Adherence to Anti-Malarial Treatment in Malaria Endemic Areas of Bangladesh.

Ensuring adherence to antimalarial treatment is crucial for achieving a radical cure and elimination of malaria, especially in hard-to-reach areas. We conducted this study to assess the current scenario of drug adherence in four endemic sub-districts of Bangladesh. Among 110 enrolled participants, 70% were mono-infected with Plasmodium falciparum and the remaining 30% with P. vivax. The overall treatment adherence frequency was 92.7% (95% CI: 83.0-96.3%). A total of eight participants were found to be nonadherent to treatment and all of them were from Bandarban. Level of nonadherence was equally observed in two age groups: 11-17 and 18+ years. However, male participants (n = 6) were found to be more nonadherent than females (n = 2). Among 7.3% with nonadherence to treatment, a single participant with P. falciparum mono-infection refused to take medication and became nonadherent. Remaining participants stated that they were feeling well and going to work, thus leaving treatment course uncompleted. Although overall compliance with malaria medication seems good, a gradual increase in noncompliance to P. vivax malaria treatment suggests that the National Malaria Elimination Program must be enhanced and monitored to fulfil the projected malaria elimination goal before 2030 from Bangladesh.

Synthesis and Evaluation of a Self-Adjuvanting Pseudomonal Vaccine Based on Major Outer Membrane Porin OprF Epitopes Formulated with Low-Toxicity QS-21-Containing Liposomes.

Pseudomonas aeruginosa (PA) is a Gram-negative pathogen that the World Health Organization has ranked as a priority 1 (critical) threat. One potential prophylactic approach to preventing or reducing the incidence of PA would be development of a long sought-after vaccine. Both antibody and CD4+ T-cell responses have been noted as playing key roles in protection against infection. In these studies, we have designed a prototype vaccine consisting of several known linear B-cell epitopes derived from an outer membrane porin F (OprF). The resulting thiol-containing protein was conjugated to a version of the lipopeptide-based Toll-like receptor agonist Pam3CysSK4Mal (10) containing a maleimide moiety and formulated into dipalmitoylphosphatidylcholine (DPPC)/cholesterol (Chol) liposomes. Mice immunized with the resulting vaccine generated antibodies that bound PA14 (serotype O10) in vitro and induced opsonization in the presence of rabbit complement and murine macrophage RAW264.7 cells. The liposome was optimized to contain 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), 1,2-dimyristoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (DMPG), Chol, Pam3CysSK4-OprF (12) and the Quillaja saponaria-derived saponin adjuvant QS-21. The resulting vaccine formulation produced significantly higher antibody titers, increased the IgG2a antibody isotype, and increased the number of IgG-producing B-cells as well as splenic primed T-cells. In summary, the liposomal vaccine platform was found highly useful for the generation of a robust and balanced TH1/TH2 response.

Influence of thermal conductivity on transient mixed convection in a vented cavity with a hollow cylinder and filled with CNT-water nanofluid.

This study is aimed to perform a numerical time-dependent investigation thermal conductivity effect of the annular cylinder within a vented cavity using CNT based-water nanofluid. For demonstrating the effect of thermal conductivity, four distinct hollow cylinder materials such as Ks = 0.5(Plastic tiles), Ks = 0.84(Clay tiles), Ks = 1.1(Concrete tiles), and Ks = 2(Slate tiles) are introduced together with a suitable variation of dimensionless time (0 ≤ τ ≤ 1). The governing equations of the model with associated boundary conditions is solved using finite element based Galerkin's weighted residual method. Different contour plots for thermal and flow field transformation and mean Nusselt number, mean fluid temperature, bulk convective field temperature, temperature gradient, pressure gradient, vortices, and fluid velocity magnitude are presented for qualitative and quantitative thermal performance analysis. With the decrease of solid thermal conductivity, 27.3% thermal transport enhancement is noted from the heated surface of the cylinder. However, a 16.3% increase in the bulk fluid temperature has been recorded with the increase in cylinder conductivity. The numerical outcomes from this investigation propose a better thermo-fluid efficiency compared to the existing methodology which can be suggestive to engineers and researchers for designing heat exchangers, heat pipes, and other thermal systems.

Scaling-up an early childhood parenting intervention by integrating into government health care services in rural Bangladesh: A cluster-randomised controlled trial.

AIMS: We evaluated the feasibility and effectiveness of utilising government health supervisors to train and supervise primary health care workers (HWs) in community clinics to deliver parenting sessions as part of their usual duties. METHODS: We randomly allocated 16 unions in the Mymensing district of Bangladesh 1:1 to an intervention or control group. HWs in clinics in the eight intervention unions (n = 59 health workers, n = 24 clinics) were trained to deliver a group-based parenting intervention, with training and supervision provided by government supervisors. In each of the 24 intervention clinics, we recruited 24 mothers of children aged 6-24 months to participate in the parenting sessions (n = 576 mother/child dyads). Mother/child dyads attended fortnightly parenting sessions at the clinic in groups of four to five participants for 6 months (13 sessions). We collected data on supervisor and HW compliance in implementing the intervention, mothers' attendance and the observed quality of parenting sessions in all intervention clinics and HW burnout at endline in all clinics. We randomly selected 32 clinics (16 intervention, 16 control) and 384 mothers (192 intervention, 192 control) to participate in the evaluation on mother-reported home stimulation, measured at baseline and endline. RESULTS: Supervisors and HWs attended all training, 46/59 health workers (78%) conducted the majority of parenting sessions, (only two HWs [3.4%] refused) and mothers' attendance rate was 86%. However, supervision levels were low: only 32/57 (56.1%) of HWs received at least one supervisory visit. Intervention HWs delivered the parenting sessions with acceptable levels of quality on most items. The intervention significantly benefitted home stimulation (effect size = 0.53SD, 95% confidence interval: 0.50, 0.56, p < 0.001). HW burnout was low in both groups. CONCLUSION: Integration into the primary health care service is a promising approach for scaling early childhood development programmes in Bangladesh, although further research is required to identify feasible methods for facilitator supervision.

Identification of Selective BRD9 Inhibitor via Integrated Computational Approach.

Bromodomain-containing protein 9 (BRD9), a member of the bromodomain and extra terminal domain (BET) protein family, works as an epigenetic reader. BRD9 has been considered an essential drug target for cancer, inflammatory diseases, and metabolic disorders. Due to its high similarity among other isoforms, no effective treatment of BRD9-associated disorders is available. For the first time, we performed a detailed comparative analysis among BRD9, BRD7, and BRD4. The results indicate that residues His42, Gly43, Ala46, Ala54, Val105, and Leu109 can confer the BRD9 isoform selectivity. The predicted crucial residues were further studied. The pharmacophore model's features were precisely mapped with some key residues including, Gly43, Phe44, Phe45, Asn100, and Tyr106, all of which play a crucial role in BRD9 inhibition. Docking-based virtual screening was utilized with the consideration of the conserved water network in the binding cavity to identify the potential inhibitors of BRD9. In this workflow, 714 compounds were shortlisted. To attain selectivity, 109 compounds were re-docked to BRD7 for negative selection. Finally, four compounds were selected for molecular dynamics studies. Our studies pave the way for the identification of new compounds and their role in causing noticeable, functional differences in isoforms and between orthologues.

Lewis Acid-Catalyzed Halonium Generation for Morpholine Synthesis and Claisen Rearrangement.

We disclose here practical strategies toward the synthesis of morpholines and Claisen rearrangement products based on the divergent reactivity of a common halonium intermediate. These reactions employ widely available alkenes in a Lewis acid-catalyzed halo-etherification process that can then transform them into the desired products with exceptional regioselectivity for both activated and unactivated olefins. Our mechanistic probe reveals an interesting regiochemical kinetic resolution process.

Chiral Hypervalent Iodine Catalysis Enables an Unusual Regiodivergent Intermolecular Olefin Aminooxygenation.

A novel iodide-catalyzed intermolecular aminooxygenation strategy is described here. Amide is used as the O- and N- source to probe for regiocontrol strategies. Notably, simple additives can be selectively introduced to achieve regiodivergent oxyamination processes for electronically activated alkenes while being regio-complementary for unactivated alkenes. Our preliminary data demonstrates that this regiocontrol strategy based on nucleophile can also be applied in asymmetric processes using chiral hypervalent iodine catalysis.

Halogen-Bond-Induced Consecutive Csp3-H Aminations via Hydrogen Atom Transfer Relay Strategy.

The utilization of a halogen bond in a number of chemical fields is well-known. Surprisingly, the incorporation of this useful noncovalent interaction in chemical reaction engineering is rare. We disclose here an uncommon use of halogen bonding to induce intermolecular Csp3-H amination while enabling a hydrogen atom transfer relay strategy to access privileged pyrrolidine structures directly from alkanes. Mechanistic studies support the presence of multiple halogen bond interactions at distinct reaction stages.

Oxyamination of Unactivated Alkenes with Electron-Rich Amines and Acids via a Catalytic Triiodide Intermediate.

An aerobic catalytic oxidation process is described for the olefin oxyamination using acids and primary amines as the sources of O and N. Our mechanistic findings point to the formation of triiodide as a critical catalytic intermediate to account for the tolerance of electron-rich nucleophiles. This dual iodide and copper catalytic system is suitable for a formal [5+1] annulation process to access valuable lactam structures and highlighted by the synthesis of the pharmaceutical Zamifenacin.

Adapting an Evidence-Based, Early Childhood Parenting Programme for Integration into Government Primary Health Care Services in Rural Bangladesh.

This paper describes the process of adapting an early childhood development programme, with proven effectiveness in Bangladesh, for integration into government health services in rural Bangladesh. Through a three-stage process, we adapted an evidence-based, home-visiting, programme (Reach-Up and Learn) for delivery in government health clinics by government health staff as part of their regular duties. Stage one involved preparing an initial draft of two parenting interventions for use with: (1) pairs of mother/child dyads, and (2) small groups of mother/child dyads. In stage two, we piloted the adapted interventions in nine clinics with a total of twenty-seven health staff and 357 mother/child dyads. We used data from mothers' attendance, feedback from participating mothers and health staff and observations of parenting sessions by the research team to revise the interventions. Stage three involved piloting the revised interventions in six clinics with eighteen health staff and 162 mother/child dyads. We gathered additional data on mothers' attendance and used observations by the research team to finalize the interventions. Through this three-stage process, adaptations were made to the intervention content, process of delivery, materials, and engagement strategies used. The largest challenges were related to incorporating the parenting programme into health staff's existing workload and promoting mothers' engagement in the programme. We also simplified the content and structure of the curriculum to make it easier for health staff to deliver and to ensure mothers understood the activities introduced. This iterative piloting was used prior to implementing and evaluating the interventions through an effectiveness trial.

Antioxidant Potential, Subacute Toxicity, and Beneficiary Effects of Methanolic Extract of Pomelo (Citrus grandis L. Osbeck) in Long Evan Rats.

The aim of this study was to investigate the antioxidant potentials, subacute toxicity, and beneficiary effects of methanolic extract of pomelo (Citrus grandis L. Osbeck) in rats. Long Evans rats were divided into four groups of eight animals each. The rats were orally treated with three doses of pomelo (250, 500, and 1000 mg/kg) once daily for 21 days. Pomelo extract contained high concentrations of polyphenols, flavonoids, and ascorbic acid while exhibiting high 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity and ferric reducing antioxidant power values. There was no significant change in the body weight, percentage water content, and relative organ weight at any administered doses. In addition, no significant alterations in the hematological parameters were also observed. However, rats which received 1000 mg/kg dose had a significant reduction in some serum parameters, including alanine transaminase (15.29%), alkaline phosphatase (2.5%), lactate dehydrogenase (15.5%), γ-glutamyltransferase (20%), creatinine (14.47%), urea (18.50%), uric acid (27.14%), total cholesterol (5.78%), triglyceride (21.44%), low-density lipoprotein cholesterol (40.74%), glucose (2.48%), and all atherogenic indices including cardiac risk ratio (24.30%), Castelli's risk index-2 (45.71%), atherogenic coefficient (42%), and atherogenic index of plasma (25%) compared to control. In addition, the highest dose (1000 mg/kg) caused a significant increase in iron (12.07%) and high-density lipoprotein cholesterol (8.87%) levels. Histopathological findings of the vital organs did not indicate any pathological changes indicating that pomelo is nontoxic, safe, and serves as an important source of natural antioxidants. In addition, the fruit extract has the potential to ameliorate hepato- and nephrotoxicities and cardiovascular diseases as well as iron deficiency anemia.

Regioselective Formal [3+2] Cycloadditions of Urea Substrates with Activated and Unactivated Olefins for Intermolecular Olefin Aminooxygenation.

A new class of intermolecular olefin aminooxygenation reaction is described. This reaction utilizes the classic halonium intermediate as a regio- and stereochemical template to accomplish the selective oxyamination of both activated and unactivated alkenes. Notably, urea chemical feedstock can be directly introduced as the N and O source and a simple iodide salt can be utilized as the catalyst. This formal [3+2] cycloaddition process provides a highly modular entry to a range of useful heterocyclic products with excellent selectivity and functional-group tolerance.

Effects of adding psychosocial stimulation for children of lactating mothers using an unconditional cash transfer platform on neurocognitive behavior of children in rural Bangladesh: protocol for a cluster randomized controlled trial.

BACKGROUND: There is sufficient evidence that psychosocial stimulation (PS) benefits children's neurocognitive behavior, however, there is no information on how it works when delivered through an Unconditional Cash Transfer (UCT) platform for poor rural population in developing countries. The objective of this study is to measure effects of adding PS for children of lactating mothers enrolled to receive UCT with health education (HE) on neurocognitive behavior of children in rural Bangladesh. METHODS: The study will be conducted at 11 unions of Ullapara sub-district in Bangladesh. The study is a cluster randomized controlled trial with three-arms; (i) PS and UCT with HE (ii) UCT with HE and iii) Comparison arm. The cluster will be considered as an old Ward of a Union, the lowest tier of local government system in rural Bangladesh. There are three old Wards in a union. These three clusters will be randomized to one of the three arms. Similarly, randomization will be done for each 11 Unions and then 11 clusters will be assigned to an arm. Eighteen participants will be recruited from each cluster randomly (n = 196 in each arm). The intervention designed for one year includes UCT with HE for the poor as a safety net program in rural Bangladesh with or without PS. An age-based curriculum of PS is already available for Bangladeshi children and this will be administered by trained local women; play leaders (PL) in intervention clusters. The government of Bangladesh is providing UCT of taka 500 ($6.25) as maternity allowance per month with HE. The primary outcomes will be cognitive, motor and language composite scores measured by Bayley-III and behavior using Wolke's behavior rating scale. The secondary outcomes will be children and mothers' growth, family food security status, health seeking behavior, mothers' depressive symptoms and self-esteem and violence against mothers. DISCUSSION: The study will provide a unique opportunity to assess an integrated early childhood development intervention using UCT platform to mitigate developmental delays in poor vulnerable children of rural Bangladesh. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT03281980, registered on September 13, 2017.

Catalytic Regio- and Stereoselective Alkene Sulfenoamination for 1,4-Benzothiazine Synthesis.

An alkene sulfenoamination reaction with 2-aminothiophenol is developed using iodide catalysis. This reaction renders access to useful 1,4-benzothiazines with good functional group compatibility including both electron-donating and electron-withdrawing substituents. The reaction is proposed to proceed through an inversion of the polarity of the thiol functionality. Our mechanistic studies reveal that both thiiranium and thiyl radical pathways are plausible and that the disulfide reagent can also function as a viable substrate in this reaction.

Intermolecular alkene difunctionalizations for the synthesis of saturated heterocycles.

Saturated heterocycles are important structural motifs in a range of pharmaceuticals and agrochemicals. As a result of their importance, syntheses of these molecules have been extensively investigated. Despite the progress in this area, the most adopted strategies are still often characterized with inefficiency or relying on functionalizations with specialized precursors and pre-existing cores. This review highlights a dynamic synthetic strategy for the direct synthesis of saturated heterocycles from intermolecular alkene difunctionalizations. These coupling processes are highly modular, and therefore, offer perhaps the most convenient means to prepare diverse heterocyclic structures in compound libraries for bioactivity evoluations.

Antihyperglycemic, Antidiabetic, and Antioxidant Effects of Garcinia pedunculata in Rats.

The antihyperglycemic, antidiabetic, and antioxidant potentials of the methanolic extract of Garcinia pedunculata (GP) fruit in rats were investigated. The acute antihyperglycemic effect of different doses of GP was studied in normal male Wistar rats. Diabetes was induced by streptozotocin (STZ) injection in another cohort of male Wistar rats and they showed significantly higher blood glucose and glycated hemoglobin (HbA1c) levels, altered lipid profiles, and lower insulin levels compared to nondiabetic control animals. There were increased lipid peroxidation and reduced levels of cellular antioxidant enzymes in different tissues of diabetic rats. However, oral administration of GP extracts, especially the highest dose (1000 mg/kg), significantly ameliorated hyperglycemia (42%); elevated insulin levels (165%); decreased HbA1c (29.4%); restored lipid levels (reduction in TG by 25%, TC by 15%, and LDL-C by 75% and increase in HDL-C by 4%), liver and renal function markers, and lipid peroxidation (reduction by 52% in the liver, 39% in the kidney, 44% in the heart, and 46% in the pancreas); and stimulated tissue antioxidant enzymes to near normalcy. Overall, the findings suggest that GP fruit is effective against hyperglycemia and could be used in the treatment of diabetes and its complications and other oxidative stress-mediated pathological conditions.

Intermolecular Regio- and Stereoselective Sulfenoamination of Alkenes with Thioimidazoles.

An intermolecular sulfenoamination reaction utilizing a stable sulfur precursor with a broad range of alkene structures is described. More importantly, these reactions proceed in a highly regio- and stereoselective manner to afford interesting heterocyclic motifs ready for biological studies. In addition, a highly regiodivergent approach to access the opposite regioisomers for styrene derivatives was also developed.

One-Pot Strategy for Thiazoline Synthesis from Alkenes and Thioamides.

A convenient synthesis of a privileged pharmaceutical motif, thiazoline is accomplished. This reaction utilizes simple and readily available alkene and thioamide substrates in an intermolecular fashion via a simple one-pot procedure. A wide range of functional groups is tolerated, and the thiazoline product has been further utilized for the synthesis of the corresponding ß-aminothiol and thiazole from routine hydrolysis and oxidation protocols.

Overextended Criteria Donors: Experience of an Italian Transplantation Center.

The increasing gap between the number of patients who could benefit from liver transplantation and the number of available donors has fueled efforts to maximize the donor pool using marginal grafts that usually were discarded for transplantation. This study included data of all patients who received decreased donor liver grafts between January 2004 and January 2013 (n = 218) with the use of a prospectively collected database. Patients with acute liver failure, retransplantation, pediatric transplantation, and split liver transplantation were excluded. Donors were classified as standard donor (SD), extended criteria donor (ECD), and overextended criteria donor (OECD). The primary endpoints of the study were early allograft primary dysfunction (PDF), primary nonfunction (PNF), and patient survival (PS), whereas incidence of major postoperative complications was the secondary endpoint. In our series we demonstrated that OECD have similar outcome in terms of survival and incidence of complication after liver transplantation as ideal grafts.

Diagnosis and Management of Hepatic Artery Complications After Liver Transplantation.

BACKGROUND: We assessed the usefulness of color Doppler imaging in diagnosis and monitoring hepatic artery complications after liver transplantation. METHODS: Subjects were 421 liver transplant recipients who underwent serial ultrasound (US) color Doppler evaluations of the hepatic arteries after surgery. RESULTS: We saw 4 hepatic arterial complications after liver transplantation (13 thrombosis, 29 stenosis, 2 kinking, 2 pseudo-aneurysm, and 2 pseudo-aneurysm rupture). All subjects underwent US color Doppler examination periodically after surgery. In 6 cases of early thrombosis, hepatic arterial obstruction was diagnosed with absence of Doppler signals; in the other 7 cases (late hepatic artery thrombosis), thrombosis was suspected for the presence of intra-parenchymal "tardus-parvus" waveforms. In all of the cases, computed tomography angiography showed obstruction of the main arterial trunk and the development of compensatory collateral circles (late hepatic artery thrombosis). In 10 of the 29 cases of stenosis, Doppler ultrasonography examination revealed stenotic tract and intra-hepatic tardus-parvus waveforms; in 17 stenosis cases, the site of stenosis could not be identified, but intra-parenchymal tardus-parvus waveforms were recorded. In 2 patients, hepatic artery stenosis occurred with ischemic complications. CONCLUSIONS: The use of US color Doppler examination allows the early diagnosis of hepatic arterial complications after liver transplantation. Tardus-parvus waveforms indicated severe impairment of hepatic arterial perfusion from either thrombosis or severe stenosis. The presence of these indirect signs enhanced the accuracy of color Doppler diagnosis, and detection should prompt therapy.