceptibility.Material and methodsA total of 21 studies comprising 4281 confirmed PTB cases and 5186 healthy controls were included in this meta-analysis by searching the PubMed (Medline), EMBASE, and Google Scholar web-databases.ResultsWe observed reduced risk of PTB in allelic contrast (T vs. A: p = 0.001; OR = 0.818, 95% CI: 0.723–0.926), homozygous (TT vs. AA: p = 0.017; OR = 0.715, 95% CI: 0.543–0.941), heterozygous (AT vs. AA: p = 0.002; OR = 0.782, 95% CI: 0.667–0.917), dominant (TT+AT vs. AA: p = 0.002; OR = 0.768, 95% CI: 0.652–0.906), and recessive (TT vs. AA+AT: p = 0.042; OR = 0.802, 95% CI: 0.649–0.992) genetic models. In ethnicity-wise subgroup analysis, reduced risk of PTB was found in the Caucasian population. However, we did not find an association with any of the genetic models in the Asian population.ConclusionsIn conclusion, the IFN-γ +874 A>T gene polymorphism is significantly associated with reduced risk of PTB, showing a protective effect in the overall and in the Caucasian population. However, this polymorphism is not associated with PTB risk in the Asian population.

Massive utilizations of chemical fertilizer in agriculture sector to improve the farming productivity have created increasing possibility of environmental damages. Severe human health issues, global warming, poor fertility and high cost of soil maintenance are the major side effects of the utilizations of inorganic fertilizers and needs immediate attention. To overcome these issues, agriculture farming has been shifted towards the development of organic fertilizers using natural bio-resources. Organic fertilizers have several advantages like low-cost, being produced from the renewable resources and are highly efficient to improve the productivity of soil and agriculture product, rapidly. Additionally, bio-fertilizers not only increase the production, nutrients and organic matter but also neutralize the harmful impacts caused by the chemical fertilizers due to the potential combination of the microorganisms with organic wastes. Food wastes have tremendous potential to enhance the production of bio-fertilizers because these wastes are present in bio-degradable forms and may efficiently accelerate the activity of the microbial metabolic. Thus, the present review summarizes an overview of the production strategy of bio-fertilizers using the combination of food wastes and microorganisms. Further, in depth discussion have been done about the microbial digestion of food wastes to produce biofertilizer along with discussions about the possible mechanisms involved therein. Plant growth promoting microorganisms and their mechanisms have been also analyzed in the present review along with the existing limitations and sustainable future prospective.

Petroleum hydrocarbons and heavy metals are the two major soil contaminants that are released into the environment in the forms of industrial effluents. These contaminants exert serious impacts on human health and the sustainability of the environment. In this context, remediation of these pollutants via a biological approach can be effective, low-cost, and eco-friendly approach. The implementation of microorganisms and metagenomics are regarded as the advanced solution for remediating such pollutants. Further, microbiomes can overcome this issue via adopting specific structural, functional and metabolic pathways involved in the microbial community to degrade these pollutants. Genomic sequencing and library can effectively channelize the degradation of these pollutants via microbiomes. Nevertheless, more advanced technology and reliable strategies are required to develop. The present review provides insights into the role of microbiomes to effectively remediate/degrade petroleum hydrocarbons and heavy metals in contaminated soil. The possible degradation mechanisms of these pollutants have also been discussed in detail along with their existing limitations. Finally, prospects of the bioremediation strategies using microbiomes are discussed.

The present review explores fruit wastes as potential and low-cost substrates for economical production of cellulase enzymes. Being renewable, vast availability and having rich organic nutrient, these fruit wastes can be exploited to produce cellulase enzyme for various industrial applications. This review aimed to explore recent insight in sustainable production of microbial cellulolytic enzymes following solid state fermentation (SSF) wherein different types of fruit wastes as a potentially viable and alternative form of substrates have been utilized. In addition, detailed about the characteristics, mechanisms and market scenario of cellulase enzymes produced through a range of microbial species have been discussed. Further, impacts of different physicochemical parameters on solid-state fermentation based enzyme production and scale up issues have also analyzed. Moreover, applications of cellulases to produce different types of biofuels have been evaluated while emphases are made on existing hindrances and the possible strategies to improve the enzyme production process using fruit wastes.

Applications of thermostable enzymes in various industries are highly demanding, and considered as one of the most feasible solutions to gain the high productivity of the related bio-processing. Nevertheless, cost-intensive production of enzymes with low reactivity and stability make them non-suitable for different sustainable industrial applications. Focusing on this aspect, the present study deals with the sustainable and low-cost green synthesis of Iron oxide nanoparticles (IONPs) using rice straw extract as the food waste which function as the natural reducing reagent and investigates the utility of IONPs to improve the thermo-stability of enzyme. Herein, physiochemical properties of newly synthesized IONPs have been analyzed through X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR) and field emission scanning electron microscope (FE-SEM). Moreover, impact of green route synthesized IONPs is studied to improve the thermal stability of commercially available endo-glucanase (EG) enzyme as a model system. It is noticed that IONPs significantly supported to enhance the thermal stability of EG enzyme, wherein enzyme exhibited thermal stability at 70 °C up to 15 h, and suggesting high potential of thermally stable enzyme for numerous industrial applications.

Microbes recycling nutrient and detoxifying ecosystems are capable to fulfil the future energy need by producing biohydrogen by due to the coupling of autotrophic and heterotrophic microbes. In granules microbes mutualy exchanging nutrients and electrons for hydrogen production. The consortial biohydrogen production depend upon constituent microbes, their interdependence, competition for resources, and other operating parameters while remediating a waste material in nature or bioreactor. The present review deals with development of granular algae-bacteria consortia, hydrogen yield in coculture, important enzymes and possible engineering for improved hydrogen production.

Background Human Cytomegalovirus (CMV), because of its ability to extensively manipulate host immunity during active infection, has been suggested to be involved in autoimmunity. However, its influence on T-cells and cytokines in systemic autoimmune diseases like systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) is indistinct. Methods We investigated the in-vitro response of T lymphocytes from SLE and SSc patients to CMV antigen. Functional activity of T lymphocytes was determined by estimating Th1 (IL-2 and IFN-γ) and Th2 (IL-4 and IL-10) cytokines. Results We observed that CMV antigen stimulation in-vitro resulted in significant increase in CD4:CD8 T-cell ratio in peripheral blood mononuclear cells (PBMCs) from SLE and SSc patients; response dominated by CD4+ than CD8+ memory T-cells. SSc T-cell response was differentiated by aberrant increase in CD4+CD25+ T-cells. CMV antigen caused elevation in IL-4 and IFN-γ production in both patient PBMCs, whereas IL-2 was also raised in SLE PBMCs. The development of large pool of memory T-cells and overproduction of IFN-γ may result in flare-up of autoimmunity in these patients. Conclusion Our study provides an insight into the immunopathological potential of CMV-reactive immune cells to develop new potential strategies for targeted therapeutic intervention.

Powassan virus (POWV) is responsible for encephalitis and severe neurological sequelae globally. Peptide target based designing offers a promising therapeutic invention for the eradication of viral infection. Immunoinformatics serves as a powerful tool to screen and select antigenic peptide sequences as potential epitopes for binding affinity with HLA alleles. In the present study, a computational pipeline was developed for the identification of B-cell and T-cell epitopes for suitable vaccine candidates. Further, immunogenicity and physico-chemical prediction studies enable the discrimination between antigens and non-antigens. Considering the population setting globally, population coverage analysis was also performed for the identification of possible binding alleles (MHC class-I and MHC class-II) of T-cell epitopes.This computational prediction analysis will enhance our understanding of B-cell/T-cell immune response and assist in selecting the antigenic peptide(s) for the formulation of antigen based diagnostic kit or peptide based subunit vaccine design against POWV.

// Raju K. Mandal 1, * , Sajad A. Dar 1, 2, * , Arshad Jawed 1 , Mohd Wahid 1, 3 , Mohtashim Lohani 1 , Aditya K. Panda 4 , Bhartendu N. Mishra 5 , Naseem Akhter 6 , Mohammed Y. Areeshi 1 and Shafiul Haque 1 1 Research and Scientific Studies Unit, College of Nursing and Allied Health Sciences, Jazan University, Jazan 45142, Saudi Arabia 2 The University College of Medical Sciences and GTB Hospital University of Delhi, Delhi 110095, India 3 Department of Biosciences, Faculty of Natural Sciences, Jamia Millia Islamia A Central University, New Delhi 110025, India 4 Centre for Life Sciences, Central University of Jharkhand, Ranchi, Jharkhand 835205, India 5 Department of Biotechnology, Institute of Engineering and Technology, Lucknow, Uttar Pradesh 226021, India 6 Department of Laboratory Medicine, Faculty of Applied Medical Sciences, Albaha University, Albaha 65431, Saudi Arabia * These authors contributed equally to this work Correspondence to: Shafiul Haque, email: shafiul.haque@hotmail.com Keywords: meta-analysis; LMP7; cancer susceptibility; polymorphism; trial sequential analysis Received: March 21, 2017 Accepted: November 01, 2017 Published: December 21, 2017 ABSTRACT Genetic variant LMP7 (low molecular weight polypeptide 7) –145 C > A may influence the function of immune surveillance of an individual and lead to cancer development. Various studies have investigated the relevance of LMP7 –145 C > A gene polymorphism with cancer risk; but, their results are conflicting and inconsistent. To obtain a comprehensive conclusion, a meta-analysis was performed by including eight eligible published studies retrieved from PubMed (Medline), EMBASE and Google Scholar web search until December 2016. Individuals with AA genotype (AA vs CC: p = 0.001; OR = 2.602, 95% CI = 1.780 to 3.803) of LMP7 -145 C > A were found to have 2 folds higher risk of cancer than those with CC genotype. The recessive genetic model (AA vs AC + CC) also indicated that individuals with AA genotype have 2 folds higher cancer risk than AC and CC genotypes ( p = 0.001; OR = 2.216, 95% CI = 1.525 to 3.221). Also, significant increased cancer risk was observed in Asians but not in Caucasians. No publication bias was observed during the analysis. Trial sequential analysis also strengthened our current findings. These results suggest that genetic variant LMP7–145 C > A has significant role in increasing cancer risk in overall and Asian population, and could be useful as a prognostic marker for early cancer predisposition.

The macrophage migration inhibitory factor (MIF) is a cytokine that plays an important role in inhibiting the growth of pathogenic Mycobacterium tuberculosis (M.tb) and regulates immune responses against M.tb pathogen. MIF -173 G > C gene polymorphism may affect immunity in an individual and leads to susceptibility to tuberculosis (TB). A large number of studies have investigated the relevance of this polymorphism with TB risk, but their results were inconclusive. To obtain a precise conclusion, a meta-analysis was performed by retrieving six eligible studies from Google Scholar, PubMed (Medline), and EMBASE online databases. Overall combined analysis suggested increased TB risk between MIF -173 G > C polymorphism and overall risk in four genetic models, i.e., allelic (C vs. G: p = 0.001; OR = 1.517, 95% CI = 1.312 to 1.753), homozygous (CC vs. GG: p = 0.026; OR = 1.874, 95% CI = 1.079 to 3.257), heterozygous (GC vs. GG: p = 0.001; OR = 1.542, 95% CI = 1.273 to 1.868) and dominant model (CC + GC vs. GG: p = 0.001; OR = 1.631, 95% CI = 1.362 to 1.955). Similarly, increased TB risk was observed in subgroup analysis of Asian ethnicity. No publication bias was observed. These results suggested that MIF -173 G > C variant is a significant risk factor for TB in overall and in Asian populations, and can be used as prognostic marker for TB susceptibility.

The emergence of multi-drug resistant strains and co-occurrence of tuberculosis with HIV creates a major burden to the human health globally. Failure of primary antibacterial therapy necessitates the identification of new mycobacterial drugs. In this study, a comprehensive analysis involving bottom-up systems biology approach was applied wherein we have identified potential therapeutic targets of Mycobacterium tuberculosis infections. Our study prioritized M. tuberculosis therapeutic targets [aspartate-β-semialdeyhde dehydrogenase (ASD), dihydrodipicolinate reductase and diaminopimelate decarboxylase] based on flux and elementary mode analysis using direct mathematical modeling of the relevant metabolic pathways. Molecular docking and simulation studies of the priority target (i.e., ASD) revealed the therapeutic potential of the selected natural products (Huperzine A, Rosmarinic acid and Curcumin) based ASD inhibitors. The study highlights the crucial role of systems biology in conjunction with molecular interaction (docking) for probing novel leads against an increasingly resistant pathogen, M. tuberculousis. This article is protected by copyright. All rights reserved

The incidences of melanomas are increasing by leaps and bounds across the globe despite early detection and intervention. The numbers of patients dying from metastatic melanoma have been continually increased over the past thirty years. It has been considered as one of the most therapy-resistant malignancies due to the cross-resistant mechanism developed by the metastatic cells. With time, many new therapies came and they failed miserably. Ipilimumab, a monoclonal antibody that works to activate the immune system by targeting CTLA-4 proved to be a boon for advance melanoma very recently. But it could not stand firmly against the resistant metastatic skin cancer cells. Now, the new skin cancer drug named pembrolizumab proved as a new miraculous molecule. It's a humanized monoclonal antibody that blocks a biological pathway called programmed cell death-1 (PD-1), which melanoma cells activate to suppress the immune system. This antibody has surpassed ipilimumab at all the stages of clinical trials because of its non-cross resistant mechanism to malignant cells. The present review critically analyses the reasons of efficacy success of pembrolizumab over ipilizumab shown at various stages of clinical trials.

The association of interleukin-6 (IL-6)-174G C (rs1800795) single nucleotide polymorphism (SNP) with the risk of acquiring rheumatoid arthritis (RA) is a relevant issue because of conflicting and consensus lacking reports published in literature. We investigated IL-6-174G C promoter polymorphism in 34 RA patients, attending a tertiary care hospital in north India. We also performed a meta-analysis, of the previously published studies reporting this genetic relationship, in overall population, and independently in Asian and Caucasian ethnicities to further elucidate this association. A total of 13 studies, including the current one, involving 3291 RA cases and 3812 controls were analyzed. Out of the 13 studies, 6 were from Asian, 6 from Caucasian and 1 from a mixed population. Our case-control study showed significant association of IL-6-174G C SNP with increased RA risk: allelic (OR = 3.750, 95% CI = 1.800-7.813, p 0.001); dominant (OR = 2.800, 95% CI = 1.167-6.721, p = 0.021); and recessive (OR = 36.72, 95% CI = 2.004-672.7, p = 0.015). The meta-analysis revealed the increased RA risk associated with IL-6-174G C SNP in overall population: allelic (OR = 1.650, 95% CI = 1.169-2.329, p = 0.004); homozygous (OR = 1.380, 95% CI = 0.906-2.101, p = 0.133); heterozygous (OR = 1.559, 95% CI = 1.001-2.428, p = 0.049); dominant (OR = 1.663, 95% CI = 1.078-2.567, p = 0.022); and recessive (OR = 1.366, 95% CI = 0.964-1.935, p = 0.079). Subgroup analysis also showed this polymorphism to be associated with increased RA risk in Asian population: allelic (OR = 3.724, 95% CI = 1.361-10.190, p = 0.010); dominant (OR = 3.823, 95% CI = 1.320-11.074, p = 0.013); and recessive (OR = 4.357, 95% CI = 1.634-11.623, p = 0.003), but not in Caucasian population. This meta-analysis shows that IL-6-174G C SNP is significantly associated with increased RA risk in overall, and specifically in Asian population.

Background: DNA methyltransferase-3B (DNMT3B) plays a key role in establishment and maintenance of genomic methylation patterns. Polymorphism in promoter region -149 C>T (C46359T) of DNMT3B gene may alter DNMT3B activity which leads to increased susceptibility to cancer. Inconsistent results regarding this have been reported in a number of studies. Objective: To carry out a meta-analysis of the studies reported to assess the precise relationship between the DNMT3B -149 C>T polymorphism and the overall cancer risk. Method: PubMed (MEDLINE) web database was searched for the studies concerning DNMT3B -149 C>T polymorphism and its association with cancer risk. The pooled odds ratios (ORs) along with 95% confidence intervals (95% CIs) were calculated for all the genetic models, from the selected case-control studies, by meta-analysis. Results: Overall eighteen studies containing 5583 cancer cases and 7618 controls were analyzed. No significant risk was observed overall for T allele carrier (T vs. C: p=0.303; OR=1.032, 95% CI=0.972-1.097), homozygous (TT vs. CC: p=0.336; OR=1.063, 95% CI=0.939–1.204), heterozygous (CT vs. CC: p=0.802; OR=1.022, 95% CI=0.860-1.216), dominant (TT vs. CC+CT: p=0.298; OR=1.101, 95% CI=0.919-1.319) and recessive (TT+CT vs. CC: p=0.656; OR=1.021, 95% CI=0.931-1.121) genetic models. Subgroup analysis of Asian and Caucasian populations also did not demonstrate any cancer risk in all the genetic models studied. Conclusion: Our meta-analysis proposes that the DNMT3B -149 C>T polymorphism may not be an independent predisposing factor for the risk of cancer. However, larger sample size and expression studies are required to confirm the observation.

The association of A1513C (rs3751143) polymorphism of P2X7 gene with the risk of extrapulmonary tuberculosis (EPTB) has been extensively analyzed, but no consensus has been achieved. In this study, a meta-analysis was done to assess this precise association. Online web databases, like PubMed (MEDLINE) and EMBASE were searched for pertinent reports showing association of P2X7 A1513C polymorphism with EPTB risk. To assess the strength of this association, we calculated pooled odds ratios (ORs) and 95% confidence intervals (95% CIs). A total of eight reports involving 2237controls and 594 EPTB cases were included in this study. Four genetic models, viz. allele (C vs. A: p=0.011; OR= 1.677, 95% CI = 1.125-2.501), homozygous (CC vs. AA: p = 0.053; OR= 2.362, 95% CI = 0.991-5.632), heterozygous (AC vs. AA: p = 0.003; OR= 1.775, 95% CI = 1.209-2.607) and dominant (CC + AC vs. AA: p = 0.005; OR= 1.890, 95% CI = 1.207-2.962) showed significant associations compared with wild type genotypes. Subgroup analysis stratified by ethnicity was also performed and the results suggested that homozygous and heterozygous genotypes were associated significantly with increased susceptibility of EPTB in Asian population. Similarly, heterozygous and dominant models showed increased EPTB risk in Caucasian population. The present meta-analysis suggests that P2X7 A1513C polymorphism may be an important risk factor for EPTB. Also, our sub-group analysis indicates that P2X7 A1513C polymorphism confers increased EPTB risk among Asians and Caucasians. However, future larger studies are needed to provide more precise conclusion and endorse the present results.

Background: Basic Life Support [BLS; including cardiopulmonary resuscitation (CPR)] is a part of medical skills utilized in case of an emergency medical care to save human lives. It is well established that the young students can become major healthcare supportive workforce for a community including the cases of emergency. Therefore, adequate knowledge of BLS is necessary for all the university attending students. This study evaluated the awareness of BLS knowledge and attitude towards BLS training among the students of Jazan University, Saudi Arabia.Methods: A self-administered survey questionnaire using cross-sectional design was employed.Results: Out of 360 participants, the majority were male students (84.2%). The participants have mediocre knowledge of BLS, and their mean score was 7.83 out of 14. The knowledge score, i.e., correct response of male and female students was almost similar. Not a single student answered all the questions correctly. About 28% participants had received BLS training previously during their study course and showed better BLS knowledge (mean score 10.41) in comparison with the other participants. In contrast with the students of health science related courses, the highest mean knowledge score (11.5) was opted by the students of emergency medical services, whereas the lowest score (6.58) was opted by the students of nursing background.Conclusions: Overall, a majority of the students of Jazan University did not have complete knowledge of BLS (CPR). The outcomes of this study will be helpful for education and healthcare service providers of the Saudi kingdom as a whole and for Jazan region.Keywords: Basic life support, Health occupations, Students’ knowledge, Medical education, Saudi Arabia

The linkage of human T-cell leukemia virus type 1 (HTLV-1) to fatal diseases is a well known fact for many years. However, there has been no significant progress in the field of the treatment that can lead to the development of a successful vaccine. Furthermore, there are no means of assessing the risk of disease and its prognosis in the infected people.The current study has taken the cognizance of the importance of host's immune response in reducing the risk of infectious diseases to carry out immunoinformatics driven epitope screening strategy of vaccine candidates against HTLV-1. In this study, a genetic variability and HLA distribution analysis among the documented HTLV-1 genotypes I, II, III, IV, VVI was performed to ensure the coverage of the vast majority of population, where vaccine would be employed. The meticulous screening of effective dominant immunogens was done with the help of ABCPred and Immune Epitope Database.The results showed that the identified epitopes might be protective immunogens with high conservancy and potential of inducing both protective neutralizing antibodies and T-cell responses. The peptides "PSQLPPTAPPLLPHSNLDHI", "PCPNLVAYSSYHATY", and "YHATYSLYLF", were 100% conserved among different isolates from far and wide separated countries, suggesting negligible antigenic drift in HTLV-1.Overall, the mentioned epitopes are soluble, non-toxic suitable candidates for the development of vaccine against HTLV-1 and warrant further investigation and experimental validation.

Objectives: The role of caveolin-1 (CAV1)(G>A, rs3807987) polymorphism is still dubious in cancer causation in Taiwanese population. The present study is an effort to assess the above relation for precise conclusion. Methods: EMBASE and PubMed (MEDLINE) databases were explored for the pertinent case–control studies reporting the connection of CAV1 G14713A polymorphism to the vulnerability to cancer. A cumulative analysis using meta-analytic approach was accomplished and pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated for all the polymorphs. Results: Overall, 2549 subjects and 3161 controls were analyzed from six selected studies. Our study showed no confirmation of noteworthy risk between CAV1 G14713A polymorphism and susceptibility to cancer in any of the polymorph, for instance, allele (A vs. G: P = 0.165; OR = 1.252, 95% CI = 0.911–1.721), homozygous (AA vs. GG: P = 0.252; OR = 1.328, 95% CI = 0.817–2.157), heterozygous (AG vs. GG: P = 0.091; OR = 1.356, 95% CI = 0.952–1.930), dominant (AA vs. GG + AG: P = 0.345; OR = 1.191, 95% CI = 0.829–1.709), and recessive (AA + AG vs. GG: P = 0.125; OR = 1.344, 95% CI = 0.921–1.961). Conclusions: We conclude that CAV1 G14713A polymorphism does not contribute as an independent predisposing risk factor for developing cancer in Taiwanese population.

Efforts to develop preventatives against HIV infection through sexual route have identified, among many, algal lectins as the potent molecules for scaffolding HIV entry inhibition. Algal lectin scytovirin (SVN) from Scytonema varium, a cyanobacterium, has anti-HIV effects with the potential for use in sculpting HIV neutralization. We created a recombinant strain of human vaginal L. plantarum for extracellular expression of recombinant (r)SVN. The rSVN protein containing culture supernatant was analyzed for its binding with HIV-1 gp160, and for inhibiting infection with primary R5 and X4 HIV-1 strains in TZM-bl cells. The rSVN protein extant in recombinant L. plantarum culture supernatant binds to HIV-1 gp160 and reduces the HIV-induced cytopathic effect to nearly 56.67% and 86.47% in R5 and X4 HIV-1 infected TZM-bl cells, respectively. The fortified L. plantarum may be explored for its use as a live virucide in vaginal mucosa of high risk women to prevent HIV entry.

This study suggests an efficient strategy for the maximal extraction of human consumable metabolites in a safe and non-toxic solvent system for the cases where the best extraction solvent belongs to the restricted class (ICH, Quality Guidelines). An optimum composition of extraction system components (chloroform:acetone:ethyl alcohol) was determined for the maximum and chloroform free recovery of 3-demethylated colchicine (3-DMC) from a fermentation broth. A feed forward backprop artificial neural network (ANN) was trained and validated to establish a mathematical relationship between the inputs (volumes of extraction system components) and outputs (concentration of 3-DMC). Inputs to the ANN were kept under strict constraints, always satisfying the azeotropic ratio for chloroform:acetone with an excess of ethyl alcohol forming a complex ternary azeotrope. A genetic algorithm (GA) with linear equality matrices defining ternary azeotropic constraints was implemented to perform an exhaustive search for the global optimum composition of the extraction system components with the validated ANN as the selection function. Since, this strategy only allows for the azeotropic ratio, the global optimum is a typical azeotrope with maximum 3-DMC recovery. The purpose of the azeotrope is to safely distil out all the chloroform after extraction, by performing an azeotropic distillation at a lower temperature (63.2 °C) leaving only an excess of ethyl alcohol, which boils at a higher temperature (78 °C). The final optimized volumes of chloroform: 63.055 mL, acetone: 44.138 and ethanol: 92.807 mL resulted in a maximum recovery of 6.5 g L−1 of 3-DMC. This approach was also tested successfully for the energy efficient recovery of betulinic acid in a Class 3 solvent.

Efficient cell lysis for intracellular protein recovery is a major bottleneck in the economics and commercial feasibility of any biotechnological process. Grinding of cells with abrasive beads, also known as bead milling remains a method of choice, as it can handle a large volume of cells. Bead mills when operated in a continuous mode substantiate to be economical, and more productive as compared to a batch mode process. In this study, the recovery of recombinant cholesterol oxidase (COD) was investigated and optimized using response surface methodology (RSM) based on Central Composite Design (CCD) in a continuous bead milling process. Process parameters, viz. slurry feed rate (A), bead loading (B), cell loading (C) and process time (D) were found to be significant during the continuous bead milling process. A polynomial model was developed to correlate the participating factors for efficient cell disruption. Optimized conditions yielded 3.20 g L−1 (∼90%) of COD with A = 300.6 mL h−1, B = 77.5% (v/v), C = 69.9 (OD600 nm) and D = 29.7 (min), when compared to existing batch mode operations (3.56 g L−1). This is the very first study that attempts to optimize a continuous bead milling process using RSM to maximize the intracellular protein (COD in this case) recovery with minimum inputs to make the process economical and scalable to industrial levels. The developed model in this study can be scaled-up to large-scale for efficient recovery of intracellular proteins in similar expression systems.

Purification of any bioactive compound obtained by biotransformation process is a critical aspect for its quality and recovery leading to its commercial viability. In this study, several solvents and their interactions were studied for the recovery of 3-demethylated colchicine (3-DMC; anti-cancer drug) from the fermentation medium. Due to inherent toxicity of chloroform, we also aimed at its removal from the solvent extraction system. A quadratic mixture model was developed using RSM with interaction terms as shown by contour/3D plots. A set of 15 experiments were performed and validated with different solvent combinations. In this study, the developed polynomial model showed a high F -value (362.36) and R 2 value (0.99) which suggests the suitability of D-optimal design to predict the responses accurately. The results indicated higher recoveries of 5.95 g/l of 3-DMC, without the use of chloroform enabling efficient extraction of 3-DMC for commercial applications.

Metastatic melanoma is a least common form of cancer as it accounts only for 1% of all cancer cases. But, it is most deadly in nature and is haunting mankind for long emotionally as well as economically. The sites for the onset of the disease are pigment-producing cells of the skin, mucosa, eye etc. It has the potential to spread other sites like subcutaneous tissue, lymph nodes, lungs, liver, bone and brain. The United States Food & Drug Administration has approved various drug molecules from time to time. The molecules (Dabrafenib-BRAF inhibitor and Trametinib-MEK inhibitor) have proved their credentials alone and in combination as well. These molecules have demonstrated good results for various end points like median progression free survival, overall survival, objective response etc. The median progression free survival for patients using dabrafenib and trametinib were 5.1 and 4.8 months, respectively (administered singly). It has increased to 11.4 months in the combination treatment “dabrafenib + trametinib”, which is approximately 104% and 138% greater than dabrafenib and trametinib treated groups alone. Similarly, the overall survival rate and objective response rate for the patients administered with “dabrafenib + trametinib” have been increased by 72% 64%, respectively. All these increments in these parameters were for a short period of time as the molecules were unable to withstand the pressure of resistance developed in the patients. So, the current review suggests the use of BRAF and MEK inhibitors as intermittent therapy along with heat shock protein 90 (HSP90) molecules.

Background: Earlier studies have shown that interlukin-10 (IL-10) -1082 A>G gene polymorphism is implicated in susceptibility to pulmonary tuberculosis (PTB), but their results are inconsistent and inconclusive. In the present study, a meta-analysis was performed to analyze the potential association between IL-10 -1082 A>G gene polymorphism and PTB susceptibility. Methods: A quantitative synthesis was done using PubMed (Medline), EMBASE, and Google Scholar web databases search and meta-analysis was performed by calculating pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) for all the genetic models. Results: A total of 22 eligible studies comprising 4956 PTB cases and 6428 healthy controls were included in the analysis. We did not observe any increased or decreased risk of PTB in allelic contrast (G vs. A: P=0.985; OR = 1.001, 95% CI = 0.863–1.162), homozygous (GG vs. AA: P=0.889; OR = 1.029, 95% CI = 0.692–1.529), heterozygous (GA vs. AA: P=0.244; OR = 0.906, 95% CI = 0.767–1.070), dominant (GG + AG vs. AA: P=0.357; OR = 1.196, 95% CI = 0.817–1.752), and recessive (GG vs. AA + AG: P=0.364; OR = 0.921, 95% CI = 0.771–1.100) genetic models. Likewise, no association of IL-10 -1082 A>G polymorphism with PTB risk was observed in Asian and African population for all the genetic models. Interestingly, the dominant model (GG + AG vs. AA: P=0.004; OR = 1.694, 95% CI = 1.183–2.425) demonstrated increased risk of PTB in Caucasian population. Conclusions: This meta-analysis concludes that IL-10 -1082 A>G gene polymorphism is not significantly associated with overall, Asian and African population. However, this polymorphism is associated with Caucasian population.

Purpose: Earlier studies have shown that tumor necrosis factor (TNF) -308 G>A (rs1800629) gene polymorphism is implicated in the susceptibility to leprosy, but results were inconsistent. Methods: A meta-analysis of 14 studies involving 3327 leprosy cases and 3203 controls was performed to appraise the association of TNF -308 G>A polymorphism with leprosy using MEDLINE (PUBMED), EMBASE, and Google Scholar web databases. Results: Overall, no significant association was observed in allelic (A vs. G: P=0.068; OR = 0.836, 95% CI = 0.689–1.013), homozygous (AA vs. GG: P=0.394; OR = 0.810, 95% CI = 0.499–1.315), heterozygous (GA vs. GG: P=0.059; OR = 0.780, 95% CI = 0.603–1.010), dominant (AA + GA vs. GG: P=0.067; OR = 0.797, 95% CI = 0.625–1.016), and recessive (AA vs. GG + GA: P=0.594; OR = 0.877, 95% CI = 0.542– 1.420) genetic models. Subgroup analysis showed no association in Asians. Whereas, reduced risk was found in allelic contrast (A vs. G: P=0.014; OR = 0.832, 95% CI = 0.718–0.963) and dominant models (AA + GA vs. GG: P=0.004; OR = 0.790, 95% CI = 0.673–0.928) of the mixed population. Conclusions: TNF -308 G>A polymorphism is not associated with leprosy risk in the overall population. However, subgroup analysis demonstrated protective effect of the said polymorphism in leprosy risk in the Latin American population, but showed no association in the Asians.

The involvement of the VDR ApaI gene polymorphism in the development of pulmonary tuberculosis (PTB) has been reported by numerous published studies and yielded inconsistent results. The present meta-analysis evaluated the association of VDR ApaI polymorphism and risk of PTB occurrence.PubMed (Medline), EMBASE and Google Scholar web-databases were searched and a meta-analysis was performed by calculating the pooled odds ratios (ORs) and 95% confidence intervals (95% CIs).This meta-analysis included a total of 14 eligible studies comprising of 1958 confirmed PTB cases and 2938 controls. We observed decreased risk of PTB in allelic (a vs. A:In conclusion, VDR ApaI polymorphism is significantly associated with decreased risk of PTB for in overall and African population, but not in Asians.

Fullerenes have tremendous potential for human biological studies which may further lead to their therapeutic applications. Hence, it has become necessary to explore the possibility of their interference with various important cellular processes. The current study was designed to explore how the presence of fullerenes can affect the binding of DNA with different enzymes and factors involved in transcription and translation process.Various bioinformatics approaches and software programs were used to study the effect of fullerenes on the binding pattern of DNA with different enzymes and factors involved in transcription and translation process.Fullerenes of different molecular weights were interacted with various transcription enzymes and factors and no significant effects were observed on transcription machinery. On the contrary, the factors involved in translation process when docked with their functional partners in the presence/absence of fullerenes display reduced activity of eIF2, eIF4A, eIF4H, eIF4G, eIF4B, eIF5B, and eEF1 with fullerenes of different molecular weights.We conclude that these molecules mostly control the translation of a number of genes. The reduced expression of these factors may cause a number of clinical pathological conditions including neurodegenerative disorders like Alzheimer's, Parkinson's, and Huntington's diseases.

BsmI (rs1544410) polymorphism located in intron 8 at the 3′-end of the vitamin D receptor (VDR) gene is known to be involved in the regulation of mRNA stability. Many studies evaluated the possible correlation between VDR BsmI polymorphism and the risk of pulmonary tuberculosis (PTB), and reported conflicting results. In the present study, an updated meta-analysis was performed to evaluate the above-said association. PubMed, Embase, and Google Scholar web-databases were searched for the relevant studies and a meta-analysis was performed by calculating pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) for all the genetic models. A total of 19 studies comprising 3644 controls and 2635 cases were included in the present study. Overall no association of PTB in allelic contrast (b compared with B: P=0.285; OR =0.909, 95% CI =0.762–1.083), homozygous (bb compared with BB: P=0.881; OR =0.975, 95% CI =0.700–1.359), heterozygous (bB compared with BB: P=0.834; OR =1.017, 95% CI =0.872–1.185), dominant (bb compared with BB + Bb: P=0.451; OR =0.954, 95% CI =0.843–1.079) and recessive (bb + Bb compared with BB: P=0.983; OR =1.002, 95% CI =0.868–1.156) genetic models in comparison with wild-type allele and genotype BB were observed. However, variant allele (b compared with B: P=0.001; OR =2.289, 95% CI =1.661–3.154) showed increased risk of PTB in Asians. In conclusion, VDR BsmI polymorphism is not a risk factor for PTB in overall population. However, this polymorphism may be interrelated to an increased risk of PTB amongst Asians.

Genetic variant LMP7 (low molecular weight polypeptide 7) –145 C > A may influence the function of immune surveillance of an individual and lead to cancer development. Various studies have investigated the relevance of LMP7 –145 C > A gene polymorphism with cancer risk; but, their results are conflicting and inconsistent. To obtain a comprehensive conclusion, a meta-analysis was performed by including eight eligible published studies retrieved from PubMed (Medline), EMBASE and Google Scholar web search until December 2016. Individuals with AA genotype (AA vs CC: p = 0.001; OR = 2.602, 95% CI = 1.780 to 3.803) of LMP7 -145 C > A were found to have 2 folds higher risk of cancer than those with CC genotype. The recessive genetic model (AA vs AC + CC) also indicated that individuals with AA genotype have 2 folds higher cancer risk than AC and CC genotypes (p = 0.001; OR = 2.216, 95% CI = 1.525 to 3.221). Also, significant increased cancer risk was observed in Asians but not in Caucasians. No publication bias was observed during the analysis. Trial sequential analysis also strengthened our current findings. These results suggest that genetic variant LMP7–145 C > A has significant role in increasing cancer risk in overall and Asian population, and could be useful as a prognostic marker for early cancer predisposition.

Introduction: The prevalence of drug resistance in clinical isolates of Mycobacterium tuberculosis from the Gulf Cooperation Council (GCC; Saudi Arabia, Qatar, Bahrain, Kuwait, Oman, United Arab Emirates [UAE]) countries was appraised using reports published between January 2002 and March 2013. Methodology: A total of 11,393 tuberculosis (TB) isolates from the GCC were studied through published literature and were analyzed statistically. Results: Most of the isolates were resistant to isoniazid, followed by streptomycin, rifampin, ethambutol, and pyrazinamide. The highest prevalence rate of multidrug-resistant-TB (MDR-TB) was found in UAE (9.2%), followed by Kuwait (5.9%) and Saudi Arabia (4.3%). The overall MDR-TB prevalence rate was recorded as 4.0% in the entire GCC region. Automated linear modeling revealed that isoniazid resistance had a strong relationship with the prevalence of MDR-TB in all the GCC countries and was found to be the strongest predictor for MDR-TB. Interestingly, rifampicin resistance was significantly associated with the prevalence of MDR-TB in Oman, Kuwait, and Saudi Arabia, while isoniazid was identified for UAE. On the basis of a number of reports and isolates, the principal component analysis showed that, among all GCC member countries, the highest burden of TB was in Saudi Arabia and Kuwait, and maximum drug resistance was present in UAE. Conclusion: The study demonstrates that the prevalence of MDR-TB in GCC countries is almost equal to other developing and developed countries, and requires immediate attention for surveillance and control.

Clostridium difficile is an enteric pathogen that causes approximately 20% to 30% of antibiotic-associated diarrhea. In recent years, there has been a substantial rise in the rate of C. difficile infections as well as the emergence of virulent and antibiotic resistant C. difficile strains. So, there is an urgent need for the identification of therapeutic potential targets and development of new drugs for the treatment and prevention of C. difficile infections. In the current study, we used a hybrid approach by combining sequence similarity-based approach and protein-protein interaction network topology-based approach to identify and characterize the potential drug targets of C. difficile. A total of 155 putative drug targets of C. difficile were identified and the metabolic pathway analysis of these putative drug targets using DAVID revealed that 46 of them are involved in 9 metabolic pathways. In-silico characterization of these proteins identified seven proteins involved in pathogen-specific peptidoglycan biosynthesis pathway. Three promising targets viz. homoserine dehydrogenase, aspartate-semialdehyde dehydrogenase and aspartokinase etc. were found to be involved in multiple enzymatic pathways of the pathogen. These 3 drug targets are of particular interest as they can be used for developing effective drugs against multi-drug resistant C. difficile strain 630 in the near future.

Celiac disease (CD) remains one of the most significant autoimmune diseases worldwide. The pathogenesis of CD is not clearly understood and is probably attributed to genomic variations and host genetic make-up. Case-control and cohort studies of the association between the TNF-α -308 G > A (rs1800629) polymorphism and CD susceptibility have yielded inconsistent results. In this study, PubMed, EMBASE, and Google Scholar web-databases were searched for pertinent reports showing association of TNF-α -308 G > A gene with CD risk. A total of eleven reports involving 1774 controls and 1147 CD cases were included. Significant associations in four genetic models, viz. variant allele (A vs. G: p = 0.001; OR = 2.051, 95% CI = 1.452–2.895), variant homozygous (AA vs. GG: p = 0.001; OR = 6.626, 95% CI = 3.569–12.300), recessive (AA vs. GG + AG: p = 0.001; OR = 4.766, 95% CI = 3.177–7.152) and dominant (AA + AG vs. GG: p = 0.008; OR = 1.910, 95% CI = 1.181–3.088) were found in comparison with wild type homozygous GG genotype. However, heterozygous genetic model did not show any association. Sensitivity analysis revealed stable and statistically robust results. Our results suggest that TNF-α -308 G > A gene polymorphism significantly contributes to CD susceptibility.

Objective To summarize the precise association between pulmonary tuberculosis (PTB) and P2x7 A1513C gene polymorphism. Methods PubMed and Google Scholar web-databases were searched for the studies reporting the association of P2x7 A1513C polymorphism and PTB risk. A meta-analysis was performed for the selected case–control studies and pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated for all the genetic models. Results Eleven studies comprising 2 678 controls and 2 113 PTB cases were included in this meta-analysis. We observed overall no significant risk in all the five genetic models. When stratified population by the ethnicity, Caucasian population failed to show any risk of PTB in all the genetics models. In Asian ethnicity, variant allele (C vs. A: P = 0.001; OR = 1.375, 95% CI = 1.159–1.632) and heterozygous genotype (AC vs. AA: P = 0.001; OR = 1.570, 95% CI = 1.269–1.944) demonstrated significant increased risk of PTB. Likewise, recessive genetic model (CC + AC vs. AA: P = 0.001; OR = 1.540, 95% CI = 1.255–1.890) also demonstrated increased risk of PTB in Asians. Conclusions Our meta-analysis did not suggest the association of P2x7 A1513C polymorphism with PTB risk in overall or separately in Caucasian population. However, it plays a significant risk factor for predisposing PTB in Asians. Future larger sample and expression studies are needed to validate this association.

MBL2 gene encodes mannose-binding lectin, is a member of innate immune system. Earlier studies revealed that MBL2 gene variants, rs1800451, rs1800450, rs5030737, rs7096206, rs11003125 and rs7095891 are associated with impaired serum level and susceptibility to TB, but their results are inconsistent. A meta-analysis was performed by including 22 studies (7095 TB-patients and 7662 controls) and data were analyzed with respect to associations between alleles, genotypes and minor allele carriers to evaluate the potential association between MBL2 polymorphisms and TB risk. Statistically significant results were found only for the homozygous variant genotype (CC vs. AA: p = 0.045; OR = 0.834, 95% CI = 0.699 to 0.996) of rs1800451 and showed reduced risk of TB in overall population. However, other genetic models of rs1800450, rs5030737, rs7096206, rs11003125, rs7095891 and combined rs1800450, rs1800451, rs5030737 polymorphisms of MBL2 gene did not reveal any association with TB risk. Stratified analysis by ethnicity showed decreased risk of TB in African population for rs1800450 and rs1800451. Whereas, no association was observed between other MBL2 polymorphisms and TB risk in all the evaluated ethnic populations. In conclusion, MBL2 rs1800450 and rs1800451 polymorphisms play a protective role in TB infection and reinforce their critical significance as a potential genetic marker for TB resistance.

Cryptosporidium is a coccidian protozoan parasite of the intestinal tract that causes severe and sometimes fatal watery diarrhea in immunocompromised patients, and self-limiting but prolonged diarrheal disease in immunocompetent individuals. It exists naturally in animals and can be zoonotic. Although cryptosporidiosis is a significant cause of diarrheal diseases in both developing and developed countries, it is more prevalent in developing countries and in tropical environments. We examined the epidemiology and disease burden of Cryptosporidium in Saudi Arabia and neighboring countries by reviewing 23 published studies of Cryptosporidium and the etiology of diarrhea between 1986 and 2006. The prevalence of Cryptosporidium infection in humans ranged from 1% to 37% with a median of 4%, while in animals it was different for different species of animals and geographic locations of the studies. Most cases of cryptosporidiosis occurred among children less than 7 years of age, and particularly in the first two years of life. The seasonality of Cryptosporidium varied depending on the geographic locations of the studies, but it was generally most prevalent in the rainy season. The most commonly identified species was Cryptosporidium parvum while C. hominis was detected in only one study from Kuwait. The cumulative experience from Saudi Arabia and four neighboring countries (Kuwait, Oman, Jordan and Iraq) suggest that Cryptosporidium is an important cause of diarrhea in humans and cattle. However, the findings of this review also demonstrate the limitations of the available data regarding Cryptosporidium species and strains in circulation in these countries.

DNA repair capacity is crucial in maintaining cellular functions and homeostasis. However, it can be altered based on DNA sequence variations in DNA repair genes and this may lead to the development of many diseases including malignancies. Identification of genetic polymorphisms responsible for reduced DNA repair capacity is necessary for better prevention. Homologous recombination (HR), a major double strand break repair pathway, plays a critical role in maintaining the genome stability. The present study was performed to determine the frequency of the HR gene XRCC3 Exon 7 (C18067T, rs861539) polymorphisms in Saudi Arabian population in comparison with epidemiological studies by “MEDLINE” search to equate with global populations. The variant allelic (T) frequency of XRCC3 (C>T) was found to be 39%. Our results suggest that frequency of XRCC3 (C>T) DNA repair gene exhibits distinctive patterns compared with the Saudi Arabian population and this might be attributed to ethnic variation. The present findings may help in high-risk screening of humans exposed to environmental carcinogens and cancer predisposition in different ethnic groups.

Aim Many case-control studies have been performed in the recent past to investigate the association between CCL5 -403 G>A (rs2107538) gene polymorphism and tuberculosis (TB) susceptibility in various ethnic groups. However, these studies have produced inconsistent and contradictory results. In the present study, meta-analysis was performed to assess the association between CCL5 -403 G>A polymorphism and TB risk. Methodology Quantitative synthesis was done for the published studies based upon association between CCL5 -403 G>A polymorphism and TB risk from PubMed (Medline), EMBASE web search. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated for allele contrast, homozygous, heterozygous, dominant and recessive genetic models. Results A total of six studies comprising 1638 confirmed TB cases and 1519 healthy controls were included in this meta-analysis. Variant A allele (A vs. G: p = 0.035; OR = 1.301, 95% CI = 1.019 to 1.662) and variant homozygous (AA vs. GG; p = 0.001; OR = 1.520, 95% CI = 1.202 to 1.923) carriers were significantly associated with TB susceptibility. Similarly, recessive model (AA vs. GG+GA: p = 0.016; OR = 1.791, 95% CI = 1.117 to 2.873) also indicated increased TB risk. Whereas, heterozygous (GA vs. GG: p = 0.837; OR = 1.028, 95% CI = 0.791 to 1.335) and dominant (AA+GA vs. GG: p = 0.222; OR = 1.188, 95% CI = 0.901 to 1.567) models failed to show increased risk of developing TB. Conclusions This meta-analysis suggests that there is a significant association between the CCL5 -403 G>A polymorphism and increased risk of TB. However, larger well-designed epidemiological studies with stratified case control and biological characterization may be helpful to validate this association.

Cluster of differentiation 14 (CD14) gene is an important component of the human innate immune system and its role in tuberculosis (TB) has been sparsely documented. The enhanced plasma CD14 levels in TB patients as compared to healthy controls are associated with CD14 gene promoter (C-159T) polymorphism. In the past few years, the relationship between CD14 −159 C>T (rs2569190) polymorphism and risk of TB has been reported in various ethnic populations; however, those studies have yielded contradictory results. In this study systemic assessment was done for the published studies based on the association between CD14 −159 C>T polymorphism and TB risk retrieved from PubMed (Medline) and EMBASE search. A total number of 1389 TB cases and 1421 controls were included in this study and meta-analysis was performed to elucidate the association between CD14 −159 C>T polymorphism and its susceptibility towards TB. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated for allele contrast, homozygous comparison, heterozygous comparison, dominant and recessive genetic model. It was found that T allele carrier was significantly associated with increased TB risk (T vs. C: p-value = 0.023; OR = 1.305, 95% CI = 1.038 to 1.640). Similarly, homozygous mutant TT genotype also revealed 1.6 fold increased risk of TB (TT vs. CC; p-value = 0.040; OR = 1.652, 95% CI = 1.023 to 2.667). Additionally, dominant genetic model demonstrated increased risk of developing TB (TT vs. CC+CT: p-value = 0.006; OR = 1.585, 95% CI = 1.142 to 2.201). The study demonstrates that CD14 gene (−159 C>T) polymorphism contributes increased susceptibility for TB. Moreover, this meta-analysis also suggests for future larger studies with stratified case control population and biological characterization for validation studies.

A 13-month study of children presenting with acute diarrhoeal disease at hospitals and rehydration clinics in Antananarivo, Madagascar, was undertaken between May 2004 and May 2005. Cryptosporidiosis accounted for diarrhoea in 12 (5.6%) of the 215 children investigated. Cases of cryptosporidiosis were detected only in the rainy season, and the median age of cases was 13.5 months (range=1 day-27 months). As 11 of the cases of cryptosporidiosis were caused by Cryptosporidium hominis and only one by C. parvum, most of the cases were probably the result of anthroponotic transmission. GP60/45/15 gene polymorphisms indicated that the causative pathogens were of subtypes Ia, Id, Ie and IIc.

To assess the circulating rotavirus strains among hospitalized children and adults in Gizan City.This cross-sectional study was based in 5 hospitals in the Gizan area. Stool samples were collected between November 2004 and March 2005, from sequential patients with acute, dehydrating diarrhea. Rotavirus antigen was detected in stool by enzyme-linked immunosorbent assay. The diversity of rotavirus strains was investigated using electropherotying and reverse transcription-polymerase chain reaction amplification of the VP7 and VP4 genes (G and P genotyping).Rotavirus was detected in 54 of 454 (12%) subjects. The ages of those infected with rotavirus ranged from 15 days to 20 years, with a median age of 36 months. The highest rotavirus detection rate (24%) occurred in children aged 48-59 months. Overall, 50 (93%) of strains could be assigned both a G- and P-type; G1P[8] was the most frequently detected strain type (n=48, 89%) with one rotavirus each of G2P[4] and G9P[8].Rotavirus strains circulating in Gizan would be well covered by current rotavirus vaccines. Rotavirus serotype G9 has been detected in Saudi Arabia for the first time. Continued surveillance of rotavirus strains is required.

Objectives: Vitamin D has been shown to hamper the growth of Mycobacterium tuberculosis in macrophages. The actions of vitamin D are exerted through a vitamin D receptor (VDR). The genetic variant TaqI of VDR has been implicated in tuberculosis (TB) risk in several case-control studies. However, these studies have shown inconsistent results. Hence, a meta-analysis was conducted to investigate the potential relationship between VDR TaqI polymorphism and risk of developing TB. Materials and Methods: We performed a quantitative synthesis for published studies based upon the relationship between TaqI polymorphism and TB risk from PubMed (Medline) and Embase databases. The meta-analysis was performed and pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for all genetic models. Results: A total of 21 studies including 2,960 TB cases and 3,894 controls were included in this study. The pooled analysis demonstrated no evidence of association between VDR TaqI genotypes and risk of TB in any of the genetic models; variant (t vs T: P = 0.618; OR = 1.051, 95% CI = 0.864-1.278), homozygous (tt vs TT: P = 0.120; OR = 1.336, 95% CI = 0.927-1.924), heterozygous (Tt vs TT: P = 0.925; OR = 0.988, 95% CI = 0.774-1.262), dominant model (tt + Tt vs TT: P = 0.805; OR = 1.032, 95% CI = 0.805-1.322), and recessive model (tt vs TT + Tt: P = 0.180; OR = 1.229, 95% CI = 0.909-1.660). No publication bias was detected during the analysis. Conclusions: Overall findings of this meta-analysis suggest that genetic polymorphism TaqI of VDR gene may not contribute to the risk of TB. However, future larger studies with group of populations are warranted to analyze this relationship.

Aim Association studies of serotonin transporter gene SLC6A4 I/S polymorphism and irritable bowel syndrome (IBS) have shown inconsistent and contradictory results among different populations. In the present study, meta-analysis was performed to evaluate the association between SLC6A4 I/S polymorphism and IBS susceptibility. Methodology Systemic assessment was performed for the published studies based on the association of SLC6A4 I/S polymorphism and IBS risk from PubMed (Medline), EMBASE search. A meta-analysis was done to appraise the said association. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for allele contrast, homozygous, heterozygous, dominant and recessive genetic model. Results A total of twelve studies comprising 2068 IBS cases and 2076 controls were included in this meta-analysis. Overall, no significant results were obtained for S allele carrier (S vs. I: p=0.488; OR=1.073, 95% CI=0.879 to 1.311) Co-dominant (SS vs. II; p=0.587; OR=1.112, 95% CI=0.758 to 1.631), (IS vs. II; p=0.361; OR=0.878, 95% CI=0.665 to 1.160). Similarly, dominant (SS+IS vs. II: p=0.853; OR=0.974, 95% CI=0.736 to 1.288) and recessive (SS vs. II+IS: p=0.267; OR=1.172, 95% CI=0.886 to 1.522) genetic models did not demonstrate risk. In the subgroup population based analysis, reduced risks were found in American (IS vs. II: p=0.009; OR=0.685, 95% CI=0.516 to 0.908) and Asian (SS+IS vs. II; p=0.001; OR=0.116, 95% CI=0.068 to 0.197) population. However, no risk was observed in European population. Conclusions This investigation clearly demonstrates that SLC6A4 (Ins/Del) polymorphism is associated with reduced risk of IBS in American and Asian population. However, future well-designed studies with stratified case control and biological characterization will be needed to validate this finding.