Enzyme inhibition and antibacterial potential of 4-Hydroxycoumarin derivatives

The 4-Hydroxycoumarin derivatives are known to show a broad spectrum of pharmacological applications. In this paper we are reporting the synthesis of a new series of 4-Hydroxycoumarin derivatives synthesized through Knovenegal condensation; they were characterized by using UV-Vis, FT-IR, NMR spectroscopies. The synthesized compounds were evaluated for antibacterial activity against Staphylococcus aureus and Salmonella typhimurium strains. The compounds (2), (3) and (8) showed favorable antibacterial activity with zone of inhibitions 26.5± 0.84, 26.0 ± 0.56 and 26.0 ± 0.26 against Staphylococcus aureus (Gram-positive) respectively. However, the compounds (5) and (9) were found more active with 19.5 ± 0.59 and 19.5 ± 0.32 zone of inhibitions against Salmonella typhimurium (Gram-negative). Whereas, in urease inhibition assay, none of the synthesized derivatives showed significant anti-urease activity; although, in carbonic anhydrase-II inhibition assay, the compound (2) and (6) showed enzyme inhibition activity with IC50 values 263±0.3 and 456±0.1, respectively

Comparative ambient and indoor particulate matter analysis of operation theatres of government and private (trust) Hospitals of Lahore, Pakistan

The link between infection and indoor air quality (IAQ) in operating theatres is well established. The level of airborne particulate matter (PM) in operating theatres in Pakistan has not yet been studied comprehensively. Monitoring of both indoor (operating theatre) and outdoor concentrations of PM in both activity and non-activity time periods was done using a DUSTTRAK Aerosol Monitor (TSI Model 8520) and DRX Aerosol Monitor (TSI Model 8533) for 24 hours. Two hospitals in Lahore were selected: Services Hospital (government – site 1) and Shalamar Hospital (private – site 2). The highest concentration of PM was observed in the orthopaedic operating theatre at site 1 during working hours with an average concentration of 757(±540), 809(±58), 824(±585), 875(±586) and 970(±581) μg/m3 of PM1,PM2.5, PM4, PM10 and PMTotal respectively while the average PM2.5 outdoor concentration was 294 μg/m3. The minimum average PM concentration was found in the orthopaedic operating theatre at site 2 during working hours: 18(±8), 19(±8), 20(±9), 26(±9) and 39(±9) μg/m3 for PM1, PM2.5, PM4, PM10 and PMTotal respectively. The use of vertical laminar air flow ventilation strategy was found to be an effective measure in reducing PM levels and it might be possible to predict the air quality of operating theatres by determining PM dust load. Factors such as ventilation system, door opening /closing rates, building age, possible sources of infiltration, number of people present in the operating area all play a role in influencing PM concentrations in operating theatres

Knowledge, attitudes and practices survey on organ donation among a selected adult population of Pakistan

Background: To determine the knowledge, attitudes and practices regarding organ donation in a selected adult population in Pakistan. Methods: Convenience sampling was used to generate a sample of 440, 408 interviews were successfully completed and used for analysis. Data collection was carried out via a face to face interview based on a pre-tested questionnaire in selected public areas of Karachi, Pakistan. Data was analyzed using SPSS v. 15 and associations were tested using the Pearson\u27s Chi square test. Multiple logistic regression was used to find independent predictors of knowledge status and motivation of organ donation. Results: Knowledge about organ donation was significantly associated with education (p = 0.000) and socioeconomic status (p = 0.038). 70/198 (35.3%) people expressed a high motivation to donate. Allowance of organ donation in religion was significantly associated with the motivation to donate (p = 0.000). Multiple logistic regression analysis revealed that higher level of education and higher socioeconomic status were significant (p \u3c 0.05) independent predictors of knowledge status of organ donation. For motivation, multiple logistic regression revealed that higher socioeconomic status, adequate knowledge score and belief that organ donation is allowed in religion were significant (p \u3c 0.05) independent predictors. Television emerged as the major source of information. Only 3.5% had themselves donated an organ, with only one person being an actual kidney donor. Conclusion: Better knowledge may ultimately translate into the act of donation. Effective measures should be taken to educate people with relevant information with the involvement of media, doctors and religious scholars

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

A Review of Antifungal Susceptibility Testing for Dermatophyte Fungi and It’s Correlation with Previous Exposure and Clinical Responses

Background: An increase in the number of recurrent and recalcitrant dermatophytoses calls for a tool to guide the clinician to correlate in vitro minimum inhibitory concentration (MIC) data, antifungal treatment with clinical outcomes. This systematic review aims to explore a possible correlation between one aspect of this, previous antifungal exposure, and clinical outcomes. Methods: A systematic literature search for articles on previous antifungal treatment, treatment outcome, susceptibility methods used, organism (genus/species), and MIC values was conducted. Results: A total of 720 records were identified of which 19 articles met the inclusion criteria. Forty percent of the cases had contact with or travel to India, 28% originated from or had traveled to other countries where treatment unresponsive tinea infections had been reported. Tinea corporis was the most common clinical presentation and the species involved were Trichophyton (T.) indotineae and T. rubrum, followed by T. mentagrophyte/interdigitale complex and T. tonsurans. Nearly all patients had previously been exposed to one or more antifungals. The studies were too heterogeneous to perform a statistical analysis to test if previous antifungal exposure was related to resistance. Conclusions: Only a few studies were identified, which had both sufficient and robust data on in vitro susceptibility testing and clinical treatment failure. Further research on the value of susceptibility testing to improve clinical practice in the management of dermatophyte infections is needed

Irrigation suitability, health risk assessment and source apportionment of heavy metals in surface water used for irrigation near marble industry in Malakand, Pakistan.

Water is a vital, finite resource whose quantity and quality are deteriorating as the world population increases. The current study aims to investigate the concentration of heavy metals (HM) in surface water for irrigation purposes with associated human health risks and pollution sources near the marble industry in Malakand, Pakistan. Twenty-seven water samples were randomly collected and analyzed for HM concentration by inductively coupled plasma‒optical emission spectrometry (ICP‒OES). pH, electrical conductivity (EC), total dissolved solids (TDS), biological oxygen demand (BOD), and chemical oxygen demand (COD) were measured using standard methods of American Public Health Association (APHA). Irrigation suitability was assessed using specific water quality parameters. The associated health risks from ingestion and dermal exposure to heavy metals were calculated by USEPA health risk indices. Pollution sources and spatial distribution mapping were studied using compositional data analysis (CoDa) and the application of a geographic information system (GIS) to understand the changing behavior of heavy metals in surface waters. The concentrations of BOD (89%), COD (89%), Al (89%), Ca (89%), Cr (56%), Cu (78%), Fe (56%), K (34%) Mg (23%), Mn (56%), Na (89%), Ni (56%), P (89%), and Zn (11%) exceeded the safety limits of National Environmental Quality standards (NEQs) of Pakistan. The results of Kelly's ratio (KR) classified surface water as unsuitable for irrigation. The average daily doses (ADD, mg/kg/day) for Al, Cu, Cr, Fe, Mn, Ni, and Zn were higher in children than in adults. The hazard index (HI) for children and adults was above the threshold (HI > 1), indicating a significant risk of non-carcinogenic toxicity. The carcinogenic risk values for Cr and Ni were above the USEPA limit (1 × 10-6 to 1 × 10-4), suggesting a potential carcinogenic risk for the target population. Principal component analysis (PCA), biplot (CLR), and the CoDa-dendrogram allowed for the identification of elemental associations, and their potential source was anthropogenic rather than natural in origin. Regular monitoring and phytoremediation strategies are proposed to safeguard crops and human health

Impact of pharmacist-led educational intervention on knowledge of self-management among asthmatic patients:a prospective cohort study

OBJECTIVES: Poor control of asthma in the majority of patients could be partly due to their lack of knowledge concerning disease management, its triggering agents and when to seek advice from the healthcare provider. This study aims to assess the impact of pharmacist-led educational intervention on knowledge of self-management among asthmatic patients. DESIGN: A pre–post cohort study. SETTING: Outpatient department of a tertiary care hospital affiliated with Quaid-i-Azam University, Pakistan. PARTICIPANTS: Approximately 265 adult asthmatic patients selected through a spirometry process, aged ≥18 years, were approached. 240 patients gave consent to participate in the study and were divided into control and treatment groups. INTERVENTIONS: The educational intervention consisted of individual patient counselling using educational material with time varied according to each patient’s comprehension and previous knowledge. PRIMARY AND SECONDARY OUTCOME MEASURES: Assessment consisted of a 14-item Asthma Self-Management Knowledge Questionnaire (ASMQ) quantifying a patient’s self-management knowledge through an ASMQ score and its change following an educational intervention. RESULTS: Disease self-management knowledge was low with an average raw ASMQ score of 4.1 (max 14); which equates to a transformed score of 29.34 (max 100) and the proportion of patients who correctly answered more than 50% of questions were 16.7% preintervention. More than half of the participants (55%) did not know that asthma cannot be cured. The administration of educational intervention protocols resulted in significantly improved level of knowledge of asthma self-management (<0.001) in the treatment group (mean ASMQ score improved from 4.20 to 9.77). CONCLUSION: On baseline visit, patients possessed a poor knowledge about asthma self-management. Educational intervention protocols had a positive impact on improving patients’ knowledge about disease self-management. This would suggest that education and self-management skills should be seen as an integral component of asthma management and should be incorporated in structured patient care to achieve optimal asthma control

A comprehensive review on the impact of calcium and vitamin D insufficiency and allied metabolic disorders in females

Abstract Calcium is imperative in maintaining a quality life, particularly during later ages. Its deficiency results in a wide range of metabolic disorders such as dental changes, cataracts, alterations in brain function, and osteoporosis. These deficiencies are more pronounced in females due to increased calcium turnover throughout their life cycle, especially during pregnancy and lactation. Vitamin D perform a central role in the metabolism of calcium. Recent scientific interventions have linked calcium with an array of metabolic disorders in females including hypertension, obesity, premenstrual dysphoric disorder, polycystic ovary syndrome (PCOS), multiple sclerosis, and breast cancer. This review encompasses these female metabolic disorders with special reference to calcium and vitamin D deficiency. This review article aims to present and elaborate on available data regarding the worldwide occurrence of insufficient calcium consumption in females and allied health risks, to provide a basis for formulating strategies and population‐level scientific studies to adequately boost calcium intake and position where required

Biochemical basis of resistance in rice against Bacterial leaf blight disease caused by Xanthomonas oryzae pv. oryzae

Background: Bacterial Leaf Blight (BLB) is the most devastating disease of rice. This disease can reduce grain production by 20-50% and yield by 25%. The disease is widespread in Asia, United State, Latin America and Australia. In Pakistan, it is reported from all rice growing areas and it is increasing its area year by year. All famous Pakistan’s Basmati varieties are susceptible to BLB disease. The most economical way of controlling disease is to produce resistant varieties. Many different compounds are involved in resistance mechanism in host including phenolic compounds.Methods: Plants inoculated with Xanthomonas oryzae pv. oryzae isolates i.e. 78.3 and 2.2 caused disease on all varieties were selected for investigation of phenolic compound. Randomized complete block design was used in field for inoculation and leaf collections for phenolic compounds determination. Data was phenolic compounds were analyzed through factorial ANOVA.Results: The response of four varieties was different when inoculated with BLB isolate 2.2. Basmati 2000 variety of rice produced maximum amount of phenolic compounds after one week of inoculation of bacterial isolate 2.2 while the minimum total phenols were found in basmati 385 at 0 hrs. of inoculation (before inoculation). Xoo isolate 78.3 produced maximum phenolic compounds after 2 weeks in Basmati 2000.Conclusions: Biochemical resistance due to high phenolic contents in Basmati-385 and Basmati-2000 is suggested. High phenol production may be due to loss of virulence in bacterial isolates. Both 78.3 and 2.2 Xoo isolates are significantly different in producing total phenols in all the varieties tested