Identification of bioflavonoid as fusion inhibitor of dengue virus using molecular docking approach

AbstractDengue virus with four distinct serotypes belongs to Flavivirus, poses a significant threat to human health and becomes an emerging global problem. Membrane fusion is a central molecular event during viral entry into host cell. To prevent viral infection it is necessary to interrupt the virus replication at an early stage of attachment. Dengue Virus (DENV) envelope protein experiences conformational changes and it causes the virus to fuse with host cell. Hinge region movement of domain I and II in envelope protein facilitates the fusion process. Small molecules that bind in this pocket may have the ability to interrupt the conformational changes that trigger fusion process. We chose different flavonoids (baicalein, fisetin, hesperetin, naringenin/ naringin, quercetin and rutin) that possess anti dengue activity. Molecular docking analysis was done to examine the inhibitory effect of flavonoids against envelope protein of DENV-2. Results manifest quercetin (flavonoid found in Carica papaya, apple and even in lemon) as the only flavone that can interrupt the fusion process of virus by inhibiting the hinge region movement and by blocking the conformational rearrangement in envelope protein. These novel findings using computational approach are worthwhile and will be a bridge to check the efficacy of compounds using appropriate animal model under In vivo studies. This information can be used by new techniques and provides a way to control dengue virus infection

IMPACT OF RESEARCH & DEVELOPMENT ON THE PERFORMANCE OF PHARMACEUTICAL FIRMS: EVEDENCE FROM PAKISTAN

The goal of this study is to investigate the financial performance of listed Pharmaceuticalcompanies in Pakistan impacted by different board characteristics. These board characteristics are discussedthrough two theories: agency theory and resource dependency. The understudy characteristics include research& development, independent board directors, leverage, CEO/Chair duality, board size and audit committee. Thepaper used panel regression analysis on 11 firms from period of 2010 to 2019. It was found that investment inresearch & development and audit committee have significant and positive impact on the performance of firmsas per agency theory. Whereas the characteristics like Independent directors, CEO duality, leverage and boardsize had negative impact on the performance of the firms. The study helps to clarify the Board's performancerelationship and offers academic proof of existing and future governance changes for policy makers in Pakistan.The conclusions add to the literature by presenting fresh and original perspectives into how the existingknowledge of corporate governance and financial performance is applied within a developing context ofPakistan

Association Of Electroencephalogram Patterns With Ammonia Levels In Hepatic Encephalopathy Patients

Objective: To find out the association between electroencephalogram (EEG) and hepatic encephalopathy. Methodology: This cross-sectional study included 100 patients (with the age of52.5±6.09years for males and 51.7 ± 6.10 years for females) of reported hepatic encephalopathy, visiting the medical department (indoor and OPD) at Federal Government Polyclinic Hospital, Islamabad. The study was conducted from January 2020 to May 2021. Patients who had known epileptic and structural brain lesions or strokes were excluded from the study. Statistical analysis was done using GraphPad Prism software. The significance of data (p-value or R2 value) was calculated through a two-tailed test or correlation coefficient. Results: All the patients in hepatic encephalopathy grade IV reported abnormal EEG representing triphasic waves and flattening of EEG pattern. There was no correlation observed between age, gender and hepatic encephalopathy grades. However, a significant correlation (R2= 0.9032) was observed between serum ammonia levels and hepatic encephalopathy grades. Elevated serum ammonia levels depicted the severity of hepatic encephalopathy. Overall, the percentage of patients with abnormal EEG increased with increasing grade of hepatic encephalopathy. It was quite intriguing to note that EEG, being the common method to diagnose hepatic encephalopathy grades, is not dependent on patients’ socio-economic status. Conclusion: Data concluded that serum ammonia levels are well associated with the progression of hepatic encephalopathy. Moreover, the EEG patter provides the appropriate information about the neurological abnormalities associated with the severity of hepatic encephalopathy. Hence, serum ammonia levels and EEG both should accurately be used as indicators for diagnosis and monitoring the response to the treatment of various grades of hepatic encephalopathy. Data warrant further investigations to get a better insight into hepatic encephalopathy's relationship with EEG patterns through the inclusion of molecular parameters

Impact of Bronchoscopic Lavage and Aggressive Chest Physiotherapy on Clinical Pulmonary Infection Score of Patients of Severe Traumatic Brain Injury

Introduction:  Traumatic brain injury patients present in the emergency room with a variable conscious status depending upon the severity of the injury. The process of aspiration starts from the scene of trauma as the patients with Traumatic brain injury and chest trauma have higher rates of aspiration pneumonia. Materials and Methods:  We conducted a prospective study to assess the impact of bronchoscopy lavage and aggressive chest physiotherapy on the Critical Pulmonary Infection Score of Patients with Severe Traumatic Brain Injury in the Neurocritical Care Unit. Patients with severe traumatic brain injury who met the inclusion criteria were enrolled in the study. Patients of both genders, ages ranging from 05 – 70 years were included in the study. Results:  48 patients who met the inclusion criteria were enrolled in the study. 8 patients expired before 7 days and were excluded from the study. 88% were male and 12 % were females. Out of 40 patients, 30 were ventilated and 10 were managed without ventilation. Brain contusion was the most common CT scan finding. Out of 40 patients, 18 underwent surgical intervention, with decompressive hemicraniectomy being the most commonly performed procedure. Out of 40 patients, 32 patients underwent bronchoscopy. 8 patients out of 32 had more than two sessions of bronchoscopy. Conclusion:  As Critical Pulmonary Infection Score is an important indicator for pneumonia in the neurocritical care unit, the importance of standardized chest care with the help of bronchoscopic lavage and chest physiotherapy in keeping the Critical Pulmonary Infection Score on the lower side can prevent patients from developing life-threatening pneumonia

Formulating DNA Chains Using Effective Calculability

Nearly all computational algorithms are modeled as ‘Effective Calculability’ i.e Finite State Model and Lambda Calculus. Effectively calculable function Comprise of three parts: the info, the yield, and the finite state function or transition function. It takes stream of data as input and translates to specific output, as defined by transition function [1]. The aftereffect of this conversion is another flood of information or the yield. Both i.e info and yield information streams comprise of arrangements of characters and are known as strings. DNA exhibits a property of being a pattern of strings. Automatic machines like automata and Lambda Calculus or simply the Effective Calculability [8] can be an efficient approach to study these patterns. By the introduction of Effective Calculability we can express the pattern of DNA in much better way. The transition function runs stepwise each character of the information string to produce the output string. The transformations achieved by the transition function are relatively simple in nature. Complex computations and operations can be affected by linking together several Effective Calculability switches so that the output string of one switch becomes the input string of another switch

Prevalence of Black Quarter in Association with Patho-Morphological Alterations in Affected Tissues at Different Zones of Punjab-Pakistan

Background: Blackleg or Black Quarter (BQ) is a serious bacterial disease caused by Clostridium chauvoei. It causes edematous and gaseous changes in skeletal muscles of animals. The study was designed to find prevalence of BQ in 6 districts of Punjab, Pakistan from June 2018 to June 2019.Methods: Animals were randomly monitored, and selected in each union council regardless of age, sex and species, but lameness and hyperthermia were the selection parameters. A proforma was used to record the experimental readings of each animal. A total of 1500 swab samples from bovines (cattle and buffaloes) were processed through conventional PCR and culture sensitivity tests to examine the comparative diagnostic efficacy and suitability of the test.Results: Sensitivity and specificity of culture tests were 87.6% and 34.19% respectively, whereas PCR demonstrated 81% and 47.3% results for the said aspects, respectively. Alpha toxin gene (Ccta) was amplified at 52.2oC yielding an amplicon size of 1400 base pairs. Area wise and season wise prevalence of each animal was also determined. The prevalence of BQ in cattle was significantly higher (P 0.05) in Lahore (0%) and Nankana Sahib (8%) which belonged to the canal irrigated zones.Conclusion: There was higher prevalence of BQ in different areas of Punjab, Pakistan that show the higher risk of disease transmission. A systematic surveillance system is essential to regularly monitor the disease incidence and prevalence in these areas of Pakistan.Keywords: Black Quarter; Prevalence; Pathological; Ruminants;  Zone

Determinants of business success of small and medium enterprises

The small and medium enterprises (SMEs) play critical role in the development of the country. The success of SMEs depends on number of factors. This study examines the role of key factors in the success of SMEs in Pakistan. The study also investigates the relationship between SMEs success and its determinants. Target population of the study was SMEs operating in different lines of business from service to manufacturing. Sample size of this study was 520 small and medium lines of businesses. Responses of the subjects were collected through questionnaires. SPSS software is used for analysis. This study concludes that there is a significant relationship between business success and its determinants. The result also shows that financial resources are the most important factor in the success of business perceived by small and medium enterprises. The success of small and medium enterprises can contribute significantly in the development of the country

The Karachi intracranial stenosis study (KISS) Protocol: an urban multicenter case-control investigation reporting the clinical, radiologic and biochemical associations of intracranial stenosis in Pakistan.

Background: Intracranial stenosis is the most common cause of stroke among Asians. It has a poor prognosis with a high rate of recurrence. No effective medical or surgical treatment modality has been developed for the treatment of stroke due to intracranial stenosis. We aim to identify risk factors and biomarkers for intracranial stenosis and to develop techniques such as use of transcranial doppler to help diagnose intracranial stenosis in a cost-effective manner. Methods/Design: The Karachi Intracranial Stenosis Study (KISS) is a prospective, observational, case-control study to describe the clinical features and determine the risk factors of patients with stroke due to intracranial stenosis and compare them to those with stroke due to other etiologies as well as to unaffected individuals. We plan to recruit 200 patients with stroke due to intracranial stenosis and two control groups each of 150 matched individuals. The first set of controls will include patients with ischemic stroke that is due to other atherosclerotic mechanisms specifically lacunar and cardioembolic strokes. The second group will consist of stroke free individuals. Standardized interviews will be conducted to determine demographic, medical, social, and behavioral variables along with baseline medications. Mandatory procedures for inclusion in the study are clinical confirmation of stroke by a healthcare professional within 72 hours of onset, 12 lead electrocardiogram, and neuroimaging. In addition, lipid profile, serum glucose, creatinine and HbA1C will be measured in all participants. Ancillary tests will include carotid ultrasound, transcranial doppler and magnetic resonance or computed tomography angiogram to rule out concurrent carotid disease. Echocardiogram and other additional investigations will be performed at these centers at the discretion of the regional physicians. Discussion: The results of this study will help inform locally relevant clinical guidelines and effective public health and individual interventions