Plant-Based Alternative Treatment for Leishmaniasis: A Neglected Tropical Disease

Leishmaniasis is a third most important vector born disease caused by intracellular parasite belongs to genus Leishmania. The leishmaniasis is prevalent in 102 countries/areas worldwide. Approximately, it effected 350 million people worldwide. Leishmaniasis effects developing and undeveloped countries globally. Antileishmanial drugs (pentavalent antimonials, stibogluconate, miltefosine, paramycin, and amphotericin) are most vital tool for curing leishmaniasis. However, none of these drugs is free from side effect including cost, toxicity, drug resistance, administration route, and prolong time, these disadvantages are main obstacle in the Leishmania infection eradication. Considering the increasing cases of leishmaniasis and drug resistance there is an urgent need for an effective and novel approach against leishmaniasis. Therefore, many researchers have tried to develop new medicines for the treatment of Leishmania infection. In the course of new therapies identification, plant based compounds were found to be an alternative that can be either used directly or with structural modifications. Several plants have been known for ages to be the source of phytochemicals with high values of medicines. These phytochemicals have been extracted by various techniques and have shown efficacy for the curing of several diseases. This chapter study explain various applications based on green approaches drugs for the treatment of leishmaniasis

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

Improving osteoporosis treatment rates in inpatients admitted with hip fracture: A healthcare improvement initiative in a tertiary referral hospital

Abstract Objective This healthcare improvement initiative was designed to increase inpatient osteoporosis treatment after hip fracture. Methods A new protocol was developed by Geriatric Medicine and Endocrinology departments at a tertiary care hospital in Sydney. Its aim was to standardize assessment and treatment of osteoporosis in patients admitted with hip fracture. Eligible inpatients would receive intravenous zoledronic acid during their admission. A 6‐month sample of hip fracture patients admitted after the protocol's implementation was compared to a group admitted before. Data collected included demographics, biochemistry, treatment rates, adverse effects, and admission survival. Results There was a considerable increase in osteoporosis treatment after introducing the protocol. Before the protocol's introduction, none of 36 eligible patients received treatment. After the intervention 79% (23 out of 29) of eligible patients were treated. All treated patients had renal function and serum calcium levels checked post‐infusion with no adverse outcomes. Eight patients developed flu‐like symptoms within 24 h of the infusion. There were no instances of arrhythmias, ocular inflammation, or death. The cost per patient treated was AUD $87. Conclusion Adopting a standardized protocol for osteoporosis treatment in patients admitted for hip fracture was effective in improving treatment rates whilst being relatively safe and inexpensive

Biocidal action, characterization, and molecular docking of Mentha piperita (Lamiaceae) leaves extract against Culex quinquefasciatus (Diptera: Culicidae) larvae.

Mosquitoes are found in tropical and subtropical areas and are the carriers of a variety of diseases that are harmful to people's health. e.g., malaria, filariasis, chikungunya, dengue fever, etc. Although several insecticides are available, however, due to insect resistance and environmental hazards, more eco-friendly chemicals are needed for insect control. So, the current research was planned to explore the prospective of Mentha piperita to be used for the formulation of larvicides against mosquito Culex quinquefasciatus. The ethanolic and water extracts of M. piperita leaves were prepared using the soxhlet apparatus. The extracts were dried and subjected to prepare five concentrations multiple of 80 ppm. Each concentration was applied for its larvicidal efficacy setting an experiment (in triplicate) in plastic containers of 1000 ml with extracts, 30 larvae of all four instars separately, and fed with dog biscuits along with controls. Observations were taken after each 12 hrs. till 72 hrs. The antioxidant perspective of M. piperita was determined by DPPH radical scavenging, total antioxidant capacity, and ferric reducing power assays. Using brine shrimp lethality bioactivity, the cytotoxic study was perceived. Standard techniques were used to classify the M. piperita extract using preliminary qualitative and quantitative phytochemicals, UV-Vis spectroscopy, FT-IR, and GC-MS analysis. M. piperita ethanolic leaves extract after 24 hrs. of exposure in 400 ppm showed 93% (LC50 = 208.976 ppm) mortality in ethanolic extract and 80% (LC90 = 246.900 ppm) in the water extract. In treated larvae, biochemical examination revealed a substantial (P<0.05) decrease in proteins, carbohydrates, and fat contents. The ethanol extract of M. piperita was the most efficient, killing brine shrimp nauplii in 50% to 90% of cases. TAC (125.4 3.5gAAE/mg DW) and FRP (378.1 1.0gAAE/mg DW) were highest in the ethanolic extract of M. piperita. The presence of medicinally active components such as alkaloids, carbohydrates, flavonoids, and others in M. piperita leaves extract in ethanol was discovered. The UV-Vis spectrum showed two peaks at 209.509 and 282.814 nm with the absorption of 2.338 and 0.796 respectively. The FT-IR consequences exhibited the occurrence of alcohols, alkanes, aldehyde, aromatic rings, ether linkage, ester, and halo- compounds. The GC-MS analysis according to peak (%) area and retention time showed ten phytochemicals consisting of six major and four minor compounds. Among all the compounds, 1, 2-benzene dicarboxylic acid, and 3-ethyl-5, 5-dimethyl -6-phenyl bound well to the NS3 protease domain with PDB ID: 2FOM. Hence, for the prevention of health hazards and mosquito control, M. Piperita is a potential source of chemicals for insecticide formulation

Practical aspects of telehealth: doctor-patient relationship and communication

The fourth in a series of articles about the practical aspects of telehealth, this paper provides advice and information for specialists to communicate effectively with patients during a telehealth video consultation

A dyadic approach to depression, resilience and quality of life on marital adjustment among infertile couples in Karachi, Pakistan: A cross-sectional study

Background: Infertility is a major reproductive health problem in Pakistan. It has the potential to cause serious negative impact on a couple\u27s marital life and psychological health.Aim: This study aimed to assess the factors associated with maladjustment among infertile couples.Method: An analytical cross-sectional design was employed. Validated scales were used to assess marital adjustment, depression, resilience and quality of life among infertile couples. Purposive sampling was employed to enrol 334 infertile couples from a private infertility medical centre, of Karachi, Pakistan.Results: Among couples, marital adjustment scores were comparable, but resilience and quality of life were significantly low among wives whereas depression was significantly high among wives compared with husbands. Wives\u27 marital adjustment was positively correlated with husband\u27s resilience and quality of life and negatively related with his depression. After employing adjusted actor-partner interdependence modelling, wives\u27 own depression and resilience had significant effect on their marital adjustment and their partner\u27s resilience, depression and quality of life did not have any impact on their outcome. On the contrary, wives\u27 resilience had a significant effect in increasing the marital adjustment of their husband.Conclusion: This study highlights the need to promote psychological support (resilience building skills) or couples\u27 therapy to all those couples undergoing infertility treatment

Non-Lethal Doses of RSL3 Impair Microvascular Endothelial Barrier through Degradation of Sphingosie-1-Phosphate Receptor 1 and Cytoskeletal Arrangement in A Ferroptosis-Independent Manner

The excess microvascular endothelial permeability is a hallmark of acute inflammatory diseases. Maintenance of microvascular integrity is critical to preventing leakage of vascular components into the surrounding tissues. Sphingosine-1-phosphate (S1P) is an active lysophospholipid that enhances the endothelial cell (EC) barrier via activation of its receptor S1PR1. Here, we delineate the effect of non-lethal doses of RSL3, an inhibitor of glutathione peroxidase 4 (GPX4), on EC barrier function. Low doses of RSL3 (50–100 nM) attenuated S1P-induced human lung microvascular barrier enhancement and the phosphorylation of AKT. To investigate the molecular mechanisms by which RSL3 attenuates S1P’s effect, we examined the S1PR1 levels. RSL3 treatment reduced S1PR1 levels in 1 h, whereas the effect was attenuated by the proteasome and lysosome inhibitors as well as a lipid raft inhibitor. Immunofluorescence staining showed that RSL3 induced S1PR1 internalization from the plasma membrane into the cytoplasm. Furthermore, we found that RSL3 (100 and 200 nM) increased EC barrier permeability and cytoskeletal rearrangement without altering cell viability. Taken together, our data delineates that non-lethal doses of RSL3 impair EC barrier function via two mechanisms. RSL3 attenuates S1P1-induced EC barrier enhancement and disrupts EC barrier integrity through the generation of 4-hydroxynonena (4HNE). All these effects are independent of ferroptosis