Prevalence of depression and anxiety among male patients with COVID-19 in Lebsayyer Field Hospital, Qatar.

BACKGROUND: Depression and anxiety are major health problems found to be associated with various conditions. COVID-19 is a global pandemic that has a substantial effect on the worldwide population. This study aimed to assess the prevalence of depression and anxiety among male patients with COVID-19 and explore their relationship with participants' characteristics. METHODS: This cross-sectional study was conducted among expatriate male patients with COVID-19 admitted to Lebsayyer Field Hospital in Qatar with mild COVID-19 (according to World Health Organization classification) from July till August 2020. The sample size was calculated using Cochran's formula based on disease prevalence. All eligible patients were invited to participate until reaching 400 participants, who then completed an anonymous survey of sociodemographic questions, Patient Health Questionnaire-9, and Generalized Anxiety Disorder-7 questionnaire, which are validated screening tools for depression and anxiety, respectively. RESULTS: Of the 400 participants, 148 (37.0%) and 77 (19.3%) reported depressive and anxiety symptoms, respectively. Depression was more prevalent among those 40-49 years old (p = 0.029), while anxiety was more prevalent among people aged  ≥ 50 (p = 0.456). Both depression (p = 0.009) and anxiety (p = 0.042) were more prevalent among Bangladeshi, followed by Filipino participants. Depression was more prevalent among those with the highest income (> 15,000 QR; p = 0.004), in contrast to anxiety, which was more prevalent among those with the lowest monthly income ( <  2,000 QR; p = 0.039). CONCLUSION: The prevalence of depressive and anxiety symptoms is high among the study participants. Associated factors identified by the study were unsteady income, poor self-rated health, living with family, Southeast Asian ethnicity, and age group of 40-49 years.

Introduction and evolution of dengue virus type 2 in Pakistan: a phylogeographic analysis.

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.

Inpatient satisfaction at tertiary care public hospitals of a metropolitan city of Pakistan.

OBJECTIVE: To determine the satisfaction of in-patients towards quality of service provision and environment of public-sector hospitals. METHODS: The cross-sectional study was conducted in four major public-sector hospitals of Karachi from December 2010 to February 2012. The questionnaire, besides the demographic details, also had 5-point Likert scale questions regarding satisfaction of patients with doctors, staff, administration and the hospital environment. SPSS 20 was used for statistical analysis and results were expressed as frequencies with percentages. RESULTS: Of the 710 subjects in the study, 475(67%) agreed that their doctors checked them with concentration and care. Staff was reported as being kind natured and well-mannered by 423(59.6%) and 451(63.5%) patients respectively. However, 414(58.3%) were not pleased with the sanitary condition of the hospital. Only 225(31.7%) got comfortable beds, while 498(70.14%) patients found bugs in beds. In terms of overall satisfaction 452(63.7%) were satisfied with the staff, 463(65.2%) with doctors, and 385(54.2%) with the hospital environment. CONCLUSION: Patients were relatively satisfied with the staff, but sanitary conditions and hospital environment were a concern for majority of the patients.

High Blood Pressure-Associated Symptoms: Insights From a Population-Based Study in Pakistan.

Background All over the world, millions die of hypertension (HTN) every year. Given the influence of healthcare expenses, HTN represents a serious public health issue in developed and developing countries. HTN is common in Pakistan; however, there are several myths about the symptoms of raised blood pressure that need to be identified. Objective The objective of this study is to compare the frequency of high blood pressure-associated symptoms in normotensive and hypertensive adult populations in Karachi, Pakistan. Methodology A community-based cross-sectional observational study was conducted among 277 patients aged 18 years and above who were attending the OPD of different community health centers in Karachi, with and without HTN. Ethical approval was obtained, and data were collected using a convenient sampling technique on a predesigned questionnaire and analyzed using IBM SPSS Statistics for Windows, Version 20.0 (Released 2011; IBM Corp., Armonk, NY, USA). Results Out of the total study population, 88 (31.65%) were normotensive, and 189 (67.98%) were hypertensive. In the hypertensive group, approximately 100 (52.9%) were men and 89 (47.1%) were women. The mean ages of normotensives and hypertensives were 44.13 + 11.0 and 49.2 + 13.1 years, respectively. Mean age, heart rate, and smoking status were significantly different between the two groups. Among several perceived blood pressure symptoms like vision problems, sleep apnea, and abnormal heartbeat was significantly higher in the hypertensive group. Conversely, although headache, vertigo, edema, and epistaxis were more frequent in the hypertensive group, the difference was not statistically significant. Conclusions In our study, >65% of patients visiting OPD had high blood pressure. Several symptoms were found to be more prevalent in hypertensive individuals compared with non-hypertensive ones. More large-scale studies are recommended to further explore the common symptoms associated with HTN in our population.

Perceived needs of disease vector control programs: A review and synthesis of (sub)national assessments from South Asia and the Middle East.

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.

Toxicity profiling of Burgmansia aurea Lagerh. Leaves using acute and sub-acute toxicity studies in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: 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. AIM OF THE STUDY: This study was designed to detect any hazardous effects of B. aurea on animals and find out its LD50. MATERIALS & METHODS: An acute toxicity study was performed to find out the LD50 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: 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. CONCLUSION: This study concluded that B. aurea can be safely used for pharmacological purposes.

Antagonistic impact on cadmium stress in alfalfa supplemented with nano-zinc oxide and biochar via upregulating metal detoxification.

Eco-toxicological estimation of cadmium induced damages by morpho-physiological and cellular response could be an insightful strategy to alleviate negative impact of Cd in agricultural crops. The current study revealed novel patterns of Cd-bioaccumulation and cellular mechanism opted by alfalfa to acquire Cd tolerance under various soil applied zinc oxide nanoparticles (nZnO) doses (0, 30, 60, 90 mg kg-1), combined with 2% biochar (BC). Herein, the potential impact of these soil amendments was justified by decreased Cd and increased Zn-bioaccumulation into roots by 38 % and 48 % and shoots by 51 % and 72 % respectively, with co-exposure of nZnO with BC. As, the transmission electron microscopy (TEM) and scanning electron microscopy and energy dispersive spectroscopy (SEM-EDS) ultrastructural observations confirmed that Cd-exposure induced stomatal closure, and caused damage to roots and leaves ultrastructure as compared to the control group. On the contrary, the damages to the above-mentioned traits were reversed by a higher nZnO dose, and the impact was further aggravated by adding BC along nZnO. Furthermore, higher nZnO and BC levels efficiently alleviated the Cd-mediated reductions in alfalfa biomass, antioxidant enzymatic response, and gaseous exchange traits than control. Overall, soil application of 90 mg kg-1 nZnO with BC (2 %) was impactful in averting Cd stress damages and ensuring better plant performance. Thereby, applying soil nZnO and BC emerge as promising green remediation techniques to enhance crop tolerance in Cd-polluted soil.

Targeting hypoxia in solid and haematological malignancies.

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.

Serendipita indica-A Review from Agricultural Point of View.

Fulfilling the food demand of a fast-growing population is a global concern, resulting in increased dependence of the agricultural sector on various chemical formulations for enhancing crop production. This leads to an overuse of chemicals, which is not only harmful to human and animal health, but also to the environment and the global economy. Environmental safety and sustainable production are major responsibilities of the agricultural sector, which is inherently linked to the conservation of the biodiversity, the economy, and human and animal health. Scientists, therefore, across the globe are seeking to develop eco-friendly and cost-effective strategies to mitigate these issues by putting more emphasis on the use of beneficial microorganisms. Here, we review the literature on Serendipita indica, a beneficial endophytic fungus, to bring to the fore its properties of cultivation, the ability to enhance plant growth, improve the quality of produced crops, mitigate various plant stresses, as well as protect the environment. The major points in this review are as follows: (1) Although various plant growth promoting microorganisms are available, the distinguishing character of S. indica being axenically cultivable with a wide range of hosts makes it more interesting for research. (2) S. indica has numerous functions, ranging from promoting plant growth and quality to alleviating abiotic and biotic stresses, suggesting the use of this fungus as a biofertiliser. It also improves the soil quality by limiting the movement of heavy metals in the soil, thus, protecting the environment. (3) S. indica's modes of action are due to interactions with phytohormones, metabolites, photosynthates, and gene regulation, in addition to enhancing nutrient and water absorption. (4) Combined application of S. indica and nanoparticles showed synergistic promotion in crop growth, but the beneficial effects of these interactions require further investigation. This review concluded that S. indica has a great potential to be used as a plant growth promoter or biofertiliser, ensuring sustainable crop production and a healthy environment.

Foliar application of zinc oxide nanoparticles: An effective strategy to mitigate drought stress in cucumber seedling by modulating antioxidant defense system and osmolytes accumulation.

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.

Nanosized zinc oxide (n-ZnO) particles pretreatment to alfalfa seedlings alleviate heat-induced morpho-physiological and ultrastructural damages.

Global efforts are in rapid progress to tackle the emerging conundrum of climate change-induced heat stress in grassland ecosystems. Zinc oxide nanoparticles (n-ZnO) are known to play a crucial role in plants' abiotic stress regulation, but its response in alfalfa against heat stress has not been explored. This study aimed at assessing the effects of n-ZnO on alfalfa under heat stress by various morpho-physiological and cellular approaches. Five-week-old alfalfa seedlings were subjected to foliar application of n-ZnO as a pretreatment before the onset of heat stress (BHS) to evaluate its effect on heat tolerance, and as a post-treatment after heat stress (AHS) to evaluate recovery efficiency. In vitro studies on Zn release from n-ZnO by Inductively coupled plasma mass spectroscopy (ICPMS) disclosed that the particle uptake and Zn release were concentration dependent. The uptake and translocation of n-ZnO examined by transmission electron microscope (TEM) reveling showed that n-ZnO was primarily localized in the vacuoles and chloroplasts. TEM images showed that ultrastructural modifications to chloroplast, mitochondria, and cell wall were reversible by highest dose of n-ZnO applied before heat stress, and damages to these organelles were not recoverable when n-ZnO was applied after heat stress. The results further enlightened that 90 mg L-1 n-ZnO better prevented the heat stress-mediated membrane damage, lipid peroxidation and oxidative stress by stimulating antioxidant systems and enhancing osmolyte contents in both BHS and AHS. Although, application of 90 mg L-1 n-ZnO in BHS was more effective in averting heat-induced damages and maintaining better plant growth and morpho-physiological attributes compared to AHS. Conclusively, foliar application of n-ZnO can be encouraged as an effective strategy to protect alfalfa from heat stress damages while minimizing the risk of nanoparticle transmission to environmental compartments, which could happen with soil application.

Zinc Oxide Nanoparticles Interplay With Physiological and Biochemical Attributes in Terminal Heat Stress Alleviation in Mungbean (Vigna radiata L.).

Gradually rising atmospheric temperature is the vital component of the environment, which is anticipated as the riskiest abiotic stress for crop growth. Nanotechnology revolutionizing the agricultural sectors, notably, zinc oxide nanoparticles (nano-ZnO) has captured intensive research interests due to their distinctive properties and numerous applications against abiotic stresses. Mungbean (Vigna radiata L.), being a summer crop, is grown all over the world at an optimum temperature of 28-30°C. A rise in temperature above this range, particularly during the flowering stage, can jeopardize the potential performance of the plant. Hence, an outdoor study was performed to evaluate the effect of multiple suspensions of nano-ZnO (0, 15, 30, 45, and 60 mg l-1) on physicochemical attributes and yield of mungbean crop under heat stress. Heat stress was induced by fine-tuning of sowing time as: S1 is the optimal sowing time having day/night temperatures <40/25°C and S2 and S3 are late sown that were above >40/25°C during the flowering stage. In vitro studies on Zn release from nano-ZnO by inductively coupled plasma mass spectroscopy (ICPMS) disclosed that the Zn release and particles uptake from nano-ZnO were concentration-dependent. Exogenous foliar application of nano-ZnO significantly upstreamed the production of antioxidants and osmolytes to attenuate the shocks of heat stress in S2 and S3. Likewise, nano-ZnO substantially rebated the production of reactive oxygen species in both S2 and S3 that was associated with curtailment in lipid peroxidation. Adding to that, foliar-applied nano-ZnO inflates not only the chlorophyll contents and gas exchange attributes, but also the seeds per pod (SPP) and pods per plant (PPP), which results in the better grain yield under heat stress. Thus, among all the sowing dates, S1 statistically performed better than S2 and S3, although foliar exposure of nano-ZnO boosted up mungbean performance under both the no heat and heat-induced environments. Hence, foliar application of nano-ZnO can be suggested as an efficient way to protect the crop from heat stress-mediated damages with the most negligible chances of nanoparticles delivery to environmental compartments that could be possible in case of soil application.

Serotype and genotype analysis of dengue virus by sequencing followed by phylogenetic analysis using samples from three mini outbreaks-2007-2009 in Pakistan.

BACKGROUND: Since the first reported outbreak of dengue hemorrhagic fever in Pakistan, several mini outbreaks have erupted in the region. Dengue virus serotype 3 (DEN-3) was first documented in 2005 outbreak in Karachi. Reports show that serotype 3 is prevalent in Lahore since 2008. Serotype 2 (DEN-2) is the major circulating serotype in Pakistan as it is documented since 1994. We have conducted a detailed study of three outbreaks of dengue virus infection that occurred in years 2007, 2008 and 2009 in Lahore by using molecular techniques such as PCR and nucleotide sequencing of the C-prM gene junction of Dengue virus. RESULTS: Through the analysis of 114 serum samples collected over the period of three years (2007-2009), total 20 patients were found to be infected with dengue virus. In year 2007, four were positive for serotype 2 and one sample was positive for serotype DEN-3. In 2008, five samples had concurrent infection with serotypes DEN-2 and DEN-3 while three samples were infected only with serotype DEN-2. In year 2009, one sample had concurrent infection with serotypes DEN-2 and DEN-3 while six were positive for serotype DEN-2 only. CONCLUSIONS: Our study showed that serotype DEN-2 was dominant in positive samples of dengue virus infection collected during the period of three years (2007-2009). The other serotype present was serotype DEN-3. Genotypes of serotype DEN-2 and serotype DEN-3 were subtype IV and subtype III, respectively.

Establishment of stable Huh-7 cell lines expressing various hepatitis C virus genotype 3a protein: an in-vitro testing system for novel anti-HCV drugs.

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.

An overview of treatment response rates to various anti-viral drugs in Pakistani hepatitis B virus infected patients.

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-α 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-α 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.

Positional effect of phosphorylation sites 266 and 267 in the cytoplasmic domain of the E2 protein of hepatitis C virus 3a genotype: interferon resistance analysis via sequence alignment.

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-α) 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.

Hepatitis B virus in Pakistan: a systematic review of prevalence, risk factors, awareness status and genotypes.

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%.

Envelope 2 protein phosphorylation sites S75 & 277 of hepatitis C virus genotype 1a and interferon resistance: a sequence alignment approach.

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.

Effects of host and virus related factors on interferon-α+ribavirin and pegylated-interferon+ribavirin treatment outcomes in chronic Hepatitis C patients.

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.

Performance indicators for aquatic centres in Canada: Identification and selection using fuzzy based methods.

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.