Simian Virus 40 Large T Antigen as a Model to Test the Efficacy of Flouroquinolones against Viral Helicases

Simian virus 40 large T-antigen (SV40 LT-Ag) is a 708 amino acid nuclear phosphoprotein. Among many functions of LT-Ag is its ability to perform as an ATPase-helicase, catalyzing the unwinding of viral genome during replication. The LT-Ag has been employed in the studies of helicase structure and function, and has served as a model helicase for the screening of antiviral drugs that target viral helicase. In this study, using in vitro enzyme assays and in silico computer modeling, we screened a batch of 18 fluoroquinolones to assess their potential as antivirals by virtue of their inhibition of the LT-Ag helicase. We found all fluoroquinolones to be inhibitory to the helicase activity of LT-Ag. In our docking analysis, most of these tested drugs showed similarity in their interactions with LT-Ag. Our study shows the potential of fluoroquinolones as antiviral drugs and of SV40 LT-Ag as a model protein for screening drugs against viral helicases

An in silico approach to analyze HCV genotype-specific binding-site variation and its effect on drug-protein interaction

Genotype variation in viruses can affect the response of antiviral treatment. Several studies have established approaches to determine genotype-specific variations; however, analyses to determine the effect of these variations on drug-protein interactions remain unraveled. We present an in-silico approach to explore genotype-specific variations and their effect on drug-protein interaction. We have used HCV NS3 helicase and fluoroquinolones as a model for drug-protein interaction and have investigated the effect of amino acid variations in HCV NS3 of genotype 1a, 1b, 2b and 3a on NS3-fluoroquinolone interaction. We retrieved 687, 667, 101 and 248 nucleotide sequences of HCV NS3 genotypes 1a, 1b, 2b, and 3a, respectively, and translated these into amino acid sequences and used for genotype variation analysis, and also to construct 3D protein models for 2b and 3a genotypes. For 1a and 1b, crystal structures were used. Drug-protein interactions were determined using molecular docking analyses. Our results revealed that individual genotype-specific HCV NS3 showed substantial sequence heterogeneity that resulted in variations in docking interactions. We believe that our approach can be extrapolated to include other viruses to study the clinical significance of genotype-specific variations in drug-protein interactions

CLINICOPATHOLOGICAL CHARACTERISTICS OF PATIENTS WITH SYNCHRONOUS PRIMARY OVARIAN AND ENDOMETRIAL CANCERS

Purpose: Synchronous primary endometrial and ovarian cancers are infrequent. The objective of this study is to evaluate clinicopathological characteristics of synchronous endometrial and ovarian cancers treated in our institution.Materials and Methods: The clinicopathological characteristics of 12 patients with synchronous ovarian and endometrial cancers treated at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan, from July 2005 to July 2015, were reviewed retrospectively in depth from hospital database. The WHO committee classification was used for the histologic determination and staged based on International Federation of Gynaecology and Obstetrics (FIGO) staging. Results: The median age at the time of diagnosis was 50 years (range 23–66 years). The incidence of synchronous primary endometrial and ovarian cancers was 2.01% in patients with endometrial cancer. A total of seven patients were menopausal (58%) and eight patients were nulliparous (66%); the median body mass index (BMI) was 29 kg/m2 (range, 20–38). Abnormal uterine bleeding was the most common presenting symptom. According to FIGO stage, 10 cases of endometrial were Stage I/II (84%) and two cases were Stage III (16%). Of the ovarian cancers, nine cases were Stage I/II (83.3%) and two cases were Stage III (16.7%). Endometrial cancer was the main pathological type in uterine carcinoma (86%) followed by serous carcinoma (14%), and similarly, for ovarian cancer, endometrial was the most common pathology (67%) followed by serous/clear cell (16%) and mucinous (16.7%). Most endometrial and ovarian primaries in our series were Grade I and II tumours, 83% and 66%, respectively. 8 patients (66%) had similar histology in both primaries. All patients underwent surgical intervention. Only one patient did not receive any post-operative adjuvant therapy. 10 patients received platinum-based adjuvant chemotherapy and six patients received adjuvant radiotherapy. Conclusion: Synchronous primary endometrial and ovarian cancers are infrequent and distinct set of patients. Abnormal per vaginal bleed was the most common symptom which helped in early detection. Majority of the patients belong to concordant endometrial histology, low grade, had younger age and high BMI. Treatment should be tailored to the stage, histology and grade of the individual tumours. Key words: Endometrial cancer, ovarian cancer, synchronous tumour

Malpractice awareness among surgeons at a teaching hospital in Pakistan

BACKGROUND: The duty of a doctor to take care presumes the person who offers medical advice and treatment to unequivocally possess the skills and knowledge to do so. However, a sense of responsibility cannot be guaranteed in the absence of accountability, which in turn requires a comprehensive medical law system to be in place. Such a system is almost non-existent in Pakistan. Keeping the above in mind, we designed this study to assess the knowledge, attitudes and practices of surgeons regarding malpractice at a tertiary care center in Pakistan. METHODS: This was an observational, cross-sectional, questionnaire-based study conducted during a three month period from 31st March, 2012 to 30th June, 2012 at Civil Hospital, Karachi. Surgeons who were available during the period of our study and had been working in the hospital for at least 6 months were included. Self-administered questionnaires were distributed after seeking informed, written consent. The specialties included were general surgery, cardiothoracic surgery, neurosurgery, ophthalmology, otolaryngology, plastic surgery, pediatric surgery, orthopedic surgery, oral and maxillofacial surgery and gynecology and obstetrics. The study questionnaire comprised of four sections. The first section was concerned with the demographics of the surgeons. The second section analyzed the knowledge of the respondents regarding professional negligence and malpractice. The third section assessed the attitudes surgeons with regard to malpractice. The last section dealt with the general and specific practices and experiences of surgeons regarding malpractice. RESULTS: Of the 319 surgeons interviewed, 68.7% were oblivious of the complete definition of malpractice. Leaving foreign objects inside the patient (79.6%) was the most commonly agreed upon form of malpractice, whereas failure to break news in entirety (43.9%) was most frequently disagreed. In the event of a medical error, majority (67.7%) were ready to disclose their error to the patient. The most common perceived reason for not disclosing the error was threat of a claim or assault (90.9%). Majority (68.3%) believed that malpractice had a negative effect on reputation. Only 13(4.1%) had received at least one legal claim for damages. Only about three-fourths (75.5%) had the habit of frequently obtaining informed consent from the patients. 83(26.0%) expressed reluctance in accepting a case that was deemed to be difficult. Financial gains and liabilities were responsible for biased approach in 8.5% and 12.2% of the respondents respectively. CONCLUSION: There is a dire need of programs aimed at increasing awareness among practicing surgeons in our setup. Proactive measures are required for the formulation of an efficient system of litigation. Physician accountability will not only arouse a greater sense of responsibility in them, but will also augment the confidence placed by patients on the healthcare system

A Time Series Analysis of Energy Consumption, Energy Prices and Economic Growth in Pakistan

The present study is conducted to investigate the impact of Energy Consumption (EC) on the Economic Growth (EG) in Pakistan by using a trivariate model. Time series data of macroeconomic determinants of Energy Consumption (EC), Energy Prices (EP) and Economic Growth (EG) are used to analyze the linkage among the variables. Annual data are collected from different published sources like World Development Indicators (WDI), BP Statistical Review and Economic Surveys of Pakistan for the period 1971-2014. Augmented Dickey Fuller (ADF) unit root test and Phillips Perron unit root test are used to examine the stationarity of data and all the variables are found stationary in differenced form. Short run and long run linkage among the variables is examined through Johansen co-integration test and the results confirm the existence of one co-integrating vector among the variables. Granger causality test under Vector Error Correction Model (VECM) is applied to observe the direction of between Energy Consumption (EC), Energy Prices (EP) and economic growth (EG). Unidirectional causality is found from Economic Growth (EG) to Energy Consumption (EC) and unidirectional causality from Energy Consumption (EC) to Energy Prices (EP) is also found in short run as well as in long run. On the basis of result of the study, conservation policy regarding to the Energy Consumption (EC) is suggested with a negligible or no effect on Economic Growth (EG)

Psychological Drivers of Alternative Fuel Vehicles' Adoption and Ecologically Responsible Use

Environmental problems caused by global warming are becoming alarming with every passing day. To curb greenhouse gas (GhG) emissions, promoting alternative fuel vehicles (AFVs) and sustainable transport mode choices is critical. This study explores the predictors of eco-social purchase, use, and conservation intentions in a developing country by employing an extended model of the theory of planned behaviour (TPB). Using a self-administered survey technique, data were collected from a nationally representative sample of 1372 customers of three leading automobile manufacturers from eight big cities of Pakistan. Partial Least Squares Structural Equation Modelling (PLS-SEM) was applied to test the measurement and structural models. Results showed that the extended model of TPB received support in the context of Pakistani culture and for the targeted behaviours related to eco-social purchase, use, and conservation intentions concerning AFVs. Implications for marketers and theoretical contribution are discussed at the end

Image forgery detection using deeplearning by recompressing the images

Capturing images has been increasingly popular in recent years, owing to the widespread availability of cameras. Images are essential in our daily lives because they contain a wealth of information, and it is often required to enhance images to obtain additional information. A variety of tools are available to improve image quality; nevertheless, they are also frequently used to falsify images, resulting in the spread of misinformation. This increases the severity and frequency of image forgeries, which is now a major source of concern. Numerous traditional techniques have been developed over time to detect image forgeries. In recent years, convolutional neural networks (CNNs) have received much attention, and CNN has also influenced the field of image forgery detection. However, most image forgery techniques based on CNN that exist in the literature are limited to detecting a specific type of forgery (either image splicing or copy-move). As a result, a technique capable of efficiently and accurately detecting the presence of unseen forgeries in an image is required. In this paper, we introduce a robust deep learning based system for identifying image forgeries in the context of double image compression. The difference between an image’s original and recompressed versions is used to train our model. The proposed model is lightweight, and its performance demonstrates that it is faster than state-of-the-art approaches. The experiment results are encouraging, with an overall validation accuracy of 92.23%

Prevalence of HER-2/ neu receptor amplification and its effects over prognosis of the patients with breast cancer

Background: The diagnosis and prognosis of patients with breast cancer is routinely carried out with biopsy of growth by H&E staining but it is not commonly practice with various immunomarkers including HER2/neu. However HER2/neu association in breast tumour patients with prognosis has not been studied much, so this study is aim to evaluate the frequency of HER2 (human epidermal growth factor receptor) amplification and its effects over prognosis among the patients with breast cancer.Methods: After ethical approval, retrospective observational study was conducted from October 2014 to September 2017. All operated patients with biopsy proven breast cancer, the patients having any stage of disease, with sufficient data present in hospital record and patients who received neo-adjuvant chemo-therapy/radio-therapy were included. Patients unfit for surgery due to co-morbidities like cardio renal diseases and patients having insufficient hospital record or who missed follow-ups were excluded. SPSS version 20.0 was used for data analysis for data analysis with qualitative data presented as frequency and percentages.Results: A Total 120 patients, 48(40%) had HER-2/ neu positive. Among the HER2 +ve patients, 17(35.4%) had local recurrence within 03 years while 21(43.7%) cases had distant recurrence. The disease free survival rate in 03 years was observed in 22(45.83%) out of 48 HER2 +ve cases.Conclusions: Study reveals 40% patients had HER-2/neu positive expression and was associated with poor outcomes and disease free survival time period in comparison to patient with HER-2/ neu negative

A Time Series Analysis of Energy Consumption, Energy Prices and Economic Growth in Pakistan

The present study is conducted to investigate the impact of Energy Consumption (EC) on the Economic Growth (EG) in Pakistan by using a trivariate model. Time series data of macroeconomic determinants of Energy Consumption (EC), Energy Prices (EP) and Economic Growth (EG) are used to analyze the linkage among the variables. Annual data are collected from different published sources like World Development Indicators (WDI), BP Statistical Review and Economic Surveys of Pakistan for the period 1971-2014. Augmented Dickey Fuller (ADF) unit root test and Phillips Perron unit root test are used to examine the stationarity of data and all the variables are found stationary in differenced form. Short run and long run linkage among the variables is examined through Johansen co-integration test and the results confirm the existence of one co-integrating vector among the variables. Granger causality test under Vector Error Correction Model (VECM) is applied to observe the direction of between Energy Consumption (EC), Energy Prices (EP) and economic growth (EG). Unidirectional causality is found from Economic Growth (EG) to Energy Consumption (EC) and unidirectional causality from Energy Consumption (EC) to Energy Prices (EP) is also found in short run as well as in long run. On the basis of result of the study, conservation policy regarding to the Energy Consumption (EC) is suggested with a negligible or no effect on Economic Growth (EG)