Medium-Ring Keto Bislactams with Antischistosomal Activity.

We discovered medium-ring keto bislactams as a new antischistosomal chemotype. The ketone functional group and isoindolinone substructure were required for high antischistosomal activity. Aryl substitution with EWG functional groups decreased the chemical stability.

Antimalarial Dibenzannulated Medium-Ring Keto Lactams.

We discovered dibenzannulated medium-ring keto lactams (11,12-dihydro-5-dibenzo[,]azonine-6,13-diones) as a new antimalarial chemotype. Most of these had chromatographic LogD values ranging from <0 to 3 and good kinetic solubilities (12.5 to >100 μg/mL at pH 6.

Skin aging associated with chromium among rural housewives in northern China.

Previous studies have found associations between chromium exposure and skin damage. However, few studies have focused on both chromium and skin aging. This study aimed to assess the degree of skin aging symptoms and estimate the relationship between hair chromium and skin aging among rural housewives.

Antischistosomal tetrahydro-γ-carboline sulfonamides.

We discovered tetrahydro-γ-carboline sulfonamides as a new antischistosomal chemotype. The aryl sulfonamide and tetrahydro-γ-carboline substructures were required for high antischistosomal activity. Increasing polarity improved solubility and metabolic stability but decreased antischistosomal activity.

Introduction of Mycobacterium ulcerans disease in the Bankim Health District of Cameroon follows damming of the Mapé River.

Buruli ulcer (BU) is an emerging ulcerative skin disease caused by infection with Mycobacterium ulcerans. Efforts to control its spread have been hampered by our limited understanding of M. ulcerans reservoirs and transmission, and the factors leading to the emergence of BU disease in a particular region.

Antiprotozoal activity of diterpenoids isolated from Zhumeria majdae- absolute configuration by circular dichroism.

Purpose: Zhumeria majdae, a unique species of the Zhumeria genus, is an endemic Iranian plant in the Lamiaceae family. Phytochemical investigation and biological activity of this plant are rarely reported. The current study aimed to find new antiprotozoal compounds from the roots of Z.

Serological and molecular evidence of Brucella species in the rapidly growing pig sector in Kenya.

Background: Brucellosis is an emerging yet neglected zoonosis that has been reported in Kenya. Epidemiological data on brucellosis in ruminants is readily accessible; however, reports on brucellosis in pigs remain limited. This study sought to detect Brucella infection in pig serum by both serological and molecular techniques.

A new chemotype with promise against Trypanosoma cruzi.

Pyridyl benzamide 2 is a potent inhibitor of Trypanosoma cruzi, but not other protozoan parasites, and had a selectivity-index of ≥10. The initial structure-activity relationship (SAR) indicates that benzamide and sulfonamide functional groups, and N-methylpiperazine and sterically unhindered 3-pyridyl substructures are required for high activity against T. cruzi.

Multiplicity of Asymptomatic Plasmodium falciparum Infections and Risk of Clinical Malaria: A Systematic Review and Pooled Analysis of Individual Participant Data.

Background: The malaria parasite Plasmodium falciparum holds an extensive genetic polymorphism. In this pooled analysis, we investigate how the multiplicity in asymptomatic P. falciparum infections-that is, the number of coinfecting clones-affects the subsequent risk of clinical malaria in populations living under different levels of transmission.

SAR of a new antischistosomal urea carboxylic acid.

Urea carboxylic acids, products of aryl hydantoin hydrolysis, were recently identified as a new antischistosomal chemotype. We now describe a baseline structure-activity relationship (SAR) for this compound series. With one exception, analogs of lead urea carboxylic acid 2 were quite polar with Log D values ranging from -1.

Maternal age at delivery, lung function and asthma in offspring: a population-based survey.

There is limited information about potential impact of maternal age on the respiratory health of offspring. We investigated the association of maternal age at delivery with adult offspring's lung function, respiratory symptoms and asthma, and potential differences according to offspring sex.10 692 adults from 13 countries participating in the European Community Respiratory Health Survey (ECRHS) II responded to standardised interviews and provided lung function measurements and serum for IgE measurements at age 25-55 years.

Progress in antischistosomal N,N'-diaryl urea SAR.

N,N'-Diaryl ureas have recently emerged as a new antischistosomal chemotype. We now describe physicochemical profiling, in vitro ADME, plasma exposure, and ex vivo and in vivo activities against Schistosoma mansoni for twenty new N,N'-diaryl ureas designed primarily to increase aqueous solubility, but also to maximize structural diversity. Replacement of one of the 4-fluoro-3-trifluoromethylphenyl substructures of lead N,N'-diaryl urea 1 with azaheterocycles and benzoic acids, benzamides, or benzonitriles decreased lipophilicity, and in most cases, increased aqueous solubility.

Hippeastrum reticulatum (Amaryllidaceae): Alkaloid Profiling, Biological Activities and Molecular Docking.

The Amaryllidaceae family has proven to be a rich source of active compounds, which are characterized by unique skeleton arrangements and a broad spectrum of biological activities. The aim of this work was to perform the first detailed study of the alkaloid constituents of (Amaryllidaceae) and to determine the anti-parasitological and cholinesterase (AChE and BuChE) inhibitory activities of the epimers (6α-hydroxymaritidine and 6β-hydroxymaritidine). Twelve alkaloids were identified in : eight known alkaloids by GC-MS and four unknown (6α-hydroxymaritidine, 6β-hydroxymaritidine, reticulinine and isoreticulinine) by NMR.

African animal trypanosomiasis as a constraint to livestock health and production in Karamoja region: a detailed qualitative and quantitative assessment.

Background: Nagana (African Animal Trypanosomiasis-AAT) and tick-borne diseases (TBDs) constrain livestock production in most parts of sub-Saharan Africa. To this realisation, Uganda government set up an African trypanosomiasis (AT) control unit, which among other activities generates national tsetse control priority maps using apparent tsetse density data. Such maps underestimate mechanically transmitted AAT and thus ought to be refined using actual AT prevalence data.

Alkaloid Constituents of the Amaryllidaceae Plant Amaryllis belladonna L.

The plant family Amaryllidaceae is well-known for its unique alkaloid constituents, which exhibit a wide range of biological activities. Its representative, , has a geographical distribution covering mainly southern Africa, where it has significant usage in the traditional medicine of the native people. In this study, samples collected in Brazil were examined for alkaloid content.

Lead selection of antiparasitic compounds from a focused library of benzenesulfonyl derivatives of heterocycles.

A library of 89 synthetic benzenesulfonyl derivatives of heterocycles with drug-like properties was assayed for in vitro antiparasitic activity and the results were added to our previously reported derivatives for a comprehensive SAR evaluation. Four compounds showed an IC between 0.25 and 3μM against Leishmania donovani and low cytotoxicity.

Elimination of Schistosoma mansoni in infected mice by slow release of artemisone.

The current treatment of schistosomiasis is based on the anti-helminthic drug praziquantel (PZQ). PZQ affects only the adult stages of schistosomes. In addition, resistance to PZQ is emerging.

Evaluating decontamination protocols for the isolation of Mycobacterium ulcerans from swabs.

Background: Mycobacterium ulcerans (M. ulcerans) is the causative agent of Buruli Ulcer (BU) disease. In order to inhibit the growth of the microbial contaminants during culture of M.

Revisiting the SAR of the Antischistosomal Aryl Hydantoin (Ro 13-3978).

The aryl hydantoin 1 (Ro 13-3978) was identified in the early 1980s as a promising antischistosomal lead compound. However, this series of aryl hydantoins produced antiandrogenic side effects in the host, a not unexpected outcome given their close structural similarity to the antiandrogenic drug nilutamide. Building on the known SAR of this compound series, we now describe a number of analogs of 1 designed to maximize structural diversity guided by incorporation of substructures and functional groups known to diminish ligand-androgen receptor interactions.

Maximizing microscopy as a diagnostic tool in peripheral health centres of BU endemic areas in Ghana.

Buruli ulcer (BU) disease, a skin condition caused by Mycobacterium ulcerans (M. ulcerans) is endemic in remote rural areas. Disease diagnosis on clinical basis alone can be misleading, requiring definitive diagnosis based on laboratory tests.

A generic schema and data collection forms applicable to diverse entomological studies of mosquitoes.

Background: Standardized schemas, databases, and public data repositories are needed for the studies of malaria vectors that encompass a remarkably diverse array of designs and rapidly generate large data volumes, often in resource-limited tropical settings lacking specialized software or informatics support.

Results: Data from the majority of mosquito studies conformed to a generic schema, with data collection forms recording the experimental design, sorting of collections, details of sample pooling or subdivision, and additional observations. Generically applicable forms with standardized attribute definitions enabled rigorous, consistent data and sample management with generic software and minimal expertise.

Epidemiological evidence that indoor air pollution from cooking with solid fuels accelerates skin aging in Chinese women.

Background: Recently, we showed that outdoor air pollution exposure from traffic and industry is associated with an increased risk of skin aging in Caucasian women. In China, indoor air pollution exposure caused by the use of solid fuels like coal is a major health problem and might also increase the risk of skin aging in Chinese women.

Objective: As cooking with solid fuels is a major source of indoor air pollution exposure in China, we aimed to test if cooking with solid fuels is associated with more pronounced skin aging in Chinese women.

The burden and spatial distribution of bovine African trypanosomes in small holder crop-livestock production systems in Tororo District, south-eastern Uganda.

Background: African animal trypanosomiasis (AAT) is considered to be one of the greatest constraints to livestock production and livestock-crop integration in most African countries. South-eastern Uganda has suffered for more than two decades from outbreaks of zoonotic Human African Trypanosomiasis (HAT), adding to the burden faced by communities from AAT. There is insufficient AAT and HAT data available (in the animal reservoir) to guide and prioritize AAT control programs that has been generated using contemporary, sensitive and specific molecular techniques.

Interaction between asthma and smoking increases the risk of adult airway obstruction.

The aim of the present study was to analyse the interaction between asthma and smoking in the risk of adult airway obstruction, accounting for atopy. In the European Community Respiratory Health Survey, 15 668 persons aged 20-56 years underwent spirometry in 1991-1993 and 9 years later (n=8916). Risk of airway obstruction and lung function decline associated with smoking and early-onset (<10 years of age) and late-onset (>10 years of age) asthma were analysed with generalised estimating equation models and random-effect linear models, adjusting for covariates.