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Objective: To assess any association between the type of cataract and the central corneal thickness at pre-operative and postoperative three-day and one-month appointments after phacoemulsification surgery. Study Design: Prospective, comparative study. Place and Duration of Study: Eye Department Combined Military Hospital Multan, from Jun 2020 to Apr 2021. Methodology: A total of 89 patients requiring cataract surgery by phacoemulsification were recruited. Age and gender were recorded for each patient. Patient’s type of cataract based on maturity was recorded before the surgery. Phacoemulsification cataract surgery using ‘divide and conquer’ technique was carried out. Patients’ central corneal thickness was measured at the pre-operative, three-day post-operative and one-month post-operative appointment using traditional non-contact tonopachymeter. Results: There were 49 (55.1%) male and 40 (44.9%) female patients with a mean age of 62.15 ± 12.40 years. No significant association was found between the type of cataract and central corneal thickness at the three-time intervals (p=0.14). Central corneal thickness significantly increased from 0.48 ± 0.04 mm pre-operatively to 0.51 ± 0.04 mm at the three-day post-operative appointment (p

Introduction Vitiligo is disfiguring and devastating condition that can humans feel stigmatic and devalued. Melasma is a general condition of hyperpigmentation particularly involving the face. The pigmentation disorders of vitiligo (hypopigmentation or de-pigmentation) and melasma (Hypermelanosis) are common among the world’s population (around 1% for vitiligo). Objective The identification of medicinal plants used in the treatment of vitiligo and hypermelanosis. A systematic literature review on harms associated with the medicinal plants used in the treatment of vitiligo and hypermelanosis. To review and summarize information on reported adverse drug reactions (ADRs) associated with these medicinal plants contained in (where access is available) national and global individual case safety report databases. Methods A systematic review of the literature with special reference to all types of clinical trial and case reports using biomedical databases including Medline, EMBASE, Scopus, International Pharmaceutical Abstracts and so forth to identify medicinal plants alone or as an adjuvant with other treatments and their safety/tolerability in the treatment of vitiligo and Hypermelanosis. Other sources of this search were medicinal plants text books, pharmacopoeias and authentic websites discussing possible treatments for vitiligo/hypermelanosis. It also included databases such as VigiAccess containing data from spontaneous reporting schemes for ADRs. Results A total of 55 articles (47 clinical trials and 8 case reports) met the inclusion criteria. Some trials did not reported safety information, some did report, but not very well. Reports of blistering, erythema, acute hepatitis and mutagenesis with Psoralea corylifolia. Adverse effects of erythema (mild to severe), phototoxic reactions, mild raise in liver transaminases, gastrointestinal disturbances, burns, itching, scaling, depigmented macules, pruritis, and giddiness with the use of psoralens. Khellin-related erythema, perilesional hyperpigmentation, gastrointestinal disturbances, mild raise in liver transaminases and orthostatic complaints. Infrequent side effects with Ginkgo biloba. Lower grade of erythema and edema reported with the use of Polypodium leucotomos. Conclusion Primarily the retrieved clinical studies were efficacy oriented and safety parameters were secondary in priority whilst the general protocol of clinical trials requires the screening of drugs/medicinal plants on the basis of safety studies before testing the clinical aspects of efficacy. Thereby it is recommended that efficacy studies may be followed once the safety has been established for a particular medicinal plant in treating vitiligo and hypermelanosis.

Herein, we report a polysaccharide-based hydrogel isolated from psyllium husk (a well-known dietary fiber) and evaluated for its swelling properties in deionized water (DW) at different physiological pH values, i.e., 1.2, 6.8 and 7.4. Swelling of psyllium hydrogel (PSH) in DW under the influence of temperature and at different concentrations of NaCl and KCl solutions was also examined. A pH-dependent swelling pattern of PSH was observed following the order DW > pH 7.4 > pH 6.8 > pH 1.2. Stimuli-responsive swelling and deswelling (on–off switching) behavior of PSH was observed in DW and ethanol, DW and normal saline, at pH 7.4 and pH 1.2 environments, respectively. Similar swelling behavior and on–off switching attribute of PSH-containing tablets indicated the unaltered nature of PSH even after compression. Scanning electron micrographs of swollen and then freeze-dried PSH via transverse and longitudinal cross-sections revealed hollow channels with an average pore size of 6 ± 2 μm. Furthermore, PSH concentration-dependent sustained release of theophylline from tablet formulation was witnessed for >15 h following the non-Fickian diffusion mechanism. Subacute toxicity studies revealed the non-toxic nature of PSH. Therefore, dietary fiber-based material, i.e., PSH could be a valuable pharmaceutical excipient for intelligent and targeted drug delivery.

Neisseria gonorrhoeae is among the most multidrug-resistant bacteria in circulation today, and new treatments are urgently needed. In this work, we demonstrate the ability of 5-mercapto-2-nitrobenzoic acid-coated silver nanoclusters (MNBA-AgNCs) to kill strains of Neisseria gonorrhoeae. Using an in vitro bactericidal assay, MNBA-AgNCs had been found to show significantly higher anti-gonococcal bioactivity than the antibiotics ceftriaxone and azithromycin and silver nitrate. These nanoclusters were effective against both planktonic bacteria and a gonococcal infection of human cell cultures in vitro. Treatment of human cells in vitro with MNBA-AgNCs did not induce significant release of lactate dehydrogenase, suggesting minimal cytotoxicity to eukaryotic cells. Our results suggest that MNBA-AgNCs hold great potential for topical treatment of localized gonorrhoeae.

Introduction Aleutian mink disease virus (AMDV) causes a serious health problem for mink globally. The disease has no cure nor an effective vaccine and selection for tolerance using antibody titer is adopted by many mink farmers. The objective of this study was to investigate the effects of various doses of a local AMDV isolate on the response of black American mink to infection with AMDV. Methods Eight black American mink were each inoculated intranasally with 0.5 mL of eight serial 10‐fold dilutions (100 to 10−7) of a 10% spleen homogenate containing a local AMDV isolate. Blood samples were collected on days 0, 20, 35, 56, 84, 140, and 196 postinoculation (dpi). Anti‐AMDV antibodies and viral DNA were tested by counter‐immunoelectrophoresis (CIEP) and PCR, respectively. Animals that were PCR or CIEP positive at 196 dpi (n = 41) were killed at 218 dpi, and samples of blood and seven organs were tested by CIEP and PCR. Results Antibody production persisted in all seroconverted mink until the termination of the experiment, whereas 71.1% of the mink showed short‐lived viremia. Significant associations were observed between inoculum dose and the incidence of viremia until 84 dpi which disappeared thereafter, whereas associations between inoculum dose and the incidence of seropositive mink were significant on all sampling occasions. Antibody titer at 218 dpi significantly decreased with decreasing inoculum dose. AMDV DNA was detected in the bone marrow, lymph nodes, and spleen samples of almost all mink inoculated at every dose but was not detected in other organs of some mink. Conclusions CIEP is more accurate than PCR for detecting AMDV infection in mink. Using antibody titer in naturally infected mink may not be accurate for the identification of tolerant mink., The predicted probabilities for viremia across all inoculum doses were the greatest at 20 dpi, and the effect became smaller as times after inoculation prolonged, and almost disappeared after 84 dpi. The predicted probabilities for viremia across all eight inoculum doses (100 to 10‐7) on the six sampling occasions (20, 35, 56, 84, 140 and 196 day post‐inoculation) were the greatest at 20 dpi, and the effect became smaller as times after inoculation prolonged, and almost disappeared after 84 dpi.

Heliotropium crispum-mediated assembly of silver nanoparticles exhibit profound antibacterial and anti-biofilm effects against multiple drug-resistant bacteria, but its stability and biocompatibility remain a hurdle in commercialization. Herein, we adopted a surface chemistry-based steric repulsion approach to investigate the colloidal stability of H. crispum silver nanoparticles (HC-AgNPs) and determine its application as a commercial antibacterial formulation. Two primary silver nanoparticles (AgNPs) were synthesized, i.e., HC-AgNPs and citrate-HC-AgNPs initially, which were then modulated to assemble various derivatives of AgNPs using polyethylene glycol (PEG) and polyvinylpyrrolidone (PVP) as stabilizing agents. Various parameters were assessed to investigate the morphology, colloidal physio-chemistry, and surface capping using various analytical techniques, such as UV–Vis spectrophotometer, zeta–dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM, and transmission electron microscopy (TEM). Selective AgNPs were then screened on the basis of stability for up to 8 months, heat resistance at 100 °C, and bioactivity via MTT assay using HEP-2, MCF-7, and HCEC cell lines. The UV–Vis and electron microscope results revealed that HC-AgNPs confer near-spherical and slight triangular-shaped morphology and the size of all synthesized AgNPs is in the range of 400–450 nm. All AgNPs synthesized from HC-source have characteristic FTIR peaks recorded near 2931 cm−1, 1996 cm−1, and 825 cm−1. This study highlights promising evidence for the commercial application of HC-AgNPs as an antimicrobial agent. Additionally, it provides a methodology for modulating the surface capping of biological nanoparticles and assesses its corresponding effect on the stability.

Artemisia vulgaris seeds extrude hydrogel (AVH), which shows extraordinary swelling in water, at pH 6.8, and 7.4, which follows second-order kinetics. AVH exhibits reversible swelling/deswelling in ethanol and normal saline as well at pH 7.4 and pH 1.2. Therefore, AVH shows stimuli-responsiveness in different physiological conditions, solvents, and electrolytes. The superporous nature of AVH in swollen/freeze-dried sculpture is exposed in their SEM micrographs. AVH-based aceclofenac tablet formulations offer sustained-release under simulated conditions of the gastrointestinal tract (GIT) in terms of pH and transit time. Pharmacokinetic studies also show the delay and prolonged plasma concentration with tmax of 8 h, therefore, such formulations can be used to enhance the bioavailability of aceclofenac. The swelling behavior of the AVH tablet is also assessed using MRI. The in vivo fate of the AVH tablet is monitored by X-ray during the transit through the GIT. Acute toxicity studies of AVH indicate the absence of any toxicity which reveals the safety profile of AVH. Therefore, AVH can be used for oral, topical and ophthalmic drug delivery systems. These results establish the potential of AVH as a stimuli sensitive, pH-dependent, and sustained-release biomaterial for targeted drug delivery.

Background and Aim: To assess the autonomic nerve functions in latent and manifest patients of acute intermittent porphyria. The aim of the present study was to study cardiovascular responses to autonomic nerve functions in patients of acute intermittent porphyria, we also tried to find out the relative sensitivity of the various tests employed to study cardiac dysautonomia in these cases. Methods: The study was carried out on thirty cases of acute intermittent porphyria to assess the cardiovascular reflexes. Twenty five healthy subjects closely matched for age and sex served as control. The cases were diagnosed by modified Watson Schwartz test, the cases of acute intermittent porphyria were divided into three groups. Results: The values of different autonomic nerve function tests were compared with control group and among the different groups of patients. The results were complied, compared and a conclusion was drawn. Immediate heart rate response to standing is more sensitive test than the Valsalva maneuver. Immediate heart rate response to standing is more sensitive and quite reliable which can easily be performed at bed side or even in outpatient departments, the test is simple and non–invasive. In our opinion, the test, beat to beat variation of heart rate to single deep breath is though easy to perform and more understandable, but lacks the sensitivity of other two tests. Conclusion: Significant cardiac dysautonomia is present in asymptomatic group, it is more marked in acute attack group. Immediate heart rate response to standing could be a more sensitive and reliable test in this dysfunction.

Background Tranexamic acid reduces blood loss in surgery and the risk of death in trauma patients. Meta-analyses of small trials suggest that tranexamic acid decreases the number of deaths from gastrointestinal bleeding, but these meta-analyses are prone to selection bias. Objective The trial provides reliable evidence of the effect of tranexamic acid on mortality, rebleeding and complications in significant acute gastrointestinal bleeding. Design A multicentre, randomised, placebo-controlled trial and economic analysis. Patients were assigned by selecting one treatment pack from a box of eight, which were identical apart from the pack number. Patients, caregivers and outcome assessors were masked to allocation. The main analyses were by intention to treat. Setting The setting was 164 hospitals in 15 countries, co-ordinated from the London School of Hygiene & Tropical Medicine. Participants Adults with significant upper or lower gastrointestinal bleeding (n = 12,009) were eligible if the responsible clinician was substantially uncertain about whether or not to use tranexamic acid. The clinical diagnosis of significant bleeding implied a risk of bleeding to death, including hypotension, tachycardia or signs of shock, or urgent transfusion, endoscopy or surgery. Intervention Tranexamic acid (a 1-g loading dose over 10 minutes, then a 3-g maintenance dose over 24 hours) or matching placebo. Main outcome measures The primary outcome was death due to bleeding within 5 days of randomisation. Secondary outcomes were all-cause and cause-specific mortality; rebleeding; need for endoscopy, surgery or radiological intervention; blood product transfusion; complications; disability; and days spent in intensive care or a high-dependency unit. Results A total of 12,009 patients were allocated to receive tranexamic acid (n = 5994, 49.9%) or the matching placebo (n = 6015, 50.1%), of whom 11,952 (99.5%) received the first dose. Death due to bleeding within 5 days of randomisation occurred in 222 (3.7%) patients in the tranexamic acid group and in 226 (3.8%) patients in the placebo group (risk ratio 0.99, 95% confidence interval 0.82 to 1.18). Thromboembolic events occurred in 86 (1.4%) patients in the tranexamic acid group and 72 (1.2%) patients in the placebo group (risk ratio 1.20, 95% confidence interval 0.88 to 1.64). The risk of arterial thromboembolic events (myocardial infarction or stroke) was similar in both groups (0.7% in the tranexamic acid group vs. 0.8% in the placebo group; risk ratio 0.92, 95% confidence interval 0.60 to 1.39), but the risk of venous thromboembolic events (deep-vein thrombosis or pulmonary embolism) was higher in tranexamic acid-treated patients than in placebo-treated patients (0.8% vs. 0.4%; risk ratio 1.85, 95% confidence interval 1.15 to 2.98). Seizures occurred in 38 patients who received tranexamic acid and in 22 patients who received placebo (0.6% vs. 0.4%, respectively; risk ratio 1.73, 95% confidence interval 1.03 to 2.93). In the base-case economic analysis, tranexamic acid was not cost-effective and resulted in slightly poorer health outcomes than no tranexamic acid. Conclusions Tranexamic acid did not reduce death from gastrointestinal bleeding and, although inexpensive, it is not cost-effective in adults with acute gastrointestinal bleeding. Future work These results caution against a uniform approach to the management of patients with major haemorrhage and highlight the need for randomised trials targeted at specific pathophysiological processes. Limitations Although this is one of the largest randomised trials in gastrointestinal bleeding, we cannot rule out a modest increase or decrease in death due to bleeding with tranexamic acid. Trial registration Current Controlled Trials ISRCTN11225767, ClinicalTrials.gov NCT01658124 and EudraCT 2012-003192-19. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 58. See the NIHR Journals Library website for further project information.

This study focused on examining the effects of personality traits in moderating relationship between religiosity and mental health of university students. It was conducted on a sample of (N = 372) university students aged between 20 and 26 years equated to gender: 186 male and 186 female students at Bahauddin Zakariya University Multan. The religiosity, mental health and personality traits were measured by using the scale of Religiosity of Islam, Inventory of Mental Health and Big Five Inventory, respectively. The correlation analyses showed the significant relationship of religiosity with behavioral control but negatively associated with anxiety and depression as two dimensions of mental health. The results further demonstrated that openness to experience and agreeableness as traits of students' personality considerably moderated the relationship of religiosity and mental health.

Background: Use of the World Health Organization’s (WHO) Safe Childbirth Checklist (SCC) has been associated with a significant reduction of maternal mortality. Method: A descriptive cross-sectional survey conducted at a tertiary care hospital of Rawalpindi in labour room and postnatal ward from February 2018 to July 2018. A sample size of 359 was estimated using WHO sample size calculator and were enrolled using purposive sampling technique. A close ended WHO standardized questionnaire covering the 22 elements of WHO SCC was used. Frequencies and percentages were documented of variables and data was analysed using SPSS version 23. Results: Mean age of participants was 27 ± 4.25 years. On admission, it was observed that being centre of excellence and referral, there was 100% availability of gloves and supplies to clean hands before and after each vaginal examination. Just before pushing or caesarean, it was found that in 342 (95.3%) patients, assistant was identified to help at time of birth. Immediately after one hour of birth, it was noted that 79 (22%) patients were bleeding abnormally and were immediately addressed. We also found out that only 79 (22%) of the mothers were counselled regarding family planning. Almost half of the participant mothers 182 (50.7%) or their companions were counselled regarding danger signs and to seek care immediately which should have been 100%. Conclusion: Excellent adoption of some of the element up to 100% was observed while some of the elements of checklist were poorly adopted; noticeable was counselling regarding family planning options immediate postpartum.

Intranasal, with (INS) and without (IN) sedation, and oral inoculation were compared with intraperitoneal (IP) injection for establishing infection with a local isolate of Aleutian mink disease virus (AMDV) in 35 American mink. Blood samples were collected on 0, 21, 36 and 56 day post-inoculation (dpi). Antiviral-antibodies and viral DNA in plasma and tissues were measured by counter-immunoelectrophoresis (CIEP) and PCR, respectively. The presence of AMDV DNA was tested by PCR in saliva, rectal and fecal samples collected on 0, 6, 10, 15, 21, 28, 36 and 56 dpi. Animals were killed at 56 dpi, samples of six organs were tested for antibody and AMDV DNA, and samples of the lungs, liver, kidneys and heart were subjected to histology. Viral DNA was detected in the spleen, lungs and lymph nodes of all inoculated mink on 56 dpi, indicating that all inoculation routes caused infection in mink. Viral DNA and antibodies were detected in plasma of all IP and INS inoculated mink by 36 dpi, but some animals which were inoculated orally or via IN remained seronegative by 56 dpi. It was concluded that INS route was the most effective method for establishing infection in mink without breaking the integrity of the animals' anatomical barriers. Viremia was short-lived in some mink, whereas antibody production persisted in seroconverted animals during the duration of the experiment. Saliva, rectal and fecal samples did not accurately detect infection. Histologic lesions of AD were observed on the four organs of most mink.

The dramatic increase in antimicrobial resistance for pathogenic bacteria constitutes a key threat to human health. The Centers for Disease Control and Prevention has recently stated that the world is on the verge of entering the "post-antibiotic era", one where more people will die from bacterial infections than from cancer. Recently, nanoparticles (NPs) have emerged as new tools that can be used to combat deadly bacterial infections. Nanoparticle-based strategies can overcome the barriers faced by traditional antimicrobials, including antibiotic resistance. In this tutorial review, we have highlighted multiple nanoparticle-based approaches to eliminate bacterial infections, providing crucial insight into the design of elements that play critical roles in creating antimicrobial nanotherapeutics. In particular, we have focused on the pivotal role played by NP-surface functionality in designing nanomaterials as self-therapeutic agents and delivery vehicles for antimicrobial cargo.

Bacterial multidrug resistance (MDR) is a serious healthcare issue caused by the long-term subtherapeutic clinical treatment of infectious diseases. Nanoscale engineering of metal nanoparticles has great potential to address this issue by tuning the nano–bio interface to target bacteria. Herein, we report the use of branched polyethylenimine-functionalized silver nanoclusters (bPEI–Ag NCs) to selectively kill MDR pathogenic bacteria by combining the antimicrobial activity of silver with the selective toxicity of bPEI toward bacteria. The minimum inhibitory concentration of bPEI–Ag NCs was determined against 12 uropathogenic MDR strains and found to be 10- to 15-fold lower than that of PEI and 2- to 3-fold lower than that of AgNO3 alone. Cell viability and hemolysis assays demonstrated the biocompatibility of bPEI–Ag NCs with human fibroblasts and red blood cells, with selective toxicity against MDR bacteria.

Coronavirus Disease 2019 (COVID-19) ranks third in terms of fatal coronavirus diseases threatening public health, coming after SARS-CoV (severe acute respiratory syndrome coronavirus), and MERS-CoV (Middle East respiratory syndrome coronavirus). SARS-CoV-2 (severe acute respiratory syndrome coronavirus type 2) causes COVID-19. On January 30, 2020, the World Health Organization (WHO) announced that the current outbreak of COVID-19 is the sixth global health emergency. As of December 3, 2020, 64 million people worldwide have been affected by this malaise, and the global economy has experienced a loss of more than $1 trillion. SARS-CoV-2 is a positive-sense single-stranded RNA virus belonging to the Betacoronavirus genus. The high nucleotide sequence identity of SARS-CoV-2 with the BatCoV RaTG13 genome has indicated that bats could be the possible host of SARS-CoV-2. SARS-CoV-2 penetrates the host cell via binding its spike protein to the angiotensin-converting enzyme 2 (ACE2) receptor, which is similar to the mechanisms of SARS-CoV and MERS-CoV. COVID-19 can spread from person to person via respiratory droplets and airborne and contaminated fomites. Moreover, it poses a significant risk to smokers, the elderly, immunocompromised people, and those with preexisting comorbidities. Two main approaches are used to control viral infections, namely, vaccination, and biosecurity. Studies to analyze the antigenicity and immunogenicity of SARS-CoV-2 vaccine candidates are underway, and few vaccines may be available in the near future. In the current situation, the Human Biosecurity Emergency (HBE) may be the only way to cope effectively with the novel SARS-CoV-2 strain. Here, we summarize current knowledge on the origin of COVID-19 as well as its epidemiological relationship with humans and animals, genomic resemblance, immunopathogenesis, clinical-laboratory signs, diagnosis, control and prevention, and treatment. Moreover, we discuss the interventional effects of various nutrients on COVID-19 in detail. However, multiple possibilities are explored to fight COVID-19, and the greatest efforts targeted toward finding an effective vaccine in the near future. Furthermore, antioxidants, polyphenols, and flavonoids, both synthetic and natural, could play a crucial role in the fight against COVID-19.

International audience; Aim: To fabricate and evaluate curcumin-loaded transfersomes (Cur-TF) for the targeted delivery and enhanced therapeutic efficacy of curcumin for the treatment of rheumatoid arthritis (RA). Methods: Modified thin-film hydration method was used to prepare Cur-TF which were then embedded into carbopol-934 gel. They were further evaluated through in vitro techniques and in an in vivo arthritis model. Results: Cur-TF had optimal particle size, spherical morphology, high encapsulation efficiency and sustained drug release profiles. The Cur-TF gel had better in vitro skin penetration than plain curcumin. In vivo findings demonstrated improved clinical, histological and x-ray scores and reduced pro-inflammatory cytokines through NF-κβ inhibition. Conclusion: Cur-TF gel delivered curcumin to the arthritic dermal tissue through a topical route and demonstrated promising therapeutic efficacy by significantly alleviating complete Freud's adjuvant (CFA)-induced arthritis.

The current pandemic of coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) has challenged healthcare structures across the globe. Although a few therapies are approved by FDA, the search for better treatment options is continuously on rise. Clinical management includes infection prevention and supportive care such as supplemental oxygen and mechanical ventilatory support. Given the urgent nature of the pandemic and the number of companies and researchers developing COVID‐19 related therapies, FDA has created an emergency program to move potential treatments with already approved drugs to patients as quickly as possible in parallel to the development of new drugs that must first pass the clinical trials. In this manuscript, we have reviewed the available literature on the use of sequence‐specific degradation of viral genome using short‐interfering RNA (siRNA) suggesting it as a possible treatment against SARS‐CoV‐2. Delivery of siRNA can be promoted by the use of FDA approved lipids, polymers or lipid‐polymer hybrids. These nanoparticulate systems can be engineered to exhibit increased targetability and formulated as inhalable aerosols.

Metabesity refers to metabolic aberrations associated with obesity. These include low- grade inflammation, mitochondrial dysfunction, and changes in gut microbiome. Along with a genetic component, the phenotypes in metabesity are largely the result of sedentary lifestyle and unhealthy eating habits. Metabesity is associated with several co-morbidities including an increased risk for cardiovascular conditions like hypertension, heart failure, myocardial infarction, stroke, and sudden death. Insulin resistance, high blood pressure and glucose levels, visceral adiposity, progressive atherosclerosis, dyslipidaemia and fatty liver are common in obese individuals. Obesity increases the risk for and overall mortality due to cancer. Metabesity adversely impacts endocrine balances in the body and increases the risk of degenerative conditions like dementia. Metabesity is an impending epidemic of huge public health implications with enormous clinical, socioeconomic, and humanistic burden. Interventions to combat sedentary lifestyle and unhealthy eating should be introduced early in life to prevent the onset and progression of metabesity. This review also summarizes the experts' recommendation from Pakistan to manage the rising metabesity concern in their geography based on the literature evidences.

Summary 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. Funding UK National Institute for Health Research Health Technology Assessment Programme.

Present research demonstrated the crosslinking of Cydonia oblonga seeds hydrogel using citric acid (CA) and evaluated its stimuli-responsive swelling properties at different biomimetic pH, swelling/deswelling behavior against different fluids and sustained release potential in orally administered tablet formulation. Cross-linked C. oblonga hydrogel (CL-COH) was synthesized using four concentrations of CA, i.e., 1.25%, 2.5%, 5% and 10% and characterized through Fourier transform infrared (FTIR) spectroscopic analysis. CL-COH exhibited high swelling capacity at pH 6.8, 7.4 and in deionized water whereas, insignificant swelling was observed at pH 1.2. Swelling/deswelling response of CL-COH (2.5% CA) at pH 7.4 and 1.2, in deionized water and ethanol, and deionized water and normal saline were remarkable and reproducible results were obtained even after four cycles. Scanning electron microscopy (SEM) images of CL-COH indicated evenly distributed web of interconnected macro-pores. CL-COH was used as a pH-sensitive sustained release material for the preparation of oral tablet formulation of levosulpiride. In vitro drug release study revealed that the drug release followed zero-order kinetics and drug release mechanism was found as a super case II transport. Non-thrombogenic and non-hemolytic potential of CL-COH was ascertained through haemocompatibility studies. Therefore, CL-COH can be a versatile stimuli-responsive and biocompatible polysaccharide-based material for zero-order sustained release of drugs.

Microneedle patch is a prominent strategy with minimal invasion and painless application to improve skin penetration of drug molecules. Herein, we report microneedle patch (MNP) as an alternative to the oral route for the systemic delivery of tacrolimus (TM), an immunosuppressant drug. Thiolated chitosan (TCS) based microneedle patch was fabricated and characterized in vitro and in vivo for its mechanical strength, skin penetration, drug release, and skin irritation. The MNP having 225 needles with 575 μm showed good mechanical properties in terms of tensile strength and percentage elongation. The skin penetration showed 84% penetration with no breakage. Histology of the mice skin after insertion showed the penetration of needles into the dermis. In vitro release and ex vivo permeation studies through Franz diffusion cell showed the sustained release (82.5%) of TM from the MNP with significantly higher (p

The oral delivery of cancer chemotherapeutic drugs is challenging due to low bioavailability, gastrointestinal side effects, first-pass metabolism and P-glycoprotein efflux pumps. Thus, chemotherapeutic drugs, including Docetaxel, are administered via an intravenous route, which poses many disadvantages of its own. Recent advances in pharmaceutical research have focused on designing new and efficient drug delivery systems for site-specific targeting, thus leading to improved bioavailability and pharmacokinetics. A decent number of studies have been reported for the safe and effective oral delivery of Docetaxel. These nanocarriers, including liposomes, polymeric nanoparticles, metallic nanoparticles, hybrid nanoparticles, dendrimers and so on, have shown promising results in research papers and clinical trials. The present article comprehensively reviews the research efforts made so far in designing various advancements in the oral delivery of Docetaxel. Different strategies to improve oral bioavailability, prevent first-pass metabolism and inhibition of efflux pumping leading to improved pharmacokinetics and anticancer activity are discussed. The final portion of this review article presents key issues such as safety of nanomaterials, regulatory approval and future trends in nanomedicine research.

We propose a facile, cost-effective and commercially viable method to prepare durable superhydrophobic surfaces using a bio-waste material. The naturally available nanostructured sawdust particles were combined with polychlroprene adhesive, carbon soot and silicon polymer to formulate superhydrophobic coatings. Saw dust particles were bonded on the substrate using polychloroprene adhesive, which was followed by depositing silicone by dip-coating to produce a superhydrophobic surface. To further improve the mechanical and superhdyrophobic properties, a thin layer of carbon soot was deposited and stabilized by second layer of silicone. Electron microscopy, spectroscopy and goniometry were employed for microstructural analysis, chemical nature and the contact angle measurements of the coatings. After quantifying the excellent response against mechanical abrasion, the superhydrophobic coating was employed on a mesh to demonstrate its application for oil/water separation. It was observed that the coated mesh successfully separated both light and heavy oils from oil/water mixtures with high separation efficiency and therefore has the potential for large-scale separation of oil/water mixtures.

In the present study, we evaluated attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy for the differential diagnosis hepatitis C virus (HCV) and Dengue virus (DENV) infected freeze-dried sera along with healthy freeze-dried sera. Spectral signatures were recorded from 50 freeze-dried sera samples of each sample type. To achieve improved classification accurateness between the three sample types, multivariate data classification algorithms principal component analysis (PCA) and principal component regression (PCR) were used. Outcomes show 96 % inter-class variation as depicted by PCA and a classification accuracy of 99.2 % using PCR as shown by the value of R2; therefore, we propose that ATR-FTIR coupled with chemo metric data classification algorithms has considerable potential to distinguish HCV and DENV infected freeze-dried sera samples.

Salmonella typhi infections are difficult to treat due to poor penetration of current antibiotic ciprofloxacin (CIP) modalities into the intracellular compartments of macrophages owing to poor solubilization and oral bioavailability. Poor penetration and dissolution of CIP lead to development of intracellular pathogens induced multi-drug resistance and resistant biofilms formation. Here we developed a novel strategy for the design and development of mucopenetrating self-emulsifying drug delivery system (SEDDS) of CIP to target intracellular Salmonella typhi bacterium with high specificity and selectivity. Oleic oil, Tween 80, and PEG 200 were selected as oil, surfactant and co-surfactant based on solubilizing capacity and pseudo ternary diagram emulsification capability. Mucopenetration feature of the SEDDS was enhanced by inclusion of poly-L-lysine functionalized carbohydrates (mannose, preactivated hyaluronic acid) co-block pluronic F127 (PLL-M-PTHA-F127) polymeric excipient. PLL-M-PTHA-F127 was developed as an amphiphilic muco-penetrating targeted anti-bacterial biological entity for intracellular targeting of Salmonella typhi infection reservoirs. Characterization of these self-nanoemulsifying carriers was carried out via dynamic light scattering (DLS), transmission electron microscopy (TEM) and fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), x-ray diffraction (XRD) and thermogravimetric analysis (TGA) The observed hydrodynamic diameter of PLL-M-PTHA-F 127 self- nano emulsifying drug delivery system (SEDDS) was 247 nm with low PDI and negatively charged zeta potential showing the stabilization of as-prepared formulation. In vitro drug release kinetics of nanocarriers exhibited 85% sustained release within 72 h under sink conditions. PLL-M-PTHA-F127 SEDDS of CIP showed very strong killing capability against Salmonella typhi strains even at lowest concentrations as compared to CIP and were found to be hemocompatible and biocompatible. The intracellular Salmonella typhi survival rate has been minimized with PLL-M-PTHA-F127 SEDDS as compared to CIP alone. Fluorescence microscopy images confirmed the proficient cellular uptake within the intracellular compartment of macrophages and rapid gallstone biofilm dispersion/clearance activity as compared to other formulations and CIP. In summary, PLL-M-PTHA-F127-SEDDS of CIP seemed to be an ideal candidate for eradication of Salmonella typhi intracellularly.

Current study was designed to investigate micromeritic properties, water absorption capacity, stimuli (pH, ethanol and saline) responsive swelling-deswelling (on-off switching) and controlled drug release from the polysaccharide glucuronoxylan isolated from the seeds of Quince. The water retention capacity of Quince hydrogel (QH) was found admirable. The hydrogel also exhibited privileged swelling in water and basic buffers (pH 6.8 and 7.4) while insignificant swelling in acidic buffer (pH 1.2). The swelling kinetics of QH follows second order. Moreover, QH deswells in salt (KCl and NaCl) solutions and ethanol. SEM of swollen then freeze dried QH revealed hollow channels with an average diameter of 67.8μm. Furthermore, QH sustained the release of levosulpiride (LS) tablet formulation and drug release mechanism was ascertained super case-II transport. These results signify QH a smart material for sustained release formulations.

Hydrogel forming polysaccharides are attracting attention for the design of diverse nature silver nanoparticles (Ag NPs) with potential biological applications. Herein, we report the green synthesis of Ag NPs and their antimicrobial activity along with their potential application in wound dressings. Glucuronoxylan (GX) isolated from seeds of Mimosa pudica (MP) was used as a stabilizing/capping agent to prepare the NPs under diffused sunlight using different concentrations of AgNO3. The progress of the reaction was monitored using a UV-visible spectrophotometer and characteristic surface plasmon absorption (SPR) bands were found in the range of 390–465 nm. The morphology and elemental composition of the synthesized Ag NPs were analyzed using scanning electron microscopy equipped with STEM and EDS detectors and the diameter of the Ag NPs was found to be in the range of 2 to 18 nm. The synthesized NPs exhibited antimicrobial potential against Staphylococcus epidermidis, Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, Staphylococcus aureus, Aspergillus niger, Penicillium notatum, Rhizopus stolonifer and Actinomycetes odontolyticus. The minimal inhibitory concentrations (MICs) of the Ag NPs against different pathogenic strains were determined. Moreover, the dressing prepared from Ag NP impregnated GX exhibited a remarkable wound healing potential in rabbits. In situ synthesized Ag NPs were stored in the form of GX thin films and their UV/vis spectra exhibited that the texture of the Ag NPs remained intact after a six month storage period.

Ratodero is Taluka of population 224,000 in the district Larkana of Sindh, Pakistan. In the HIV outbreak (2019), 1132 HIV patients were reported in the Ratodero, amongst them, 901 (80%) were children, and the majority (735) below the age of 5 years.1 Larkana district is included among the cities where eight (8) COVID-19 carrier pilgrims from Iran were first confirmed as virus positive.2 Followed by community transmission in the area with the confirmation of the virus in the two individuals.3 There was reported shortage of the personnel protection equipment (PPEs) for the Medical Professional engaged in the tests of the COVID-19 as well as the shortage of Kits, so less number of COVID-19 tests were conducted, therefore the actual number of COVID-19 positive can abruptly raise with the availability of Kits and PPEs.4 There is a complete lockdown in the area since last week of March 2020. There is one medical University with an affiliated hospital. Collaborative efforts of the University teaching hospital and the district administration have constituted a team of experts for necessary actions to combat with expected Corona-19 outbreak. In such circumstances of the existence of HIV in Ratodero as an alarm of threats for another health risk for the poor HIV children of Ratodero Larkana. Dated 09 April 2020. there was a random selection of 20 such HIV children of Ratodero below the age 5, to have look on their physical health and to confirm the quantity/availability of ART (antiretroviral treatment) at their home. It was found that 30% of children were found physically weak. The confirmed average availability of remaining ART drugs was found available for use in the next 14 days. Generally, the children are the population of developing immunity (vulnerable age group) hence there can be increased risk if Co-Infection of COVID-19 if hits the Ratodero Taluika. Therefore the District of Larkana in general but the Taluka Ratodero, in particular, need special attention from the health administration. Following preventive measures can be useful to prevent the spread of COVID-19 among the HIV children of Ratodero, Larkana. • Better compliance of prophylactic SOPs verses COVID-19 through proper surveillance at the rural level in Ratodero. • Availability of Rashan on priority for the families of registered HIV children of Ratodero, taking into account the inclusion of all requirements of good nutrients in the daily intake. • COVID-19 screening of registered HIV children. • HIV Screening of any COVID-19 career of Ratodero if the individual is not amongst already registered HIV patients. • Establishment of a dedicated isolation ward in case of Co-Infection in these children along with the provision of special care to prevent the onset of COVID-19 symptoms in these patients. • Advance Supply of 03 to 06 month ART at home as per instructions of the World Health Organization (WHO) for such HIV patients.5

We investigated type 2 diabetes (T2D) genetic susceptibility in a multi-ethnic meta-analysis of 228,499 cases and 1,178,783 controls in the Million Veteran Program (MVP) and other biobanks. We identified 558 autosomal and 10 X-chromosome T2D-associated variants, of which 286 autosomal and 7 X-chromosome variants were previously unreported. Ancestry-specific analyses identified 25 additional novel T2D-susceptibility variants. Transcriptome-wide association analysis detected 3,568 T2D-associations with T2D-colocalized genetically predicted gene expression of 804 genes in 52 tissues, of which 687 are novel. Fifty-four of these genes are known to interact with FDA-approved drugs and chemical compounds. T2D polygenic risk score was strongly associated with increased the risk of T2D-related retinopathy, and additionally showed evidence for association with chronic kidney disease (CKD), neuropathy, and peripheral artery disease (PAD). We investigated the genetic etiology of T2D-related vascular outcomes in the MVP and observed statistical SNP-T2D interactions at 13 variants, including 3 for coronary heart disease, 1 for PAD, 2 for stroke, 4 for retinopathy, 2 for CKD, and 1 for neuropathy. Our findings may identify potential novel therapeutic targets for T2D and genomic pathways that link T2D and its vascular outcomes.

Introduction The adequate management of thoracic trauma requires a systematic approach including pain control, respiratory therapy, and mobility achieved by surgical fixation. Failure to achieve pain control prolongs hospital stay. There are several options for achieving analgesia including epidural catheters, intravenous narcotics, intercostal, paravertebral or interpleural blocks, oral opioids, or simply a combination of the aforementioned interventions. In this study, we aim to compare the efficacy of thoracic epidural analgesia with systemic analgesia in patients with polytrauma. Methods This prospective study was conducted in the intensive care unit (ICU) of District Headquarters Hospital in Dera Ghazi Khan, Pakistan. Patients of age ≥18 years with skeletal trauma - rib fractures, limb fractures, and pelvic fractures - were included in the study. Group A patients were given epidural - bupivacaine and tramadol. Group B patients were given systemic analgesia with intravenous opioids. The severity of pain was assessed on the visual analogue scale (VAS) at time 0, 24 hours, and 48 hours. Data was entered and analysis was performed using Statistical Package for Social Sciences version 22.0. Results At 24 hours and 48 hours interval, group A showed a lower mean VAS score than group B (p = 0.74; p = 0.03). Group A required lesser mean doses of additional short-acting analgesics than group B (4.87 ± 1.06 vs. 6.77 ± 1.44; p < 0.0001). In Group A, 94% were discharged and the mortality rate was 6%; in group B, 86% were discharged and the mortality rate was 14% (p = 0.21). Conclusion Epidural analgesia provides better pain relief and requires fewer short-acting supplementing analgesics as compared to systemic analgesia in patients with multi-trauma.

Objective To find the association between hyperuricemia and ischemic stroke. Study design Case-control study. Place and duration of study Departments of Medicine and Neurology, Mayo Hospital, Lahore, from October 2015 to September 2016. Methodology A total of 100 patients were recruited in the study. Fifty cases were of acute ischemic stroke and fifty were age- and gender-matched healthy controls. Serum uric acid level was estimted by photometry method at the time of admission. Hyperuricemia was defined as the serum uric acid level of more than 6 mg/dl. Results Mean serum uric acid levels in cases and controls were 5.996 ±1.99 mg/dl and 5.042 ±0.91 mg/dl, respectively. Hyperuricemia was present in 23 (46%) patients with ischemic stroke and in 10 (20%) controls. Among ischemic stroke patients, the frequency of hyperuricemia was significantly higher than in controls (p-value =0.006, Odds Ratio (OR) =3.41.) Conclusion: Serum uric acid was found significantly elevated in ischemic stroke patients versus controls with 3.41 times more risk of having hyperuricemia in ischemic stroke patients. Key Words: Hyperuricemia, Ischemic stroke, Serum uric acid (SUA).

[Image: see text] Direct infusion high-resolution mass spectrometry (DIHRMS) is a novel, high-throughput approach to rapidly and accurately profile hundreds of lipids in human serum without prior chromatography, facilitating in-depth lipid phenotyping for large epidemiological studies to reveal the detailed associations of individual lipids with coronary heart disease (CHD) risk factors. Intact lipid profiling by DIHRMS was performed on 5662 serum samples from healthy participants in the Pakistan Risk of Myocardial Infarction Study (PROMIS). We developed a novel semi-targeted peak-picking algorithm to detect mass-to-charge ratios in positive and negative ionization modes. We analyzed lipid partial correlations, assessed the association of lipid principal components with established CHD risk factors and genetic variants, and examined differences between lipids for a common genetic polymorphism. The DIHRMS method provided information on 360 lipids (including fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, and sterol lipids), with a median coefficient of variation of 11.6% (range: 5.4–51.9). The lipids were highly correlated and exhibited a range of associations with clinical chemistry biomarkers and lifestyle factors. This platform can provide many novel insights into the effects of physiology and lifestyle on lipid metabolism, genetic determinants of lipids, and the relationship between individual lipids and CHD risk factors.

Pseudomonas aeruginosa and Staphylococcus aureus are among the hazardous biofilm forming bacteria ubiquitous in industrial/clinical wastes. Serious efforts are required to develop effective strategies to control surface-growing antibiotic resistant pathogenic bacterial communities which they are emerging as a global health issue. Blocking hazardous biofilms would be a useful aspect of biosurfactant coated nanoparticles (NPs). In this regard, we report a facile method for the synthesis of rhamnolipid (RL) coated silver (Ag) and iron oxide (Fe3O4) NPs and propose the mechanism of their synergistic antibacterial and anti-adhesive properties against biofilms formed by P. aeruginosa and S. aureus. These NPs demonstrated excellent anti-biofilm activity not only during the biofilms formation but also on the pre-formed biofilms. Mechanistically, RL coated silver (35 nm) and Fe3O4 NPs (48 nm) generate reactive oxygen species, which contribute to the antimicrobial activity. The presence of RLs shell on the nanoparticles significantly reduces the cell adhesion by modifying the surface hydrophobicity and hence enhancing the anti-biofilm property of NPs against both mentioned strains. These findings suggest that RL coated Ag and Fe3O4 NPs may be used as potent alternate to reduce the infection severity by inhibiting the biofilm formation and, therefore, they possess potential biomedical applications for antibacterial coatings and wound dressings.