Study protocol of DIVERGE, the first genetic epidemiological study of major depressive disorder in Pakistan

INTRODUCTION: Globally, 80% of the burdenof major depressive disorder (MDD) pertains to low- and middle-income countries. Research into genetic and environmental risk factors has the potential to uncover disease mechanisms that may contribute to better diagnosis and treatment of mental illness, yet has so far been largely limited to participants with European ancestry from high-income countries. The DIVERGE study was established to help overcome this gap and investigate genetic and environmental risk factors for MDD in Pakistan. METHODS: DIVERGE aims to enrol 9000 cases and 4000 controls in hospitals across the country. Here, we provide the rationale for DIVERGE, describe the study protocol and characterise the sample using data from the first 500cases. Exploratory data analysis is performed to describe demographics, socioeconomic status, environmental risk factors, family history of mental illness and psychopathology. RESULTS AND DISCUSSION: Many participants had severe depression with 74% of patients who experienced multiple depressive episodes. It was a common practice to seek help for mental health struggles from faith healers and religious leaders. Socioeconomic variables reflected the local context with a large proportion of women not having access to any education and the majority of participants reporting no savings. CONCLUSION: DIVERGE is a carefully designed case-control study of MDD in Pakistan that captures diverse risk factors. As the largest genetic study in Pakistan, DIVERGE helps address the severe underrepresentation of people from South Asian countries in genetic as well as psychiatric research

Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial

Background Post-partum haemorrhage is the leading cause of maternal death worldwide. Early administration of tranexamic acid reduces deaths due to bleeding in trauma patients. We aimed to assess the effects of early administration of tranexamic acid on death, hysterectomy, and other relevant outcomes in women with post-partum haemorrhage. Methods In this randomised, double-blind, placebo-controlled trial, we recruited women aged 16 years and older with a clinical diagnosis of post-partum haemorrhage after a vaginal birth or caesarean section from 193 hospitals in 21 countries. We randomly assigned women to receive either 1 g intravenous tranexamic acid or matching placebo in addition to usual care. If bleeding continued after 30 min, or stopped and restarted within 24 h of the first dose, a second dose of 1 g of tranexamic acid or placebo could be given. Patients were assigned by selection of a numbered treatment pack from a box containing eight numbered packs that were identical apart from the pack number. Participants, care givers, and those assessing outcomes were masked to allocation. We originally planned to enrol 15 000 women with a composite primary endpoint of death from all-causes or hysterectomy within 42 days of giving birth. However, during the trial it became apparent that the decision to conduct a hysterectomy was often made at the same time as randomisation. Although tranexamic acid could influence the risk of death in these cases, it could not affect the risk of hysterectomy. We therefore increased the sample size from 15 000 to 20 000 women in order to estimate the effect of tranexamic acid on the risk of death from post-partum haemorrhage. All analyses were done on an intention-to-treat basis. This trial is registered with ISRCTN76912190 (Dec 8, 2008); ClinicalTrials.gov, number NCT00872469; and PACTR201007000192283. Findings Between March, 2010, and April, 2016, 20 060 women were enrolled and randomly assigned to receive tranexamic acid (n=10 051) or placebo (n=10 009), of whom 10 036 and 9985, respectively, were included in the analysis. Death due to bleeding was significantly reduced in women given tranexamic acid (155 [1·5%] of 10 036 patients vs 191 [1·9%] of 9985 in the placebo group, risk ratio [RR] 0·81, 95% CI 0·65–1·00; p=0·045), especially in women given treatment within 3 h of giving birth (89 [1·2%] in the tranexamic acid group vs 127 [1·7%] in the placebo group, RR 0·69, 95% CI 0·52–0·91; p=0·008). All other causes of death did not differ significantly by group. Hysterectomy was not reduced with tranexamic acid (358 [3·6%] patients in the tranexamic acid group vs 351 [3·5%] in the placebo group, RR 1·02, 95% CI 0·88–1·07; p=0·84). The composite primary endpoint of death from all causes or hysterectomy was not reduced with tranexamic acid (534 [5·3%] deaths or hysterectomies in the tranexamic acid group vs 546 [5·5%] in the placebo group, RR 0·97, 95% CI 0·87-1·09; p=0·65). Adverse events (including thromboembolic events) did not differ significantly in the tranexamic acid versus placebo group. Interpretation Tranexamic acid reduces death due to bleeding in women with post-partum haemorrhage with no adverse effects. When used as a treatment for postpartum haemorrhage, tranexamic acid should be given as soon as possible after bleeding onset. Funding London School of Hygiene & Tropical Medicine, Pfizer, UK Department of Health, Wellcome Trust, and Bill & Melinda Gates Foundation

Negative faculty role modelling - is it a reflection of deteriorating societal values?

BACKGROUND: Negative faculty role modelling is an area of growing concern especially due to its implications on medical professionalism. The study aims to explore the impacts of negative role modelling on professionalism of medical students in the context of Pakistan.METHODS: This qualitative study is part of a larger study exploring impacts of role modelling on professionalism of students. It is based on Constructivist Grounded Theory involving six semi-structured interviews with clinical faculty and three focus group discussions with 22 students. Initial, focused, selective coding and thematic analysis was used to find the core category.RESULTS: Three overarching categories were developed: traits observed with negative role models; impact of negative role modelling; factors promoting negative role modelling. Subcategories of impacts included negative impact on professionalism, emotional impact, and its paradoxical positive impact. Negative role modelling, a manifestation of declining professionalism, was attributed to deteriorating societal values; further compounded by the lack of required mechanisms by institutions and the regulatory authority at their respective levels.CONCLUSIONS: In the absence of a strong moral platform at societal level, the burden of responsibility rests with the faculty and more importantly with institutions and regulatory bodies to discourage negative role modelling and educate students to recognize, reflect on and avoid negative behaviours and adopt strong professional values.</p

Negative faculty role modelling – is it a reflection of deteriorating societal values?

Negative faculty role modelling is an area of growing concern especially due to its implications on medical professionalism. The study aims to explore the impacts of negative role modelling on professionalism of medical students in the context of Pakistan. This qualitative study is part of a larger study exploring impacts of role modelling on professionalism of students. It is based on Constructivist Grounded Theory involving six semi-structured interviews with clinical faculty and three focus group discussions with 22 students. Initial, focused, selective coding and thematic analysis was used to find the core category. Three overarching categories were developed: traits observed with negative role models; impact of negative role modelling; factors promoting negative role modelling. Subcategories of impacts included negative impact on professionalism, emotional impact, and its paradoxical positive impact. Negative role modelling, a manifestation of declining professionalism, was attributed to deteriorating societal values; further compounded by the lack of required mechanisms by institutions and the regulatory authority at their respective levels. In the absence of a strong moral platform at societal level, the burden of responsibility rests with the faculty and more importantly with institutions and regulatory bodies to discourage negative role modelling and educate students to recognize, reflect on and avoid negative behaviours and adopt strong professional values.</p

Biogenic Silver Nanoparticles as a Stress Alleviator in Plants: A Mechanistic Overview

Currently, the growth and yield of crops are restrained due to an increase in the occurrence of ecological stresses globally. Biogenic generation of nanomaterials is an important step in the development of environmentally friendly procedures in the nanotechnology field. Silver-based nanomaterials are significant because of their physical, chemical, and biological features along with their plentiful applications. In addition to useful microbes, the green synthesized Ag nanomaterials are considered to be an ecologically friendly and environmentally biocompatible method for the enhancement of crop yield by easing stresses. In the recent decade, due to regular droughts, infrequent precipitation, salinity, and increased temperature, the climate alternation has changed certain ecological systems. As a result of these environmental changes, crop yield has decreased worldwide. The role of biogenic Ag nanomaterials in enhancing methylglyoxal detoxification, antioxidant defense mechanisms, and generating tolerance to stresses-induced ROS injury has been methodically explained in plants over the past ten years. However, certain studies regarding stress tolerance and metal-based nanomaterials have been directed, but the particulars of silver nanomaterials arbitrated stresses tolerance have not been well-reviewed. Henceforth, there is a need to have a good understanding of plant responses during stressful conditions and to practice the combined literature to enhance tolerance for crops by utilization of Ag nanoparticles. This review article illustrates the mechanistic approach that biogenic Ag nanomaterials in plants adopt to alleviate stresses. Moreover, we have appraised the most significant activities by exogenous use of Ag nanomaterials for improving plant tolerance to salt, low and high temperature, and drought stresses

Exogenous Application of Green Titanium Dioxide Nanoparticles (TiO₂ NPs) to Improve the Germination, Physiochemical, and Yield Parameters of Wheat Plants under Salinity Stress

Agriculture is the backbone of every developing country. Among various crops, wheat (Triticum aestivum L.) belongs to the family Poaceae and is the most important staple food crop of various countries. Different biotic (viruses, bacteria and fungi) and abiotic stresses (water logging, drought and salinity) adversely affect the qualitative and quantitative attributes of wheat. Among these stresses, salinity stress is a very important limiting factor affecting the morphological, physiological, biochemical attributes and grain yield of wheat. This research work was carried out to evaluate the influence of phytosynthesized TiO2 NPs on the germination, physiochemical, and yield attributes of wheat varieties in response to salinity. TiO2 NPs were synthesized using TiO2 salt and a Buddleja asiatica plant extract as a reducing and capping agent. Various concentrations of TiO2 nanoparticles (20, 40, 60 and 80 mg/L) and salt solutions (NaCl) (100 and 150 mM) were used. A total of 20 mg/L and 40 mg/L improve germination attributes, osmotic and water potential, carotenoid, total phenolic, and flavonoid content, soluble sugar and proteins, proline and amino acid content, superoxide dismutase activity, and reduce malondialdhehyde (MDA) content at both levels of salinity. These two concentrations also improved the yield attributes of wheat varieties at both salinity levels. The best results were observed at 40 mg/L of TiO2 NPs at both salinity levels. However, the highest concentrations (60 and 80 mg/L) of TiO2 NPs showed negative effects on germination, physiochemical and yield characteristics and causes stress in both wheat varieties under control irrigation conditions and salinity stress. Therefore, in conclusion, the findings of this research are that the foliar application of TiO2 NPs can help to improve tolerance against salinity stress in plants

Biogenic Titanium Dioxide Nanoparticles Ameliorate the Effect of Salinity Stress in Wheat Crop

Crop productivity worldwide is being hampered by salt stress. Nanotechnology and its applications in agriculture are noteworthy and fruitful. The current work investigates the potential significance of TiO2 NPs in alleviating salt stress in wheat cultivars. TiO2 NPs were prepared by green synthesis; their characterizations were carried out by UV–visible spectroscopy, SEM, and EDX. In the greenhouse control condition, different concentrations of salt (NaCl) with and without TiO2 NPs were administered to wheat crops. Plants treated with TiO2 NPs showed an enhanced germination rate, morphological, and metabolic profiling with and without salt stress. Different concentrations of TiO2 NPs (25, 50, 75, and 100 µg/mL) and salt solutions (NaCl 50, 100, and 150 mM) were used. TiO2 NP concentrations of 25 µg/mL and 50 µg/mL improved the germination attributes, physio-morphic parameters: plant length, the fresh and dry weight of plants, the number of leaves, the leaf area, the RWC, the MSI, and different chlorophyll contents at all saline conditions. These two concentrations also enhanced the biochemical attributes: free amino acids, soluble sugar content, proline content, SOD, and POD, of wheat varieties at all salinity levels. Wheat subjected to salt stress responded best to the application of TiO2 NPs at a concentration of 50 µg/mL. However, the highest concentrations (75 and 100 µg/mL) of TiO2 NPs showed detrimental effects on germination, agronomic, physiological, and biochemical attributes, and caused stress in both wheat varieties (Pirsabak-05 and NARC-09) under control and saline conditions. The outcomes of the current research work are notable, and NPs with such capabilities may be a useful supply of fertilizer in the agricultural industry

Effects of Phytogenically Synthesized Bimetallic Ag/ZnO Nanomaterials and Nitrogen-Based Fertilizers on Biochemical and Yield Attributes of Two Wheat Varieties

Wheat is the most important staple food worldwide, but wheat cultivation faces challenges from high food demand. Fertilizers are already in use to cope with the demand; however, more unconventional techniques may be required to enhance the efficiency of wheat cultivation. Nanotechnology offers one potential technique for improving plant growth and production by providing stimulating agents to the crop. In this study, plant-derived Ag/ZnO nanomaterials were characterized using UV-Vis spectroscopy, SEM, EDX, FTIR, and XRD methods. Various concentrations of phytogenically synthesized Ag/ZnO nanomaterials (20, 40, 60, and 80 ppm) and nitrogen-based fertilizers (urea and ammonium sulphate 50 and 100 mg/L) were applied to wheat varieties (Galaxy-13 and Pak-13). The results obtained from this research showed that application of 60 ppm Ag/ZnO nanomaterials with nitrogenous fertilizers (50 and 100 mg/L) were more effective in improving biochemistry and increasing yield of wheat plants by reducing enzymatic and non-enzymatic antioxidants (proline content, soluble sugar content, malondialdehyde, total phenolic content, total flavonoid content, superoxide dismutase, peroxidase, and catalase); and significantly increasing the protein content, number of grains per pot, spike length, 100-grain weight, grain yield per pot, and harvest index of both wheat varieties, compared to untreated plants. These findings allow us to propose Ag/ZnO nanomaterial formulation as a promising growth- and productivity-improvement strategy for wheat cultivation.This research was funded by projects APOGEO (Cooperation Program INTERREG-MAC 2014–2020, with European Funds for Regional Development-FEDER). “Agencia Canaria de Investigación, Innovación y Sociedad de la Información (ACIISI) del Gobierno de Canarias” (Project ProID2020010134), CajaCanarias (Project 2019SP43).Peer reviewe