Assessment of derangement in biochemical profile in primary open angle glaucoma patients presenting at a tertiary care hospital

Objective: To assess the changes in high sensitivity C Reactive protein (hs-CRP), serum cholesterol, uric acid, creatinine, bilirubin and ALT in patients of primary open angle glaucoma. Material and methods: Comparative cross-sectional study conducted between April 2021 and October 2021 at departments of Ophthalmology and Pathology, --removed for blind review----44 POAG patients and 54 healthy controls volunteered to participate in the study. POAG was diagnosed as per criteria. Venous blood was drawn for analysis of serum cholesterol, uric acid, creatinine, bilirubin, ALT and hs-CRP.  hs-CRP was performed on ELISA plate reader Platos R496 while spectrophotometric analysis of serum uric acid, creatinine, and cholesterol was carried on Beckman Coulter AU-700. Results: Mean hemoglobin (Hb), Total leukocyte count (TLC), serum urea, creatinine, uric acid, ALT, bilirubin, cholesterol and HbA1c were 12.80 ±1.50g, 8.88±1.92 mm3, 5.95±5.47 µmol/l, 92.19±21.81 µmol/l, 305.85±79.92 mmol/l, 34.31±18.26 IU/L, 9.26±3.11 µmol/l, 5.18±0.96 mmol/l,6.70±1.28 %respectively whereas the Mean IOP in POAG patients was 28mmHg, mean CCT was 516.6 µm, and mean vertical CDR was 0.6. High frequency of hs-CRP positivity (50 percent) was reported in our patients. Significantly lower uric acid levels were observed in primary open angle glaucoma patients versus controls ie 305.85±79.92 mmol/l vs 344.36±37.24 mmol/l (P value < 0.05). Serum creatinine was significantly different between mild and severe groups i.e. 88±14.7 vs 113.1±32.4. (p value <0.001*) Conclusion: High frequency of hs-CRP positivity and low uric acid levels suggest the presence of para inflammation in patients of POAG. Key words: Primary open angle glaucoma (POAG), intraocular pressure (IOP), high sensitivity CRP (hs-CRP), uric acid (UA

Comparison of analgesic efficacy of diclofenac suppository with intramuscular diclofenac sodium in post-operative pain relief after cesarean delivery in the first 24 hours

Background About 80% of the patients experience enough post-operative pain to require analgesia. Adequate pain relief  is needed after caesarean section to assist ambulation , mother / baby bonding & above all, a  pleasant experience of being a mother. Different analgesics with  various routes of administrations are available for pain relief which include opioids and NSAIDS. Opiods are known for their undesireable side effects . Diclofenac sodium is an NSAID & acts via blocking prostaglandin production. The WHO recommends diclofenac as a first line drug in pain relief. It  is available in various preparations which include injections, tablets and suppositories. We  compared the mean pain experienced by the women after use of diclofenac suppositories and intramuscular diclofenac sodium after elective cesarean section in first 24 hours. Methodology This RCT was done in  the department of Obstetrics and Gynecology, --removed for blind review---from 1st March 2018 till 30th August 2018. Total of 100  antenatal women already planned for elective caesarean section ,who fulfilled inclusion criteria were selected after taking  informed consent & ethical approval by employing non probability consecutive sampling . The age , parity ,gestational age, weight  ,BMI & ASA status of all women was documented. 50 women were randomly assigned to the each group A & B. Group A was given 75 mg intramuscular diclofenac injection  immediately & then 8 hrly for the first 24 hrs after caesarean section while group B was given  100 mg rectal diclofenac suppository immediately & then  after 12 hrs  post caesarean for the first 24 hrs. if needed ,50 mg tramadol I/V was given to the women as rescue analgesia, Visual analogue pain  (VAS) score was used to assess the pain intensity of post operative  women after 24 hrs of caesarean and poltted  in the proforma. The number  of women needing rescue analgesia  in each group was also documented. & compared between the two groups. RESULTS:             Data was analyzed on the SPSS version 23.  In group A; mean age was 26.34 years with STD of 3.69. Mean gestational age was 37.82 weeks with STD of 1.79. In group B; mean age was 25.3 years with STD of 3.47. Mean gestational age was 37.70 weeks with STD of 1.59. In group A; mean weight was 84.62 kgs with STD of 5.76 and mean BMI was 32.18 with STD of 3.16. In group B; mean weight was 84.84 kgs with STD of 7.27 and mean BMI was 31.13 with STD of 3.57. In group A (intramuscular diclofenic injection group) the mean score of pain was 3.72 with STD of 0.57.  In group B (Diclofenic Suppository Group) the mean score of pain was 1.84 with STD of 0.68. P-value was significant. 26 women (52%) in group A (I/M diclofenac group) and 20 women (40%) in group B (rectal diclofenac suppository group) needed rescue analgesia with I/V Tramadol .P value was not significant.     CONCLUSION:             Dicolofenac is an effective post caesarean analgesic . Rectal route of diclofenac  is more effective than the intramuscular route as post caesarean analgesia . Almost less than half number of post caesarean women needed rescue analgesia after using diclofenac suppository

Development and optimization of virus neutralization test in chicken embryonated eggs for indirect identification of avian influenza and Newcastle disease virus

Avian viral problems have been consistently reported in commercial poultry of Pakistan causing heavy economic losses to the poultry farmers. Authentic idenfication and confirmation of the causative agent is always been question mark for the selection of vaccinal strain in this regard. Current study was therefore undertaken to optimize the virus neutralization test for the serological survey of vaccinated poultry particularly for avian influenza virus’s subtypes and Newcastle disease virus. Various physiochemical factors such as concentration of antigen and antibody, Incubation temperature and incubation period for in vitro and in-vivo reaction of antigen and antibody were optimized in chicken embryonated eggs. Serum samples were obtained from vaccinated breeder birds of five commercial poultry breeder companies and subjected for VNT using different concentration of three antigen and their respective homologous antibodies under optimized conditions. AIV H9 (EID50-1×109.0/ml) and NDV (EID50-1×108.2/ml) having biological titer of 10-7 /50ul  HA units were neutralize with 10-2/50ul HIU of antibody and incubated at 37°C for 30 minutes was injected subsequently into 10 day old chicken embryo followed by incubation at 37°C for 38 hours showed ≥90% neutralizing specificity. Furthermore, sera obtained from five AIV-H9, AIV-H5 and NDV exposed commercial poultry farms revealed that Big bird broiler, Big bird breeders and A&S chicks are 100% sensitive and specific whereas, Gateway chicks and Waqas poultry breeders showed 100% homology for AIV-H5 virus but do not confers similarity with prevailing AIV-H9 and NDV field strains. Therefore, high sensitivity, reproducibility and specificity VNT, it could be a tool for indirect detection of homology between vaccinal strain and wild virus antigen using known antisera. Particularly, for those organisms possess natural ability to mutate in the adverse climatic conditions. Keywords: Virus neutralization test, Avian Influenza Virus, Newcastle Disease Virus, Sensitivity, Specificit

In-vivo antiviral potential of crude extracts derived from Tribulus terrestris against newcastle disease virus

Viral problems have been in focused of the scientists due to their high metabolic rate, drug resistance and unique nature of pathological mechanism. The failure of novel synthetic allopathic antiviral drugs propels the scientists to investigate other sources of alternative antiviral agents. Thin layer chromatography (TLC) and spectrophotometry were conducted by using standard methods of phytochemical analysis of bioactive components. The methanolic extracts of Tribulus terrestris showed higher phytochemical phenols followed by tannins, alkaloids, carotenoid, saponins quantified by spectrophotometer assay.  The current study was done to evaluate the in vivo antiviral potential of crude extracts of medicinal plant by means of NDV Haemagglutination (HA) titer in vivo vero cell line culture. Furthermore, different doses of crude extract such as 20µl/ml, 40µl/ml, 60µlml and 80µl/ml were interacted with Lasota strain of the NDV (EID50= 1×105, HAU= I05) in 90% saturated vero cell line with constant supply of CO2 at 37°C. It is evaluated that the prevention dose (80µl/ml) of Tribulus terrestris (Pre-treatment) against Newcastle disease virus on vero cell line (2.5±1.0) just before 24 hour of infection is declared as optimum effective time period to counter these agents as compared to Co-treatment (80ul/ml) (3.0±1.15) and Post treatment (80µl/ml) (3.50±1.00). It is suggested from the results of current study that T. terristris showed enormous anti Newcastle disease virus effect in vero cell line adapted virus particularly when used as preventive antiviral therapy at the dose rate not less than 80ul/ml just before onset of disease

Staphylococcus aureus Floating Biofilm Formation and Phenotype in Synovial Fluid Depends on Albumin, Fibrinogen, and Hyaluronic Acid

Biofilms are typically studied in bacterial media that allow the study of important properties such as bacterial growth. However, the results obtained in such media cannot take into account the bacterial localization/clustering caused by bacteria–protein interactions in vivo and the accompanying alterations in phenotype, virulence factor production, and ultimately antibiotic tolerance. We and others have reported that methicillin-resistant or methicillin-susceptible Staphylococcus aureus (MRSA or MSSA, respectively) and other pathogens assemble a proteinaceous matrix in synovial fluid. This proteinaceous bacterial aggregate is coated by a polysaccharide matrix as is characteristic of biofilms. In this study, we identify proteins important for this aggregation and determine the concentration ranges of these proteins that can reproduce bacterial aggregation. We then test this protein combination for its ability to cause marked aggregation, antibacterial tolerance, preservation of morphology, and expression of the phenol-soluble modulin (PSM) virulence factors. In the process, we create a viscous fluid that models bacterial behavior in synovial fluid. We suggest that our findings and, by extension, use of this fluid can help to better model bacterial behavior of new antimicrobial therapies, as well as serve as a starting point to study host protein–bacteria interactions characteristic of physiological fluids

The impact of COVID-19 safety interventions on creating a controlled environment on campus

Objectives: During COVID-19 the re-opening of educational institutes was frequently debated, however with the decline in the number of COVID-19 cases, The Aga Khan University (AKU) in Karachi, Pakistan opened its campus for medical and nursing students after more than 6 months of closure. To ensure gradual resumption of activities on-campus, a combination of interventions was diligently deployed to minimize student infection rates. Scarce literature exists on students' perceptions regarding decisions implemented by university leadership. The aim of the study was to determine the efficacy of these interventions. Methods: We conducted a convergent, parallel, mixed-methods observational study targeting medical and nursing students. An online questionnaire was disseminated to elicit students' degree of (dis)agreement on a four-point Likert scale. Focused group discussions (FGDs) were conducted to comprehend reasons for (dis)agreement. Results: Total of 183 students responded to questionnaire (59.0% nursing, 67.8% female), 11 FGDs were conducted with 85 students. Interventions with highest agreement were mandatory face masks policy (94.54%), weekly mandated COVID-testing (92.35%) and students' Academic Bubble (91.26%); highest disagreement was for Sehat Check application (41.53%); and stay strong campaign (40.44%). Four themes emerged from FGDs: Effective safety interventions, Safety interventions with limited effectiveness, Utility of Sehat Check Application and Future recommendations for informing policy. Conclusion: It is paramount to seek student-feedback at forefront of university re-opening strategy. Clear communication channels are as important as an administrative response system's robustness. Bidirectional communication channels are fundamental and requisite during ever-changing policies and regulations. Engaging student representatives in decision making or implementation processes (such as “pilot” before “roll-out”) would allow any potential issues to be managed early on. Gather real-time anonymous feedback and identify key areas that need further promulgation and those that need to be replaced with more effective ones

Microbubble Cavitation Restores Staphylococcus Aureus Antibiotic Susceptibility in Vitro and in a Septic Arthritis Model

Treatment failure in joint infections is associated with fibrinous, antibiotic-resistant, floating and tissue-associated Staphylococcus aureus aggregates formed in synovial fluid (SynF). We explore whether antibiotic activity could be increased against Staphylococcus aureus aggregates using ultrasound-triggered microbubble destruction (UTMD), in vitro and in a porcine model of septic arthritis. In vitro, when bacterially laden SynF is diluted, akin to the dilution achieved clinically with lavage and local injection of antibiotics, amikacin and ultrasound application result in increased bacterial metabolism, aggregate permeabilization, and a 4-5 log decrease in colony forming units, independent of microbubble destruction. Without SynF dilution, amikacin + UTMD does not increase antibiotic activity. Importantly, in the porcine model of septic arthritis, no bacteria are recovered from the SynF after treatment with amikacin and UTMD-ultrasound without UTMD is insufficient. Our data suggest that UTMD + antibiotics may serve as an important adjunct for the treatment of septic arthritis

Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial

Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). Interpretation: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Path Dependence in Energy System and Ecological Footprint in Pakistan: Evidence from Time Series Data

Path dependence refers to the consumption of fossil fuels in energy production system. This study empirically examines the effect of path dependence in energy systems on ecological footprint of Pakistan from 1981-2014. Unit root test determines the integrated order of variables, while Auto-Regressive Distributed Lag model investigates the existence of a long-run association between variables. The negative and significant speed of adjustment coefficient ensures the adjustment of the model used in long run after unexpected shocks. Fossil fuel consumption significantly increases ecological footprint in Pakistan. If fossil fuel consumption increases by 1 percent, ecological footprint rises by 2.07 percent. Increase in biocapacity increases ecological footprint by 1.1 percent. Urbanization and population density significantly decrease ecological footprint as 1 percent increase in population density decreases ecological footprint by 0.96 percent and one percent rise in urbanization reduces ecological footprint by 3.28 percent. Foreign direct investment does not show any significant association with the ecological footprint. Standard diagnostic tests support the empirical results of the study and confirm that no heteroscedasticity and serial correlation exists. The policy implication is to implement measures to diminish the usage of fossil fuels in energy systems and increased usage of alternative and renewable energy sources. This can abate the burden on environment and biocapacity of Pakistan making it feasible to reduce ecological footprint levels in Pakistan