Enhancing Knowledge Acquisition in Pharmaceutical Organisations based in Pakistan

Absorptive Capacity (ACAP) depicts the sequential order of activities connecting externally generated knowledge into an organisation; this involves a company’s ability to acquire new knowledge from an external source, assimilate and transform it, and eventually exploit it via its industrial processes and products/services. The sandwiched role of middle managers, being interlinked between decision makers and employees, has been argued as vital to organisational success. However, their role is often viewed as having conflicts astride management i.e. between employees and decision makers. This study, using a thematic analysis approach, explores and identifies the common and conflicting role of middle managers, as viewed by different respondents in organisational hierarchies. Results, based on a sample of 33 employees operating in the Pakistan Pharmaceutical sector, indicate that conflicting roles of middle managers also persist with more common roles in organisations

Down-regulation of IRES containing 5'UTR of HCV genotype 3a using siRNAs

<p>Abstract</p> <p>Background</p> <p>Hepatitis C virus (HCV) is a major causative agent of liver associated diseases leading to the development of hepatocellular carcinoma (HCC) all over the world and genotype-3a responsible for most of the cases in Pakistan. Due to the limited efficiency of current chemotherapy of interferon-α (IFN-α) and ribavirin against HCV infection alternative options are desperately needed out of which the recently discovered RNAi represent a powerful silencing approach for molecular therapeutics through a sequence-specific RNA degradation process to silence virus infection or replication. HCV translation is mediated by a highly conserved internal ribosome entry site (IRES) within the 5'UTR region making it a relevant target for new drug development.</p> <p>Materials and methods</p> <p>The present study was proposed to assess and explore the possibility of HCV silencing using siRNA targeting 5'UTR. For this analysis full length HCV 5'UTR of HCV-3a (pCR3.1/5'UTR) was tagged with GFP protein for <it>in vitro </it>analysis in Huh-7 cells. siRNA targeting 5'UTR were designed, and tested against constructed vector in Huh-7 cell line both at RNA and Protein levels. Furthermore, the effect of these siRNAs was confirmed in HCV-3a serum infected Huh-7 cell line.</p> <p>Results</p> <p>The expression of 5'UTR-GFP was dramatically reduced both at mRNA and protein levels as compared with Mock transfected and control siRNAs treated cells using siRNAs against IRES of HCV-3a genotype. The potential of siRNAs specificity to inhibit HCV-3a replication in serum-infected Huh-7 cells was also investigated; upon treatment with siRNAs a significant decrease in HCV viral copy number and protein expression was observed.</p> <p>Conclusions</p> <p>Overall, the present work of siRNAs against HCV 5'UTR inhibits HCV-3a expression and represents effective future therapeutic opportunities against HCV-3a genotype.</p

A brief review on molecular, genetic and imaging techniques for HCV fibrosis evaluation

<p>Abstract</p> <p>Background</p> <p>Chronic HCV is one of the major causes of morbidity and mortality in the present day world. The assessment of disease progression not only provides useful information for diagnosis and therapeutic supervision judgment but also for monitoring disease. Different invasive and non invasive methods are applied to diagnose the disease from initial to end stage (mild fibrosis to cirrhosis). Although, liver biopsy is still considered as gold standard to identify liver histological stages, an assessment of the disease development based on non-invasive clinical findings is also emerging and this may replace the need of biopsy in near future. This review gives brief insight on non-invasive methods currently available for predicting liver fibrosis in HCV with their current pros and cons to make easier for a clinician to choose better marker to assess liver fibrosis in HCV infected patients.</p> <p>Methods</p> <p>More than 200 studies regarding invasive and noninvasive markers available for HCV liver disease diagnosis were thoroughly reviewed. We examined year wise results of these markers based on their sensitivity, specificity, PPV, NPV and AUROCs.</p> <p>Results</p> <p>We found that in all non-invasive serum markers for HCV, FibroTest, Forn's Index, Fibrometer and HepaScore have high five-year predictive value but with low AUROCs (0.60~0.85) and are not comparable to liver biopsy (AUROC = 0.97). Even though from its beginning, Fibroscan is proved to be best with high AUROCs (> 0.90) in all studies, no single noninvasive marker is able to differentiate all fibrosis stages from end stage cirrhosis. Meanwhile, specific genetic markers may not only discriminate fibrotic and cirrhotic liver but also differentiate individual fibrosis stages.</p> <p>Conclusions</p> <p>There is a need of marker which accurately determines the stage based on simplest routine laboratory test. Genetic marker in combination of imaging technique may be the better non invasive diagnostic method in future.</p

A roadmap to develop dementia research capacity and capability in Pakistan: a model for low- and middle-income countries

Objective To produce a strategic roadmap for supporting the development of dementia research in Pakistan. Background While global research strategies for dementia research already exist, none is tailored to the specific needs and challenges of low- and middle-income countries (LMIC) like Pakistan. Methods We undertook an iterative consensus process with lay and professional experts to develop a Theory of Change-based strategy for dementia research in Pakistan. This included Expert Reference Groups (ERGs), strategic planning techniques, a “research question” priority survey, and consultations with Key Opinion Leaders. Results We agreed on ten principles to guide dementia research in Pakistan, emphasizing pragmatic, resource sparing, real-world approaches to support people with dementia, both locally and internationally. Goals included capacity/capability building. Priority research topics included raising awareness and understanding of dementia, and improving quality of life. Conclusion This roadmap may be a model for other LMIC health ecosystems with emerging dementia research cultures

Duplex PCR assay for the detection of avian adeno virus and chicken anemia virus prevalent in Pakistan

Avian Adeno viruses and Chicken Anemia Viruses cause serious economic losses to the poultry industry of Pakistan each year. Timely and efficient diagnosis of the viruses is needed in order to practice prevention and control strategies. In the first part of this study, we investigated broilers, breeder and Layer stocks for morbidity and mortality rates due to AAV and CAV infections and any co-infections by examining signs and symptoms typical of their infestation or post mortem examination. In the second part of the study, we developed a duplex PCR assay for the detection of AAV and CAV which is capable to simultaneously detect both the viral types prevalent in Pakistan with high sensitivity and 100% specificity

A solvable model for the diffusion and reaction of neurotransmitters in a synaptic junction

<p>Abstract</p> <p>Background</p> <p>The diffusion and reaction of the transmitter acetylcholine in neuromuscular junctions and the diffusion and binding of Ca²⁺in the dyadic clefts of ventricular myocytes have been extensively modeled by Monte Carlo simulations and by finite-difference and finite-element solutions. However, an analytical solution that can serve as a benchmark for testing these numerical methods has been lacking.</p> <p>Result</p> <p>Here we present an analytical solution to a model for the diffusion and reaction of acetylcholine in a neuromuscular junction and for the diffusion and binding of Ca²⁺in a dyadic cleft. Our model is similar to those previously solved numerically and our results are also qualitatively similar.</p> <p>Conclusion</p> <p>The analytical solution provides a unique benchmark for testing numerical methods and potentially provides a new avenue for modeling biochemical transport.</p

RetroSpective cohort stUdy of PD-L1 expression in REcurrent and/or MEtastatic squamous cell carcinoma of the head and neck (SUPREME-HN)

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‘Smart’ BLE wearables for digital contact tracing in care homes during the COVID-19 pandemic—a process evaluation of the CONTACT feasibility study

Background Rapid and mass transmission of the SARS-CoV-2 virus amongst vulnerable people led to devastating effects from COVID-19 in care homes. The CONTACT intervention introduced Bluetooth Low Energy ‘smart’ wearable devices (BLE wearables) as a basis for automated contact tracing in, and feedback on infection risks and patterns to, care homes to try and improve infection prevention and control (IPC). We planned a cluster randomised controlled trial (RCT) of CONTACT. To be feasible, homes had to adopt CONTACT’s technology and new ways of working. This paper reports on the process evaluation conducted alongside CONTACT’s feasibility study and explains why it lacked the feasibility and acceptability for a definitive RCT. Methods This mixed method process evaluation used Normalisation Process Theory (NPT) qualitative (interviews, field notes, study case report forms and documents, and observation) and quantitative (survey instruments, counts of activity) data to plan, implement, and analyse the mechanisms, effects, and contextual factors that shaped the feasibility and acceptability of the CONTACT intervention. Results Thirteen themes within four core NPT constructs explained CONTACT’s lack of feasibility. Coherence: the home’s varied in the scale and extent of commitment and understanding of the technology and study procedures. Leadership credibility was important but compromised by competing priorities. Management and direct care staff saw CONTACT differently. Work to promote (cognitive participation) and enact (collective action) CONTACT was burdensome and failed to be prioritised over competing COVID-19-related demands on time and scarce human and cognitive resources. Ultimately, staff appraisal of the value of CONTACT-generated information and study procedures (reflexivity) was that any utility for IPC was insufficient to outweigh the perceived burden and complexity involved. Conclusions Despite implementation failure, dismissing BLE wearables’ potential for contact tracing is premature. In non-pandemic conditions, with more time, better co-design and integration of theory-driven implementation strategies tailored to care homes’ unique contexts, researchers could enhance normalisation in readiness for future pandemic challenges