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bjective: COVID-19 is caused by SARS-CoV-2. Although pulmonary manifestations have been identified as the major symptoms, several hematological abnormalities play a vital role in disease treatment and monitoring. This study summarizes the hematological abnormalities (platelets, white blood cells, hemoglobin, coagulation alterations) as well as changes in inflammatory markers. Study Design And Setting: A retrospective cross-sectional study was conducted among PCR positive COVID-19 patients. The study was conducted at pathology department of CMH Malir between Aug 2021 and Jan 2022. Methodology: All the individuals with positive real-time reverse transcription-polymerase chain reaction (PCR) results were involved in the study. One hundred and twenty six COVID-19 patients were included using convenience sampling. Six ml venous blood was collected and analyzed. The data were entered and analyzed using SPSS version 23. Results: Among 126 patients different hematological and inflammatory parameters were noted. Significantly raised CRP, ESR in 96.8% and 92.9 % were noted respectively. Other parameters like raised D-dimers was found in 60.3 %, leukocytosis 65.1%, neutrophilia in 62.7 %. Significantly elevated neutrophil lymphocyte ratio was seen in 62 % of patients. Parameters like anemia and prolonged PT / APTT were not significant. Conclusion: The study concluded that CRP, ESR, leukocytosis, neutrophilia, elevated Neutrophil to lymphocyte ratio and D-dimers are significantly raised among serious patients with COVID-19 disease and can be used as monitoring, prognosis and severity index.

Background. Pakistan’s contraceptive prevalence rate (CPR) has remained static (less than 1% annual increase since 2006) due to several demand and supply issues. The Akhter Hameed Khan Foundation implemented a community-driven, demand-generation intervention with complementary supply side family planning (FP) services in a large urban informal settlement in Rawalpindi, Pakistan. Methods. The intervention recruited local women as outreach workers called Aapis (sisters), who conducted household outreach and provided counseling, contraceptives, and referrals. Program data were used to guide in-program corrections, identify the most willing to use married women of reproductive age (MWRA), and target specific geographic locations. The evaluation compared results from two surveys. The baseline survey included 1485 MWRA while the endline included 1560 MWRA that were sampled using the same methodology. A logit model was used with survey weights and clustered standard errors, to estimate the odds of using a contraceptive method. Results. CPR in Dhok Hassu increased from 33% at the baseline to 44% at endline. Long-acting reversible contraceptives (LARCs) usage increased from 1% at baseline to 4% at endline. Increase in CPR is correlated with increasing number of children and education of MWRA and is the highest between the ages of 25 and 39 and for working women. Qualitative evaluation of the intervention provided lessons about in-program corrections using data and empowerment of the female outreach workers and MWRA. Conclusion. The Aapis Initiative is a unique community-based demand-supply side intervention that successfully increased modern contraceptive prevalence rate (mCPR) by economically engaging the women from within the community as outreach workers and enabling healthcare providers to establish a sustainable ecosystem for increasing knowledge and access to family planning services.

The need for multi-attribute decision-making brings more and more complexity, and this type of decision-making extends to an ever wider range of areas of life. A recent model that captures many components of decision-making frameworks is the complex $ q $-rung picture fuzzy set (C$ q $-RPFS), a generalization of complex fuzzy sets and $ q $-rung picture fuzzy sets. From a different standpoint, linguistic terms are very useful to evaluate qualitative information without specialized knowledge. Inspired by the ease of use of the linguistic evaluations by means of 2-tuple linguistic term sets, and the broad scope of applications of C$ q $-RPFSs, in this paper we introduce the novel structure called 2-tuple linguistic complex $ q $-rung picture fuzzy sets (2TLC$ q $-RPFSs). We argue that this model prevails to represent the two-dimensional information over the boundary of C$ q $-RPFSs, thanks to the additional features of 2-tuple linguistic terms. Subsequently, some 2TLC$ q $-RPF aggregation operators are proposed. Fundamental cases include the 2TLC$ q $-RPF weighted averaging/geometric operators. Other sophisticated aggregation operators that we propose are based on the Hamacher operator. In addition, we investigate some essential properties of the new operators. These tools are the building blocks of a multi-attribute decision making strategy for problems posed in the 2TLC$ q $-RPFS setting. Furthermore, a numerical instance that selects an optimal machine is given to guarantee the applicability and effectiveness of the proposed approach. Finally, we conduct a comparison with other existing approaches.

The present study is intended to explore the impact brought about by parental demise among female adolescents. Moreover, examining the societal role, particularly the part played by the family system, after the death of a father and its effect on an adolescent’s life perception. Data was collected through in-depth interviews from 4 adolescents aged between 17-19 years, accumulated by a purposive sampling method and analyzed through interpretative phenomenological analysis. Findings demonstrated that adolescents who encountered the loss of their fathers face numerous problems impacting their emotional, cognitive, and behavioural well-being. The absence of parents brings a drastic change in an entire life affecting their mental health leading to low self-esteem, depression, anxiety as well as emotional sufferings. The major issues highlighted during the study were life disruption, financial crisis, lack of support in terms of both financial and emotional aspects from extended family. Moreover, the family system played a detrimental role in the adversities encountered. Furthermore, participants stressed that children having both parents attained support, attention, emotional bonding, and encountered fewer social, psychological, and emotional issues. They constantly grieved the parental loss and faced a lack of care, that significantly affected their well-being. These findings help in understanding the problems associated with lack of parental bonding in connection with father’s loss, whereas its long-lasting impact spread throughout one's life.

The forkhead transcription factor FOXE3 is critical for vertebrate eye development. Recessive and dominant variants cause human ocular disease but the full range of phenotypes and mechanisms of action for the two classes of variants are unknown. We identified FOXE3 variants in individuals with congenital eye malformations and carried out in vitro functional analysis on selected alleles. Sixteen new recessive and dominant families, including six novel variants, were identified. Analysis of new and previously reported genetic and clinical data demonstrated a broad phenotypic range with an overlap between recessive and dominant disease. Most families with recessive alleles, composed of truncating and forkhead-domain missense variants, had severe corneal opacity (90%; sclerocornea in 47%), aphakia (83%) and microphthalmia (80%), but some had milder features including isolated cataract. The phenotype was most variable for recessive missense variants, suggesting that the functional consequences may be highly dependent on the type of amino acid substitution and its position. When assessed, aniridia or iris hypoplasia were noted in 89% and optic nerve anomalies in 60% of recessive cases, indicating that these defects are also common and may be underrecognized. In dominant pedigrees, caused by extension variants, normal eye size (96%), cataracts (99%) and variable anterior segment anomalies were seen in most, but some individuals had microphthalmia, aphakia or sclerocornea, more typical of recessive disease. Functional studies identified variable effects on the protein stability, DNA binding, nuclear localization and transcriptional activity for recessive FOXE3 variants, whereas dominant alleles showed severe impairment in all areas and dominant-negative characteristics.

Summary Background COBRA-BPS (Control of Blood Pressure and Risk Attenuation-Bangladesh, Pakistan, Sri Lanka), a multi-component hypertension management programme that is led by community health workers, has been shown to be efficacious at reducing systolic blood pressure in rural communities in Bangladesh, Pakistan, and Sri Lanka. In this study, we aimed to assess the budget required to scale up the programme and the incremental cost-effectiveness ratios. Methods In a cluster-randomised trial of COBRA-BPS, individuals aged 40 years or older with hypertension who lived in 30 rural communities in Bangladesh, Pakistan, and Sri Lanka were deemed eligible for inclusion. Costs were quantified prospectively at baseline and during 2 years of the trial. All costs, including labour, rental, materials and supplies, and contracted services were recorded, stratified by programme activity. Incremental costs of scaling up COBRA-BPS to all eligible adults in areas covered by community health workers were estimated from the health ministry (public payer) perspective. Findings Between April 1, 2016, and Feb 28, 2017, 11 510 individuals were screened and 2645 were enrolled and included in the study. Participants were examined between May 8, 2016, and March 31, 2019. The first-year per-participant costs for COBRA-BPS were US$10·65 for Bangladesh, $10·25 for Pakistan, and $6·42 for Sri Lanka. Per-capita costs were $0·63 for Bangladesh, $0·29 for Pakistan, and $1·03 for Sri Lanka. Incremental cost-effectiveness ratios were $3430 for Bangladesh, $2270 for Pakistan, and $4080 for Sri Lanka, per cardiovascular disability-adjusted life year averted, which showed COBRA-BPS to be cost-effective in all three countries relative to the WHO-CHOICE threshold of three times gross domestic product per capita in each country. Using this threshold, the cost-effectiveness acceptability curves predicted that the probability of COBRA-BPS being cost-effective is 79·3% in Bangladesh, 85·2% in Pakistan, and 99·8% in Sri Lanka. Interpretation The low cost of scale-up and the cost-effectiveness of COBRA-BPS suggest that this programme is a viable strategy for responding to the growing cardiovascular disease epidemic in rural communities in low-income and middle-income countries where community health workers are present, and that it should qualify as a priority intervention across rural settings in south Asia and in other countries with similar demographics and health systems to those examined in this study. Funding The UK Department of Health and Social Care, the UK Department for International Development, the Global Challenges Research Fund, the UK Medical Research Council, Wellcome Trust.

Objectives: To identify patient characteristics and treatment factors of patients presenting to the emergency department (ED) with cancer-related pain that may affect patient outcomes. Methods: We conducted a retrospective cohort study to evaluate adult patients with active cancer, who presented to the ED with a chief complaint of pain between June first, 2012 and January first, 2016. We utilized multivariable logistic regression to evaluate the association of several exposure variables, including disease and demographic characteristics, primary pain site, and treatment methods, on ED disposition and revisit rate. Results: We included 483 patients with active cancer with a chief complaint of pain. Patients with severe pain on arrival tended to be younger than those who did not present with severe pain (median: 58 vs 62 respectively, OR 8.0 p

The number of International Medical Graduate (IMG) physicians matching into categorical psychiatry decreased steadily over the past decade. The authors sought to understand if this trend was occurring in other specialties, if US IMG physicians and non-US IMG physicians were equally affected, and if certain regions of the USA were more affected by this decrease than others. Finally, the authors compared the proportion of foreign-born individuals within a US census region to the proportion of non-US IMG physicians within that region. The authors analyzed data from the National Resident Matching Program from the years 2014–2020. Statewide data was aggregated into nine geographic regions, as per the US Census Bureau. The number of foreign-born individuals within each US census region was calculated from the 2018 American Community Survey data. In comparison to eight other specialties, psychiatry saw the greatest decrease (46.3%) in IMG physicians matching into PGY-1 positions. Both US IMG physicians and non-US IMG physicians were equally affected. The percentage of IMG physicians decreased in each of the nine US census regions. In six out of nine geographic regions, non-US IMG physicians were under-represented when comparing their proportion to the number of foreign-born people that lived within that region. Decreasing numbers of IMG physicians in psychiatry training may have long-term implications for cultural competency, serving underserved populations, and fellowship recruitment. We advocate for program directors to recognize IMG physicians as an important source of diversity and to recruit residents that reflect the communities they serve.

The present study was designed to determine the anti-nutritional compounds in the wild plants of Soone valley Punjab, Pakistan. A wide range of anti-nutritional factors exists in the wild plants of this area which are consumed as forages by the ruminants. Few anti-nutritional compounds i.e. oxalate, phytate, saponins and tannins were analyzed during the course of study. Oxalate content ranged from 0.4467% to 0.6267%. The highest oxalate content was found in Chenopodium album and lowest oxalate content was available in Mentha arvensis. The content of phytate ranged from 3.8167% to 4.9767% in all wild forages. The maximum amount was observed in Buxus papillosa and minimum amount was found in Ahadota vasica. Saponins ranged from 2.2700% to 3.7833%. The percentage of tannins varies from 1.3167% to 1.6300% in all plant species. The optimum value of tannins was found in Adatoda vasica and low value of tannins was investigated in the Mentha arvensis among the investigated plant species. Overall, the maximum factors observed in Buxus papillosa and lowest in Mentha arvensis plants. The values estimated in the present study are below the mark as compared to the toxic levels. Nutritional and health issues are developed due to the large consumption of monotypic wild edible plant parts during one meal. However, anti-nutritional compounds related to respective risks are less with the use of traditional methods.

An rare pandemic of viral pneumonia occurs in December 2019 in Wuhan, China, which is now recognized internationally as Corona Virus Disease 2019 (COVID-19), the etiological agent classified as Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2). According to the World Health Organization (WHO), it has so far expanded to more than 213 countries/territories worldwide. Our study aims to find the viral peptides of SARS-COV-2 by peptide mass fingerprinting (PMF) in order to predict its novel structure and find an inhibitor for each viral peptide. For this reason, we calculated the mass of amino acid sequences translated from the SARS-CoV2 whole genome and identify the peptides that may be a target for inhibition. Molecular peptide docking with Moringa oleifera, phytochemicals (aqueous and ethanolic) leaf extracts of flavonoids (3.56 ± 0.03), (3.83 ± 0.02), anthraquinone (11.68 ± 0.04), (10.86 ± 0.06) and hydroxychloroquine present therapy of COVID-19 in Pakistan for comparative study. Results indicate that 15 peptides of SARS-CoV2 have been identified from PMF, which is then used as a selective inhibitor. The maximum energy obtained from AutoDock Vina for hydroxychloroquine is –5.1 kcal/mol, kaempferol (flavonoid) is –6.2 kcal/mol, and for anthraquinone –6 kcal/mol. Visualization of docking complex, important effects are observed regarding the binding of peptides to drug compounds. In conclusion, it is proposed that these compounds are effective antiviral agents against COVID-19 and can be used in clinical trials. Communicated by Ramaswamy H. Sarma

The objective was to measure the impact of the Society for Academic Emergency Medicine Foundation's (SAEMF) Research Training Grant (RTG) by comparing academic success in grant recipients versus non-recipient applicants. Our primary outcome was subsequent federal funding as a principal investigator (PI) or multiple principal investigator (MPI). Our secondary outcomes included subsequent K-award funding, R-series funding, R01 funding, and academic productivity measured by first author peer-reviewed publications.The authors examined all SAEMF RTG applicants from 2002 through 2019 (n = 109). Data were collected using the National Institutes of Health RePORTER database, a literature search using PubMed, and an online survey sent to all RTG applicants. Relative risks (RRs) with 95% confidence intervals (95% CI) were calculated.Over 18 years, 18 of 109 (16.5%) RTG applicants were awarded by SAEMF. Subsequent federal funding as PI or MPI was obtained by 11 of the 18 RTG recipients compared to 29 of the 91 nonrecipients (61% vs. 33%, RR = 1.9; 95% CI = 1.2-3.1). The RTG award was also associated with increased probability of receiving a federal Career Development Award (K-series) (RR 2.0; 95% CI 1.1-3.9) and R-series award (RR 2.0; 95% CI 1.1-3.9) but not an R01 award (RR 2.1; 95% CI 0.8-5.3). The median number of first-authored peer reviewed manuscripts did not differ between RTG award recipients (14, IQR 8,44) and nonrecipients (14, IQR 6,30) (p = 0.5) though RTG recipients had a higher percentage of their publications as a first author (49% vs. 33%, p = 0.04).SAEMF RTG awards were associated with increased probability of future federal funding, including career development awards and R-series awards but not R01 awards. RTG recipients also had a higher percentage of their peer reviewed publications as first author.

The future of healthcare is an organic blend of technology, innovation, and human connection. As artificial intelligence (AI) is gradually becoming a go-to technology in healthcare to improve efficiency and outcomes, we must understand our limitations. We should realize that our goal is not only to provide faster and more efficient care, but also to deliver an integrated solution to ensure that the care is fair and not biased to a group of sub-population. In this context, the field of cardio-cerebrovascular diseases, which encompasses a wide range of conditions—from heart failure to stroke—has made some advances to provide assistive tools to care providers. This article aimed to provide an overall thematic review of recent development focusing on various AI applications in cardio-cerebrovascular diseases to identify gaps and potential areas of improvement. If well designed, technological engines have the potential to improve healthcare access and equitability while reducing overall costs, diagnostic errors, and disparity in a system that affects patients and providers and strives for efficiency.

Graphdiyne (GDY), which possess sp- and sp2-hybridized carbon and Dirac cones, offers unique physical and chemical properties, including an adjustable intrinsic bandgap, excellent charge carrier transfer efficiency, and superior conductivity compared to other carbon allotropes. These exceptional qualities of GDY and its derivatives have been successfully used in a variety of fields, including catalysis, energy, environmental protection, and biological applications. Herein, we focus on the potential application of GDY and its derivatives in the biomedical domain, including biosensing, biological protection, cancer therapy, and antibacterial agents, demonstrating how the biomimetic behavior of these materials can be a step forward in bridging the gap between nature and applications. Considering the excellent biocompatibility, solubility and selectivity of GDY and its derived materials, they have shown great potential as biosensing and bio-imaging materials. The unusual combination of properties in GDY has been used in biological applications such as “OFF–ON” DNA detection and enzymatic sensing, where GDY has a greater adsorption capacity than graphene and other 2D materials, resulting in increased sensitivity. GDY and its derivatives have also been used in cancer treatment due to their high doxorubicin (DOX) loading capacity (using-stacking) and photothermal conversion ability, and radiation protection since their initial biological use. The poor biodegradation rate of graphene demands the search for new nanomaterials. Accordingly, GDY has better biocompatibility and bio-safety than other 2D nanomaterials, especially graphene and its oxide, due to its absence of aggregation in the physiological environment. Thus, GDY-based nanomaterials have become promising candidates as bio-delivery carriers. Besides, GDY and GDY-based materials have also shown interesting applications in the fields of cell-culture, cell-growth and tissue engineering. Herein, we present a comprehensive review on the applications of GDY and its derivatives as biomedical materials, followed by their future perspectives. This review will provide an outlook for the application of graphene and its derivatives and may open up new horizons to inspire broader interests across various disciplines. Finally, the future prospects for GDY-based materials are examined for their potential biological use.

Community service learning (CSL) activities in undergraduate programs are associated with improvements in self-efficacy (confidence related to performing a specific task) and academic achievement. This study aimed to understand the impact of a CSL assignment on self-efficacy related to teaching community members about evidence-based nutrition and on the overall learning experience. Students were invited to participate in this mixed-methods study (surveys and focus groups), and the results indicate that the CSL activity not only increased students’ self-efficacy related to nutrition science communication, but also gave students a greater feeling of connection to their community and an opportunity to practice skills needed for future careers. Les activités d’apprentissage par l’engagement communautaire dans les programmes de premier cycle sont liées à une amélioration de l’autoefficacité (la confiance en sa propre capacité d’accomplir une tâche particulière) et du rendement universitaire. La présente étude vise à comprendre l’incidence d’un devoir d’apprentissage par l’engagement communautaire sur l’expérience d’apprentissage dans son ensemble et sur l’autoefficacité au sujet de la nutrition s’appuyant sur des données probantes – par rapport aux membres du corps enseignant. Les étudiants étaient invités à participer à une étude employant des méthodes mixtes (des sondages et des groupes de discussion). Les résultats indiquent que les activités d’apprentissage par l’engagement communautaire augmentent l’autoefficacité en matière de communication de la science de la nutrition. Qui plus est, ces activités donnent aux étudiants un sentiment accru d’appartenance à leur communauté ainsi qu’une occasion de mettre en pratique les compétences requises dans leur future carrière.

The principle objective of this research was to investigate the effects of fermenter technology on yield of various cash crops grown in Malakand division of Khyber Pakhtunkhwa Pakistan. A total of 128 farmers using fermenter technology in six districts of Malakand division were the universes of the study.50.8% of the farmers using fermenter were holding a land between the groups of 1.6 to 2.5 hectares. Majority of the farmer’s 84.4% source of awareness about the fermenter technology were extension worker. Major cash crops grown by the respondents in the study area were tomato, onion and wheat. T-test results reveal a highly significant (P=0.000) increase in yield of tomato, onion and wheat. On average 1668.868 kg ha-1 increased were recorded in tomato, 1293.478 kg ha-1 increased in onion and 98.791 kg ha-1 in wheat crop. The finding of study suggests that various crops yield were increased with adopting fermenter technology. So the fermenter technology should be promoted and imparted to the entire farming community to meet with the increasing demand.

ImportanceAccelerated diagnostic protocols (ADPs) for chest pain using high-sensitivity troponin (hsTn) levels have excellent sensitivity and negative predictive value for rapid risk stratification of patients with chest pain. However, little is known about the outcomes of patients who are discharged despite abnormal ADP results, ie, after “ruling-in” with a modest elevation of hsTn.ObjectiveTo determine outcomes of patients discharged following ADP, including those who were ruled in with modestly elevated levels of hsTnT but discharged nonetheless.Design, Setting, and ParticipantsThis retrospective cohort study included patients with chest pain who presented to the emergency departments (EDs) of a large multisite health system ED between January 2017 to September 2019. Patients were assessed using an ADP, had a peak hsTnT level measured between the limit of quantitation and 52 ng/L, were discharged, and had follow-up in the electronic medical record. Data analysis was conducted from January 2017 to September 2019.ExposuresApplication of an hsTnT ADP.Main Outcomes and MeasuresThirty-day major adverse cardiac events (MACE), including myocardial infarction, urgent coronary revascularization, and all-cause death, comparing patients who were discharged following ADP-concordant vs ADP-discordant results.ResultsOf 10 342 patients with chest pain (mean [SD] age 51 [17] years; 5902 [57%] women) discharged following ADP, 29 (0.28%) had MACE. Patients with MACE were older (median [IQR] age, 66 [53-75] years vs 50 [38-62] years; P P = .002) and hyperlipidemia (13 [44.8%] vs 2248 [21.8%]; P = .006). Additionally, patients with MACE were 5-fold more likely to have been discharged despite ADP discordance (16 [55.2%] vs 1145 [11.1%]; P P P Conclusions and RelevanceIn this cohort study, an hsTnT ADP identified patients who could be discharged from the ED with low 30-day risk of MACE, provided the discharge was based on ADP-concordant “rule-out.” Conversely, the rate of MACE was significantly higher among patients discharged despite ADP discordance. Most patients with ADP-discordant discharges who experienced MACE had a HEART score of 4 or greater, suggesting that application of this score may augment discharge decisions of patients despite ADP-discordant troponin series.

The main purpose of research was to investigate the underlying strategies for enhancing “organizational sustainability” (OS). The study categorizes the existing literature, based on strategic choice theory and the attribution model, which reveals that green human resource management (GHRM) practices play a crucial role in environmental management and organizational sustainability. This study investigates the impact of GHRM practices including training and development, performance appraisal, and reward and compensation on organizational sustainability through the mediating role of environmental performance and employee performance. A survey questionnaire methodology was used for data collection; data were collected from 165 managerial personnel in the textile industrial sector of Pakistan. The findings of the study showed significant effects of GHRM practices, i.e. (training and development, performance appraisal, and reward and compensation), on Organizational Sustainability, Similarly, this study empirically investigates the distinct mediating role of environmental performance and employee’s performance between GHRM practices and organizational sustainability. The study findings support the hypothesized model of mediation. The GHRM is an innovative idea in developing countries, and additional studies are needed to identify sustainability issues and evaluate the impacts of GHRM practices in the textile and manufacturing industries in Pakistan.

Background: The long-term risk of recurrent ischemic stroke, estimated to be between 17% and 30%, cannot be reliably assessed at an individual level. Our goal was to study whether machine-learning can be trained to predict stroke recurrence and identify key clinical variables and assess whether performance metrics can be optimized. Methods: We used patient-level data from electronic health records, six interpretable algorithms (Logistic Regression, Extreme Gradient Boosting, Gradient Boosting Machine, Random Forest, Support Vector Machine, Decision Tree), four feature selection strategies, five prediction windows, and two sampling strategies to develop 288 models for up to 5-year stroke recurrence prediction. We further identified important clinical features and different optimization strategies. Results: We included 2091 ischemic stroke patients. Model area under the receiver operating characteristic (AUROC) curve was stable for prediction windows of 1, 2, 3, 4, and 5 years, with the highest score for the 1-year (0.79) and the lowest score for the 5-year prediction window (0.69). A total of 21 (7%) models reached an AUROC above 0.73 while 110 (38%) models reached an AUROC greater than 0.7. Among the 53 features analyzed, age, body mass index, and laboratory-based features (such as high-density lipoprotein, hemoglobin A1c, and creatinine) had the highest overall importance scores. The balance between specificity and sensitivity improved through sampling strategies. Conclusion: All of the selected six algorithms could be trained to predict the long-term stroke recurrence and laboratory-based variables were highly associated with stroke recurrence. The latter could be targeted for personalized interventions. Model performance metrics could be optimized, and models can be implemented in the same healthcare system as intelligent decision support for targeted intervention.

Mondello, Stefania/0000-0002-8587-3614; Alizada, Orkhan/0000-0003-0942-9906; Ghorbani, Mohammad/0000-0002-7709-3095; Abedi, Vida/0000-0001-7689-933X WOS:000575454600010 PubMed ID: 32818804 Background: There is an increased attention to stroke following SARS-CoV-2. The goal of this study was to better depict the short-term risk of stroke and its associated factors among SARS-CoV-2 hospitalized patients. Methods: This multicentre, multinational observational study includes hospitalized SARS-CoV-2 patients from North and South America (United States, Canada, and Brazil), Europe (Greece, Italy, Finland, and Turkey), Asia (Lebanon, Iran, and India), and Oceania (New Zealand). The outcome was the risk of subsequent stroke. Centres were included by non-probability sampling. The counts and clinical characteristics including laboratory findings and imaging of the patients with and without a subsequent stroke were recorded according to a predefined protocol. Quality, risk of bias, and heterogeneity assessments were conducted according to ROBINS-E and Cochrane Q-test. The risk of subsequent stroke was estimated through meta-analyses with random effect models. Bivariate logistic regression was used to determine the parameters with predictive outcome value. The study was reported according to the STROBE, MOOSE, and EQUATOR guidelines. Findings: We received data from 26,175 hospitalized SARS-CoV-2 patients from 99 tertiary centres in 65 regions of 11 countries until May 1st, 2020. A total of 17,799 patients were included in meta-analyses. Among them, 156(0.9%) patients had a stroke-123(79%) ischaemic stroke, 27(17%) intracerebral/subarachnoid hemorrhage, and 6(4%) cerebral sinus thrombosis. Subsequent stroke risks calculated with meta-analyses, under low to moderate heterogeneity, were 0.5% among all centres in all countries, and 0.7% among countries with higher health expenditures. The need for mechanical ventilation (OR: 1.9, 95% CI:1.1-3.5, p = 0.03) and the presence of ischaemic heart disease (OR: 2.5, 95% CI:1.4-4.7, p = 0.006) were predictive of stroke. Interpretation: The results of this multi-national study on hospitalized patients with SARS-CoV-2 infection indicated an overall stroke risk of 0.5%(pooled risk: 0.9%). The need for mechanical ventilation and the history of ischaemic heart disease are the independent predictors of stroke among SARS-CoV-2 patients. (C) 2020 The Authors. Published by Elsevier B.V.

A series of novel superporous hydrogels for regenerative medicine were prepared by oil-in-water (o/w) or inverse high internal phase emulsion (i-HIPE) copolymerization of glycerol monomethacrylate (GMMA), 2-hydroxy ethyl methacrylate (HEMA) and glycerol dimethacrylate (GDMA) as a cross-linker using a non toxic solvent and a redox initiator system at the physiological temperature (37 °C). The monomer GMMA was synthesized from glycidyl methacrylate (GMA) by an alternative facile method using Amberlyst-15. The described i-HIPEs showed a significantly wider stability window. The polyHIPE hydrogels were characterized by FTIR, BET method for surface area, mercury porosimetry, SEM, DSC, TGA, XRD, compressive strain and strain recovery. The swelling ratio of the hydrogels and their degradation in 0.007 M NaOH and lipase B (Candida antarctica) solutions were determined gravimetrically and the rate of degradation was explained in terms of the molecular structure of the hydrogels. The morphological studies showed that the pore diameter varied between 20 and 30 μm and the pore throats (interconnecting windows) diameter was in the range of 4–8 μm. The described polyHIPE hydrogels were found to have an open cell morphology and interconnected pore architecture, which are important characteristics for scaffold applications. The initial cytotoxicity study performed according to ISO-10993-5 indicated cytocompatibility (97% cell viability) and the subsequent cell seeding and proliferation study exhibited 55–88% cell viability (increased monotonously from GHG-1 to GHG-5), which could be attributed to modulation of the physical and chemical properties of the hydrogels. The described super porous hydrogels are considered as potential candidates for scaffold materials in tissue engineering applications.

Dear EditorWe read with interest the article by Bakker et al. (2021) on fostering the next generation of medical teachers. We would like to offer our opinions and experiences as medical students al...

Purpose To report a case of macular telangiectasia Type 2 in a teenage boy with consanguineous parents. Method Clinical case report and literature review. Results A healthy 14-year-old boy presented with mildly reduced vision in both eyes. Visual acuity was 20/30 in the right eye and 20/25 in the left eye. Fundus examination revealed intraretinal crystals in both eyes and an intraretinal pigment plaque temporal to the fovea in the left eye. Neither eye showed evidence of choroidal neovascular membrane or peripheral telangiectasia. Fluorescein angiography revealed temporal juxtafoveal leakage in both eyes. Spectral-domain optical coherence tomography showed ellipsoid layer and external limiting membrane disruption in the right eye and an inner retinal pigment plaque with shadowing in the left eye. The patient was of South Asian descent, and his parents were first cousins. His younger brother and parents were unaffected with a normal fundus examination. Conclusion This is the youngest reported case of a healthy individual with MacTel Type 2, which usually manifests in the fifth or sixth decade. This is also the only reported case of MacTel Type 2 with consanguineous parents. This proband offers a unique opportunity to study possible monogenic etiologies of the condition.

Background Disability faced by a young person can impact the school-to-work transition and shape health and well-being over the life course. Unique barriers to entry and advancement within the labor market that are relevant to young people with disabilities underscore the need for tailored policy-level supports. Objectives To examine and describe policies that support the school-to-work transition of young people with disabilities in Canada. Methods A scan of policies which focused on the school-to-work transition of young people with disabilities across Canada was conducted between June 2019 and January 2020. Searches were completed within federal, provincial and territorial policy portals. Each policy relating to employment participation of people with disabilities was summarized. Policies that focused on the school-to-work-specific were synthesized using Bemelmans-Vidic, Rist and Vedung's policy tool framework. Results A total of 36 policies were identified by our scan that focused on the employment of people with disabilities. Only five policies explicitly addressed the school-to-work transition. All existing policies were implemented at the provincial level and aimed to promote entry into employment. The synthesis of policies revealed that financial policy tools were primarily used to incentivize employment, provision of workplace accommodations, or the development and implementation of job readiness programs. Conclusion Our analysis of federal, provincial and territorial policies in Canada uncovered a limited number of policies that specifically support the school-to-work transition. Addressing these policy gaps can increase the inclusion of young people with disabilities in the labor market.

α-Glucosyl diacylglycerols (αGlc-DAGs) play an important role in providing protective immunity against Streptococcus pneumoniae infection through the engagement of the Macrophage inducible C-type lectin (Mincle). Herein, we efficiently synthesised αGlc-DAGs containing C12, C14, C16 and C18 acyl chains in 7 steps and 44-47% overall yields, and demonstrated that Mincle signaling was dependent on lipid length using mMincle and hMincle NFAT-GFP reporter cells. The greatest production of GFP in both cell types was elicited by C14 αGlc-DAG. Accordingly, C14 αGlc-DAG has potential to act as an adjuvant to augment the immune response against S. pneumoniae antigens.

Background & Objective: Spontaneous pregnancy loss has always been the frustrating experience for the couples and concern clinician. Chromosomal abnormality in either of the parent is considered to be the one of the leading cause of recurrent spontaneous miscarriages. This study was designed to evaluate the possible chromosomal etiology of miscarriage and the subsequent intimacy of maternal or paternal genetic abnormality. Methods: This case-control study was conducted between January 2016 and October 2016 at a tertiary care hospital in Karachi. A total of thirty-two couples were selected who had suffered with recurrent spontaneous miscarriages (RSM). Using conventional cytogenetic technique karyotyping was performed on all of the subjects. For the control twenty couples were also selected with no history of pregnancy loss. All the karyotypes were recorded on the standard method. Data was analyzed through SPSS version 22. Results: Among thirty-two cases nine cases were found to have abnormal karyotype. In which sex chromosomal trisomy=02 (46,XY/47,XXY), marker chromosome=01 (47,XX,+mar), Robertsonian translocation=01 (45,XY,der,(14:21),(q10;q10)), reciprocal translocation=01 (46,XX,t(11;22)(q23;q11.2)), inversion=02 (46,XX,inv(9)(p11q13)) and minor structural abnormalities=02 (46,XX,15PS+) were found. Approximately equal ratio with 1:1.25 was observed among male and female carrier respectively. Non-significant difference was found between the ages of both carriers (p=0.34). Though a significant different value was calculated in the case of number of miscarriage (p=0.004*). Moreover, no significant association was found among spontaneous miscarriage (SM) and recurrent spontaneous miscarriage (RSM) with respect to maternal age (p= 0.157). Conclusion: In the recent study possible chromosomal abnormalities suggested the evaluation of the patient with the history of recurrent spontaneous miscarriage must include conventional cytogenetic. Moreover, probe development and extended investigation can ease the prognosis among pregnancy related complication. doi: https://doi.org/10.12669/pjms.35.5.678 How to cite this:Hanif MI, Khan A, Arif A, Shoeb E. Cytogenetic investigation of couples with recurrent spontaneous miscarriages. Pak J Med Sci. 2019;35(5):1422-1427. doi: https://doi.org/10.12669/pjms.35.5.678 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Objective: To evaluate the correlation between clinical hyperandrogenism-hirsutism assessed by modified Ferriman-Gallwey (F-G) score, anthropometric, metabolic and endocrine parameters among PCOS infertile women. Methods: This observational study after approval of FRC & ERC of BUMDC was conducted from September 2018-March 2019. It included seventy women aged 20-40 years who presented in infertility clinic of a local Hospital in Karachi. After written informed consent participants were enrolled as per the inclusion criteria of the study and evaluated for cyclical pattern (oligomenorrhoea, amenorrhoea, polymenorrhea), physical (weight, height, BMI), anthropometric, (waist circumference, hip circumference, waist to hip ratio, hirsutism), metabolic (carbohydrate, lipid & protein) and endocrine parameters (serum FSH, LH, LH/FSH ratio, serum testosterone, prolactin and progesterone level). Hirsutism was assessed by visual method through modified F-G score and Pearson correlation was determined between hirsutism and other study parameters. Results: A positive Pearson correlation is found between hirsutism and body weight, BMI, waist and hip circumference, waist to hip ratio (WHR), very low density lipoprotein, cholesterol, triglycerides and testosterone levels. Conclusion: Hirsutism has correlation with anthropometric, metabolic and hyperandrgenic disorders in PCOS infertile women as assessed by modified F-G score. doi: https://doi.org/10.12669/pjms.35.5.742 How to cite this:Khan A, Karim N, Ainuddin JA, Fahim MF. Polycystic Ovarian Syndrome: Correlation between clinical hyperandrogenism, anthropometric, metabolic and endocrine parameters. Pak J Med Sci. 2019;35(5):1227-1232. doi: https://doi.org/10.12669/pjms.35.5.742 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Radiation chemical studies of thioesculetin (1), a thioketone derivative of coumarin, were performed by both pulse radiolysis technique and DFT calculations. Hydroxyl (•OH) radical reaction...

Objectives To validate and assess reliability of a novel triage system, one-two-triage (OTT), that can be applied by inexperienced providers in low-resource settings. Methods This study was a two-phase prospective, comparative study conducted at three hospitals. Phase I assessed criterion validity of OTT on all patients arriving at an American university hospital by comparing agreement among three methods of triage: OTT, Emergency Severity Index (ESI) and physician-defined acuity (the gold standard). Agreement was reported in normalised and raw-weighted Cohen κ using two different scales for weighting, Expert-weighted and triage-weighted κ. Phase II tested reliability, reported in Fleiss κ, of OTT using standardised cases among three groups of providers at an urban and rural Cambodian hospital and the American university hospital. Results Normalised for prevalence of patients in each category, OTT and ESI performed similarly well for expert-weighted κ (OTT κ=0.58, 95% CI 0.52 to 0.65; ESI κ=0.47, 95% CI 0.40 to 0.53) and triage-weighted κ (κ=0.54, 95% CI 0.48 to 0.61; ESI κ=0.57, 95% CI 0.51 to 0.64). Without normalising, agreement with gold standard was less for both systems but performance of OTT and ESI remained similar, expert-weighted (OTT κ=0.57, 95% CI 0.52 to 0.62; ESI κ=0.6, 95% CI 0.58 to 0.66) and triage-weighted (OTT κ=0.31, 95% CI 0.25 to 0.38; ESI κ=0.41, 95% CI 0.35 to 0.4). In the reliability phase, all triagers showed fair inter-rater agreement, Fleiss κ (κ=0.308). Conclusions OTT can be reliably applied and performs as well as ESI compared with gold standard, but requires fewer resources and less experience.

An efficient route for the synthesis of benzimidazole nucleosides 1–8 from readily available d -glucose via 3,5-dihydroxy-1,2-O-isopropylidene-α- d -ribofuranose and 3-azido-3-deoxy-1,2-O-isopropylidene-α- d -xylofuranose intermediates has been adopted. Ribofuranosyl nucleosides 1–4 with different benzimidazole bases, and 3ʹ-deoxy-3ʹ-azido-ribofuranosyl nucleosides 5–8, as another series, were obtained. All these newly synthesized analogs were evaluated for anticancer activity using MDA-MB-231 cell line. Among the differently substituted derivatives, 3ʹ-azide substituted nucleosides (5–8) are more potent compared to ribofuranosyl analogs 1–4. The C-3ʹ-azido analog 8 having anthryl group at 2-position of nucleobase show almost similar potency as that of standard etoposide.

Background Access to a trained, competent health care workforce remains a challenge globally, particularly in rural settings. To bridge this gap, the World Health Organization calls for innovations in electronic learning and task shifting. Yet, these approaches are underutilized due to cost, challenges associated with implementing technology, and a lack of suitably educated trainees. Objective We explored the feasibility of the Acute Care Providers Project (ACPP) to remotely train community members to be health care providers in 2 sites: Haiti and India. Methods The ACP program is an asynchronous curriculum that provides core health content and a structured approach to clinical care through an electronic curriculum. The curriculum is reinforced with case-based practice and hands-on workshops for procedural skills. ACPP was deployed in rural Haiti and India. Evaluation of the program included multiple-choice pretests and posttests, an objective structured clinical examination (OSCE), and direct observation of skills. Results Four Haitian and 55 Indian trainees completed the course. In Haiti, mean scores were 34.8% (SD 12.4) on the pretest and 78.0% (SD 6.5) on the posttest (P = .004). Trainees scored 100% on the OSCE and passed the skills checklist. In India, mean scores were 16.5% (SD 3.9) on the pretest and 81.7% (SD 9.0) on the posttest (P < .001). Trainees scored a median of 91.8% (SD 3.95) on the OSCE and all passed the skills checklist. Conclusions The ACPP offers a scalable, replicable asynchronous curriculum to train lay individuals to provide basic health care in rural communities.

Background: Gender is the main social determinant of health in India and affects women's health outcomes even before birth. As women mature into adulthood, lack of education and empowerment increases health inequities, acting as a barrier to seeking medical care and to making medical choices. Although the process of women's empowerment is complex to measure, one indicator is confidence in ability. We sought to increase the confidence of rural Indian women in their abilities by training them as health-care providers for their community. Methods: Our partner organisation selected women through an application process requiring (1) 1 year experience as community health facilitators and (2) availability to travel and participate in a lay provider programme. Women educated to primary school level were trained by adapting an application-based curriculum previously successful in training secondary-school graduates in Haiti. We adapted the curriculum to suit the gendered context and cultivate the following skills: (1) public speaking (each woman had to teach her small group a portion of the curriculum); (2) leadership (each woman led a large group discussion on the topic); and (3) autonomy and decision making (each woman had to care for several simulated patients, making decisions about diagnosis, treatment, and transportation, and simulating a phone call to an urban doctor laying out her plan for the patient). An 11-question survey assessing confidence as care providers was administered before and after the course. Answer choices varied from “not confident” to “completely confident”. Findings: 55 women from villages in Uttar Pradesh and Bihar underwent training between August and December 2016. 54 participants completed both the pre-training and post-training surveys. Changes in mean number of responses corresponding to each confidence level are as follows: “not confident” 39·6 (SD 14·4) pre-training to 0 post-training (p

Occupational exposure accounts for a contact between workers and different toxicants. Present study was designed to measure the arsenic-induced DNA fragmentation and oxidative stress in exposed workers. Blood, hair, and nail samples were collected from welding, brick kiln, furniture, pesticide, and paint industries (n = 50/industry) of Pakistan along with 200 controls. DNA damage was calculated using DNA fragmentation assay. Antioxidant enzymes (CAT, SOD, GPx) were measured using ELISA. Results revealed that arsenic exposure induced DNA fragmentation in brick kiln, furniture, and welding industries. Enzyme activity was reduced in five industries compared to control. In exposed group, significant depletion of enzymes was observed in furniture, welding, and brick kiln workers. Based on age and time of exposure, significant difference was observed in welding and brick kiln group. Smokers of exposed group showed significantly reduced levels of enzymes compared to controls. Arsenic deposition was observed higher in the hair, nail, and blood samples of exposed group (P

Frequent reuse of syringes during medical injections is fuelling epidemics of human immunodeficiency virus and hepatitis C virus infections in many low- and middle-income countries including Pakistan.To explore specific factors related to syringe reuse during therapeutic injections.We randomly surveyed 319 healthcare providers from 2 socioeconomically diverse districts in Pakistan, along with 625 of their patients.Providers see 12-25 patients per day, and provide 7-14 therapeutic injections or intravenous drips. Comparing daily stocks with injections provided, we estimated that 38% of providers (Rawalpindi: 14%, Tando Allah Yar: 44%) likely reuse syringes 2 or 3 times. Rural location and longer duration of practice predict a higher likelihood of reuse. Physicians and non-physicians were equally likely to reuse. Most patients were unaware when a syringe had been reused.High rate of syringe reuse is driven by high injection demand by patients, to which providers comply. Patients are generally unaware of the harm of injections with syringe reuse or that reuse happens. Our findings suggest that patient focused approaches may help reduce syringe reuse.إعادة استعمال المحاقن للحَقْن العِلاَجِيّ في باكستان: إعادة النظر في استعمال المحاقن ومحدداته.عدنان خان، أرشد ألطف، هوما قرشي، مزدجان أركازي، عايشة خان.إن إعادة استعمال المحاقن تَكراراً من شأنه أن يؤجج الأوبئة المرتبطة بفيروس العوز المناعي البشر ي والعدوى بفيرو س التهاب الكبد C في كثير من البلدان المنخفضة الدخل والمتوسطة الدخل، ومنها باكستان.هدفت الدراسة إلى استكشاف العوامل المُحددة المرتبطة بإعادة استعمال المحاقن للحَقْن العِلاجِيّ.أجرينا مسحاً عشوائياً شمل 319 مرفقاً من مرافق تقديم خدمات الرعاية الصحية من منطقتين بينهما تبايُن من الناحية الاجتماعية والاقتصادية في باكستان، بالإضافة إلى 625 مريضاً ممن يرتادون هذه المرافق.يفحص مقدمو الخدمة ما يتراوح بين 12–25 مريضاً يومياً، ويعطون الحقن العلاجي أو التقطير داخل الوريد لما يتراوح ما بين 7–14 مريضاً. وبمقارنة المخزون اليومي بعمليات الحقن التي تحدث، قدرنا أنه في 38٪ من مقدمي خدمات الرعاية الصحية (روالبندي: 14٪، تاندو الله يار: 44٪) يُرجح إعادة استعمال المحاقن بمقدار مرتين أو 3 مرات. ويُرجح بنسبة أعلى إعادة استعمال المحاقن في المناطق الريفية وأثناء الممارسات الطبية التي تستغرق وقتاً أطول. ويتساوى الأطباء وغير الأطباء في احتمال إعادتهم استعمال المحاقن. وأفاد معظم المرضى بأنهم لا يكونون على دراية بأن المِحْقَنَة المُستعملة في الحقن مُعاد استعمالها.يرجع ارتفاع معدل إعادة استعمال المحاقن إلى ارتفاع الطلب على المحاقن من جانب المرضى، وتلبية مقدمي خدمات الرعاية الصحية لهذا الطلب. وعامةً، لا يكون المرضى مُدركين لضرر الحقن عن طريق إعادة استعمال المِحْقَنَة، أو ربما لا يكونون مدركين في الأساس أن المحاقن يُعاد استعمالها. ووفقاً للنتائج التي توصلنا إليها، نرى أن النهوج التي تركز على المرضى قد تساعد في الحد من إعادة استعمال المحاقن.Réutilisation des seringues pour injections thérapeutiques au Pakistan : réflexion sur ses déterminants.La réutilisation fréquente des seringues lors des injections thérapeutiques alimente des épidémies d’infections par les virus de l’immunodéficience humaine et de l’hépatite C dans de nombreux pays à revenu faible et intermédiaire, y compris le Pakistan.Étudier les facteurs spécifiques liés à la réutilisation des seringues lors des injections thérapeutiques.Nous avons interrogé 319 prestataires de soins, de façon aléatoire, dans deux districts du Pakistan présentant une diversité socio-économique, ainsi que 625 de leurs patients.Les prestataires voient de 12 à 25 patients et effectuent de 7 à 14 injections thérapeutiques ou perfusions intraveineuses goutte-à-goutte par jour. En comparant les stocks journaliers avec les injections réalisées, nous avons estimé que 38 % des prestataires (Rawalpindi : 14 %, Tando Allah Yar : 44 %) réutilisent vraisemblablement les seringues deux ou trois fois. L’implantation rurale et l’ancienneté d’exercice laissent anticiper une plus grande probabilité de réutilisation. Les médecins et les autres membres du personnel soignant étaient aussi susceptibles de réutiliser les seringues. Lorsqu’une seringue était réutilisée, la plupart des patients n’en avaient pas conscience.Le taux élevé de réutilisation des seringues est induit par une forte demande d’injections par les patients, à laquelle répondent les prestataires de soins. En général, les patients n’ont pas conscience de la dangerosité des injections effectuées avec des seringues réutilisées, ni même de la pratique de réutilisation. Les résultats de notre enquête indiquent que des approches centrées sur le patient pourraient aider à réduire la réutilisation des seringues.

More and more Canadian post-secondary institutions are introducing a fall break into their term calendars. In 2015, a full week fall break was introduced at our university in order to enhance academic performance and improve mental health amongst students. Our interdisciplinary team surveyed undergraduate students at our university about their experience of the fall break, collected standardized measures of experienced stressors and perceptions of stress before and after the break, and hosted several focus groups to develop a detailed narrative of students’ experience. Stress can also be assessed through non-invasive hormone measures. We collected saliva samples to profile metabolic hormones, cortisol, and dehydroepiandrosterone (DHEA), from first-year male engineering students in order to document possible changes in their stress levels before and after the week-long break. This group was compared to male engineering students at a similar university that does not hold a fall break. Students exhibited a lower ratio of cortisol to DHEA after a fall break than those that did not experience a break. Our survey results indicate that the majority of students thought the fall break was a positive experience. However, self-reports of stress show a more complex picture, with many students reporting increased perceived stress after the break. Additionally, a portion of students reported that the fall break was a negative experience. To the best of our knowledge, our study is the first of its kind to use a mixed-methods approach to examine the impacts of a fall break.

Objective: To compare the intravenous Labetalol versus intravenous hydralazine in patients having severe Pregnancy induced hypertension (PIH) and pre eclampsia (PE) in pregnancy. Methods: Seventy eight women admitted in the Department of Gynecology and Obstetrics, Civil Hospital Karachi, having severe PIH/PE and fulfilling the inclusion criteria were included in the study. Random selection of patients was performed using sealed opaqe envelop for administration of either intravenous noted (IV) Labetalol or Hydrallazine. The mean fall in the MAP in each group was noted. This data was analyzed by applying SPSS version 13. The study was conducted from November 2012 to April 2013. Results: The mean (±SD) age of the labetalol group was 27.46 (±5.28) years while that in the hydralazine group was 26.28 (±5.17) years. The mean fall in MAP observed in the labetalol group was 29.10 ± 7.21 mmHg and that in the hydralazine group was 25.05 ± 10.15 mmHg which was statistically significant with the p value being 0.046. Conclusion: Intra Venous labetalol lowered MAP more than hydralazine, when administered to pregnant females with severe Pregnancy induced hypertension and pre eclampsia in pregnancy.

Item does not contain fulltext BACKGROUND: Leber congenital amaurosis, caused by mutations in RPE65 and LRAT, is a severe form of inherited retinal degeneration leading to blindness. We aimed to assess replacement of the missing chromophore 11-cis retinal with oral QLT091001 (synthetic 9-cis-retinyl acetate) in these patients. METHODS: In our open-label, prospective, phase 1b trial, we enrolled patients (aged >/=6 years) with Leber congenital amaurosis and RPE65 or LRAT mutations at McGill University's Montreal Children's Hospital. Patients received 7 days of oral QLT091001 (10-40 mg/m(2) per day). We assessed patients at baseline and days 7, 9, 14, and 30, and then 2 months and every 2 months thereafter for up to 2.2 years for safety outcomes and visual function endpoints including Goldmann visual fields (GVF), visual acuity, and functional MRI assessment. We regarded patients as having an improvement in vision if we noted at least a 20% improvement in retinal area on GVF compared with baseline or a visual acuity improvement of five or more letters compared with baseline in two consecutive study visits (or any improvement from no vision at baseline). This study is registered with ClinicalTrials.gov, number NCT01014052. FINDINGS: Between December, 2009, and June, 2011, we enrolled and treated 14 patients aged 6-38 years who were followed up until March, 2012. Ten (71%) of 14 patients had an improvement in GVF areas (mean increase in retinal area of 28-683%). Six (43%) patients had an improvement in visual acuity (mean increase of 2-30 letters). Self-reported or parent-reported improvements in activities of daily living supported these findings. After 2 years, 11 (79%) patients had returned to their baseline GVF retinal area and ten (71%) had returned to baseline visual acuity letter values. Thus, three (21%) patients had a sustained GVF response and four (30%) had a sustained visual acuity response. Four patients had functional MRI scans, which correlated with visual response or absence of response to treatment. No serious adverse events occurred, although we noted transient headaches (11 patients), photophobia (11 patients), reduction in serum HDL concentrations (four patients), and increases in serum triglycerides (eight patients) and aspartate aminotransferase concentrations (two patients). INTERPRETATION: Non-invasive oral QLT091001 therapy is well tolerated, and can rapidly improve visual function in some patients with Leber congenital amaurosis and RPE65 and LRAT mutations. FUNDING: QLT, Foundation Fighting Blindness Canada, CIHR, FRSQ, Reseau Vision.

Objective To assess the outcome and safety of sacrohysteropexy as uterus conserving surgery for pelvic organ prolapse in young women and to assess patients' satisfaction with the procedure. Methods This is a case series of patients operated at Sind Government Lyari General Hospital and Civil Hospital Karachi, between January, 2007 to October, 2015. Data of the patients who had sacrohysteropexy were reviewed. Complications during surgery and post-operative period including haemorrhage, visceral injury, paralytic ileus and peritonitis were studied. Success of procedure, need of blood transfusion, hospital stay and condition on discharge and six weeks follow-up were noted. Data were analyzed using SPSS version 16. Mean ± SD was calculated for numerical, while frequencies were computed for categorical variables. Results Data of 60 patients were reviewed. Early post-operative success was 100%. Duration of surgery was less than two hours in 57 (95%) patients. Blood loss was negligible in majority of cases. Out of all 60 cases, 52 (86.7%) did not suffer any complication. One patient had ureteric injury, while one patient sustained bowel injury. Two patients had paralytic ileus. Four patients suffered from abdominal wound infection. All patients were managed satisfactorily. Mean duration of stay in hospital was four days. Upon follow up 96.7% patients were satisfied with results of operative procedure. Sixteen (26.7%) patients complained of backache on follow-up visit. Conclusion This review concludes that sacrohysteropexy was successful in all cases in early post-operative period. It is a safe procedure and should be considered as an option for the treatment of pelvic organ prolapse in young women, in whom uterine conservation is required.

An efficient and short route was established for the synthesis of anti-bovine viral diarrhea virus agents, namely 4-methyl-γ-carboline (SK4M) 1, 3-methyl-γ-carboline (SK3M) 2, 5-methyl-γ-carboline (SK5M) 3, and a new γ-carboline derivative 4, using thermal electrocyclization reaction as a key step. The evaluation of cytotoxicity of compound 4 against human cervical cancer cell line HeLa and leukemic cell line HL-60 furnished CC50 value of 19.5 and 18.8 µM respectively.