Sharing data from clinical trials: the rationale for a controlled access approach.

The move towards increased transparency around clinical trials is welcome. Much focus has been on under-reporting of trials and access to individual patient data to allow independent verification of findings. There are many other good reasons for data sharing from clinical trials. We describe some key issues in data sharing, including the challenges of open access to data. These include issues in consent and disclosure; risks in identification, including self-identification; risks in distorting data to prevent self-identification; and risks in analysis. These risks have led us to develop a controlled access policy, which safeguards the rights of patients entered in our trials, guards the intellectual property rights of the original researchers who designed the trial and collected the data, provides a barrier against unnecessary duplication, and ensures that researchers have the necessary resources and skills to analyse the data

Impact of the coronavirus pandemic (COVID-19) on the professional practice and personal well-being of community pharmacy teams in the UK

Objectives: Community pharmacy teams (CPTs) were at the frontline of dealing with patients throughout the COVID-19 pandemic. This study aimed to explore the impact on professional practice and personal well-being of CPTs, in the UK. // Methods: A 25-item survey was designed including a range of open and closed questions. The survey was piloted before being published online via SurveyMonkey and distributed using social media platforms. A combination of opportunity and snowball sampling was employed to recruit participants who worked in community pharmacy (CP) during the pandemic. // Results: In total 758 participants (75% completion rate) including pharmacists, owners, managers, technicians, dispensers, healthcare assistants and pre-registration pharmacists took part. Increased workloads and working hours coupled with staff shortages compromised professional practice (n = 257, 35%). Some of the key challenges of working in CP during the pandemic included: a fear of contracting and passing the virus to others (n = 578, 78%), patients stockpiling medicines (n = 530, 71%) and doctors’ surgeries being closed (n = 517, 70%) The impact on emotional well-being (n = 433, 76%) included stress, anxiety, depression and loneliness; physically (n = 322, 56%) it affected sleep, pain and weight. The effects of the pandemic left 45% (n = 258/569) of participants reconsidering their future in CP as they felt demotivated, unsupported and undervalued. // Conclusion: Despite the enhanced pressures and lack of initial recognition CPTs played a vital role in caring for the population during the pandemic. Resources to better support pharmacy teams in the future not only rely on more funding for better provisions but also investing in CPTs’ well-being

Biliary ductal variations and its clinical implications: a cadaveric study

Background: Biliary ductal region being frequently abnormal has been the subject of research since long time for anatomists, surgeons and radiologists as well.Methods: The present study was carried out in the department of Anatomy at PGIMS, Rohtak on 50 specimens of liver taken unblock with associated structures.Results: Accessory hepatic and accessory cystic ducts were observed in 4% cases each.  2% cases exhibited abnormal low fusion of cystic duct with common hepatic duct.Conclusions: These anomalies may add to postoperative complications if ignored. Present study is a step in the direction of creating awareness about these variations among the clinicians

Pharmacognostic and phytochemical evaluation of the Solanun sisymbriifolium leaf

Solanum sisymbriifolium Lam. (Solanaceae) is an important medicinal herb in Ayurvedic medicine. In the present investigation, the detailed pharmacognostic study of S. sisymbriifolium leaf was carried out to lay down the standards which could be useful in future experimental studies. The study included macroscopy, microscopy, preliminary phytochemical screening and physicochemical evaluation. These observations will help in the Pharmacognostical identification and standardization of the drug in the crude form and also to distinguish the drug from its adulteration.Keywords: Solanum sisymbriifolium, pharmacognosy, microscopy.African Journal of Biotechnology Vol. 12(42), pp. 6133-613

Microtuberization, minitubers formation and in vitro shoot regeneration from bud sprout of potato (Solanum tuberosum L.) cultivar K. badshah

Kufri badshah is one of the important medium maturing, blight resistant potato varieties with round to oblong tubers; it has yellowish skin, shallow eye and white pulp. This variety is popular among farmers. The study on development of tissue culture protocol was carried out using sprout as an explant for initiation of culture in MS media supplemented with eleven different combinations of growth hormones: indole butyric acid (IBA), kinetin, naphthalene acetic acid (NAA) and 2,4-dichlorophenoxy acetic acid (2,4-D). The response for growth proliferation was observed. The treatment involving a combination of IBA, kinetin, NAA and 2,4-D gave good response for growth of shoot. The resultant shoots were subcultured further using nodal cutting as explants in same media for further multiplication. The developed plantlets were hardened in green house. Hardened plants were transplanted in the soil for further growth and development. The plants yielded 3-17 healthy minitubers. For microtuber production, high level of sucrose (8%) gave promising results than low level of sucrose (3%).Keywords: Kufri badshah, explants, indole butyric acid (IBA), kinetin, naphthalene acetic acid (NAA), 2,4-dichlorophenoxy acetic acid (2,4-D) and microtuber.African Journal of Biotechnology Vol. 12(38), pp. 5640-564

Polyphenolic acetates: A newer anti-Mycobacterial therapeutic option

The objective of our research project was screening of various highly specific substrates of Acetoxy Drug: Protein Transacytylase (M.TAase) for antimycobacterial activity. Mycobacterial culture was done in Middlebrook’s 7H9 media. Protein purification (Mycobacterial Tranacetylase, M.TAase) was done by ion exchange chromatography and its demonstration was done on SDS- polyacrylamide gel electrophoresis (SDS-PAGE) and western blot. Middlebrook’s 7H9 broth was procured from Becton Dickinson. CM-Sepharose, DEAE-Sepharose and Q-Sephharose were purchased from Amersham Pharmacia. Anti acetyl lysine polyclonal antibody was purchased from Cell Signaling. The Middlebrook 7H9 medium was used for M. smegmatis culture. The media was prepared according to the manufacturer’s instructions. The various Polyphenol acetate compounds were tested for their antimycobacterial activities. Minimal inhibitory concentrations (MIC) were calculated by Alamar blue dye assay method. The GST protein was used as a receptor protein and purified Mycobacterial Glutamine Synthetase (GS) as TAase for acetylation by DAMC. To demonstrate the TAase catalyzed acetylation of GST by DAMC, purified M.TAase (GS) was preincubated with GST and DAMC followed by western blot using anti acetyl lysine antibody, which avidly react with the acetylated proteins. The growth pattern of M. smegmatis was diminished under the influence of various polyphenolic acetates (PA) tested for their anti-mycobacterial activity. DAMC and DAMC-5-carboxylic acid was found to have MIC of 40μg/ml whereas DAMC-6-carboxylic acid was reported to have MIC value of 35μg/ml and for ellagic acid tetra acetate (EATA) it was 60μg/ml. Previous work in our lab has led to discovery of a novel enzyme acetoxy drug: protein transacetylase (TAase), catalyzing transfer of acetyl group from various polyphenolic peracetate (PA) to certain receptor proteins such as cytochromes P-450, NADPH cytochrome reductase, nitric oxide synthase (NOS) has been established in various eukaryotic as well as prokaryotic sources. PA(s) irreversible inhibitors of mammalian CYP linked MFO, possibly due to modification of cytochrome p- 450 by acetylation in a reaction catalysed by M.TAase (GS) utilizing PA(s) as a donor of acetyl groups. Accordingly, it was hypothesized that the CYP51 of mycobacteria involved in the cell wall sterol synthesis could possibly be modified by our PA(s) through the novel unknown action of GS as transacetylase leading to the death of mycobacterial cell by way of acetylation catalyzed by acetoxy drug: protein transacetylase (M.TAase or GS).Keywords: Transacetylase; Glutamine synthetase; Mycobacterium smegmatis; Polyphenolic acetates; Acetoxy drug: protein transacetylas

A Repurposing Programme Evaluating Repurposing Transdermal Oestradiol Patches for the Treatment of Prostate Cancer Within the PATCH and STAMPEDE Trials: Current Results and Adapting Trial Design

AIMS: Androgen deprivation therapy (ADT), usually achieved with luteinising hormone releasing hormone analogues (LHRHa), is central to prostate cancer management. LHRHa reduce both testosterone and oestrogen and are associated with significant long-term toxicity. Previous use of oral oestrogens as ADT was curtailed because of cardiovascular toxicity. Transdermal oestrogen (tE2) patches are a potential alternative ADT, supressing testosterone without the associated oestrogen-depletion toxicities (osteoporosis, hot flushes, metabolic abnormalities) and avoiding cardiovascular toxicity, and we here describe their evaluation in men with prostate cancer. MATERIALS AND METHODS: The PATCH (NCT00303784) adaptive trials programme (incorporating recruitment through the STAMPEDE [NCT00268476] platform) is evaluating the safety and efficacy of tE2 patches as ADT for men with prostate cancer. An initial randomised (LHRHa versus tE2) phase II study (n = 251) with cardiovascular toxicity as the primary outcome measure has expanded into a phase III evaluation. Those with locally advanced (M0) or metastatic (M1) prostate cancer are eligible. To reflect changes in both management and prognosis, the PATCH programme is now evaluating these cohorts separately. RESULTS: to date: Recruitment is complete, with 1362 and 1128 in the M0 and M1 cohorts, respectively. Rates of androgen suppression with tE2 were equivalent to LHRHa, with improved metabolic parameters, quality of life and bone health indices (mean absolute change in lumbar spine bone mineral density of -3.0% for LHRHa and +7.9% for tE2 with an estimated difference between arms of 9.3% (95% confidence interval 5.3-13.4). Importantly, rates of cardiovascular events were not significantly different between the two arms and the time to first cardiovascular event did not differ between treatment groups (hazard ratio 1.11, 95% confidence interval 0.80-1.53; P = 0.54). Oncological outcomes are awaited. FUTURE: Efficacy results for the M0 cohort (primary outcome measure metastases-free survival) are expected in the final quarter of 2023. For M1 patients (primary outcome measure - overall survival), analysis using restricted mean survival time is being explored. Allied translational work on longitudinal samples is underway