Feasibility and acceptability of sexually transmitted infection screening during antenatal care of women in Dhaka, Bangladesh.

BACKGROUND: Sexually transmitted infections (STIs) are a major public health concern worldwide. Untreated STIs may have serious sequelae, particularly in pregnant women. The objective of this study was to assess the feasibility and acceptability of screening and treating common STIs in women during pregnancy in Bangladesh. METHODS: Women were enrolled from four maternity clinics/hospitals serving the lower-middle class population in Dhaka, Bangladesh. The participants were interviewed, and vaginal swab samples were collected by clinical staff. Specimens were tested for Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis and high-risk Human Papilloma Viruses (HPVs) using GeneXpert (Cepheid, Sunnyvale, California). Women were informed of their test results and were provided treatment for curable infections. A test of cure was performed. RESULTS: Out of 1157 pregnant women approached, 1000 (86.4%) participated. Ninety-one percent women learned of their test results on the same day of testing. Out of the 996 valid results, 7 (0.7%) tested positive for Chlamydia trachomatis and 1 (0.1%) for Trichomonas vaginalis. There were no gonorrhoea cases. Out of the 971 women with valid results for high-risk HPVs, 46 (4.7%) tested positive. CONCLUSIONS: Screening women for STIs during antenatal care was highly feasible and well-accepted in Bangladesh. While the prevalence of common curable STIs was very low, hrHPV infection prevalence was moderately high. Our findings support period monitoring of STIs and continued prevention efforts for cervical cancer in Bangladesh.

Long-Term Video Electroencephalographic Monitoring in <30-Week Gestational Age Infants With High-Grade Intraventricular Hemorrhage.

BACKGROUND: Despite recognizing high seizure risk, the current consensus guidelines on evaluating seizures in preterm neonates are based on limited data. We chose to investigate the seizure risk in high-risk preterm (<30 weeks gestation) asymptomatic (without a clinical concern for seizures) infants with high-grade intraventricular hemorrhage who underwent long-term video electroencephalographic monitoring. METHODS: We performed a comprehensive retrospective review on all infants of <30-week gestational age admitted to the University of Alabama at Birmingham Regional Neonatal Intensive Care Unit from June 2018 to October 2022. We selected those patients who underwent electroencephalographic monitoring without a prior clinical concern for seizures. We recorded gender, gestational age, APGAR scores (one and five minutes), intraventricular hemorrhage (grade, age at diagnosis), and electroencephalographic monitoring (timing and duration) data. RESULTS: Among 37 premature infants, six had seizures detected on electroencephalographic monitoring. All six infants had subclinical seizures. Only two of six patients had a clinical correlation (although not identified by the providers) with some of their seizures. Patients with seizures were significantly younger in chronological age (median age 6.5 days vs 9 days, P value 0.009) at the time of the electroencephalographic monitoring initiation and were more likely to have subsequent monitoring studies (P value 0.0418). CONCLUSIONS: Long-term video electroencephalographic monitoring performed after the diagnosis of high-grade intraventricular hemorrhage captured seizures in ∼16% of asymptomatic premature neonates of <30 weeks' gestation. Patients identified to have seizures were significantly younger (chronological age) at the time of the electroencephalographic monitoring initiation and were more likely to be remonitored.

Midwife-led birthing centres in four countries: a case study.

BACKGROUND: Midwives are essential providers of primary health care and can play a major role in the provision of health care that can save lives and improve sexual, reproductive, maternal, newborn and adolescent health outcomes. One way for midwives to deliver care is through midwife-led birth centres (MLBCs). Most of the evidence on MLBCs is from high-income countries but the opportunity for impact of MLBCs in low- and middle-income countries (LMICs) could be significant as this is where most maternal and newborn deaths occur. The aim of this study is to explore MLBCs in four low-to-middle income countries, specifically to understand what is needed for a successful MLBC. METHODS: A descriptive case study design was employed in 4 sites in each of four countries: Bangladesh, Pakistan, South Africa and Uganda. We used an Appreciative Inquiry approach, informed by a network of care framework. Key informant interviews were conducted with 77 MLBC clients and 33 health service leaders and senior policymakers. Fifteen focus group discussions were used to collect data from 100 midwives and other MLBC staff. RESULTS: Key enablers to a successful MLBC were: (i) having an effective financing model (ii) providing quality midwifery care that is recognised by the community (iii) having interdisciplinary and interfacility collaboration, coordination and functional referral systems, and (iv) ensuring supportive and enabling leadership and governance at all levels. CONCLUSION: The findings of this study have significant implications for improving maternal and neonatal health outcomes, strengthening healthcare systems, and promoting the role of midwives in LMICs. Understanding factors for success can contribute to inform policies and decision making as well as design tailored maternal and newborn health programmes that can more effectively support midwives and respond to population needs. At an international level, it can contribute to shape guidelines and strengthen the midwifery profession in different settings.

Risk Factors for Extubation Failure After Pediatric Cardiac Surgery and Impact on Outcomes: A Multicenter Analysis.

IMPORTANCE: Extubation failure (EF) after pediatric cardiac surgery is associated with increased morbidity and mortality. OBJECTIVES: We sought to describe the risk factors associated with early (< 48 hr) and late (48 hr ≤ 168 hr) EF after pediatric cardiac surgery and the clinical implications of these two types of EF. DESIGN SETTING AND PARTICIPANTS: Retrospective cohort study using prospectively collected clinical data for the Pediatric Cardiac Critical Care Consortium (PC4) Registry. Pediatric patients undergoing Society of Thoracic Surgeons benchmark operation or heart transplant between 2013 and 2018 available in the PC4 Registry were included. MAIN OUTCOMES AND MEASURES: We analyzed demographics and risk factors associated with EFs (primary outcome) including by type of surgery. We identified potentially modifiable risk factors. Clinical outcomes of mortality and length of stay (LOS) were reported. RESULTS: Overall 18,278 extubations were analyzed. Unplanned extubations were excluded from the analysis. The rate of early EF was 5.2% (948) and late EF was 2.5% (461). Cardiopulmonary bypass time, ventilator duration, airway anomaly, genetic abnormalities, pleural effusion, and diaphragm paralysis contributed to both early and late EF. Extubation during day remote from shift change and nasotracheal route of initial intubation was associated with decreased risk of early EF. Extubation in the operating room was associated with an increased risk of early EF but with decreased risk of late EF. Across all operations except arterial switch, EF portrayed an increased burden of LOS and mortality. CONCLUSION AND RELEVANCE: Both early and late EF are associated with significant increase in LOS and mortality. Study provides potential benchmarking data by type of surgery. Modifiable risk factors such as route of intubation, time of extubation as well as treatment of potential contributors such as diaphragm paralysis or pleural effusion can serve as focus areas for reducing EFs.

Compliance to playpen usages to enhance parental supervision of under-five children in rural community of Bangladesh.

INTRODUCTION: In Bangladesh, injury is one of the leading causes of death and morbidity in children. All children under 5 years of age are at high risk for drowning though the risks are highest when children first learn to walk and crawl while they do not understand the danger of water. The Centre for Injury Prevention and Research, Bangladesh (CIPRB) in collaboration with Johns Hopkins International Injury Research Unit (JH-IIRU) has been implementing two drowning prevention interventions, providing playpens and community day care centres (anchal), or both in three rural sub-districts of Bangladesh under Saving of Lives from Drowning (SoLiD) project in Bangladesh. In CIPRB intervention areas, wooden playpens were distributed among the children nine months to three years at household (HH) level. OBJECTIVE: The aim of this study was to explore and understand the acceptability and perceptions of parents towards playpen and its relevance for drowning and injury related mortality and morbidity prevention. METHODS: Anchal mothers ('anchal maa' in Bangla) distributed 30,553 playpens and collected compliance information at the HH level using a structured questionnaire. 1600 trained anchal maas collected data via face to face interviews from May 2014 to November 2015. Playpen compliance visits were conducted periodically on the second and seventh days and every two months after delivering the playpen. Data were entered using standard data entry formats and analyzed using SPSS software version 23. RESULTS: Parents reported that playpen is a safe place and protects children from drowning and other injuries. During compliance data collection, anchal maa founds that 71.8% of all children were using playpen and 93.7% (of 71.8%) children were playing inside the playpen while mothers were busy with their household chores like cooking, washing dishes and clothes, taking care of their poultry and domestic animals etc. 95.7% parents reported playpen is being used for keeping the child safe. On an average, the children were placed two to six times per day in a playpen. 99.1% of the children who reported using a playpen did not get any injuries (falls, cuts and bruises) while using the playpen. Satisfaction level with the playpen intervention among mothers was 90.5%. Some respondents suggested improving the playpen utilization by providing toys, adding wheels for ease of mobility, and increasing the height. CONCLUSION: The playpens were found to be well accepted and utilized for the children, especially when mothers were busy with their household chores.

Exploration of potential inhibitors for autophagy-related protein 8 as antileishmanial agents.

Leishmaniasis is considered a tropical neglected disease, which is caused by an intramacrophagic parasite, Leishmania. It is endemic in 89 different countries. Autophagy-related protein 8 (Ldatg8) is responsible for the transformation of parasites from promastigote to amastigote differentiation. Ldatg8 is one of the key drug targets of Leishmania donovani (L. donovani) responsible for the defense of parasites during stress conditions. Virtual screening of natural ligand library had been performed against Ldatg8 to identify novel and potent inhibitors. Molecular docking and molecular dynamics simulation studies showed that urolithin A stably blocked Ldatg8. Urolithins are combinations of coumarin and isocoumarin. Further, we evaluated the antileishmanial effects of urolithin A by antileishmanial assays. Urolithin A inhibited the growth and proliferation of L. donovani promastigotes with an IC50  value of 90.3 ± 6.014 µM. It also inhibited the intramacrophagic parasite significantly with an IC50  value of 78.67 ± 4.62 µM. It showed limited cytotoxicity to the human THP-1 differentiated macrophages with a CC50  value of 190.80 ± 16.89 µM. Further, we assayed reactive oxygen species (ROS) generation and annexin V/PI staining upon urolithin A treatment of parasites to have an insight into the mechanism of its action. It induced ROS significantly in a dose-dependent manner, which caused apoptosis partially in parasites. The potential inhibitors for Ldatg8, identified in this study, would provide the platform for the development of an effective and affordable antileishmanial drug.

Sesamol Induces Apoptosis-Like Cell Death in Leishmania donovani.

Background: Visceral leishmaniasis (VL), caused by the protozoan parasite Leishmania donovani (L. donovani), is the most severe form of leishmaniasis. It is largely responsible for significant morbidity and mortality in tropical and subtropical countries. Currently, available therapeutics have lots of limitations including high-cost, adverse side-effects, painful route of administration, less efficacy, and resistance. Therefore, it is time to search for cheap and effective antileishmanial agents. In the present work, we evaluated the antileishmanial potential of sesamol against promastigotes as well as intracellular amastigotes. Further, we tried to work out its mechanism of antileishmanial action on parasites through different assays. Methodology: In vitro and ex vivo antileishmanial assays were performed to evaluate the antileishmanial potential of sesamol on L. donovani. Cytotoxicity was determined by MTT assay on human THP-1-derived macrophages. Sesamol-induced morphological and ultrastructural changes were determined by electron microscopy. H2DCFDA staining, JC-1dye staining, and MitoSOX red staining were performed for reactive oxygen assay (ROS), mitochondrial membrane potential, and mitochondrial superoxide, respectively. Annexin V/PI staining for apoptosis, TUNEL assay, and DNA laddering for studying sesamol-induced DNA fragmentation were performed. Conclusions: Sesamol inhibited the growth and proliferation of L. donovani promastigotes in a dose-dependent manner. It also reduced the intracellular parasite load without causing significant toxicity on host-macrophages. Overall, it showed antileishmanial effects through induction of ROS, mitochondrial dysfunction, DNA fragmentation, cell cycle arrest, and apoptosis-like cell death to parasites. Our results suggested the possible use of sesamol for the treatment of leishmaniasis after further in vivo validations.

Cost-effectiveness analysis of a large-scale crèche intervention to prevent child drowning in rural Bangladesh.

BACKGROUND: Drowning is the leading cause of death among children 12-59 months old in rural Bangladesh. This study evaluated the cost-effectiveness of a large-scale crèche (daycare) intervention in preventing child drowning. METHODS: The cost of the crèches intervention was evaluated using an ingredients-based approach and monthly expenditure data collected prospectively throughout the study period from two agencies implementing the intervention in different study areas. The estimate of the effectiveness of the crèches intervention was based on a previous study. The study evaluated the cost-effectiveness from both a program and societal perspective. RESULTS: From the program perspective the annual operating cost of a crèche was $416.35 (95% CI: $221 to $576), the annual cost per child was $16 (95% CI: $8 to $23), and the incremental-cost-effectiveness ratio (ICER) per life saved with the crèches was $17,008 (95% CI: $8817 to $24,619). From the societal perspective (including parents time valued) the ICER per life saved was - $166,833 (95% CI: - $197,421 to - $141,341)-meaning crèches generated net economic benefits per child enrolled. Based on the ICER per disability-adjusted-life years averted from the societal perspective (excluding parents time), $1978, the crèche intervention was cost-effective even when the societal economic benefits were ignored. CONCLUSIONS: Based on the evidence, the crèche intervention has great potential for generating net societal economic gains by reducing child drowning at a program cost that is reasonable.

Virtual screening of natural compounds for potential inhibitors of Sterol C-24 methyltransferase of Leishmania donovani to overcome leishmaniasis.

Leishmaniasis is a neglected tropical disease caused by trypanosomatid parasite belonging to the genera Leishmania. Leishmaniasis is transmitted from one human to other through the bite of sandflies. It is endemic in around 98 countries including tropical and subtropical regions of Asia, Africa, Southern America, and the Mediterranean region. Sterol C-24 methyltransferase (LdSMT) of Leishmania donovani (L. donovani) mediates the transfer of CH3-group from S-adenosyl methionine to C-24 position of sterol side chain which makes the ergosterol different from cholesterol. Absence of ortholog in human made it potential druggable target. Here, we performed virtual screening of library of natural compounds against LdSMT to identify the potential inhibitor for it and to fight leishmaniasis. Gigantol, flavan-3-ol, and parthenolide showed the best binding affinity towards LdSMT. Further, based on absorption, distribution, metabolism, and excretion properties and biological activity prediction, gigantol showed the best lead-likeness and drug-likeness properties. Therefore, we further elucidated its antileishmanial properties. We found that gigantol inhibited the growth and proliferation of promastigotes as well as intra-macrophagic amastigotes. Gigantol exerted its antileishmanial action through the induction of reactive oxygen species in dose-dependent manner. Our study, suggested the possible use of gigantol as antileishmanial drug after further validations to overcome leishmaniasis.

Repurposing of FDA-approved drugs as inhibitors of sterol C-24 methyltransferase of Leishmania donovani to fight against leishmaniasis.

Leishmaniasis is a vector-borne disease caused by around 20 species of Leishmania. The main clinical forms of leishmaniasis are cutaneous leishmaniasis (CL) and visceral leishmaniasis (VL). VL is caused by Leishmania infantum in Central and South America, Mediterranean Basin, Middle East, and by L. donovani in Asia and Africa. Sterol C-24 methyltransferase (LdSMT) of L. donovani is a transferase enzyme of the sterol biosynthesis pathway. This pathway is one of the major targets for drug developments in Leishmania. Due to insufficient evidence about the exact function of SMT inside the cell and the uniqueness of the SMT enzyme in the Leishmania parasites made it a significant target for an effective drug development approach. We performed virtual screening of the Food and Drug Administration (FDA)-approved drug library against LdSMT and found simeprevir, an antiviral drug on top in the binding score. It showed a significant binding affinity with LdSMT. The binding was supported by hydrogen bonds and several other interactions. Simeprevir inhibited L. donovani growth of promastigotes with 50% inhibitory concentration (IC50 ) of 51.49 ± 5.87 µM. Further studies showed that simeprevir induced ROS generation in 44.7% of parasites at 125-µM concentration. Here, we for the first time reported simeprevir as an antileishmanial lead molecule using a drug repurposing approach.

Hesperidin Targets Leishmania donovani Sterol C-24 Reductase to Fight against Leishmaniasis.

Hesperidin, a naturally occurring flavanoid, is present in citrus family of fruits. It was found effective against an array of pathogens including fungi, bacteria, viruses, and protozoa. Here, we evaluated its antileishmanial activity and possible mechanism of action through different in vitro and in silico experiments. It inhibited the growth and proliferation of the parasites significantly with a IC50 value of 1.019 ± 0.116 mM in vitro. It also reduced the growth of intra-macrophagic amastigotes with a IC50 value of 0.2858 ± 0.01398 mM. It induced the reactive oxygen species (ROS) in parasites in a dose-dependent manner. Through 2,7-dichloro dihydro fluorescein diacetate (H2DCFDA) staining, it was observed that around 96.9% parasites were ROS positive at 2.0 mM concentration of hesperidin. The ROS generated led to the apoptosis of parasites in a dose-dependent manner as observed by annexin/PI staining. Molecular docking with one of the very important and unique drug-targets of Leishmania donovani sterol C-24 reductase resulted in its significant inhibition. Here, we for the first time showed that hesperidin induced the antileishmanial response through the induction of apoptosis and inhibition of sterol C-24 reductase. Our study will be helpful in the development of a cost-effective antileishmanial lead with higher efficacy.

Antileishmanial Evaluation of Bark Methanolic Extract of Acacia nilotica: In Vitro and In Silico Studies.

Acacia nilotica (A. nilotica) is an important medicinal plant, found in Africa, the Middle East, and the Indian subcontinent. Every part of the plant possesses a wide array of biologically active and therapeutically important compounds. We reported the antileishmanial activity of A. nilotica bark methanolic extract through in vitro antileishmanial assays and dissected the mechanism of its action through in silico studies. Bark methanolic extract exhibited antipromastigote and antiamastigote potential in a time and dose-dependent manner with IC50 values of 19.6 ± 0.9037 and 77.52 ± 5.167 µg/mL, respectively. It showed cytotoxicity on THP-1-derived human macrophages at very high dose with a CC50 value of 432.7 ± 7.71 µg/mL. The major constituents identified by gas chromatography-mass spectrometry (GC-MS) analysis, 13-docosenoic acid, lupeol, 9,12-octadecadienoic acid, and 6-octadecanoic acid, showed effective binding with the potential drug targets of Leishmania donovani (L. donovani) including sterol 24-c-methyltransferase, trypanothione reductase, pteridine reductase, and adenine phosphoribosyltransferase, suggesting the possible mechanism of its antileishmanial action. Pharmacokinetic studies on major phytoconstituents analyzed by GC-MS supported their use as safe antileishmanial drug candidates. This study proved the antileishmanial potential of bark methanolic extract A. nilotica and its mechanism of action through the inhibition of potential drug targets of L. donovani.

Targeting sterol alpha-14 demethylase of Leishmania donovani to fight against leishmaniasis.

Leishmaniasis is a neglected tropical disease caused by the protozoan parasite Leishmania. It is endemic in more than 89 different countries worldwide. Sterol alpha-14 demethylase (LdSDM), a sterol biosynthetic pathway enzyme in Leishmania donovani, plays an essential role in parasite survival and proliferation. Here, we used a drug repurposing approach to virtually screen the library of the Food and Drug Administration (FDA)-approved drugs against LdSDM to identify the potential lead-drug against leishmaniasis. Zafirlukast and avodart showed the best binding with LdSDM. Zafirlukast was tested for in vitro antileishmanial assay, but no significant effect on L. donovani promastigotes was observed even at higher concentrations. On the other hand, avodart profoundly inhibited parasite growth at relatively lower concentrations. Further, avodart showed a significant decrease in the number of intra-macrophagic amastigotes. Avodart-induced reactive oxygen species (ROS) in the parasites in a dose-dependent manner. ROS induced by avodart led to the induction of apoptosis-like cell death in the parasites as observed through annexin V/PI staining. Here, for the first time, we reported the antileishmanial activity and its possible mechanism of action of FDA-approved drug, avodart, establishing a nice example of the drug-repurposing approach. Our study suggested the possible use of avodart as an effective antileishmanial agent after further detailed validations.

Exploring adults as support persons for improved pre-exposure prophylaxis for HIV use among select adolescents and young adults in the Deep South.

PURPOSE: Pre-exposure prophylaxis for HIV (PrEP) is an effective yet underutilized biomedical tool for adolescents and young adults' (AYA) HIV prevention due to barriers such as PrEP adherence. We assessed HIV prevention knowledge, attitudes and beliefs from adults who self-identified as a primary support person to an AYA. METHODS: We surveyed AYA primary support persons at an academic hospital. Univariate and multivariate regression analyses were completed to identify factors associated with the belief AYAs engaging in HIV-associated behaviors should use PrEP and willingness to support AYAs on PrEP. RESULTS: 200 primary support persons completed the survey. Participants were predominately female (77%) and black (56%). Nearly all primary support persons believed AYAs engaging in HIV-associated behaviors should take PrEP (94%) and 98% would support an AYA taking PrEP via transportation to appointments, assistance with refilling prescriptions, medication reminders, or encouragement. CONCLUSIONS: Primary support persons are willing to support AYAs using PrEP.

Reconstruction of Hemiglossectomy Defects With the Lateral Arm Fasciocutaneous Flap.

INTRODUCTION: Partial tongue reconstruction requires a thin pliable flap to restore volume and mobility. The lateral arm flap is well suited to this as it is a thin fasciocutaneous flap that has consistent vascular anatomy, reliable perfusion, short harvest time and low donor site morbidity. The authors report our experience with use of this flap for reconstruction of hemi-glossectomy defects. METHODS: This is a retrospective cohort of patients who underwent reconstruction of hemi-glossectomy and floor of mouth defects with a lateral arm flap, at Aga Khan University Hospital, Karachi (Pakistan) from November 2016 to January 2020. Flaps were harvested from the nondominant upper extremity. Data were collected for patient demographics, size of defect, size of flap, recipient vessels, postoperative complications and functional outcome. RESULTS: Over a 3-year period, 8 hemi-tongue and extended hemi-tongue, and floor of mouth reconstructions were performed with a lateral arm fasciocutaneous flap. A standard lateral arm flap was harvested in 3 patients and an extended lateral arm flap in 5 patients. Mean flap size was 65.75 cm2 (48-76 cm2). The recipient artery in all cases was the superior thyroid artery. The recipient veins were the common facial vein in 1 patient, the internal jugular in 3 patients, the external jugular in 1 patient and both external and internal jugular in 3 patients. Donor sites were closed primarily. There were no total or partial flap losses. All patients were able to resume an oral diet (unrestricted in 1, soft in 4, pureed in 2 patients). Postoperative speech was intelligible to patients' family in 4 patients and to strangers in 3 patients. One patient succumbed to progressive disease in the early postoperative period. Orocutaneous fistulas developed in 3 patients, all of which healed with nonoperative management. CONCLUSIONS: The lateral arm fasciocutaneous flap is well suited for reconstruction of hemiglossectomy and floor of mouth defect. It has the advantages of straightforward harvest, thin and pliable soft tissue, and low donor site morbidity.

Molecular docking analysis of rutin reveals possible inhibition of SARS-CoV-2 vital proteins.

BACKGROUND AND AIM: COVID-19 emerged by the end of 2019 in Wuhan, China. It spreaded and became a public health emergency all over the world by mid of April 2020. Flavonoids are specialized metabolites that have antimicrobial properties including anti-viral activity. Rutin, a medicinally important flavonoid belongs to one of the best natural antioxidant classes. It has antiprotozoal, antibacterial, and antiviral properties. Keeping the antimicrobial potential of rutin in mind, we studied its role in the inhibition of essential proteins of SARS-CoV-2 including main protease (Mpro), RNA-dependent RNA polymerase (RdRp), papain-like protease (PLpro), and spike (S)-protein through different in silico approaches. EXPERIMENTAL PROCEDURE: Molecular docking, inhibition constant, hydrogen bond calculations, and ADMET-properties prediction were performed using different softwares. RESULTS AND CONCLUSION: Molecular docking study showed significant binding of rutin with Mpro, RdRp, PLpro, and S-proteins of SARS-CoV-2. Out of these four proteins, Mpro exhibited the strongest binding affinity with the least binding energy (-8.9 kcal/mol) and stabilized through hydrogen bonds with bond lengths ranging from 1.18 Å to 3.17 Å as well as hydrophobic interactions. The predicted ADMET and bioactivity showed its optimal solubility, non-toxic, and non-carcinogenic properties. The values of the predicted inhibitory constant of the rutin with SARS-CoV-2 vital proteins ranged between 5.66 µM and 6.54 µM which suggested its promising drug candidature. This study suggested rutin alone or in combination as a dietary supplement may be used to fight against COVID-19 after detailed in vitro and in vivo studies.

Assessment of the Antileishmanial Potential of Cassia fistula Leaf Extract.

Cassia fistula has a wide array of biologically active and therapeutically important class of compounds. Leishmania donovani important drug targets, sterol 24-c methyltransferase (LdSMT), trypanothione reductase (LdTR), pteridine reductase (LdPTR1), and nucleoside hydrolase (LdNH), were modelled, and molecular docking was performed against the abundant phytochemicals of its leaf extract. Molecular docking results provided the significant prima facie evidence of the leaf extract to have antileishmanial potential. To confirm this, we performed in vitro antileishmanial and cytotoxicity assays. Methanolic extract of C. fistula leaves showed growth inhibition and proliferation of L. donovani promastigote with an IC50 value of 43.31 ± 4.202 µg/mL. It also inhibited the growth of intra-macrophagic amastigotes with an IC50 value of 80.76 ± 3.626 µg/mL. C. fistula extract was found cytotoxic at a very high concentration on human macrophages (CC50 = 626 ± 39 µg/mL). Annexin V/propidium iodide (PI) staining assay suggested partial apoptosis induction in parasites by C. fistula to exert its antileishmanial activity. Here, for the first time, we have shown the antileishmanial potential of C. fistula leaves. Overall, our results could open new insight for an affordable and natural antileishmanial with high efficacy and less toxicity.

Cynaroside inhibits Leishmania donovani UDP-galactopyranose mutase and induces reactive oxygen species to exert antileishmanial response.

Cynaroside, a flavonoid, has been shown to have antibacterial, antifungal and anticancer activities. Here, we evaluated its antileishmanial properties and its mechanism of action through different in silico and in vitro assays. Cynaroside exhibited antileishmanial activity in time- and dose-dependent manner with 50% of inhibitory concentration (IC50) value of 49.49 ± 3.515 µM in vitro. It inhibited the growth of parasite significantly at only 20 µM concentration when used in combination with miltefosine, a standard drug which has very high toxicity. It also inhibited the intra-macrophagic parasite significantly at low doses when used in combination with miltefosine. It showed less toxicity than the existing antileishmanial drug, miltefosine at similar doses. Propidium iodide staining showed that cynaroside inhibited the parasites in G0/G1 phase of cell cycle. 2,7-dichloro dihydro fluorescein diacetate (H2DCFDA) staining showed cynaroside induced antileishmanial activity through reactive oxygen species (ROS) generation in parasites. Molecular-docking studies with key drug targets of Leishmania donovani showed significant inhibition. Out of these targets, cynaroside showed strongest affinity with uridine diphosphate (UDP)-galactopyranose mutase with -10.4 kcal/mol which was further validated by molecular dynamics (MD) simulation. The bioactivity, ADMET (absorption, distribution, metabolism, excretion and toxicity) properties, Organisation for Economic Co-operation and Development (OECD) chemical classification and toxicity risk prediction showed cynaroside as an enzyme inhibitor having sufficient solubility and non-toxic properties. In conclusion, cynaroside may be used alone or in combination with existing drug, miltefosine to control leishmaniasis with less cytotoxicity.

Correlates of Transitions Into Housing Instability Among Veterans Accessing Veterans Health Administration Health Care.

BACKGROUND: Prior research has explored the patterns and dynamics of homelessness; such an understanding is necessary to improve policy and programmatic responses and prevent new episodes of housing instability. OBJECTIVES: The objectives of this study are to identify correlates of veterans' transitions into housing instability and inform initiatives aimed to address their needs, with a focus on how to prevent new episodes of housing instability. METHODS: The cohort for this study includes 4,633,069 veterans who responded to the Veterans Health Administration's universal screen for housing instability at least twice between October 1, 2012, and September 30, 2016; 1.2% reported recent housing instability and 98.8% reported ongoing housing stability. The χ or Fisher exact tests, as appropriate, compared veterans' characteristics by housing status. A multivariate logistic regression identified independent risk factors associated with recent housing instability, controlling for sociodemographic, military service, diagnostic, and health services use variables. RESULTS: Sociodemographic and health services use variables increased veterans' odds of transitioning into housing instability. The diagnoses with the greatest effect sizes were drug use disorder (adjusted odds ratio=1.50, 95% confidence interval: 1.45-1.55) and opioid use disorder, which was associated with a >2-fold increase in the odds of experiencing recent housing instability (adjusted odds ratio=2.22, 95% confidence interval: 2.04-2.41). CONCLUSIONS: The present study provides evidence to inform existing and future interventions to prevent new episodes of housing instability. Veterans with opioid use disorder were at greatest risk of becoming unstably housed; increasing access to medication-assisted treatment in homeless-focused services is needed.

Exploring the perceptions, practices and challenges to maternal and newborn health care among the underprivileged teagarden community in Bangladesh: a qualitative study.

Poor health care-seeking behaviour, access to services and availability of service delivery have implications for the health of the community. This study explored the perceptions, practices and challenges related to maternal and neonatal care in the teagarden community in Bangladesh. The study also identified service gaps and problems prevalent in teagarden health facilities. A qualitative study was conducted in five teagardens in the Moulvibazar district of Bangladesh. Six focus group discussions (FGDs) were completed with individuals from the teagarden community, and twelve in-depth interviews (IDIs) were performed with health facility staff working in those teagarden facilities. Misconceptions and harmful traditional practices were found to exist among the families in the teagardens, restricting them from accessing quality health care. Pregnant women are not aware of antenatal care, and deliveries are being conducted at home by untrained birth attendants. Unhygienic and harmful postnatal practices are used. Teagarden health facilities are not well equipped or prepared to provide good care. Inequities exist within the teagarden communities, with unregistered workers having even poorer access to care. Improvement of the quality of maternal health care for this marginalised community is needed to progress maternal health.