Platelet biology in regenerative medicine of skeletal muscle

Platelet‐based applications such as platelet‐rich plasma (PRP) and platelet releasate have gained unprecedented attention in regenerative medicine across a variety of tissues as of late. The rationale behind utilizing PRP originates in the delivery of key cytokines and growth factors from α‐granules to the targeted area, which in turn act as cell cycle regulators and promote the healing process across a variety of tissues. The aim of the present review is to assimilate current experimental evidence on the role of platelets as biomaterials in tissue regeneration, particularly in skeletal muscle, by integrating findings from human, animal and cell studies. This review is composed of 3 parts: firstly, we review key aspects of platelet biology that precede the preparation and use of platelet‐related applications for tissue regeneration. Secondly, we critically discuss relevant evidence on platelet‐mediated regeneration in skeletal muscle focusing on findings from (i) clinical trials, (ii) experimental animal studies and (iii) cell culture studies; and thirdly, we discuss the application of platelets in the regeneration of several other tissues including tendon, bone, liver, vessels and nerve. Finally, we review key technical variations in platelet preparation that may account for the large discrepancy in outcomes from different studies. This review provides an up‐to‐date reference tool for biomedical and clinical scientists involved in platelet‐mediated tissue regenerative applications

Conditions of Teaching and Research in Economics: Some Preliminary Findings

This paper reports onthe preliminary findings of a study initiated two years ago, at the initiative of the P.LD.E. to review the problems of teaching and research in economics and related subjects (ERS)! during the last two decades. The need for such a study has been felt for some time not only because of the common perception of declining standards in higher education generally and, economics, in particular, but also from the perceived competition economics has faced from other disciplines, especially business studies and computer science as a passport to the job market. After having enjoyed a relatively robust period of growth in the 1960s largely through the assistance of foreign donors such as the Ford Foundation, ERS in Pakistan have suffered in their development not only from the comparative paucity of resources allocated to them, but also as a result of an adverse change in the perceptions about the primacy of their usefulness for policy purposes. The demand for economics has also suffered some decline as a result of the diminished importance of the public sector and of planned development during the last two decades. While special branches of economics, such as finance, project evaluation, transport and energy economics have shown increased demand, mainly in the private sector or donor-related institutions, the demand for general economic analysts is not as strong as in the past and does not provide many gainful opportunities for professional advancement. Due to the continued disadvantage in terms of salaries and other rewards, the academic profession, remains unattractive

Compliance to HIV treatment monitoring guidelines can reduce laboratory costs

Background: Panel tests are a predetermined group of tests commonly requested together to provide a comprehensive and conclusive diagnosis, for example, liver function test (LFT). South African HIV antiretroviral treatment (ART) guidelines recommend individual tests for toxicity monitoring over panel tests. In 2008, the National Health Laboratory Services (NHLS) request form was redesigned to list individual tests instead of panel tests and removed the ‘other tests’ box option to facilitate efficient ART laboratory monitoring.Objectives: This study aimed to demonstrate changes in laboratory expenditure, for individual and panel tests, for ART toxicity monitoring.Method: NHLS Corporate Data Warehouse (CDW) data were extracted for HIV conditional grant accounts to assess ART toxicity monitoring laboratory expenditure between 2010/2011 and 2014/2015. Data were classified based on the tests requested, as either panel (LFT or urea and electrolytes) or individual (alanine transaminase or creatinine) tests.Results: Expenditure on panel tests reduced from R340 million in 2010/2011 to R140m by 2014/2015 (reduction of R204m) and individual test expenditure increased from R34m to R76m (twofold increase). A significant reduction in LFT panel expenditure was noted, reducing from R322m in 2010/2011 to R130m in 2014/2015 (60% reduction).Conclusion: Changes in toxicity monitoring guidelines and the re-engineering of the NHLS request form successfully reduced expenditure on panel tests relative to individual tests. The introduction of order entry systems could further reduce unnecessary laboratory expenditure

A PROSPECTIVE STUDY OF CLINICAL PROFILE OF STROKE IN A TERTIARY CARE HOSPITAL

ABSTRACTObjective: The objective of the work was to study the clinical profile of stroke in a tertiary care hospital.Methods: A prospective observational study on stroke was carried out for a period of 6-month (May 2015 to October 2015). A total of 241 inpatientsfrom Shri Preethi Hospital were incorporated in the study. The data were collected and evaluated by reviewing case files and patient interview.Result and Conclusion: Out of 241 patients, an incidence of ischemic stroke was found to be higher. The occurrence of stroke steeply rises with agewith male predominance. The burden of stroke tends to be more in rural, illiterate, and low socioeconomic status population. The study reveals riskfactors such as sedentary lifestyle, previous and family history of stroke, underlying disease like hypertension, diabetes. The circadian pattern in onsetshowed a significant peak in morning (6 am-12 pm) for Ischemic and afternoon (12 pm-6 pm) for hemorrhagic stroke. Topographic distribution ofcerebral infract and hemorrhage was found to be in parietal lobe and periventricular white matter, respectively. Mostly prescribed medication forischemic and hemorrhagic patients was antihypertensive and mannitol, respectively. The contraindication for thrombolytic therapy was found to below economic status and average delay in time of presentation to hospital. The study highlights the need for aggressive management of traditionalrisk factors, need for extensive work up in patient to find etiologies and need for more active interventions in community for the prevention of stroke.Keywords: Ischemic, Hemorrhagic, Circadian pattern, Antihypertensive

A comparative analysis of active learning for biomedical text mining

Data Availability Statement: The code and data are available from https://github.com/usmaann (accessed on 14 March 2021).Copyright © 2021 by the authors. An enormous amount of clinical free-text information, such as pathology reports, progress reports, clinical notes and discharge summaries have been collected at hospitals and medical care clinics. These data provide an opportunity of developing many useful machine learning applications if the data could be transferred into a learn-able structure with appropriate labels for supervised learning. The annotation of this data has to be performed by qualified clinical experts, hence, limiting the use of this data due to the high cost of annotation. An underutilised technique of machine learning that can label new data called active learning (AL) is a promising candidate to address the high cost of the label the data. AL has been successfully applied to labelling speech recognition and text classification, however, there is a lack of literature investigating its use for clinical purposes. We performed a comparative investigation of various AL techniques using ML and deep learning (DL)-based strategies on three unique biomedical datasets. We investigated random sampling (RS), least confidence (LC), informative diversity and density (IDD), margin and maximum representativeness-diversity (MRD) AL query strategies. Our experiments show that AL has the potential to significantly reducing the cost of manual labelling. Furthermore, pre-labelling performed using AL expediates the labelling process by reducing the time required for labelling.This research received no external funding

Programmatic implications of implementing the relational algebraic capacitated location (RACL) algorithm outcomes on the allocation of laboratory sites, test volumes, platform distribution and space requirements

Introduction: CD4 testing in South Africa is based on an integrated tiered service delivery model that matches testing demand with capacity. The National Health Laboratory Service has predominantly implemented laboratory-based CD4 testing. Coverage gaps, over-/under-capacitation and optimal placement of point-of-care (POC) testing sites need investigation. Objectives: We assessed the impact of relational algebraic capacitated location (RACL) algorithm outcomes on the allocation of laboratory and POC testing sites. Methods: The RACL algorithm was developed to allocate laboratories and POC sites to ensure coverage using a set coverage approach for a defined travel time (T). The algorithm was repeated for three scenarios (A: T = 4; B: T = 3; C: T = 2 hours). Drive times for a representative sample of health facility clusters were used to approximate T. Outcomes included allocation of testing sites, Euclidian distances and test volumes. Additional analysis included platform distribution and space requirement assessment. Scenarios were reported as fusion table maps. Results: Scenario A would offer a fully-centralised approach with 15 CD4 laboratories without any POC testing. A significant increase in volumes would result in a four-fold increase at busier laboratories. CD4 laboratories would increase to 41 in scenario B and 61 in scenario C. POC testing would be offered at two sites in scenario B and 20 sites in scenario C. Conclusion: The RACL algorithm provides an objective methodology to address coverage gaps through the allocation of CD4 laboratories and POC sites for a given T. The algorithm outcomes need to be assessed in the context of local conditions

District and sub-district analysis of cryptococcal antigenaemia prevalence and specimen positivity in KwaZulu-Natal, South Africa

Background: Cryptococcal meningitis (CM) is a leading cause of mortality among HIV-positive South Africans. Reflex cryptococcal antigen (CrAg) testing of remnant plasma was offered as a pilot prior to implementation in October 2016 in KwaZulu-Natal province. The national reflex CrAg positivity was 5.4% compared to 7.3% for KwaZulu-Natal. Objectives: The aim of this study was to interrogate CrAg positivity by health levels to identify hotspots. Method: Data for the period October 2016 to June 2017 were analysed. Health district CrAg positivity and prevalence were calculated, with the latter using de-duplicated patient data. The district CrAg positivity and the number of CrAg-positive specimens per health facility were mapped using ArcGIS. For districts with the highest CrAg positivity, a sub-district CrAg positivity analysis was conducted. Results: The provincial CrAg positivity was 7.6%. District CrAg positivity ranged from 5.7% (Ugu) to 9.6% (Umkhanyakude) with prevalence ranging from 5.5% (Ugu) to 9.7% (Umkhanyakude). The highest CrAg positivity was reported for the Umkhanyakude (9.6%) and King Cetswayo (9.5%) districts. In these two districts, CrAg positivity of 10% was noted in the Umhlabuyalingana (10.0%), Jozini (10.2%), uMhlathuze (10.5%) and Nkandla (10.8%) subdistricts. In these subdistricts, 135 CrAg-positive samples were reported for the Ngwelezane hospital followed by 41 and 43 at the Hlabisa and Manguzi hospitals respectively. Conclusion: Cryptococcal antigen positivity was not uniformly distributed at either the district or sub-district levels, with identified facility hotspots in the Umkhanyakude and King Cetswayo districts. This study demonstrates the value of laboratory data to identify hotspots for planning programmatic interventions

Platelet releasate promotes skeletal myogenesis by increasing muscle stem cell commitment to differentiation and accelerates muscle regeneration following acute injury

Aim: The use of platelets as biomaterials has gained intense research interest. However, the mechanisms regarding platelet-mediated skeletal myogenesis remain to be established. The aim of this study was to determine the role of platelet releasate in skeletal myogenesis and muscle stem cell fate in vitro and ex vivo respectively. Methods: We analysed the effect of platelet releasate on proliferation and differentiation of C2C12 myoblasts by means of cell proliferation assays, immunohistochemistry, gene expression and cell bioenergetics. We expanded in vitro findings on single muscle fibres by determining the effect of platelet releasate on murine skeletal muscle stem cells using protein expression profiles for key myogenic regulatory factors. Results: TRAP6 and collagen used for releasate preparation had a more pronounced effect on myoblast proliferation versus thrombin and sonicated platelets (P<0.05). In addition, platelet concentration positively correlated with myoblast proliferation. Platelet releasate increased myoblast and muscle stem cell proliferation in a dose-dependent manner, which was mitigated by VEGFR and PDGFR inhibition. Inhibition of VEGFR and PDGFR ablated MyoD expression on proliferating muscle stem cells, compromising their commitment to differentiation in muscle fibres (P<0.001). Platelet releasate was detrimental for myoblast fusion and affected differentiation of myoblasts in a temporal manner. Most importantly we show that platelet releasate promotes skeletal myogenesis through the PDGF/VEGF-Cyclin D1-MyoD-Scrib-Myogenin axis and accelerates skeletal muscle regeneration after acute injury. Conclusion: This study provides novel mechanistic insights on the role of platelet releasate in skeletal myogenesis and set the physiological basis for exploiting platelets as biomaterials in regenerative medicine