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The respiratory structure has a broad capacity to undergo the mechanism of regeneration. The recent study was intended to determine the efficacy of Withania somnifera (L.) Dunal and expression levels of IRS-1 and SOX-2 genes in the smoke-induced Pulmonary Injury. The present study included 3 groups (n = 9): Normal/negative control (NC), positive control/disease control (PC), and treatment group (TG; treated orally with 350 mg/kg of ethanol extract). Lung injury was induced in PC and TG groups in rats by cigarette smoke (4 CG/day). Decapitation (n = 3) was done on the 14th, 18th, and 21st day of treatment. Phenolic acid quantification by HPLC-UV/VIS showed a significant concentration of p-coumaric acid (130.2 mg/kg) that may also contribute to the extract's efficacy. Hematological parameters (leukocytes, hemoglobin, hematocrit) and serum oxidative parameters (total oxidant status and malondialdehyde) were significantly improved (P ≤ 0.05) in the TG compared to the PC group. Moreover, the total antioxidant capacity, total plasma protein, albumin, globulin, and platelet count significantly decreased in the PC while increasing in the treatment group (P ≤ 0.05). Histology showed damaged histological structures in the PC group, while there was obvious regeneration of architectural damage in the TG group. The IRS-1 and SOX-2 genes were up-regulated in the PC group, indicating the role of IRS-1 and SOX-2 gene expression in tissue homeostasis and regeneration in smoke-induced Pulmonary Injury. These results rationalize the traditional use of W. somnifera in pulmonary diseases and encourage further studies to exploit it in the pharmaceutical industry. [Display omitted] • Withania somnifera is a medicinal plant and provide relief in respiratory problems also. • Rat model of cigarette smoke-induced lung injury was used to investigate the effect of W.somnifera extract acute pulmonary pathophysiology. • Hematological parameters including leukocytes, hemoglobin, hematocrit, serum oxidative parameters, total plasma protein, albumin, globulin, and platelet count significantly improved in the treatment group (P ≤ 0.05). • The results further indicated the role of IRS-1 and SOX-2 gene expression in tissue homeostasis and regeneration in smoke-induced pulmonary injury. [ABSTRACT FROM AUTHOR]

This paper investigates the evolutionary phases of a collapsing dissipative star cluster in the presence of dark matter. For this purpose, the minimal coupling model of f(R,T) gravity is used as a candidate for exotic matter in star cluster. The collapse equation is derived from generalized dynamical equations which show the total conservation of energy within the cluster. In this context, the approach of Misner and Sharp is applied to study the phenomenon and differentiate between homologous as well as non-homologous gravitational collapse. The generalized dynamical equations are also connected to modified heat transport equations related to heat flux, viscosity and shear, which deals with Israel–Stewart theory (without removing the thermodynamics heat/viscous coupling coefficients). It is found that shear-free and non-dissipative fluid give homologous collapse. The dissipation of collapsing star cluster provides a relation between tidal forces and density inhomogeneity. It is theoretically predicted that the presence of exotic matter controlled the collapsing mechanism. [ABSTRACT FROM AUTHOR]

The increased intensity of floods has become an emerging phenomenon in British Columbia, Canada. Flooding causes significant damage to properties and the built environment. The flood damage is magnified by the unthoughtful location choices for settlements and incoherent land use policies. This has severely restricted the capacity to build resilience to adapt to the unpredictable challenges of floods. Therefore, a thorough understanding of the current state of the floodplain maps that entail the spatial distribution of floods and the associated risks to the communities is paramount. Therefore, the British Columbia Real Estate Association (BCREA) attempted to identify pathways to increase awareness of the current state of the floodplain maps and prepare an updated inventory and its vitality to build resilient communities. The survey results suggested that 38.5% of the communities have created or updated their floodplain maps since 2015, and 62% of the maps meet the British Columbia Flood Hazard Area Land Use Management Guidelines. However, a survey conducted in 2020 suggested an increase in the response rate by 12.8%, which indicates a growing urgency to mitigate flood risks. Due to a lack of expertise and pertinent knowledge, 46% of the communities could not create or update the floodplain maps. In addition, the lack of provincial funding was identified as a key impediment to the floodplain mapping that was experienced by 37.5% of the communities. A schematic perception–action–state–accessibility–usage (PASAU) framework was proposed in this study to confirm the current state of floodplain mapping. The British Columbia, Canada, regions were ranked following a fuzzy rule-based approach to assess the nature and status of preparations for floodplain maps. The result suggests that the Northern Territories, Canada, lie at the low and others are at the medium scale. Communities that scored low were attributed to a lack of funding, in-house expertise, data, and planning endeavors. This study suggested actions for different tiers of the government to make the communities safer and more resilient. The frequency and impacts of flooding are increasing in British Columbia, Canada. The location choices for settlements and incoherent land use policies have increased the intensity of its impact. This stems from the need for floodplain maps that show the spatial distribution of floods and associated risks. The BCREA prepared an updated floodplain maps inventory from 2015. A survey found that 38% of the communities have created or updated their floodplain maps since then. The survey revealed an increased response (12.8%) and a growing urgency to mitigate flood risks. A lack of expertise and pertinent in-house expertise, data, and provincial funding were identified as the key impediments to the absence or lack of updates on the floodplain maps. In this study, a schematic PASAU framework was proposed to confirm the current state of floodplain mapping. The British Columbia, Canada, regions were ranked to assess the preparation status for floodplain maps. In the preparation and updating of floodplain maps, the Northern Territories, Canada, lie at the low and others at the medium level, and a few communities scored low. To make the communities safer and more resilient, a few actions on planning, management, and governance were suggested for adoption. [ABSTRACT FROM AUTHOR]

Private information puts naïve traders at a significant trading disadvantage and at the same it provide crucial signals managers for investment adjustment. These two forces have opposing effects on the cost of equity, and the overall effect is determined by which force dominates. For clinching this effect, this study finds out how investment adjustment plays the moderating role between private information and COE. The study employs data of non-financial firms listed on PSX from 2008 to 2019. Further, the study employs a two-step system GMM dynamic panel estimator to analyze the data. The findings of the study show that companies with a low investment adjustment flexibility known as "value firms" do not gain as much from information incorporated in market prices compared to firms having high flexibility in adjusting investment "growth firms." This study adds to the literature by revealing unique insight on the effect of investment adjustment in reducing the influence of private information on COE and corporate investment as well. JEL classification: D82, G14, G410. [ABSTRACT FROM AUTHOR]

Tumour hypoxia is a known and extensively researched phenomenon that occurs in both solid and haematological malignancies. As cancer cells proliferate, demand for oxygen can outstrip supply reducing tumour oxygenation. In solid tumours this is contributed to by disorganized blood vessel development. Tumour hypoxia is associated with resistance to treatment, more aggressive disease behaviour and an increased likelihood of metastatic progression. It can be measured using both invasive and non-invasive methods to varying degrees of accuracy. The presence of hypoxia stimulates a complex cellular network of downstream factors including Hypoxia Inducible Factor 1 (HIF1), C-X-C motif chemokine 4 (CXCR4) and Hypoxia‐inducible glycolytic enzyme hexokinase‐2 (HK2) amongst many others. They work by affecting different mechanisms including influencing angiogenesis, treatment resistance, immune surveillance and the ability to metastasize all of which contribute to a more aggressive disease pattern. Tumour hypoxia has been correlated with poorer outcomes and worse prognosis in patients. The correlation between hypoxic microenvironments and poor prognosis has led to an interest in trying to therapeutically target this phenomenon. Various methods have been used to target hypoxic microenvironments. Hypoxia-activated prodrugs (HAPs) are drugs that are only activated within hypoxic environments and these agents have been subject to investigation in several clinical trials. Drugs that target downstream factors of hypoxic environments including HIF inhibitors, mammalian target of rapamycin (mTOR) inhibitors and vascular endothelial growth factor (anti-VEGF) therapies are also in development and being used in combination in clinical trials. Despite promising pre-clinical data, clinical trials of hypoxia targeting strategies have proven challenging. Further understanding of the effect of hypoxia and related molecular mechanisms in human rather than animal models is required to guide novel therapeutic strategies and future trial design. This review will discuss the currently available methods of hypoxia targeting and assessments that may be considered in planning future clinical trials. It will also outline key trials to date in both the solid and haemato-oncology treatment spheres and discuss the limitations that may have impacted on clinical success to date. [ABSTRACT FROM AUTHOR]

Background: Heavy metals have their adverse effects on growth and physiology of plant. Plant growth regulators help in improving the growth and physiological phenomenon in plants. A pot culture experiment was devised to explore the ameliorative potential of Indole Acetic Acid (IAA) for toxicity of rhizospheric lead (Pb) on two varieties of Mung bean [Vigna radiate (L.) Wickzek]. Methods: Seeds of two varieties i.e., M-8 and MN-92 were grown in earthen pots filled with sandy loam soil and were arranged under complete randomization. Fifteen days after germination, the lead (Pb) was added @ 10mg/kg and 20mg/kg soil as solution Pb NO3. Indole Acetic Acid @100.0mM was foliarly sprayed twice at 15 and 30 days of plants emergence. Physiological parameters i.e., Photosynthetic Rate, Transpiration Rate, Stomatal conductance, Sub Stomatal CO2 Concentration and biomass production in the form of stem, root and leaf dry weights were determined at the age of physiological maturity for three replicates. Result: By application of IAA, photostnthetic rate reduction was declined from 24.61% to 17.78% under 10mg Pb stress and from 55.54% to 27.35% under 20mg Pb stress. Stomatal conductance reduction was declined from 0.56% to 0.28% under 10mg Pb stress and from 3.37% to 1.68% under 20mg Pb stress. Alleviation of Pb stress by IAA for transpiration rate was non significant. Similarly, the role of IAA for alleviation of Pb stress in term of dry weights of stem, root and leaves were non significant statistically. [ABSTRACT FROM AUTHOR]

The aim of this paper is to investigate the stability of Einstein static cosmos using anisotropic homogeneous perturbations in the background of f (R , T) theory in which R and T express the Ricci scalar and trace of the stress–energy tensor, respectively. To accomplish this work, we consider perfect fluid distribution and adopt small anisotropic perturbations in the scale factors and matter contents. We develop static and perturbed field equations that are simplified by using equation of state parameter. For the specific models of f (R , T) theory with conserved and non-conserved stress–energy tensor, the Einstein solutions are explored and their stability regions are analyzed graphically. We conclude that the static Einstein stable universe with anisotropic perturbations exists in this framework contrary to general relativity. [ABSTRACT FROM AUTHOR]

The aim of this paper is to investigate the existence of stable modes of the Einstein static universe in the background of f (R) theory. For this purpose, we take homogeneous anisotropic perturbations in scale factors as well as matter contents. We construct static and perturbed field equations that are further parameterized by linear equation of state parameter. We obtain the Einstein static solutions for two specific f (R) models and graphically analyze their stable regions. It is concluded that contrary to general relativity, there exists stable Einstein static universe with anisotropic perturbations. [ABSTRACT FROM AUTHOR]

Introduction: Vestibular Rehabilitation Therapy (VRT) and Dual Task (DT) training are rehabilitation approaches increasingly used in the care of stroke patients to improve balance and gait, although no comparative evidence has been provided for their efficacy. Aim: The study was aimed to compare the effectiveness of vestibular rehabilitation therapy versus dual task training on balance and gait in posterior cerebral artery stroke. Materials and Methods: A total of 30 subjects i.e., subacute Posterior Cerebral Arterystroke individuals were randomly assigned into 2 groups, group A Vestibular Rehabilitation with Conventional Therapy (n=15) and group B DT training (n=15). Each group received treatment for 45 minutes in a day, 3 times in a week for 4 weeks. Both the groups A and B were also given Conventional Physiotherapy treatment comprising of stretching, strengthening and stability exercises, over the period for 5 days for 4 weeks. Participants were assisted with Wisconsin Gait Scale (WGS) to assess the performance of gait and Mini-BEST test to assess the balance. Mean change score were calculated as the difference between post and pre-test scores and an independent t-test was used to test the difference in the changed scores between two groups. Paired t-test was used to analyse within group differences. A level of significance was set at p≤0.05. Results: The comparison of post intervention scores of Mini- BESTest between Group A and Group B showed significant difference (t-value=2.577, p-value=0.018). The comparison of post intervention scores of WGS between Group A and Group B showed significant difference (t-value= -2.356, p-value=0.028). So, result showed that Group A (Vestibular Rehabilitation) was more significant as compared to Group B (DT training) in both Mini-BESTest and WGS. Conclusion: The result of this study is encouraging to use VRT as a part of rehabilitation protocol by alleviating their gait disturbances, improving balance and gaining confidence of walking with PCA stroke patients as compared with DT Training. [ABSTRACT FROM AUTHOR]

Abstract Disinfection by-products (DBPs) in indoor swimming pool water and air have long been a critical human health risk concern. This study investigated the effects of several indoor swimming pool design and management factors (e.g. ventilation, water treatment, pool operations, pool type) on the concentrations of DBPs, such as trihalomethanes (THMs) and chloramines, in pool water and air. Two sampling campaigns, A and B, were carried out to measure the concentrations of DBPs under different conditions. In both campaigns, 46 pool water samples, seven tap water samples, and 28 ambient air samples were collected and analyzed. Regression models were also developed and validated for investigating the combined effects of design and management factors on total trihalomethanes (TTHM) and trichloramine. The model results show that pool water characteristics (e.g., total organic content, temperature, conductivity, pH and alkalinity) and management factors (e.g., the number of bathers and sprayers) have direct effects on DBP concentrations. Pool water characteristics such as UV absorbance, hardness, and oxidation-reduction potential and a management factor UV intensity have inverse effects on DBPs levels. Based on the correlation analysis, other factors such as fan speed, fresh air, pool age, and basin area were found to be correlated with the concentrations of individual THMs and trichloramine in both water and air. It was also observed that the concentration of THMs varies with pool type. It is note worthy that the effects of the number of sprayers was quantified for the first time. This study comprehensively assessed pool design and management factors and identified their effects on DBPs, providing indoor swimming pool facilities with useful information to control DBPs in the indoor swimming environment. Graphical abstract Unlabelled Image Highlights • Disinfection by-products in air and water were analyzed at five aquatic centers. • Effects of water treatment processes on trihalomethanes and trichloramine were compared. • Correlation of design and management factors with disinfection by-products was evaluated. • Regression models were developed for trihalomethanes and trichloramine. • First time to quantify the effect of number of spray features on air and water quality [ABSTRACT FROM AUTHOR]

Highlights • Pyrosequencing approach used to analyze complex viral genomes as it can determine minor variants. • NGS was used to determine intra-host viral diversity of HCV from 13 chronically infected patients. • NGS of E2 (HVR1), NS3 and NS5B of HCV-3a was performed for a comprehensive analysis of the viral population. • Phylogenetic analysis of studied genes revealed great variability within the Pakistani population. • No significant difference was seen when nucleotide variability of genotype 3a was compared with other genotypes. Abstract Background In Pakistan, HCV disease is considered a major public health issue with about 10–17 million people suffering with this infection and rate is increasing every day without any hindrance. The currently available Pyrosequencing approach used to analyze complex viral genomes as it can determine minor variants. It is crucial to understand viral evolution and quasispecies diversity in complex viral strains. Objectives To assess genetic diversity in patients with HCV using Next Generation Sequencing (NGS) and compare nucleotide diversity of genotype 3a with respect to other genotypes. Study design Intra-host viral diversity of HCV was determined using NGS from 13 chronically HCV infected individuals. NGS of three different regions (E2 (HVR1), NS3 and NS5B) of HCV-3a allowed for a comprehensive analysis of the viral population. Result Phylogenetic analysis of different HCV genes revealed great variability within the Pakistani population. The average nucleotide diversity for HVR1, NS3 and NS5B was 0.029, 0.011 and 0.010 respectively. Conclusion Our findings clearly indicate that patient-2 greater quasispecies heterogeneity than other patients of same genotype-3a using phylogenetic and one step network analyses. Initially phylogenetic analysis of these three genes showed that genotype 3a samples have greater genetic diversity. However, no significant difference was determined when nucleotide variability of genotype 3a compared with other genotypes (1a, 1b, 2a & 4a). [ABSTRACT FROM AUTHOR]

Toxicity studies in appropriate animal models are an integral and very important component of pre-clinical studies in drug development. Brugmansia aurea lagerh. is used for both medicinal and non-medical purposes, including treating skin infections, different types of physical discomfort, inflammation, cough, hallucinations, and evil protection. This study was designed to detect any hazardous effects of B. aurea on animals and find out its LD 50. An acute toxicity study was performed to find out the LD 50 value and sub-acute toxicity study was performed to find out the toxicity on repeated dose administration till 28 days. Both studies were performed according to the organization of economic cooperation and development (OECD) 425 and 407 respectively. For the acute oral toxicity study, animals were divided into two groups, group I normal control (NC) and group II received a 2000mg/kg dose of B.aurea leaves extract. In the sub-acute toxicity study, male and female animals were divided into eight groups, I-IV for males and V-VIII for females received control, 100, 200 & 400mg/kg B. aurea leaves extract respectively. Hematological and biochemical markers were estimated at the end of each study. Results revealed that no mortality and morbidity were observed in acute oral as well as sub-acute toxicity studies. Oxidative stress markers were increased significantly in all organs of the treatment groups in both studies. Animals significantly decreased their food and water intake in an acute oral toxicity study. A slight difference in renal function tests was observed in the acute oral toxicity study when compared with the normal control group. No significant change in histopathology was observed in both studies on selected organs. This study concluded that B. aurea can be safely used for pharmacological purposes. [Display omitted] • Toxicity studies are mandatory before any biological studies. • OECD guidelines for acute (425) and sub-acute (407) toxicity studies are followed. • LD50 is greater than 2000mg/kg. • No significant toxic effects were observed in repeated dose administration toxicity studies. • B. aurea are safe for pharmacological activities. [ABSTRACT FROM AUTHOR]

Objective To evaluate the association of genetic variation in interleukin 28 B ( IL-28B) gene and viral factors with treatment outcome in chronic hepatitis C virus (HCV)-infected patients in Pakistan. Methods Patients with chronic HCV infection who received interferon plus ribavirin combination therapy were enrolled in the study. The viral loads were checked at the third and sixth month of treatment and 6 months after the completion of the treatment. Genotyping of single-nucleotide polymorphism ( SNP) rs12979860 of IL-28B gene was performed by the restriction fragment length polymorphism method and direct sequence analysis. Results A total of 111 patients successfully completed antiviral therapy and the follow-up period. Early virological response ( EVR) and a sustained virological response ( SVR) were achieved in 92 and 91 patients, respectively. Patients infected with HCV genotype 3a had a higher SVR rate compared with other HCV genotypes. A higher C allele frequency (81.9%) was observed in patients with SVR than those with non- SVR ( P = 0.00001). The odds ratio of achieving SVR was more than 10-fold greater for the CC genotype than the CT/ TT genotypes of SNP rs12979860 ( OR 10.351, 95% CI 1.925-55.653, P = 0.006). Other positive predictors observed for SVR were female gender and EVR. Conclusion The CC genotype of IL-28B SNP rs12979860 is an independent predictive factor for SVR in chronic HCV-infected patients in Pakistan. [ABSTRACT FROM AUTHOR]

Drought is a major environmental threat that affects plant growth and productivity. Strategies to mitigate the detrimental impacts of drought stress on plants are under scrutiny. Nanotechnology is considered an effective tool in resolving a wide range of environmental issues by offering novel and pragmatic solutions. A pot experiment was performed to determine the efficacy of zinc oxide nanoparticles (ZnO NPs) as a foliar application (25 mg L−1 and 100 mg L−1) on the growth performance of cucumber subjected to drought stress. Applied ZnO NPs under normal conditions resulted in significant growth and biomass enhancement while reducing drought-induced decline. Photosynthetic pigments, photosynthesis, and PSII activity enhanced due to ZnO NPs application, attaining maximal values at 100 mg L−1 of ZnO NPs. Drought stress restricted growth and biomass buildup in cucumber seedlings by stimulating oxidative stress, which was manifested to excessive buildup of reactive oxygen species (ROS) and peroxidation, thereby decreasing membrane functioning. Plants exposed to ZnO NPs exhibited a reduction in ROS accumulation and lipid peroxidation. The substantial reduction in oxidative damage was manifested with the enhancement of enzymatic and non-enzymatic antioxidant components. The phenol and mineral contents were reduced due to drought stress. In addition, the content of proline, glycine betaine, free amino acids, and sugars increased due to ZnO NPs under normal and drought conditions. Furthermore, the drought-induced decline in the content of phenol and mineral nutrients was mitigated by ZnO NPs foliar application. These findings reveal that exogenous ZnO NPs application may be a pragmatic option in dealing with the drought stress of cucumber seedlings. [Display omitted] • Drought stress severely affects plant growth. • The use of ZnO NPs is a promising strategy to mitigate drought stress. • ZnO NPs show increased antioxidant defense system, nutrient absorption, and osmolytes accumulation in cucumber seedlings. • Reduction in ROS, lipid peroxidation is observed in ZnO NPs treated seedlings. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) is a member of Flaviviridae family and one of the major causes of liver disease. There are about 175 million HCV infected patients worldwide that constitute 3% of world's population. The main route of HCV transmission is parental however 90% intravenous drug users are at highest risk. Standard interferon and ribavirin remained a gold standard of chronic HCV treatment having 38-43% sustained virological response rates. Currently the standard therapy for HCV is pegylated interferon (PEG-INF) with ribavirin. This therapy achieves 50% sustained virological response (SVR) for genotype 1 and 80% for genotype 2 & 3. As pegylated interferon is expensive, standard interferon is still the main therapy for HCV treatment in under developed countries. On the other hand, studies showed that pegylated IFN and RBV therapy has severe side effects like hematological complications. Herbal medicines (laccase, proanthocyandin, Rhodiola kirilowii) are also being in use as a natural and alternative way for treatment of HCV but there is not a single significant report documented yet. Best SVR indicators are genotype 3 and 2, < 0.2 million IU/mL pretreatment viral load, rapid virological response (RVR) rate and age <40 years. New therapeutic approaches are under study like interferon related systems, modified forms of ribavirin, internal ribosome entry site (HCV IRES) inhibitors, NS3 and NS5a inhibitors, novel immunomodulators and specifically targeted anti-viral therapy for hepatitis C compounds. More remedial therapies include caspase inhibitors, anti-fibrotic agents, antibody treatment and vaccines. [ABSTRACT FROM AUTHOR]

Aquatic centres (ACs) are becoming exceedingly popular in the urban agglomerations of cold climate countries like Canada but functioning without assessing the state of their sustainability performance. Previous studies examined health and safety, water and indoor air quality, and energy consumption aspects without aiming at the holistic sustainability performance assessment. The present research is the first systematic effort for benchmarking of ACs. A hierarchical-based framework arranged 81 performance indicators to appraise the key components, including water management, indoor environment, personnel, service quality, energy, social, and operations. Fuzzy AHP and fuzzy mean clustering methods evaluated the identified PIs based on the opinion of experts (from Canadian aquatic centres) on their importance, measurability, and understandability. Finally, the selection process ranked a set of 63 most suitable PIs under 14 sub-criteria. Fuzzy-based methods efficiently handled the subjective scoring process and the difference of opinion among the experts. The criteria performance indices inform the top-level management while the sub-indices stipulate the operations management for honing in the lacking indicators. Using the selected PIs, the AC's management can allocate the available resources for both the short-term (e.g., efficient response to complaints) and long-term (e.g., replacing failed manually operated fixtures with the sensor-operated ones) improvement actions. The selected PIs will enhance the sustainability of ACs in Canada and other cold regions around the globe through a structured benchmarking process. Unlabelled Image • Aquatic centres are facing issues in attaining sustainability objectives. • Seven performance criteria and 81 indicators were identified for assessment. • Expert opinion were gathered from five aquatic centres. • Weights were generated using fuzzy analytic hierarchy process. • Sixty-three performance indicators were selected using fuzzy c-means clustering. [ABSTRACT FROM AUTHOR]

Systems for disease vector control should be effective, efficient, and flexible to be able to tackle contemporary challenges and threats in the control and elimination of vector-borne diseases. As a priority activity towards the strengthening of vector control systems, it has been advocated that countries conduct a vector-control needs assessment. A review was carried out of the perceived needs for disease vector control programs among eleven countries and subnational states in South Asia and the Middle East. In each country or state, independent teams conducted vector control needs assessment with engagement of stakeholders. Important weaknesses were described for malaria, dengue and leishmaniases regarding vector surveillance, insecticide susceptibility testing, monitoring and evaluation of operations, entomological capacity and laboratory infrastructure. In addition, community mobilization and intersectoral collaboration showed important gaps. Countries and states expressed concern about insecticide resistance that could reduce the continued effectiveness of interventions, which demands improved monitoring. Moreover, attainment of disease elimination necessitates enhanced vector surveillance. Vector control needs assessment provided a useful planning tool for systematic strengthening of vector control systems. A limitation in conducting the vector control needs assessment was that it is time- and resource-intensive. To increase the feasibility and utility of national assessments, an abridged version of the guidance should focus on operationally relevant topics of the assessment. Similar reviews are needed in other regions with different contextual conditions. Author summary: Vector control can play a major role in the control and elimination of vector-borne diseases, such as malaria, dengue, leishmaniases and other vector-borne diseases. However, to reach its potential, national vector control systems should be adequately supported by vector surveillance, community participation and intersectoral collaboration. As a step towards strengthening vector control, it has been advocated that countries conduct a vector-control needs assessment. The authors reviewed the needs or gaps as perceived by stakeholders of disease vector control programs in eleven countries and subnational states in South Asia and the Middle East. Programs for control and elimination of malaria, dengue and leishmaniases had major shortcomings in vector surveillance and entomological capacity. This was a concern because vectors develop insecticide resistance which, if unchecked, could reduce the effectiveness of interventions. Also, attaining elimination of disease demands enhanced vector surveillance support. There were major gaps in community mobilization and intersectoral collaboration. The findings imply that vector control systems should adapt to the changing disease situation and adopt a cross-disease mandate. The authors propose improvements to the methods of needs assessment. [ABSTRACT FROM AUTHOR]

BACKGROUND: Ultraviolet Radiation (UVR) from the sun is a significant environmental component that impacts on human health. Excessive UVR exposure has immediate impacts like burning and tanning, as well as long-term consequences including skin damage, photo-aging, skin malignancies. The objective for this study is to determine the student's knowledge, attitude and practice regarding solar ultraviolet exposure in Karachi, Pakistan. METHODS: A cross-sectional study was done in Public Sector University; total 361 students were recruited through stratified cluster sampling from different colleges of university. Data collection was done by validated structured questionnaire. Logistic regression was used to determine the association of outcome variables with risk factors and p-value of <0.05 as a threshold of statistical analysis. RESULTS: Most of the students were appropriate knowledge (71%), positive attitude (51%) and safe practice (54%) regarding ultraviolet solar exposure. Almost half (69%) of participants were used sun protective agents. After adjustment of covariate, female gender (OR 2.20 (95% CI 1.29-4.07) (p-value 0.004), significantly associated with in-appropriate knowledge, third year students (OR 2.93 (95% CI 1.01-8.95) p-value 0.048) were significantly associated with negative attitude. Age group 18-21 years (OR 1.75(95% CI 1.43-5.31) p-value 0.003) were significantly associated with un-safe practice regarding solar ultraviolet exposure harmful effects. CONCLUSION: This study found that knowledge level was appropriate but attitude and practice level need to improve for prevention of harmful effects of solar ultra violet ray exposure. The study encourages students to be more aware of sun protection behavior in order to avoid the long-term effects of sun exposure. [ABSTRACT FROM AUTHOR]

Background: Growth and nutritional status of plant are affected adversely by heavy metals while improved by plant growth regulators. The experiment was aimed to explore the ameliorative potential of indole acetic acid (IAA) for toxicity of Pb. Methods: Two varieties i.e., M-8 and MN-92 of mung bean were grown in pots arranged under complete randomization. Fifteen days after germination, Pb was added @ 10 and 20 mg/kg soil as solutions of PbNO3. Indole acetic acid @100.0 mM was sprayed twice at 15 and 30 days of age. Stem length, root length, leaf area and nutrient ions were recorded at physiological maturity. Three replicates from each treatment were evaluated. Result: The alleviation role of IAA for stem length was recorded as 21.46 and 26.14% for low and high lead stress. The root length was compensated to 34.78 and 31.40% for the respective low and high lead toxicity. Leaf area was affected as 18.11 and 17.32% by IAA. Similarly, Nitrogen contents were nullified to the extents of 15.34 and 8.13%. Phosphorus contents were changed as 11.62 and 4.65% while potassium contents were as 10.14 and 19.36%. The rectifying potential of IAA for leaf biomasses were as 7.64 and 7.43%. [ABSTRACT FROM AUTHOR]

Human bodies encompass very important symbiotic and mutualistic relationships with tiny creatures known as microbiota. Trillions of these tiny creatures including protozoa, viruses, bacteria, and fungi are present in and on our bodies. They play important roles in various physiological mechanisms of our bodies. In return, our bodies provide them with the habitat and food necessary for their survival. In this review, we comprehend the gut microbial species present in various regions of the gut. We can get benefits from microbiota only if they are present in appropriate concentrations, as if their concentration is altered, it will lead to dysbiosis of microbiota which further contributes to various health ailments. The composition, diversity, and functionality of gut microbiota do not remain static throughout life as they keep on changing over time. In this review, we also reviewed the various biotic and abiotic factors influencing the quantity and quality of these microbiota. These factors serve a significant role in shaping the gut microbiota population. [ABSTRACT FROM AUTHOR]

Water is a finite resource. Increasing population, rapid urbanization, and climate change incidents are continuously adding pressure on freshwater supplies. Overcoming these issues require change in current urban water management (UWM) strategy. In this study, a conceptual model of One Water Community has been developed that aims to reduce potable water use (R PWU) using One Water Approach (OWA). Based on OWA's six guiding principles, five interventions (i.e., control factors) and sixteen parameters have been identified. Each parameter is simulated twice by running 10,000 iterations to calculate a percentage reduction of potable water use at 90th, 50th, and 10th percentiles. A Taguchi-based optimization method has been used to determine the optimum combination of parameters from each of the five control factors [water saving appliances (WSA), reclaimed water use (RWU), resource recovery (RR), low impact development (LID), and good governance (GG)]. L 16 orthogonal array experimental design plan was considered in conducting the trials. ANOVA analysis showed that RWU, RR, and WSA were the most influential factors on R PWU performance at 90th, 50th, and 10th percentiles. Validation tests validated the model by predicting the S/N ratio at the optimum condition. The findings indicated that water sense labeled urinals, reclaimed water for agriculture purposes, emissions reductions from treatment plants, bioswales, and increased public awareness were the most optimum parameters in achieving the highest potable water reduction potential at the 90th percentile. The developed model will open new avenues in UWM, which will assist decision-makers in building sustainable, reliable, and resilient urban water systems. [Display omitted] • One Water Approach concept is capable to bring a change in urban water management. • A conceptual model of One Water Community was developed based on six principles. • Five factors and sixteen parameters were identified to reduce potable water use. • A Taguchi based technique was employed to determine optimum parameters combination. • Experimental values were greater than predicted values to justify the optimum condition established in the study. [ABSTRACT FROM AUTHOR]

As tourism is the mainstay of the Maldives’ economy, this country recognizes the importance of controlling mosquito-borne diseases in an environmentally responsible manner. This study sought to estimate the economic costs of dengue in this Small Island Developing State of 417,492 residents. The authors reviewed relevant available documents on dengue epidemiology and conducted site visits and interviews with public health offices, health centers, referral hospitals, health insurers, and drug distribution organizations. An average of 1,543 symptomatic dengue cases was reported annually from 2011 through 2016. Intensive waste and water management on a resort island cost $1.60 per occupied room night. Local vector control programs on inhabited islands cost $35.93 for waste collection and $7.89 for household visits by community health workers per person per year. Ambulatory care for a dengue episode cost $49.87 at a health center, while inpatient episodes averaged $127.74 at a health center, $1,164.78 at a regional hospital, and $1,655.50 at a tertiary referral hospital. Overall, the cost of dengue illness in the Maldives in 2015 was $2,495,747 (0.06% of gross national income, GNI, or $6.10 per resident) plus $1,338,141 (0.03% of GNI or $3.27 per resident) for dengue surveillance. With tourism generating annual income of $898 and tax revenues of $119 per resident, results of an international analysis suggest that the risk of dengue lowers the country’s gross annual income by $110 per resident (95% confidence interval $50 to $160) and its annual tax receipts by $14 per resident (95% confidence interval $7 to $22). Many innovative vector control efforts are affordable and could decrease future costs of dengue illness in the Maldives. [ABSTRACT FROM AUTHOR]

Pyomyositis is a common health problem with significant complications and morbidity. Surgical drainage and Antibiotic treatment is the mainstay of its treatment. Proper culture and sensitivity of etiological bacteria is crucial for successful treatment of Pyomyositis. Objectives: To determine the frequency of Pyomyositis and its common bacteria with their antibiotics sensitivity among children presenting with highly suspected clinical features. Design: Cross sectional descriptive study. Setting: Department of Orthopedics and Trauma, Khyber Teaching Hospital, Peshawar. Period: 12 months from19th July, 2012 to 18th July, 2013. Materials and Methods: 156 patients presented with highly suspected clinical features of Pyomyositis were examined clinically and were investigated by Ultra sound and CBC. Those patients who were having Pyomyositis, pus samples were taken for culture and sensitivity test and the data was analyzed by Statistical Package for Social Sciences (SPSS) version 10.0. Results: There were147 (94.23%) patients having Pyomyositis out of 156 patients. On culture and sensitivity test, 87 (59.18%) have positive growth while 60 (40.82%) have no growth. The most common bacteria isolated was Staphylococcus aureus55 (63.21%) followed by E. coli 10 (11.49%), Pseudomonas Aeruginosa 7 (8.04%), and Streptococcus Pyogenes 5 (5.74%). All isolated bacteria showed more than 95% and 90% sensitivity to Vancomycinand and Fusidic acid respectively while all bacteria showed maximum resistance to Penicillin i.e. more than 35%. Conclusion: Prompt diagnosis of pyomyositis in highly suspected patients, detection of its etiological bacteria and their antibiotic sensitivity tests are very important for the treatment of Pyomyositis. [ABSTRACT FROM AUTHOR]

Background: Pattern of Dengue periodic epidemics through the years along with sporadic cases of Dengue hemorrhagic fever followed by a severe 2011 epidemic of Dengue fever in Pakistan make Pakistan a Dengue endemic country. To study the entry and evolution of dengue virus serotype 2 (DENV-2) in Pakistan, we sequenced three full length genomes and 24 complete envelope sequences of DENV-2 from the years 2010, 2011 and 2013 collected from Punjab province of Pakistan. Methods: Phylogenetic and Bayesian phylogeographic analyses was applied to three full genome sequences as well as 24 envelope sequences to study the spatiotemporal dynamics of DENV-2 in Pakistan. Results: Most of the DENV-2 viruses from the years 2008 to 2013 formed a monophyletic Pakistani clade in IVb sublineage of cosmopolitan genotype except one 2008 DENV-2 strain. Phylogeographic analysis revealed that this 2008 DENV-2 strain was rooted to India 25.4 years ago with a location probability of 0.88. However Pakistani clade rooted back to Sri Lanka 12.6 years ago with a location probability of 0.57. Conclusion: DENV-2 genotype IV was introduced in Pakistan in two time events. First event was introduction from India to Pakistan in the late 1980s (around 1986), and second event was introduction from Sri Lanka to Pakistan around 2000. The later introduction event was responsible for major outbreaks in the Punjab region of Pakistan, including major 2011 outbreak. After the second Introduction event, DENV-2 circulated locally in the region forming a distinct Sublineage within the IVb cosmopolitan genotype of DENV-2. [ABSTRACT FROM AUTHOR]

Introduction: Dengue virus (DENV) is an arthropod-borne virus that belonged to the Flaviviridae viral family. Four known serotypes DEN-1 through DEN-4 do exist and circulate in diverse geographical regions of the world causing epidemics. The management of dengue patients, and especially dengue hemorrhagic fever (DHF)/Dengue shock syndrome (DSS) cases, has been a challenge in Pakistan now days. Method: We have carried out a comprehensive study of the current outbreaks of dengue virus infection on molecular level with the aim to find out the common serotype/s of DENV responsible for this outbreak using PCR, real-time PCR and nucleotide sequencing targeting the C-prM gene junction. For this purpose total 1129 serum samples received between from start of August till end of November 2011 from all the major hospitals of Lahore, Punjab at Division of Molecular Virology, National Centre of Excellence in Molecular Biology (CEMB) University of the Punjab Lahore were utilized for the DENV diagnosis and serotypes/genotypes analysis. Results: Male female ratio of the suspected dengue patients was 2.4:1. Their mean age were 31.14 ± 16.03 (SD) years ranging from 9 months to 90 years. Out of these 1129 serum samples, total 930 (82.37%) were found infected with DENV. Out of the 930 DENV RNA positive samples, 893 (96.02%) had DEN-2 and 37 (3.97%) sample had concurrent infection with serotypes 2 and 3. Conclusion: Based on the results of this study we conclude that DEN-2 is the responsible genotype for the current dengue epidemic that started from the beginning of year 2011 and is continuing till now. The additional serotype detected in the current study was serotype 3 that remained in very low frequency in Pakistan for last several decades. [ABSTRACT FROM AUTHOR]

Context: HCV infection is strongly associated with development of insulin resistance and type-2 diabetes, however molecular mechanism of these associations is not known. The aim of this review was to conduct a comprehensive literature search to understand the nature of the association between hepatitis C virus (HCV) infection and insulin resistance (IR). We also explored the role of HCV core protein and NS5a in modulating the course of the insulin-signaling pathway. Evidence Acquisitions: We searched Directory of Open Access Journals (DOAJ) Google Scholar, Pubmed (NLM), LISTA (EBSCO), Web of Science (TS and PakMediNet). Results: Emerging evidence suggests an association between HCV infection and carotid/coronary vascular disease. IR appears to be a dominant underlying cause of accelerated atherosclerosis in patients with chronic hepatitis C (CHC). HCV can induce IR directly through the stimulation of SOCS3 and PPA2, and both of these molecules have been shown to inhibit interferon-α signaling. Improvement of insulin sensitivity may increase the response rate to antiviral treatment and prevent IR complications, including vascular diseases. The results of several clinical trials that have used insulin sensitizers (metformin and PPAR-γ agonists) have been inconclusive. Conclusions: Beside the association between HCV and IR, the published data also have showed the possible association of HCV core and NS5A protein with IR. [ABSTRACT FROM AUTHOR]

Abstract: Hepatitis C virus (HCV), a major cause of liver disease throughout the world, is difficult to treat with interferon (IFN) (and various formulations and combinations thereof) being the only approved molecule available. It has been investigated recently that proinflammatory chemokine interleukin-8 (IL-8) induced by HCV partially inhibits the antiviral IFN-α therapy. Therefore, the current study was aimed to prospectively utilize the baseline IL-8 levels in the HCV infected serum and predicts its role in sustained virological response (SVR) to IFN-α+ribavirin therapy, in chronic HCV patients in Pakistan. One hundred and ten hepatitis C patients without any other infections underwent IFN-α+ribavirin combination treatment. Baseline IL-8 levels were determined before starting of the therapy for all these patients. Fifteen normal volunteers negative for HCV were kept as control. The baseline IL-8 levels were found significantly higher in all HCV positive patients as compared to normal healthy volunteers (1083.54±85.72pg/ml versus 6.99±1.05pg/ml [mean±SEM], p <0.01) and were also significantly higher in non-responders than responders (p <0.05). Comparatively higher mean baseline IL-8 levels were observed in non-responders (2442.02±159.92pg/ml), than late (1009.31±45.31) and rapid (540.91±27.06pg/ml) responders. Significant relation was observed between baseline IL-8 level and response to IFN therapy (p <0.01). Results of this study suggest that increased levels of IL-8 in HCV infection might be involved in pathogenesis, persistence and resistance to IFN-α+ribavirin combination therapy. [Copyright &y& Elsevier]

Background: Current standard therapy commonly followed for chronic Hepatitis C Virus (HCV) in Pakistan is interferon alpha plus ribavirin combination therapy (IFN α/ribavirin) and pegylated interferon plus ribavirin (PegIFN/ribavirin). PegIFN/ribavirin has increased rate of sustained virological response than standard IFN α/ribavirin therapy. Objective of current study was to analyze rate of early and delayed response to antiviral treatment as well as rate of relapse response in patients following standard treatment IFN α/ribavirin and in patients following pegylated interferon treatment. Methods: Baseline serum samples of 153 patients enrolled for IFN α/ribavirin and 50 patients for PegIFN/ribavirin were collected. After total RNA extraction, genotyping was and HCV RNA viral load was done. Subsequently HCV RNA viral load was estimated at 4 weeks of treatment, at 12 weeks, at 24 or 48 weeks and finally after 6 months follow up period. All the data was statistically analyzed using fisher's exact test. Results: Total 86 patients out of 153 patients following conventional IFN α/ribavirin therapy completed treatment and 69% of them showed Rapid Virological Response (RVR). Whereas 50 patients following PegIFN/ribavirin treatment completed treatment and 80% of them achieved RVR. Total 64 out of 86 patients following IFN α/ribavirin therapy completed follow up period and 53.5% of them achieved Sustainded Virologcal Response (SVR). Forty-five out of total 50 patients who received PegIFN/ribavirin treatment completed 6 months follow up period and among these 70% achieved SVR. SVR rates were significantly associated with RVR (p < 0.001), age (p < 0.001) and gender (p < 0.01) Conclusions: Rate of sustained virological response can be determined by factors like rapid virological response and age since they share significant association with one another. More over rate of SVR was more prominent in males than in females. [ABSTRACT FROM AUTHOR]

Background: Interferon is well thought-out as the key defence against all infections including HCV. The only treatment for HCV infection is pegylated interferon alpha (IFN-a) but unluckily more than half of the infected individuals do not act in response to the cure and become chronic HCV carriers. The mechanism how HCV induce interferon resistance is still elusive. It is recently reported that HCV envelope protein 2 interacts with PKR which is the interferon-inducible protein kinase and which in turn blocks the activity of its target molecule called eukaryotic initiation factor elF2. Sequence analysis of Envelope protein reveals it contains a domain homologous to phosphorylation sites of PKR andthe translation initiation factor eIF2alpha. Envelope protein competes for phosphorylation with PKR. Inhibition of kinase activity of PKR is postulated as a mechanism of to interferon (IFN) resistance. Results: Present study involves the insilico investigation of possible role of potential phosphorylation in envelope 2 protein of 3a genotype in interferon resistance. Envelope protein coding genes were isolated from local HCV isolates, cloned and sequenced. Phylogenetic analysis was done and tertiary structure of envelope gene was predicted. Visualization of phosphorylation in tertiary structure reveals that residue 266 and 267 of envelope gene 2 are surface exposed and their phosphorylation may compete with the phosphorylation of PKR protein and possibly involved in mediating Interferon Resistance. Conclusion: A hybrid in-silico and wet laboratory approach of motif prediction, evolutionary and structural analysis has pointed out serine 266 and 267 of the HCV E2 gene as a hopeful claimant for the serine phosphorylation. Recognition of these nucleotide variations may assist to propose genotype precise therapy to avoid and resolve HCV infections. [ABSTRACT FROM AUTHOR]

In Pakistan, there are estimated 7-9 million carriers of hepatitis B virus (HBV) with a carrier rate of 3-5%. This article reviews the available literature about the prevalence, risk factors, awareness status and genotypes of the HBV in Pakistan by using key words; HBV prevalence, risk factors, awareness status and genotypes in Pakistani population in PubMed, PakMediNet, Directory of Open Access Journals (DOAJ) and Google Scholar. One hundred and six different studies published from 1998 to 2010 were included in this study. Weighted mean and standard deviation were determined for each population group. The percentage of hepatitis B virus infection in general population was 4.3318% ± 1.644%, healthy blood donors (3.93% ± 1.58%), military recruits (4.276% ± 1.646%), healthcare persons (3.25% ± 1.202%), pregnant women (5.872% ± 4.984), prisoners (5.75% ± 0.212%), surgical patients (7.397% ± 2.012%), patients with cirrhosis (28.87% ± 11.90%), patients with HCC (22% ± 2.645%), patients with hepatitis (15.896% ± 14.824%), patients with liver diseases (27.54% ± 6.385%), multiple transfused patients (6.223% ± 2.121%), opthalmic patients (3.89% ± 1.004%) and users of injectable drugs (14.95% ± 10.536%). Genotype D (63.71%) is the most prevalent genotype in Pakistani population. Mass vaccination and awareness programs should be initiated on urgent basis especially in populations with HBV infection rates of more than 5%. [ABSTRACT FROM AUTHOR]

Background: Hepatitis C is a major health problem affecting more than 200 million individuals in world including Pakistan. Current treatment regimen consisting of interferon alpha and ribavirin does not always succeed to eliminate virus completely from the patient's body. Results: Interferon induced antiviral protein kinase R (PKR) has a role in the hepatitis C virus (HCV) treatment as dsRNA activated PKR has the capacity to phosphorylate the serine and threonine of E2 protein and dimerization viral RNA. E2 gene of hepatitis C virus (HCV) genotype 1 has an active role in IFN resistance. E2 protein inhibits and terminates the kinase activity of PKR by blocking it in protein synthesis and cell growth. This brings forward a possible relation of E2 and PKR through a mechanism via which HCV evades the antiviral effect of IFN. Conclusion: A hybrid in-silico and wet laboratory approach of motif prediction, evolutionary and structural anlysis has pointed out serine 75 and 277 of the HCV E2 gene as a promising candidate for the serine phosphorylation. It is proposed that serine phosphorylation of HCV E2 gene has a significant role in interferon resistance. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) is one of the leading health problem with up to 350 million affected people worldwide including 4.5 million only in Pakistan. It has mortality rate of 0.5 to 1.2 million per year worldwide. Pakistan lies in the endemic region with 3-5% HBV carrier rate in the country. The present article reviews the literature on the treatment response of HBV prevalent in Pakistani population. The average treatment response of Lamivudine and interferon-a is 25.81% and 47.95%, respectively. Peg-Interferon was shown to be not effective against the HBV/HCV (hepatitis C virus)/HDV (hepatitis Delta virus) co-infection. The present study reveals that interferon-a is the most effective therapy available for HBV infection prevalent in Pakistani population. Genotype C & D are the most common HBV genotypes in Pakistan and are associated with increased severity and less response to interferon therapy. This poses a great challenge for physicians and researchers and further studies are needed to describe the outcome of the current therapies recommended against HBV infection in Pakistani population. [ABSTRACT FROM AUTHOR]

Background: Hepatitis C virus (HCV) infection is the leading cause of chronic hepatitis which progresses to hepatocellular carcinoma (HCC) afflicting > 170 million people worldwide. HCV 3a is the most common genotype (about 70% of all genotypes) circulating in Pakistan. Expression of HCV individual gene of 3a would facilitate therapeutic and vaccines strategies against chronic HCV and liver Cirrhosis. The aim of the present study was the establishment of stable Huh-7 cell lines expressing structural and non structural proteins of HCV Genotype 3a Pakistani isolate obtained from chronic HCV patients. Methods: Blood samples were obtained from chronic HCV-3a positive patients. HCV individual genes were amplified using PCR with gene specific primers having restriction sites. These gene amplicons were cloned in mammalian expression vector PcDNA3.1+. Huh-7 cell lines were transfected with these constructed plasmids having structural or non-structural HCV genes in confluent cells with lipofectamine. Positive clones were selected with G418 and then confirmed by genome PCR. Subsequently, transcription and expression of the integrated genes were demonstrated by RT-PCR, sequencing and Western blot analysis. Results: We successfully cloned and express five HCV-3a genes in PcDNA3.1+ mammalian expression vector. Results of western blot and sequencing PCR confirmed the stable expression of these five genes. Conclusion: The stable cell-lines expressing HCV-3a individual genes would be a useful tool to investigate the role of various HCV proteins on HCV disease outcome and testing of new therapeutic strategies against HCV. [ABSTRACT FROM AUTHOR]

Abstract: The continuously mutating nature of Hepatitis B virus (HBV) is responsible for the emergence of varying genotypes in different regions of the world affecting the disease outcome. The objective of the current study was to find out the pattern of HBV genotypes circulating in Pakistan. HBV genotypes were determined in HBV chronic patients of different age and gender from all the four different geographical regions (provinces) of Pakistan for a period of 2 years (2007–2009). Out of the total 3137 consecutive patients, 300 (175; 58.3% males and 125; 41.7% females) were randomly selected for HBV genotype A through H determination using molecular genotyping methods. Total 269 (89.6%) isolates were successfully genotyped where as 31 (10.3%) samples failed to generate a type-specific PCR band and were found untypable. Out of the successfully genotyped samples, 43 (14.3%) were with type A, 54 (18%) were with type B, 83 (27.6%) were with type C, 39 (13%) were with type D, 2 (0.6%) were with type E, 4 (1.3%) were with genotype F and total 44 (14.6%) were with mixed HBV infections. Of the mixed genotype infection cases, 16 were with genotypes A/D, 9 were B/C, six were A/D/F, five were with genotypes A/F, two were with A/B/D and B/E and one each for A/C as well as A/E genotypes. Four common genotypes of HBV found worldwide (A, B, C & D) were isolated from Pakistan along with uncommon genotypes E and F for the first time in Pakistan. Overall Genotype C is the most prevalent genotype. Genotypes B and C are predominant in Punjab & Balochistan and Khyber Pakhtoonkhwa, respectively whereas genotype A in Sindh. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) is a crucial public health problem with approximately 350 million affected people and a death rate of 0.5 to 1.2 million per year worldwide. It proceeds to end-stage liver diseases including cirrhosis with hepatic decompensation and hepatocellular carcinoma (HCC). Pakistan lies in the endemic region with 3% HBV carrier rate in the country. The differences in disease outcome and antiviral treatment response among HBV infected patients are variable in different regions of the world due to marked differences in HBV genotypes. These variants are different in their serological reactivity patterns, virus replication, liver disease severity and antiviral treatment responsiveness. The highly mutating nature of HBV is the major cause of its ever increasing antiviral resistance. Importantly the tyrosinemethionine-aspartate-aspartate (YMDD)-motif mutants emerge during prolonged lamivudine treatments that elicit immune clearance. This review deals with the HBV nature, mutation appearance and particularly emphasizes on lamivudine induced mutations in a conserved region (YMDD motif) which is further worsening the antiviral therapies with passage of time. [ABSTRACT FROM AUTHOR]

A human health risk-based life cycle assessment (LCA) framework was developed for selecting low-impact water treatment systems with a focus on heavy metal(loids) removal. The framework comprises three phases, including pilot-scale water treatment, human health risk assessment (HRA), and LCA. The application of the framework was demonstrated by a case study. Two water treatment systems employing ozonation-greensand-ferric hydroxide-based sorbent (OGF) and Birm-ferric hydroxide-based sorbent (BF) processes were used to reduce arsenic and manganese concentrations in the source water of a small municipality in southwestern Canada. The heavy metal(loids) concentration as well as material and energy use data of the two systems were collected to perform HRA and LCA. The results showed that both systems can reduce arsenic and manganese concentrations; however, the removal efficiencies of OGF and BF processes decreased with the increase of treatment volume. At a constant inflow rate, the ferric hydroxide-based sorbent needed to be replaced every 31 and 25 days in the OGF and BF processes, respectively, to ensure that arsenic concentration in the effluent would not pose any significant human health risk. The LCA results indicated that the system using the OGF process generated lower life cycle environmental impacts than the system using the BF process throughout ten years' operation. It was also found that the arsenic removal process was the largest impact contributor in both systems. The manufacturing of ferric hydroxide-based sorbent and disposal of arsenic-contaminated treatment waste accounted for the highest impact in water treatment. Image 1 • A health risk-based LCA framework is proposed for assessing water treatment systems. • Two water treatment systems designed for arsenic and manganese removal are assessed. • Human health risk assessment determines acceptable adsorbent replacement frequency. • System using ozonation-greensand-ferric oxyhydroxide treatment shows lower impacts. • Arsenic removal process generates the highest life cycle environmental impacts. [ABSTRACT FROM AUTHOR]