Optimization, In Vitro and Ex Vivo Assessment of Nanotransferosome Gels Infused with a Methanolic Extract of Solanum xanthocarpum for the Topical Treatment of Psoriasis.

The goal of this investigation is to improve the topical delivery of medicine by preparing and maximizing the potential of a nanotransferosome gel infused with Solanum xanthocarpum methanolic extract (SXE) to provide localized and regulated distribution. Thin-film hydration was used to create SXE-infused nanotransferosomes (SXE-NTFs), and a Box-Behnken design was used to improve them. Phospholipon 90G (X1), cholesterol (X2) and sodium cholate (X3) were chosen as the independent variables, and their effects on vesicle size (Y1), polydispersity index (PDI) (Y2) and the percentage of entrapment efficiency (EE) (Y3) were observed both individually and in combination. For the SXE-NTFs, the vesicle size was 146.3 nm, the PDI was 0.2594, the EE was 82.24 ± 2.64%, the drug-loading capacity was 8.367 ± 0.07% and the drug release rate was 78.86 ± 5.24%. Comparing the antioxidant activity to conventional ascorbic acid, it was determined to be 83.51 ± 3.27%. Ex vivo permeation tests revealed that the SXE-NTF gel (82.86 ± 2.38%) considerably outperformed the SXE gel (35.28 ± 1.62%) in terms of permeation. In addition, it seemed from the confocal laser scanning microscopy (CLSM) picture of the Wistar rat's skin that the rhodamine-B-loaded SXE-NTF gel had a higher penetration capability than the control. Dermatokinetic studies showed that the SXE-NTF gel had a better retention capability than the SXE gel. According to the experimental results, the SXE-NTF gel is a promising and successful topical delivery formulation.

Dissolving microneedle transdermal patch loaded with Risedronate sodium and Ursolic acid bipartite nanotransfersomes to combat osteoporosis: Optimization, characterization, in vitro and ex vivo assessment.

Osteoporosis is a fatal bone-wearing malady and a substantial reason behind the impermanence of human life and economic burden. Risedronate Sodium along with Ursolic acid has been studied to ameliorate osteoporosis. To bypass problems associated with bioavailability, we have developed a microneedle transdermal patch loaded with optimized formulation nanotransfersomes. It was optimized using three factor, three-level Central composite design with independent variables namely, the concentration of phospholipid, surfactant, and sonication time on dependent variables (vesicle size, entrapment efficiency and Polydispersity index). Vesicles of size 271.9 ± 8.45 nm with PDI 0.184 ± 0.01, having entrapment efficiency of 86.12 ± 5.20% and 85.65 ± 4.88% for RIS and UA respectively were observed. In vitro release study showed the sustained release pattern with 78.16 ± 1.12% and 75.72 ± 1.01% release of RIS and UA respectively. Dissolving MN patch prepared from gelatin was found to have good strength and folding endurance with uniform drug content (98.68 ± 0.004%). Ex vivo permeation study revealed that up to 80% of the drug can be permeated within 24 h. CLSM analysis was also performed to show penetration of RU-NTRs. From the results obtained, we can conclude that dissolving MN patch loaded with RU-NTRs has great potential than its conventional counterpart.

Does the CDC COVID-19 Exposure Assessment Criteria for Healthcare Personnel Work in a Healthcare Setting in Pakistan?

OBJECTIVE: To evaluate the real-world performance of the CDC's "Interim US guidance for risk assessment and work restriction for healthcare personnel with exposure to COVID-19" at a private healthcare system in Pakistan. STUDY DESIGN: Retrospective observational study. PLACE AND DURATION OF STUDY: The Aga khan University Hospital, Karachi, and its associated healthcare facilities in all four provinces of Pakistan, from February to September 2020. METHODOLOGY: Healthcare personnel (HCPs) assessed and tested for exposures to COVID-19 were included in the study. An exposure category was assigned to each HCP presenting with exposure to COVID-19 based on the CDC criteria. Percentage positivity was recorded and compared among the different exposure categories. Logistic regression analysis was used to identify variables significantly associated with COVID-19 infection. RESULTS: Three thousand Six hundred and forty-seven HCPs were assessed for exposure to COVID-19 of whom 603 (16.5%) tested positive. Percent positivity was highest in high-risk symptomatic HCPs (18.2%), 15.6% in low-risk symptomatic HCPs, and 11% in high-risk asymptomatic HCPs. After controlling for age, gender, area of work, and source of exposure, compared to low-risk asymptomatic HCPs, the odds of a positive SARS-CoV-2 PCR were 2.13 (95%CI: 1.49-3.04) for high-risk symptomatic, 1.66 (95% CI: 1.12-2.46) for low-risk symptomatic, and 1.18 (95% CI: 0.83-1.68) for high-risk asymptomatic HCPs. CONCLUSION: Regardless of exposure category, HCPs with symptoms consistent with COVID-19 have the highest likelihood of testing positive. The CDC exposure risk assessment criteria work best for symptomatic HCPs. Testing asymptomatic HCPs with high-risk exposures may not be necessary in low-resource settings with a limited healthcare workforce. KEY WORDS: COVID-19, Employee health, Occupational health and safety programs, Medical surveillance/screening, Return to work.

Prevalence and risk factors assessment of mange mites in livestock of Malakand Division, Pakistan.

Mange mites represent a serious problem in livestock farming due to their worse effect on animals health, reducing milk and meat production. The status of mange mites prevalence was unknown from the livestock present in Malakand Division, Pakistan. Hence, the present study was conducted to determine the prevalence and risk factors assessment of mange mites in livestock of Malakand Division, Pakistan. Villages and livestock herds were visited for data collection and sampling for one year from September 2017 to August 2018. The diagnosis of mange infestation was carried out from skin scrapings collected from symptomatic animals. A total of 1437 animals were screened (240 sheep, 658 cows, 340 buffalos, 199 goats) from selected localities of the Malakand Division. The overall prevalence was 2.37%, with the highest prevalence in buffalos (5.0%) and lowest (0.42%) in sheep (p < 0.05). The locality also significantly affect the prevalence of mange mites in livestock, with a higher percentage (8.14%) in the Ouch area. The prevalence was higher in winter (3.78%) than in summer (1.07%). The prevalence was high (p < 0.05) in young animals (≤1 year) (4.7%) as compared to adults (>1 year) (1.15%). Gender was also a significant risk factor for mange infestation. The infestation was higher in females (2.85%) as compared to males (0.64%) (p < 0.05). Herd size of less than ten animals had a significantly high prevalence rate (3.69%) compared to >10 animals (1.89%). Animals having an infection history >15 days infected more than animals having infection history ≤15 days. This study documented for the first-time epidemiology of mange mites in livestock of Malakand Division, Pakistan. Further studies involving molecular characterization of mange mites will increase our understanding on the spread of mange mites in Malakand Division livestock.

Toxicological risk assessment of some commonly used insecticides on Cotesia flavipes, a larval parasitoid of the spotted stem borer Chilo partellus.

Cotesia flavipes Cameron is an important larval parasitoid exploited for the control of the spotted stem borer, Chilo partellus (Swinhoe). Several studies have evaluated the toxic effects of insecticides on C. partellus, however, little is known about non-target effects of insecticides on this parasitoid, when used to control C. partellus. This laboratory study evaluated the lethal and sublethal effects of twelve insecticides on C. flavipes. Residual toxicity tests showed that organophosphates (chlorpyrifos, triazophos and profenofos) exhibited highest contact toxicity to C. flavipes adults with a LC50 range from 0.63 to 1.05 mg a.i/l, while neonicotinoids (nitenpyram, acetamiprid and imidacloprid) were less toxic to C. flavipes with a LC50 range from 1.27 to 139.48 mg a.i/l. Sugar-insecticide feeding bioassays showed that organophosphates, pyrethroids (cypermethrin, bifenthrin and lambda-cyhalothrin) and carbamates (thiodicarb, carbaryl and methomyl) were highly toxic to C. flavipes adults and caused 100% mortality at 48 h of exposure, while imidacloprid caused 66% mortality at 48 h of exposure. Risk quotient analysis showed that among all tested insecticides, imidacloprid and acetamiprid were less toxic to C. flavipes adults with a risk quotient value of 0.88 and 1.6, respectively. Furthermore, exposure of immature C. flavipes through their host bodies significantly decreased the parasitism rate at their F1 and F2 generations. Risk quotient analysis of insecticides indicated that imidacloprid and acetamiprid were the least toxic to C. flavipes. This study provides important information that will be used in incorporating the most suitable insecticides in integrated pest management programs with reduced negative impacts on non-target beneficial arthropods.

Global burden of acute lower respiratory infection associated with human metapneumovirus in children under 5 years in 2018: a systematic review and modelling study.

BACKGROUND: Human metapneumovirus is a common virus associated with acute lower respiratory infections (ALRIs) in children. No global burden estimates are available for ALRIs associated with human metapneumovirus in children, and no licensed vaccines or drugs exist for human metapneumovirus infections. We aimed to estimate the age-stratified human metapneumovirus-associated ALRI global incidence, hospital admissions, and mortality burden in children younger than 5 years. METHODS: We estimated the global burden of human metapneumovirus-associated ALRIs in children younger than 5 years from a systematic review of 119 studies published between Jan 1, 2001, and Dec 31, 2019, and a further 40 high quality unpublished studies. We assessed risk of bias using a modified Newcastle-Ottawa Scale. We estimated incidence, hospital admission rates, and in-hospital case-fatality ratios (hCFRs) of human metapneumovirus-associated ALRI using a generalised linear mixed model. We applied incidence and hospital admission rates of human metapneumovirus-associated ALRI to population estimates to yield the morbidity burden estimates by age bands and World Bank income levels. We also estimated human metapneumovirus-associated ALRI in-hospital deaths and overall human metapneumovirus-associated ALRI deaths (both in-hospital and non-hospital deaths). Additionally, we estimated human metapneumovirus-attributable ALRI cases, hospital admissions, and deaths by combining human metapneumovirus-associated burden estimates and attributable fractions of human metapneumovirus in laboratory-confirmed human metapneumovirus cases and deaths. FINDINGS: In 2018, among children younger than 5 years globally, there were an estimated 14·2 million human metapneumovirus-associated ALRI cases (uncertainty range [UR] 10·2 million to 20·1 million), 643 000 human metapneumovirus-associated hospital admissions (UR 425 000 to 977 000), 7700 human metapneumovirus-associated in-hospital deaths (2600 to 48 800), and 16 100 overall (hospital and community) human metapneumovirus-associated ALRI deaths (5700 to 88 000). An estimated 11·1 million ALRI cases (UR 8·0 million to 15·7 million), 502 000 ALRI hospital admissions (UR 332 000 to 762 000), and 11 300 ALRI deaths (4000 to 61 600) could be causally attributed to human metapneumovirus in 2018. Around 58% of the hospital admissions were in infants under 12 months, and 64% of in-hospital deaths occurred in infants younger than 6 months, of which 79% occurred in low-income and lower-middle-income countries. INTERPRETATION: Infants younger than 1 year have disproportionately high risks of severe human metapneumovirus infections across all World Bank income regions and all child mortality settings, similar to respiratory syncytial virus and influenza virus. Infants younger than 6 months in low-income and lower-middle-income countries are at greater risk of death from human metapneumovirus-associated ALRI than older children and those in upper-middle-income and high-income countries. Our mortality estimates demonstrate the importance of intervention strategies for infants across all settings, and warrant continued efforts to improve the outcome of human metapneumovirus-associated ALRI among young infants in low-income and lower-middle-income countries. FUNDING: Bill & Melinda Gates Foundation.

Day case vs inpatient total shoulder arthroplasty: A retrospective cohort study and cost-effectiveness analysis.

BACKGROUND: Day case total shoulder arthroplasty (TSA) is a novel approach, not widely practiced in Europe. We conducted a retrospective cohort study of patients comparing elective day case and inpatient TSAs in our United Kingdom centre. AIM: To evaluate the efficacy and cost-effectiveness of day case TSA compared to standard inpatient total shoulder arthroplasty. METHODS: All patients undergoing TSA between January 2017 and July 2018 were included. Outcome measures were: Change in abduction and extension 3 mo postoperatively; 30-d postoperative adverse events and re-admissions in day case and inpatient groups. We also conducted an economic evaluation of outpatient arthroplasty. Multivariate linear and logistic regression were used to adjust for demographic and operative covariates. RESULTS: Fifty nine patients were included, 18 d cases and 41 inpatients. There were no adverse events or re-admissions at 30 d postoperatively in either group. There were no significant differences in adjusted flexion (mean difference 16.4, 95%CI: 17.6-50.5, P = 0.337) or abduction (mean difference: 13.2, 95%CI: 18.4-44.9, P = 0.405) postoperatively between groups. Median savings with outpatient arthroplasty were £529 (interquartile range: 247.33-789, P < 0.0001). CONCLUSION: Day case TSA is a safe, effective procedure, with significant cost benefit. Wider use may be warranted in the United Kingdom and beyond, with potential for significant cost savings and improved efficiency.

Selective anti-ErbB3 aptamer modified sorafenib microparticles: In vitro and in vivo toxicity assessment.

The delivery of aptamer modified therapeutic moieties to specific tissue sites has become one of the major therapeutic choices to reduce the toxicity of inhibitory drugs. Bearing this in mind, the current study was designed using sorafenib (SFB) encapsulated microparticles (MP) prepared with biodegradable poly (D, L-lactic-co-glycolic acid) (PLGA) copolymer. The surfaces of these microparticles were modified with RNA aptamer having a binding affinity towards ErbB3 receptors. SFB-loaded MP (MPS) were prepared by o/w solvent evaporation method and the surface was coupled with the amino group of aptamer by EDC/NHS chemistry. Physiochemical investigations were done by dynamic light scattering, scanning electron microscopy and FTIR. In vitro apoptosis assay, cell viability assay and metastatic progression showed a significant decrease (p < 0.001) in vitro cell viability for MPS and MPS-Apt as compared to MP. The synergistic combination of SFB and aptamer also decreased the metastatic progression of cells for an extended period. Microparticles were also evaluated for in vivo toxicity in female BALB/c mice. It was evident that the presence of aptamer decreased the generalized toxicity of MPS-Apt, as measured by mean body weight loss and blood profiles, keeping all the blood formed elements level within acceptable limits. The histopathological investigations showed some necrotic and pyknotic bodies. In a similar fashion, liver function test and renal function tests showed pronounced effects of formulations on vital organs.

Rat-bites of an epidemic proportion in Peshawar vale; a GIS based approach in risk assessment.

Contemporary studies demonstrate that rodent bites do not occur frequently. However, a huge number of cases were reported from Peshawar vale, Pakistan during 2016. Two species, the local black rat Rattus rattus (Linnaeus, 1758) and the invasive brown rat Rattus norvegicus (Berkenhout, 1769) might be the suspected cause. Several studies indicated the invasion of brown rats into Pakistan presumably via port city of Karachi. In this study, we modeled geospatial distribution of rodent bites for risk assessment in the region. Bite cases reported to tertiary care lady reading hospital were monitored from January 1 to August 31, 2016. Among 1747 cases, statistically informative data (n = 1295) was used for analyses. MaxEnt algorithm was employed for geospatial modeling, taking into account various environmental variables (temperature, precipitation, humidity, and elevation) and anthropogenic factors (human population density, distance from roads, distance from water channels, and land use/land cover). MaxEnt results revealed that urban slums (84.5%) are at highest risk followed by croplands (10.9%) and shrublands (2.7%). Anthropogenic factors affecting incidence of rodent bites included host density (contribution: 34.7), distance from water channels (3.2), land use/land cover (2.8), and distance from roads (2). Most of the cases occurred within a radius of 0.3 km from roads and 5 km from water channels. Rodent bite incidence is currently at its peak in Peshawar vale. Factors significantly affecting rodents' bite activity and their distribution and dispersal include urbanization, distance from roads, and water channels. Further studies are needed to determine the impact of invasion by brown rat on bite incidence.

Age and Sex Normalization of Intestinal Permeability Measures for the Improved Assessment of Enteropathy in Infancy and Early Childhood: Results From the MAL-ED Study.

OBJECTIVES: The aim of the study was to describe changes in intestinal permeability in early childhood in diverse epidemiologic settings. METHODS: In a birth cohort study, the lactulose:mannitol (L:M) test was administered to 1980 children at 4 time points in the first 24 months of life in 8 countries. Data from the Brazil site with an incidence of diarrhea similar to that seen in the United States and no growth faltering was used as an internal study reference to derive age- and sex-specific z scores for mannitol and lactulose recoveries and the L:M ratio. RESULTS: A total of 6602 tests demonstrated mannitol recovery, lactulose recovery, and the L:M ratio were associated with country, sex, and age. There was heterogeneity in the recovery of both probes between sites with mean mannitol recovery ranging for 1.34% to 5.88%, lactulose recovery of 0.19% to 0.58%, and L:M ratios 0.10 to 0.17 in boys of 3 months of age across different sites. We observed strong sex-specific differences in both mannitol and lactulose recovery, with boys having higher recovery of both probes. Alterations in intestinal barrier function increased in most sites from 3 to 9 months of age and plateaued or diminished from 9 to 15 months of age. CONCLUSIONS: Alterations in recovery of the probes differ markedly in different epidemiologic contexts in children living in the developing world. The rate of change in the L:M-z ratio was most rapid and consistently disparate from the reference standard in the period between 6 and 9 months of age, suggesting that this is a critical period of physiologic impact of enteropathy in these populations.

Spatial assessment of water quality parameters in Jhelum city (Pakistan).

In this study, we assess the drinking water quality of Jhelum city. Two hundred and ninety-two drinking water samples were randomly collected in the study area. These samples were chemically analyzed for three key toxic (in excess) elements such as pH, total dissolved solids (TDS), and calcium. Geostatistical techniques such as variogram and kriging were used to investigate the spatial variations of these minerals across the city. The spatial structure for each element was found to be anisotropic, and thus, anisotropic variograms were used. The kriging predictions revealed significant concentrations of the above-stated elements at some locations in the study area. While comparing with the World Health Organization, United States Environmental Protection Agency, and Pakistan Environmental Protection Agency standards, the water samples were found to be unsatisfactory for drinking. We conclude that the drinking water in this region is of poor quality and needs proper treatment to make it palatable.

Vaccine coverage and adherence to EPI schedules in eight resource poor settings in the MAL-ED cohort study.

BACKGROUND: Launched in 1974, the Expanded Program on Immunization (EPI) is estimated to prevent two-three million deaths annually from polio, diphtheria, tuberculosis, pertussis, measles, and tetanus. Additional lives could be saved through better understanding what influences adherence to the EPI schedule in specific settings. METHODS: The Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) study followed cohorts in eight sites in South Asia, Africa, and South America and monitored vaccine receipt over the first two years of life for the children enrolled in the study. Vaccination histories were obtained monthly from vaccination cards, local clinic records and/or caregiver reports. Vaccination histories were compared against the prescribed EPI schedules for each country, and coverage rates were examined in relation to the timing of vaccination. The influence of socioeconomic factors on vaccine timing and coverage was also considered. RESULTS: Coverage rates for EPI vaccines varied between sites and by type of vaccine; overall, coverage was highest in the Nepal and Bangladesh sites and lowest in the Tanzania and Brazil sites. Bacillus Calmette-Guérin coverage was high across all sites, 87-100%, whereas measles vaccination rates ranged widely, 73-100%. Significant delays between the scheduled administration age and actual vaccination date were present in all sites, especially for measles vaccine where less than 40% were administered on schedule. A range of socioeconomic factors were significantly associated with vaccination status in study children but these results were largely site-specific. CONCLUSIONS: Our findings highlight the need to improve measles vaccination rates and reduce delayed vaccination to achieve EPI targets related to the establishment of herd immunity and reduction in disease transmission.