Search results for: Fahad Javed

Authors: Ammar Boudaka, Maryam Al-Suleimani, Hajar BaOmar, Intisar Al-Lawati, Fahad Zadjali

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Background: Hypertension is increasingly becoming a matter of medical and public health importance. The maintenance of normal blood pressure requires a balance between cardiac output and total peripheral resistance. The endothelium, through the release of vasodilating factors, plays an important role in the control of total peripheral resistance and hence blood pressure homeostasis. Transient Receptor Potential Vanilloid type 4 (TRPV4) is a mechanosensitive non-selective cation channel that is expressed on the endothelium and contributes to endothelium-mediated vasodilation. So far, no data are available about the morphological and functional status of this channel in hypertensive cases. Objectives: This study aimed to investigate whether there is any difference in the morphological and functional features of TRPV4 in the mesenteric artery of normotensive and hypertensive rats. Methods: Functional feature of TRPV4 in four experimental animal groups: young and adult Wistar-Kyoto rats (WKY-Y and WKY-A), young and adult spontaneously hypertensive rats (SHR-Y and SHR-A), was studied by adding 5 µM 4αPDD (TRPV4 agonist) to mesenteric arteries mounted in a four-chamber wire myograph and pre-contracted with 4 µM phenylephrine. The 4αPDD-induced response was investigated in the presence and absence of 1 µM HC067047 (TRPV4 antagonist), 100 µM L-NAME (nitric oxide synthase inhibitor), and endothelium. The morphological distribution of TRPV4 in the wall of rat mesenteric arteries was investigated by immunostaining. Real-time PCR was used in order to investigate mRNA expression level of TRPV4 in the mesenteric arteries of the four groups. The collected data were expressed as mean ± S.E.M. with n equal to the number of animals used (one vessel was taken from each rat). To determine the level of significance, statistical comparisons were performed using the student’s t-test and considered to be significantly different at p<0.05. Results: 4αPDD induced a relaxation response in the mesenteric arterial preparations (WKY-Y: 85.98% ± 4.18; n = 5) that was markedly inhibited by HC067047 (18.30% ± 2.86; n= 5; p<0.05), endothelium removal (19.93% ± 1.50; n = 5; p<0.05) and L-NAME (28.18% ± 3.09; n = 5; p<0.05). The 4αPDD-induced relaxation was significantly lower in SHR-Y compared to WKY-Y (SHR-Y: 70.96% ± 3.65; n = 6, WKY-Y: 85.98% ± 4.18; n = 5-6, p<0.05. Moreover, the 4αPDD-induced response was significantly lower in WKY-A than WKY-Y (WKY-A: 75.58 ± 1.30; n = 5, WKY-Y: 85.98% ± 4.18; n = 5, p<0.05). Immunostaining study showed immunofluorescent signal confined to the endothelial layer of the mesenteric arteries. The expression of TRPV4 mRNA in SHR-Y was significantly lower than in WKY-Y (SHR-Y; 0.67RU ± 0.34; n = 4, WKY-Y: 2.34RU ± 0.15; n = 4, p<0.05). Furthermore, TRPV4 mRNA expression in WKY-A was lower than its expression in WKY-Y (WKY-A: 0.62RU ± 0.37; n = 4, WKY-Y: 2.34RU ± 0.15; n = 4, p<0.05). Conclusion: Stimulation of TRPV4, which is expressed on the endothelium of rat mesenteric artery, triggers an endothelium-mediated relaxation response that markedly decreases with hypertension and growing up changes due to downregulation of TRPV4 expression.

Keywords: hypertension, endothelium, mesenteric artery, TRPV4

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Authors: Arsalan Jabbar, Wajiha Javed, Nelofer Mehboob, Zahid Memon

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Introduction: There are multiple social, individual and cultural factors that influence an individual’s decision to adopt family planning methods especially among non-users in patriarchal societies like Pakistan.Non-users, if targeted efficiently, can contribute significantly to country’s CPR. A research study showed that non-users if convinced to adopt lactational amenorrhea method can shift to long-term methods in future. Research shows that if non-users are targeted efficiently a 59% reduction in unintended pregnancies in Saharan Africa and South-Central and South-East Asia is anticipated. Methods: We did secondary data analysis on Pakistan Demographic Heath Survey (2012-13) dataset. Use of contraception (never-use/ever-use) was the outcome variable. At univariate level Chi-square/Fisher Exact test was used to assess relationship of baseline covariates with contraception use. Then variables to be incorporated in the model were checked for multi-collinearity, confounding, and interaction. Then binary logistic regression (with an urban-rural stratification) was done to find the relationship between contraception use and baseline demographic and social variables. Results: The multivariate analyses of the study showed that younger women (≤ 29 years) were more prone to be never users as compared to those who were > 30 years and this trend was seen in urban areas (AOR 1.92, CI 1.453-2.536) as well as rural areas (AOR 1.809, CI 1.421-2.303). While looking at regional variation, women from urban Sindh (AOR 1.548, CI 1.142-2.099) and urban Balochistan (AOR 2.403, CI 1.504-3.839) had more never users as compared to other urban regions. Women in the rich wealth quintile were more never users and this was seen both in urban and rural localities (urban (AOR 1.106 CI .753-1.624); rural areas (AOR 1.162, CI .887-1.524)) even though these were not statistically significant. Women idealizing more children(> 4) are more never users as compared to those idealizing less children in both urban (AOR 1.854, CI 1.275-2.697) and rural areas (AOR 2.101, CI 1.514-2.916). Women who never lost a pregnancy were more inclined to be non-users in rural areas (AOR 1.394, CI 1.127-1.723) .Women familiar with only traditional or no method had more never users in rural areas (AOR 1.717, CI 1.127-1.723) but in urban areas it wasn’t significant. Women unaware of Lady Health Worker’s presence in their area were more never users especially in rural areas (AOR 1.276, CI 1.014-1.607). Women who did not visit any care provider were more never users (urban (AOR 11.738, CI 9.112-15.121) rural areas (AOR 7.832, CI 6.243-9.826)). Discussion/Conclusion: This study concluded that government, policy makers and private sector family planning programs should focus on the untapped pool of never users (younger women from underserved provinces, in higher wealth quintiles, who desire more children.). We need to make sure to cover catchment areas where there are less LHWs and less providers as ignorance to modern methods and never been visited by an LHW are important determinants of never use. This all is in sync with previous literate from similar developing countries.

Keywords: contraception, demographic and health survey, family planning, never users

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Authors: Sadeem Aljamaan, Reem Hariri, Rahaf Alghamdi, Batool Alotaibi, Batool Alsenan, Lama Althunayyan, Areej Alnemer

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The aim of this study is to correlate between radiological findings and histopathological results in regard to the breast imaging-reporting and data system scores, size of breast masses, molecular subtypes and suspicious radiological features, as well as to assess the concordance rate in histological grade between core biopsy and surgical excision among breast cancer patients, followed by analyzing the change of concordance rate in relation to neoadjuvant chemotherapy in a Saudi population. A retrospective review was conducted over 6-year period (2017-2022) on all breast core biopsies of women preceded by radiological investigation. Chi-squared test (χ2) was performed on qualitative data, the Mann-Whitney test for quantitative non-parametric variables, and the Kappa test for grade agreement. A total of 641 cases were included. Ultrasound, mammography, and magnetic resonance imaging demonstrated diagnostic accuracies of 85%, 77.9% and 86.9%; respectively. magnetic resonance imaging manifested the highest sensitivity (72.2%), and the lowest was for ultrasound (61%). Concordance in tumor size with final excisions was best in magnetic resonance imaging, while mammography demonstrated a higher tendency of overestimation (41.9%), and ultrasound showed the highest underestimation (67.7%). The association between basal-like molecular subtypes and the breast imaging-reporting and data system score 5 classifications was statistically significant only for magnetic resonance imaging (p=0.04). Luminal subtypes demonstrated a significantly higher percentage of speculation in mammography. Breast imaging-reporting and data system score 4 manifested a substantial number of benign pathologies in all the 3 modalities. A fair concordance rate (k= 0.212 & 0.379) was demonstrated between excision and the preceding core biopsy grading with and without neoadjuvant therapy, respectively. The results demonstrated a down-grading in cases post-neoadjuvant therapy. In cases who did not receive neoadjuvant therapy, underestimation of tumor grade in biopsy was evident. In summary, magnetic resonance imaging had the highest sensitivity, specificity, positive predictive value and accuracy of both diagnosis and estimation of tumor size. Mammography demonstrated better sensitivity than ultrasound and had the highest negative predictive value, but ultrasound had better specificity, positive predictive value and accuracy. Therefore, the combination of different modalities is advantageous. The concordance rate of core biopsy grading with excision was not impacted by neoadjuvant therapy.

Keywords: breast cancer, mammography, MRI, neoadjuvant, pathology, US

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Authors: Zain Ul Abadeen, Muhammad Zargham Khan, Muhammad Kashif Saleemi, Ahrar Khan, Ijaz Javed Hassan, Aisha Khatoon, Qasim Altaf

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Aflatoxins are secondary metabolites produced by toxigenic fungi, and there are four types of aflatoxins include AFB1, AFB2, AFG1 and AFG2. Aflatoxin B1 (AFB1) is considered as most toxic form. It is mainly responsible for the contamination of poultry feed and produces a condition called aflatoxicosis leads to immunosuppression in poultry birds. Saccharomyces cerevisiae is a single cell microorganism and acts as a source of growth factors, minerals and amino acids which improve the immunity and digestibility in poultry birds as probiotics. Saccharomyces cerevisiae is well recognized to cause the biological degradation of mycotoxins (toxin binder) because its cell wall contains β-glucans and mannans which specifically bind with aflatoxins and reduce their absorption or transfer them to some non-toxic compounds. The present study was designed to investigate the immunosuppressive effects of aflatoxins in broiler chicks and the reduction of severity of these effects by the use of Baker’s Yeast (Saccharomyces cerevisiae). One-day-old broiler chicks were procured from local hatchery and were divided into various groups (A-I). These groups were treated with different levels of AFB1 @ 400 µg/kg and 600 µg/kg along with different levels of Baker’s Yeast (Saccharomyces cerevisiae) 0.1% and 0.5 % in the feed. The total duration of the experiment was six weeks and different immunological parameters including the cellular immune response by injecting PHA-P (Phytohemagglutinin-P) in the skin of the birds, phagocytic function of mononuclear cells by Carbon clearance assay from blood samples and humoral immune response against intravenously injected sheep RBCs from the serum samples were determined. The birds from each group were slaughtered at the end of the experiment to determine the presence of gross lesions in the immune organs and these tissues were fixed in 10% neutral buffered formalin for histological investigations. The results showed that AFB1 intoxicated groups had reduced body weight gain, feed intake, organs weight and immunological responses compared to the control and Baker’s Yeast (Saccharomyces cerevisiae) treated groups. Different gross and histological degenerative changes were recorded in the immune organs of AFB1 intoxicated groups compared to control and Baker’s Yeast (Saccharomyces cerevisiae) treated groups. The present study concluded that Baker’s Yeast (Saccharomyces cerevisiae) addition in the feed helps to ameliorate the immunotoxigenic effects produced by AFB1 in broiler chicks.

Keywords: aflatoxins, body weight gain, feed intake, immunological response, toxigenic effect

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Authors: Hanan Badr, Fahad Manee, Rao Shashidhar, Omar Bayoumy

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Introduction: Hypertension is the major risk factor for cardiovascular diseases and stroke and a universe leading cause of disability-adjusted life years and mortality. Adopting an unhealthy lifestyle is thought to be associated with developing hypertension regardless of predisposing genetic factors. This study aimed to examine the association between recreational physical activity (RPA), and sedentary behaviors with a risk of hypertension among ministry employees, where there is no role for occupational physical activity (PA), and to scrutinize participants’ time spent in RPA and sedentary behaviors on the working and weekend days. Methods: A cross-sectional study was conducted among randomly selected 2562 employees working at ten randomly selected ministries in Kuwait. To have a representative sample, the proportional allocation technique was used to define the number of participants in each ministry. A self-administered questionnaire was used to collect data about participants' socio-demographic characteristics, health status, and their 24 hours’ time use during a regular working day and a weekend day. The time use covered a list of 20 different activities practiced by a person daily. The New Zealand Physical Activity Questionnaire-Short Form (NZPAQ-SF) was used to assess the level of RPA. The scale generates three categories according to the number of hours spent in RPA/week: relatively inactive, relatively active, and highly active. Gender-matched trained nurses performed anthropometric measurements (weight and height) and measuring blood pressure (two readings) using an automatic blood pressure monitor (95% accuracy level compared to a calibrated mercury sphygmomanometer). Results: Participants’ mean age was 35.3±8.4 years, with almost equal gender distribution. About 13% of the participants were smokers, and 75% were overweight. Almost 10% reported doctor-diagnosed hypertension. Among those who did not, the mean systolic blood pressure was 119.9±14.2 and the mean diastolic blood pressure was 80.9±7.3. Moreover, 73.9% of participants were relatively physically inactive and 18% were highly active. Mean systolic and diastolic blood pressure showed a significant inverse association with the level of RPA (means of blood pressure measures were: 123.3/82.8 among relatively inactive, 119.7/80.4 among relatively active, and 116.6/79.6 among highly active). Furthermore, RPA occupied 1.6% and 1.8% of working and weekend days, respectively, while sedentary behaviors (watching TV, using electronics for social media or entertaining, etc.) occupied 11.2% and 13.1%, respectively. Sedentary behaviors were significantly associated with high levels of systolic and diastolic blood pressure. Binary logistic regression revealed that physical inactivity (OR=3.13, 95% CI: 2.25-4.35) and sedentary behaviors (OR=2.25, CI: 1.45-3.17) were independent risk factors for high systolic and diastolic blood pressure after adjustment for other covariates. Conclusions: Physical inactivity and sedentary lifestyle were associated with a high risk of hypertension. Further research to examine the independent role of RPA in improving blood pressure levels and cultural and occupational barriers for practicing RPA are recommended. Policies should be enacted in promoting PA in the workplace that might help in decreasing the risk of hypertension among sedentary occupation workers.

Keywords: physical activity, sedentary behaviors, hypertension, workplace

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Authors: Javed Iqbal

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The growing need for energy by the human society and depletion of conventional energy sources demands a renewable, safe, infinite, low-cost and omnipresent energy source. One of the most suitable ways to solve the foreseeable world’s energy crisis is to use the power of the sun. Photovoltaic devices are especially of wide interest as they can convert solar energy to electricity. Recently the best performing solar cells are silicon-based cells. However, silicon cells are expensive, rigid in structure and have a large timeline for the payback of cost and electricity. Organic photovoltaic cells are cheap, flexible and can be manufactured in a continuous process. Therefore, organic photovoltaic cells are an extremely favorable replacement. Organic photovoltaic cells utilize sunlight as energy and convert it into electricity through the use of conductive polymers/ small molecules to separate electrons and electron holes. A major challenge for these new organic photovoltaic cells is the efficiency, which is low compared with the traditional silicon solar cells. To overcome this challenge, usually two straightforward strategies have been considered: (1) reducing the band-gap of molecular donors to broaden the absorption range, which results in higher short circuit current density (JSC) of devices, and (2) lowering the highest occupied molecular orbital (HOMO) energy of molecular donors so as to increase the open-circuit voltage (VOC) of applications devices.8 Keeping in mind the cost of chemicals it is hard to try many materials on test basis. The best way is to find the suitable material in the bulk. For this purpose, we use computational approach to design molecules based on our organic chemistry knowledge and determine their physical and electronic properties. In this study, we did DFT calculations with different options to get high open circuit voltage and after getting suitable data from calculation we finally did synthesis of a novel D–π–A–π–D type low band-gap small molecular donor material (ZOPTAN-TPA). The Aarylene vinylene based bis(arylhalide) unit containing a cyanostilbene unit acts as a low-band- gap electron-accepting block, and is coupled with triphenylamine as electron-donating blocks groups. The motivation for choosing triphenylamine (TPA) as capped donor was attributed to its important role in stabilizing the separated hole from an exciton and thus improving the hole-transporting properties of the hole carrier.3 A π-bridge (thiophene) is inserted between the donor and acceptor unit to reduce the steric hindrance between the donor and acceptor units and to improve the planarity of the molecule. The ZOPTAN-TPA molecule features a low HOMO level of 5.2 eV and an optical energy gap of 2.1 eV. Champion OSCs based on a solution-processed and non-annealed active-material blend of [6,6]-phenyl-C61-butyric acid methyl ester (PCBM) and ZOPTAN-TPA in a mass ratio of 2:1 exhibits a power conversion efficiency of 1.9 % and a high open-circuit voltage of over 1.0 V.

Keywords: high open circuit voltage, donor, triphenylamine, organic solar cells

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Authors: Shrestha Sharma, Jasjeet K. Sahni, Javed Ali, Sanjula Baboota

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Introduction: Rutin is a naturally occurring strong antioxidant molecule belonging to bioflavonoid category. Due to its free radical scavenging properties, it has been found to be beneficial in the treatment of various diseases including inflammation, cancer, diabetes, allergy, cardiovascular disorders and various types of microbial infections. Despite its beneficial effects, it suffers from the problem of low aqueous solubility which is responsible for low oral bioavailability. The aim of our study was to optimize and characterize self-nanoemulsifying drug delivery system (SNEDDS) of rutin using Box-Behnken design (BBD) combined with a desirability function. Further various antioxidant, pharmacokinetic and pharmacodynamic studies were performed for the optimized rutin SNEDDS formulation. Methodologies: Selection of oil, surfactant and co-surfactant was done on the basis of solubility/miscibility studies. Sefsol+ Vitamin E, Solutol HS 15 and Transcutol P were selected as oil phase, surfactant and co-surfactant respectively. Optimization of SNEDDS formulations was done by a three-factor, three-level (33)BBD. The independent factors were Sefsol+ Vitamin E, Solutol HS15, and Transcutol P. The dependent variables were globule size, self emulsification time (SEF), % transmittance and cumulative percentage drug released. Various response surface graphs and contour plots were constructed to understand the effect of different factor, their levels and combinations on the responses. The optimized Rutin SNEDDS formulation was characterized for various parameters such as globule size, zeta potential, viscosity, refractive index , % Transmittance and in vitro drug release. Ex vivo permeation studies and pharmacokinetic studies were performed for optimized formulation. Antioxidant activity was determined by DPPH and reducing power assays. Anti-inflammatory activity was determined by using carrageenan induced rat paw oedema method. Permeation of rutin across small intestine was assessed using confocal laser scanning microscopy (CLSM). Major findings:The optimized SNEDDS formulation consisting of Sefsol+ Vitamin E - Solutol HS15 -Transcutol HP at proportions of 25:35:17.5 (w/w) was prepared and a comparison of the predicted values and experimental values were found to be in close agreement. The globule size and PDI of optimized SNEDDS formulation was found to be 16.08 ± 0.02 nm and 0.124±0.01 respectively. Significant (p˂0.05) increase in percentage drug release was achieved in the case of optimized SNEDDS formulation (98.8 %) as compared to rutin suspension. Furthermore, pharmacokinetic study showed a 2.3-fold increase in relative oral bioavailability compared with that of the suspension. Antioxidant assay results indicated better efficacy of the developed formulation than the pure drug and it was found to be comparable with ascorbic acid. The results of anti-inflammatory studies showed 72.93 % inhibition for the SNEDDS formulation which was significantly higher than the drug suspension 46.56%. The results of CLSM indicated that the absorption of SNEDDS formulation was considerably higher than that from rutin suspension. Conclusion: Rutin SNEDDS have been successfully prepared and they can serve as an effective tool in enhancing oral bioavailability and efficacy of Rutin.

Keywords: rutin, oral bioavilability, pharamacokinetics, pharmacodynamics

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Authors: Anzal Abbas Jaffari, Wajiha Javed, Naseem Salahuddin

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Rationale: Rabies, a vaccine preventable disease, continues to be a critical public health issue as it kills around 2000-5000 people annually in Pakistan. Along with the disease spread among animals, the dog population remains a victim of brutal culling practices by the local authorities, which adversely affects ecosystem (sinking of poison in the soil – affecting vegetation & contaminating water) and the disease spread. The dog population has been exponentially rising primarily because a lack of a consolidated nationwide Animal Birth Control program and awareness among the local communities in general and children in particular. This is reflected in Pakistan’s low SARE score - 1.5, which makes the country trails behind other developing countries like Bangladesh (2.5) and Philippines (3.5).According to an estimate, the province of Sindh alone is home to almost 2.5 million dogs. The clustering of dogs in Peri-Urban areas and inner cities localities leads to an increase of reported dog bite cases in these areas specifically. Objective: Rabies Free Pakistan (RFP), which is a joint venture of Getz Pharma Private Limited and Indus Hospital & Health Network (IHHN); it was established in 2018 to eliminate Rabies from Pakistan by 2030 using the One Health Approach. Methodology: The RFP team is actively working on advocacy and policy front with both the Federal & Provincial government to ensure that all stakeholders currently involved in dog culling in Pakistan have a paradigm shift towards humane methods of vaccination and ABC. Along with the federal government, RFP aims to declare Rabies as a notifiable disease. Whereas RFP closely works with the provincial government of Sindh to initiate a province wide Rabies Control Program.RFP program follows international standards and WHO approved protocols for this program in Pakistan.RFP team has achieved various milestones in the fight against Rabies after successfully scaling up project operations and has vaccinated more than 30,000 dogs and neutered around 7,000 dogs since 2018. Recommendations: Effective implementation of Rabies program (MDV and ABC) requires a concentrated effort to address a variety of structural and policy challenges. This essentially demands a massive shift in the attitude of individuals towards rabies. The two most significant challenges in implementing a standard policy at the structural level are lack of institutional capacity, shortage of vaccine, and absence of inter-departmental coordination among major stakeholders: federal government, provincial ministry of health, livestock, and local bodies (including local councils). The lack of capacity in health care workers to treat dog bite cases emerges as a critical challenge at the clinical level. Conclusion: Pakistan can learn from the successful international models of Sri Lanka and Mexico as they adopted the One Health Approach to eliminate rabies like RFP. The WHO advised One Health approach provides the policymakers with an interactive and cross-sectoral guide, which involves all the essential elements of the eco system (including animals, humans, and other components).

Keywords: animal birth control, dog population, mass dog vaccination, one health, rabies elimination

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