Quality Testing and Antimicrobial Activity of Norfloxacin in Pakistan

Background: There are 400 licensed pharmaceutical companies in Pakistan; one third of Pakistan total consumption of pharmaceuticals is imported. Market potential is good for antibiotics, vaccines, hormones etc. Introduction: High performance liquid chromatography is an important tool for routine determination of antimicrobial drugs with specific emphasis on fluoroquinolones. The quality testing of norfloxacin was also done by Liquid chromatography coupled with mass spectrometry. Antibacterial activity of norfloxacin is good for aerobic gram negative bacteria, including Enterobacteriaceae and Pseudomonas aeruginosa. It has moderate antibacterial activity against gram positive microorganisms, such as staphylococci; anaerobic bacteria are generally resistant.Method: Our investigation focuses on the quality testing of brands of Norfloxacin available in market with variety of trade names. Reverse phase chromatographic technique RP-HPLC was used for the quality testing of norfloxacin at temperature of 35°C and a flow rate of 0.8ml/ml with Isocratic plution. Disk diffusion techniquewas used to check the antibacterial activity of norfloxacin against Proteus mirabilis, Klebsiella pnemoniae, Escherichia coli and Pseudomonas aeruginosa. Different brands of Norfloxacin (noroxin, uracin, qunor, urid , uroquin, webnor, bactinor, uritac , floxacin, norocin and ecoflaxin) from pharmaceutical companies A, B C, D,  F , G , H, I, J & and K were collected from markets of Rawalpindi and Islamabad (Pakistan). The claimed concentration of tablet was 400mg. Result: The quality testing of norfloxacin with sample and standard showed that brands from companies C and F Qunor, Webnor did not qualify the quality testing, they were of medium standard for the treatment of infections while H Company with a brand Uritac stands highest for quality test. Disk diffusion technique showed that all brands of norfloxacin were sensitive against the mentioned bacteria.Conclusion:  This research concluded that special effective measures should be taken by all the pharmaceutical companies in Pakistan to check the quality standards of pharmaceuticals especially antibiotics before manufacturing. If they qualify the quality standards they will be effective to treat infections, if they are of low standard it would be difficult for the clinician to advise the correct amount of dosage for patient.

Support for primary care prescribing for adult ADHD in England: national survey

Background: Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder with effective pharmacological treatments that improve symptoms and reduce complications. NICE guidelines recommend primary care practitioners prescribe medication for adult ADHD under shared care agreements with adult mental health services (AMHS). However, provision remains uneven, with some practitioners reporting a lack of support. Aim: This study aimed to describe supportive elements (prescribing, shared care, AMHS availability) of primary care prescribing for adult ADHD medication in England, to inform service improvement and improve access for this underserved population. Design and Setting: Three interlinked cross-sectional surveys asked every integrated care board (ICB) in England (Commissioners), and convenience samples of healthcare professionals (HP) and people with lived experience (LE), about elements supporting pharmacological treatment of ADHD in primary care. Method: Descriptive analyses used percentages and confidence intervals to summarise responses by stakeholder group. Variations in reported provision and practice were explored and displayed visually using mapping software. Results: Data from 782 respondents (42 Commissioners; 331 HP; 409 LE) revealed differences in reported provision by stakeholder group, including for prescribing (94.6% of HP vs 62.6% of LE). Over 40% of respondents reported extended AMHS waiting times of two years or more. There was some variability by NHS region, for example London had highest rates of HP reported prescribing (100%), and lowest reported extended waiting times (25.0%). Conclusion: Elements supporting appropriate shared care prescribing of ADHD medication via primary care are not universally available in England. Co-ordinated approaches are needed to address these gaps

Substantial and sustained reduction in under-5 mortality, diarrhea, and pneumonia in Oshikhandass, Pakistan : Evidence from two longitudinal cohort studies 15 years apart

Funding Information: Study 1 was funded through the Applied Diarrheal Disease Research Program at Harvard Institute for International Development with a grant from USAID (Project 936–5952, Cooperative Agreement # DPE-5952-A-00-5073-00), and the Aga Khan Health Service, Northern Areas and Chitral, Pakistan. Study 2 was funded by the Pakistan US S&T Cooperative Agreement between the Pakistan Higher Education Commission (HEC) (No.4–421/PAK-US/HEC/2010/955, grant to the Karakoram International University) and US National Academies of Science (Grant Number PGA-P211012 from NAS to the Fogarty International Center). The funding bodies had no role in the design of the study, data collection, analysis, interpretation, or writing of the manuscript. Publisher Copyright: © 2020 The Author(s).Peer reviewedPublisher PD

Adaptor protein-2 sigma subunit mutations causing familial hypocalciuric hypercalcaemia type 3 (FHH3) demonstrate genotype-phenotype correlations, codon bias and dominant-negative effects

The adaptor protein-2 sigma subunit (AP2σ2) is pivotal for clathrin-mediated endocytosis of plasma membrane constituents such as the calcium-sensing receptor (CaSR). Mutations of the AP2σ2 Arg15 residue result in familial hypocalciuric hypercalcaemia type 3 (FHH3), a disorder of extracellular calcium (Ca(2+) o) homeostasis. To elucidate the role of AP2σ2 in Ca(2+) o regulation, we investigated 65 FHH probands, without other FHH-associated mutations, for AP2σ2 mutations, characterized their functional consequences and investigated the genetic mechanisms leading to FHH3. AP2σ2 mutations were identified in 17 probands, comprising 5 Arg15Cys, 4 Arg15His and 8 Arg15Leu mutations. A genotype-phenotype correlation was observed with the Arg15Leu mutation leading to marked hypercalcaemia. FHH3 probands harboured additional phenotypes such as cognitive dysfunction. All three FHH3-causing AP2σ2 mutations impaired CaSR signal transduction in a dominant-negative manner. Mutational bias was observed at the AP2σ2 Arg15 residue as other predicted missense substitutions (Arg15Gly, Arg15Pro and Arg15Ser), which also caused CaSR loss-of-function, were not detected in FHH probands, and these mutations were found to reduce the numbers of CaSR-expressing cells. FHH3 probands had significantly greater serum calcium (sCa) and magnesium (sMg) concentrations with reduced urinary calcium to creatinine clearance ratios (CCCR) in comparison with FHH1 probands with CaSR mutations, and a calculated index of sCa × sMg/100 × CCCR, which was ≥ 5.0, had a diagnostic sensitivity and specificity of 83 and 86%, respectively, for FHH3. Thus, our studies demonstrate AP2σ2 mutations to result in a more severe FHH phenotype with genotype-phenotype correlations, and a dominant-negative mechanism of action with mutational bias at the Arg15 residue

Pakistan

Pakistan is situated between India to the east, China to the northeast, Afghanistan to the northwest and north, Iran to the west, the Arabian Sea to the south, and is separated from Tajikistan by the narrow and rugged Wakhan Corridor (part of Afghanistan) to the north. Created in 1947, Pakistan is a relatively new country, but it is home to the ancient Indus Valley and subsequent civilizations. It has a diverse geography and some unique species of fauna and flora. Pakistan is actively concerned with addressing environmental issues, though solutions require consideration of complex governmental and societal structures

Pakistan

Pakistan is situated between India to the east, China to the northeast, Afghanistan to the northwest and north, Iran to the west, the Arabian Sea to the south, and is separated from Tajikistan by the narrow and rugged Wakhan Corridor (part of Afghanistan) to the north. Created in 1947, Pakistan is a relatively new country, but it is home to the ancient Indus Valley and subsequent civilizations. It has a diverse geography and some unique species of fauna and flora. Pakistan is actively concerned with addressing environmental issues, though solutions require consideration of complex governmental and societal structures

Pulmonary function test and computed tomography features during follow-up after SARS, MERS and COVID-19: a systematic review and meta-analysis.

Background The COVID-19 pandemic follows severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronavirus epidemics. Some survivors of COVID-19 infection experience persistent respiratory symptoms, yet their cause and natural history remain unclear. Follow-up after SARS and MERS may provide a model for predicting the long-term pulmonary consequences of COVID-19. Methods This systematic review and meta-analysis aims to describe and compare the longitudinal pulmonary function test (PFT) and computed tomography (CT) features of patients recovering from SARS, MERS and COVID-19. Meta-analysis of PFT parameters (DerSimonian and Laird random-effects model) and proportion of CT features (Freeman-Tukey transformation random-effects model) were performed. Findings Persistent reduction in the diffusing capacity for carbon monoxide following SARS and COVID-19 infection is seen at 6 months follow-up, and 12 months after MERS. Other PFT parameters recover in this time. 6 months after SARS and COVID-19, ground-glass opacity, linear opacities and reticulation persist in over 30% of patients; honeycombing and traction dilatation are reported less often. Severe/critical COVID-19 infection leads to greater CT and PFT abnormality compared to mild/moderate infection. Interpretation Persistent diffusion defects suggestive of parenchymal lung injury occur after SARS, MERS and COVID-19 infection, but improve over time. After COVID-19 infection, CT features are suggestive of persistent parenchymal lung injury, in keeping with a post-COVID-19 interstitial lung syndrome. It is yet to be determined if this is a regressive or progressive disease

Integrated DNA/RNA targeted genomic profiling of diffuse large B-cell lymphoma using a clinical assay

We sought to define the genomic landscape of diffuse large B-cell lymphoma (DLBCL) by using formalin-fixed paraffin-embedded (FFPE) biopsy specimens. We used targeted sequencing of genes altered in hematologic malignancies, including DNA coding sequence for 405 genes, noncoding sequence for 31 genes, and RNA coding sequence for 265 genes (FoundationOne-Heme). Short variants, rearrangements, and copy number alterations were determined. We studied 198 samples (114 de novo, 58 previously treated, and 26 large-cell transformation from follicular lymphoma). Median number of GAs per case was 6, with 97% of patients harboring at least one alteration. Recurrent GAs were detected in genes with established roles in DLBCL pathogenesis (e.g. MYD88, CREBBP, CD79B, EZH2), as well as notable differences compared to prior studies such as inactivating mutations in TET2 (5%). Less common GAs identified potential targets for approved or investigational therapies, including BRAF, CD274 (PD-L1), IDH2, and JAK1/2. TP53 mutations were more frequently observed in relapsed/refractory DLBCL, and predicted for lack of response to first-line chemotherapy, identifying a subset of patients that could be prioritized for novel therapies. Overall, 90% (n = 169) of the patients harbored a GA which could be explored for therapeutic intervention, with 54% (n = 107) harboring more than one putative target