Antiplasmodial and anti-trypanosomial monoterpene indole alkaloids from .

Eight monoterpene indole alkaloids (-), including one new picraline-type alkaloid, 2-hydroxyakuammiline () and seven known compounds: akuammigine (), akuammine (), akuammidine (), akuammiline (), akuammiline N-oxide (), akuammiline (), rhazimol (), and alstonine () were isolated from the seeds of . Structure elucidation was done by analysis of their MS and NMR spectroscopic data. The antiplasmodial effects of compounds - were moderate.

Superior Anticancer and Antifungal Activities of New Sulfanyl-Substituted Niclosamide Derivatives.

The approved anthelmintic salicylanilide drug niclosamide has shown promising anticancer and antimicrobial activities. In this study, new niclosamide derivatives with trifluoromethyl, trifluoromethylsulfanyl, and pentafluorosulfanyl substituents replacing the nitro group of niclosamide were prepared (including the ethanolamine salts of two promising salicylanilides) and tested for their anticancer activities against esophageal adenocarcinoma (EAC) cells. In addition, antifungal activity against a panel of strains, the most abundant causative agent of the neglected tropical disease eumycetoma, was evaluated.

Correction to "Bespoke Drug Discovery Training for Low-Middle Income Countries".

[This corrects the article DOI: 10.1021/acsmedchemlett.3c00215.

Bespoke Drug Discovery Training for Low-Middle Income Countries.

Working in drug discovery is difficult for many institutions due to the need for resources, funding, and in-country expertise. The Wellcome Centre for Anti-Infective Research (WCAIR) is responding to the unmet training needs for individuals/institutions working in drug discovery in low-middle income countries. Through their training program, individuals can undertake a practical placement, either online or at the center, with access to a dedicated trainer from their field of research.

Preparation, biological evaluation and QSAR analysis of urea substituted 2,4-diamino-pyrimidine anti-malarials.

The synthesis and evaluation of twenty six new phenylurea substituted 2,4-diamino-pyrimidines against () 3D7 are reported. Compounds were prepared to improve both anti-malarial activity and selectivity of the series previously reported by our group. Additional properties have been determined to assess their potential as anti-malarial leads including; HepG2 cytotoxicity, solubility, permeability, and lipophilicity, as well as stability in human and rat microsomes.

Preparation, biological & cheminformatics-based assessment of N,N-diphenylpyrimidine-2,4-diamine as potential Kinase-targeted antimalarials.

Twenty eight new N,N-diphenylpyrimidine-2,4-diamines have been prepared in order to expand our understanding of the anti-malarial SAR of the scaffold. The aim of the study was to make structural modifications to improve the overall potency, selectivity and solubility of the series by varying the anilino groups attached to the 2- and 4-position. We evaluated the activity of the compounds against Plasmodium falciparum (Pf) 3D7, cytotoxicity against HepG2, % inhibition at a panel of 10 human kinases, solubility, permeability and lipophilicity, and human and rat in vitro clearance.

Research Techniques Made Simple: An Introduction to Drug Discovery for Dermatology.

This article aims to provide an overview of drug discovery with a focus on application within dermatology. The term "drug" can be used to describe a wide variety of agents, including small molecules, cell therapies, and antibodies, which may be dosed intravenously, orally, topically, or by other routes of administration. We summarize the economics and risks involved in drug discovery.

Development of Chemical Proteomics for the Folateome and Analysis of the Kinetoplastid Folateome.

The folate pathway has been extensively studied in a number of organisms, with its essentiality exploited by a number of drugs. However, there has been little success in developing drugs that target folate metabolism in the kinetoplastids. Despite compounds being identified which show significant inhibition of the parasite enzymes, this activity does not translate well into cellular and animal models of disease.

Effect of Electrophysiology Assessment on Mortality and Hospitalizations in Patients With New-Onset Atrial Fibrillation.

Few patients with atrial fibrillation (AF) receive care by cardiac electrophysiologists. Although previous work has highlighted differential care for patients with AF treated by electrophysiologists, it is unclear whether this is associated with improved clinical outcomes. This retrospective population-level propensity score-matched cohort study included patients aged 20 to 80 years with new-onset AF presenting to an emergency department (ED) in Ontario, Canada, between 2010 and 2012.

The Relationship Between Cardiologist Care and Clinical Outcomes in Patients With New-Onset Atrial Fibrillation.

Background: Increased mortality is well described in patients with atrial fibrillation (AF), primarily related to death from cardiovascular causes. One may hypothesize that cardiology care may be associated with a reduction in cardiovascular deaths in patients with AF, thereby improving their overall survival. The aim of this study was to assess the association between cardiologist care and clinical outcomes, including all-cause mortality, in patients with new-onset AF.

Factors Associated With Cardiac Electrophysiologist Assessment and Catheter Ablation Procedures in Patients With Atrial Fibrillation.

Objectives: This study sought to determine factors associated with cardiac electrophysiologist assessment and atrial fibrillation (AF) ablation in patients with new-onset AF.

Background: Factors driving variation in the use of AF ablation have not been well described.

Methods: All individuals with new-onset AF in Ontario, Canada, between January 1, 2010, and December 31, 2012, were identified.

Cholesterol testing among men and women with disability: the role of morbidity.

Purpose: Despite more frequent use of health services by people living with disability, the quality of preventive care received may be suboptimal. In this retrospective cohort study, we used administrative data to examine the relationship between cholesterol testing and levels of disability and morbidity among women and men in Ontario, Canada.

Methods: We linked multiple provincial-level databases in this study.

Power Mobility Training for Young Children with Multiple, Severe Impairments: A Case Series.

Aims: Young children with neurodevelopmental conditions are often limited in their ability to explore and learn from their environment. The purposes of this case series were to (1) describe the outcomes of using an alternative power mobility device with young children who had multiple, severe impairments; (2) develop power mobility training methods for use with these children; and (3) determine the feasibility of using various outcome measures.

Methods: Three children with cerebral palsy (Gross Motor Function Classification System Levels IV, V, and V) ages 17 months to 3.

Inpatient mortality of HIV-infected adults in sub-Saharan Africa and possible interventions: a mixed methods review.

Background: Despite the increased availability of anti-retroviral therapy, in-hospital HIV mortality remains high in sub-Saharan Africa. Reports from Senegal, Malawi, and Tanzania show rates of in-hospital, HIV-related mortality ranging from 24.2% to 44%.

Validation of Algorithms to Identify Invasive Electrophysiology Procedures Using Administrative Data in Ontario, Canada.

Background: Administrative database research can provide insight into the real-world effectiveness of invasive electrophysiology procedures. However, no validated algorithm to identify these procedures within administrative data currently exists.

Objective: To develop and validate algorithms to identify atrial fibrillation (AF), atrial flutter (AFL), supraventricular tachycardia (SVT) catheter ablation procedures, and diagnostic electrophysiology studies (EPS) within administrative data.

Superior outcomes and lower outpatient costs with scale-up of antiretroviral therapy at the GHESKIO clinic in Port-au-Prince, Haiti.

Background: Treatment protocols and prices of antiretroviral therapy (ART) have changed over time. Yet, limited data exist to evaluate the impact of these changes on patient outcomes and treatment costs in resource-poor settings.

Methods: We compared patient-level data on outcomes, utilization, and cost for the first 2 years of ART for a cohort of adult patients initiating ART in 2003-2004 and a cohort initiating ART in 2006-2008 at the Haitian Group for the Study of Kaposi's Sarcoma and Opportunistic Infections clinic (GHESKIO) in Port-au-Prince, Haiti.

The co-use of tobacco and cannabis among adolescents over a 30-year period.

Background: This study explores the patterns of use and co-use of tobacco and cannabis among Ontario adolescents over 3 decades and if characteristics of co-users and single substance users have changed.

Methods: Co-use trends for 1981-2011 were analyzed using the Centre for Addiction and Mental Health Ontario Student Drug Use and Health Survey, which includes 38,331 students in grades 7, 9, and 11. A co-user was defined as someone reporting daily tobacco and/or cannabis use in the past month.

Epidemiology and genetic diversity of multidrug-resistant tuberculosis in East Africa.

Multidrug-resistant tuberculosis (MDR-TB) is an emerging problem in many parts of the world, and levels of MDR-TB among new TB patients are increasing in sub-Saharan Africa. We reviewed the prevalence and molecular epidemiology of MDR-TB in East Africa, including Burundi, Kenya, Rwanda, Tanzania, and Uganda. In 16 epidemiologic surveys, the prevalence of MDR among new cases ranges from 0.

Early and efficient detection of Mycobacterium tuberculosis in sputum by microscopic observation of broth cultures.

Early, efficient and inexpensive methods for the detection of pulmonary tuberculosis are urgently needed for effective patient management as well as to interrupt transmission. These methods to detect M. tuberculosis in a timely and affordable way are not yet widely available in resource-limited settings.

Automated design of ligands to polypharmacological profiles.

The clinical efficacy and safety of a drug is determined by its activity profile across many proteins in the proteome. However, designing drugs with a specific multi-target profile is both complex and difficult. Therefore methods to design drugs rationally a priori against profiles of several proteins would have immense value in drug discovery.

Recollection training and transfer effects in older adults: successful use of a repetition-lag procedure.

We examined an approach aimed at training consciously-controlled recollection, introduced by Jennings and Jacoby (2003) , for its ability to replicate and generalize. A continuous recognition task, requiring recollection to identify the occurrence of repeated items over gradually increasing lag intervals (number of intervening items between the first and second presentation of a repeated word), was given to a group of older adults twice a week for three weeks. Pre-and-post training performance was assessed on multiple measures and compared with a recognition practice and no contact control group.