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https://www.readbyqxmd.com/read/29137663/patent-landscape-of-neglected-tropical-diseases-an-analysis-of-worldwide-patent-families
#1
Folahanmi Tomiwa Akinsolu, Vitor Nobre de Paiva, Samuel Santos Souza, Orsolya Varga
BACKGROUND: "Neglected Tropical Diseases" (NTDs) affect millions of people in Africa, Asia and South America. The two primary ways of strategic interventions are "preventive chemotherapy and transmission control" (PCT), and "innovative and intensified disease management" (IDM). In the last 5 years, phenomenal progress has been achieved. However, it is crucial to intensify research effort into NTDs, because of the emerging drug resistance. According to the World Health Organization (WHO), the term NTDs covers 17 diseases, namely buruli ulcer, Chagas disease, dengue, dracunculiasis, echinococcosis, trematodiasis, human African trypanosomiasis, leishmaniasis, leprosy, lymphatic filariasis, onchocerciasis, rabies, schistosomiasis, soil-transmitted helminthes, taeniasis, trachoma, and yaws...
November 14, 2017: Globalization and Health
https://www.readbyqxmd.com/read/29134797/the-importance-of-collaboration-between-industry-academics-and-nonprofits-in-tropical-disease-drug-discovery
#2
Lori Ferrins, Michael P Pollastri
Collaborations between academic, industrial, and nonprofit companies can provide sufficient impetus to propel projects that have little economic return; such projects are prevalent in tropical disease drug discovery. In these collaborations, each partner contributes a unique set of skills and technical expertise which is advantageous to the project as a whole. Highly product-focused processes and specialized expertise sets dominate industry groups. When coupled with the strategic guidance from public-private partnerships and the academic tendency to work on high-risk projects with low financial rewards, a powerful combination results...
November 14, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/29131822/impact-of-the-ebola-outbreak-on-trypanosoma-brucei-gambiense-infection-medical-activities-in-coastal-guinea-2014-2015-a-retrospective-analysis-from-the-guinean-national-human-african-trypanosomiasis-control-program
#3
Mariame Camara, Eric Ouattara, Alexandre Duvignaud, René Migliani, Oumou Camara, Mamadou Leno, Philippe Solano, Bruno Bucheton, Mamadou Camara, Denis Malvy
BACKGROUND: The 2014-2015 Ebola outbreak massively hit Guinea. The coastal districts of Boffa, Dubreka and Forecariah, three major foci of Human African Trypanosomiasis (HAT), were particularly affected. We aimed to assess the impact of this epidemic on sleeping sickness screening and caring activities. METHODOLOGY/PRINCIPAL FINDINGS: We used preexisting data from the Guinean sleeping sickness control program, collected between 2012 and 2015. We described monthly: the number of persons (i) screened actively; (ii) or passively; (iii) treated for HAT; (iv) attending post-treatment follow-up visits...
November 13, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29126729/indole-and-benzimidazole-bichalcophenes-synthesis-dna-binding-and-antiparasitic-activity
#4
Abdelbasset A Farahat, Mohamed A Ismail, Arvind Kumar, Tanja Wenzler, Reto Brun, Ananya Paul, W David Wilson, David W Boykin
A novel series of indole and benzimidazole bichalcophene diamidine derivatives were prepared to study their antimicrobial activity against the tropical parasites causing African sleeping sickness and malaria. The dicyanoindoles needed to synthesize the target diamidines were obtained through Stille coupling reactions while the bis-cyanobenzimidazoles intermediates were made via condensation/cyclization reactions of different aldehydes with 4-cyano-1,2-diaminobenzene. Different amidine synthesis methodologies namely, lithium bis-trimethylsilylamide (LiN[Si(CH3)3]2) and Pinner methods were used to prepare the diamidines...
October 22, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29125744/design-and-synthesis-of-brain-penetrant-trypanocidal-n-myristoyltransferase-inhibitors
#5
Tracy Bayliss, David A Robinson, Victoria C Smith, Stephen Brand, Stuart P McElroy, Leah S Torrie, Chido Mpamhanga, Suzanne Norval, Laste Stojanovski, Ruth Brenk, Julie A Frearson, Kevin D Read, Ian H Gilbert, Paul G Wyatt
N-Myristoyltransferase (NMT) represents a promising drug target within the parasitic protozoa Trpanosoma brucei (T. brucei), the causative agent for human African trypanosomiasis (HAT) or sleeping sickness. We have previously validated T. brucei NMT as a promising druggable target for the treatment of HAT in both stage 1 and 2 of the disease. We report on the use of the previously reported DDD85646 (1) as a start point for the design of a class of potent, brain penetrant inhibitors of T. brucei NMT.
November 10, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29121981/intrinsic-dna-curvature-in-trypanosomes
#6
Pablo Smircich, Najib M El-Sayed, Beatriz Garat
BACKGROUND: Trypanosoma cruzi and Trypanosoma brucei are protozoan parasites causing Chagas disease and African sleeping sickness, displaying unique features of cellular and molecular biology. Remarkably, no canonical signals for RNA polymerase II promoters, which drive protein coding genes transcription, have been identified so far. The secondary structure of DNA has long been recognized as a signal in biological processes and more recently, its involvement in transcription initiation in Leishmania was proposed...
November 9, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/29114029/rapid-selection-free-high-efficiency-genome-editing-in-protozoan-parasites-using-crispr-cas9-ribonucleoproteins
#7
Lia Carolina Soares Medeiros, Lilith South, Duo Peng, Juan M Bustamante, Wei Wang, Molly Bunkofske, Natasha Perumal, Fernando Sanchez-Valdez, Rick L Tarleton
Trypanosomatids (order Kinetoplastida), including the human pathogens Trypanosoma cruzi (agent of Chagas disease), Trypanosoma brucei, (African sleeping sickness), and Leishmania (leishmaniasis), affect millions of people and animals globally. T. cruzi is considered one of the least studied and most poorly understood tropical disease-causing parasites, in part because of the relative lack of facile genetic engineering tools. This situation has improved recently through the application of clustered regularly interspaced short palindromic repeats-CRISPR-associated protein 9 (CRISPR-Cas9) technology, but a number of limitations remain, including the toxicity of continuous Cas9 expression and the long drug marker selection times...
November 7, 2017: MBio
https://www.readbyqxmd.com/read/29110762/apol1-nephrotoxicity-what-does-ion-transport-have-to-do-with-it
#8
REVIEW
Opeyemi A Olabisi, John F Heneghan
Apolipoprotein L1 (APOL1) protein is the human serum factor that protect human beings against Trypanosoma brucei brucei, the cause of trypanosomiasis. Subspecies of T b brucei that cause human sleeping sickness-T b gambiense and T b rhodesiense evolved molecular mechanisms that enabled them to evade killing by APOL1. Sequence changes (termed G1 and G2) in the APOL1 gene that restored its ability to kill T b rhodesiense also increase the risk of developing glomerular diseases and accelerate progression to end-stage kidney disease...
November 2017: Seminars in Nephrology
https://www.readbyqxmd.com/read/29110757/a-brief-history-of-apol1-a-gene-evolving
#9
REVIEW
David J Friedman
APOL1 kidney risk variants lead to high rates of kidney disease in people of recent African ancestry. These risk variants are very common and confer a large increase in risk of kidney disease. This unusual combination of high frequency and large effect size occurs because the risk variants also appear to have beneficial properties. The risk variants show enhanced protective effects against certain pathogens, particularly the trypanosomes that cause African sleeping sickness. Here, we consider the origins and evolution of the primate-only APOL1 gene...
November 2017: Seminars in Nephrology
https://www.readbyqxmd.com/read/29110575/utility-of-neck-height-and-tonsillar-size-to-screen-for-obstructive-sleep-apnea-among-obese-youth
#10
Indra Narang, Suhail Al-Saleh, Reshma Amin, Evan J Propst, Saadoun Bin-Hasan, Paolo Campisi, Clodagh Ryan, Tetyana Kendzerska
Objectives To determine whether neck:height ratio combined with adenoid and tonsillar size is a good predictive tool for obstructive sleep apnea in obese youth. Study Design Cross-sectional study. Setting Sleep clinics at the Hospital for Sick Children, Toronto, Canada. Subjects and Methods Consented obese individuals aged 8 to 18 years were recruited between 2013 and 2015. Anthropometric measures were obtained by a trained research coordinator in a standardized manner. Otolaryngologists evaluated adenoid and tonsil sizes...
November 1, 2017: Otolaryngology—Head and Neck Surgery
https://www.readbyqxmd.com/read/29107734/involvement-of-snare-protein-ykt6-in-glycosome-biogenesis-in-trypanosoma-brucei
#11
Hiren Banerjee, Richard A Rachubinski
The kinetoplastid parasites Trypanosoma and Leishmania are etiologic agents of diseases like African sleeping sickness, Chagas and leishmaniasis that inflict many tropical and subtropical parts of the world. These parasites are distinctive in that they compartmentalize most of the usually cytosolic enzymes of the glycolytic pathway within a peroxisome-like organelle called the glycosome. Functional glycosomes are essential in both the procyclic and bloodstream forms of trypanosomatid parasites, and mislocalization of glycosomal enzymes to the cytosol is fatal for the parasite...
December 2017: Molecular and Biochemical Parasitology
https://www.readbyqxmd.com/read/29078807/relationship-between-trypanosoma-brucei-rhodesiense-genetic-diversity-and-clinical-spectrum-among-sleeping-sickness-patients-in-uganda
#12
Charles D Kato, Claire M Mugasa, Ann Nanteza, Enock Matovu, Vincent P Alibu
OBJECTIVE: Human African trypanosomiasis (HAT) due to Trypanosoma brucei rhodesiense in East and southern Africa is reported to be clinically diverse. We tested the hypothesis that this clinical diversity is associated with a variation in trypanosome genotypes. RESULTS: Trypanosome DNA isolated from HAT patients was genotyped using 7 microsatellite markers directly from blood spotted FTA cards following a whole genome amplification. All markers were polymorphic and identified 17 multi-locus genotypes with 56% of the isolates having replicate genotypes...
October 27, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/29077717/a-polymorphism-in-the-haptoglobin-haptoglobin-related-protein-locus-is-associated-with-risk-of-human-sleeping-sickness-within-cameroonian-populations
#13
Elvis Ofon, Harry Noyes, Julius Mulindwa, Hamidou Ilboudo, Martin Simuunza, Vincent Ebo'o, Flobert Njiokou, Mathurin Koffi, Bruno Bucheton, Pythagore Fogue, Christiane Hertz-Fowler, Annette MacLeod, Gustave Simo
BACKGROUND: Human African Trypanosomiasis (HAT) is a neglected disease targeted for elimination as a public health problem by 2020. Elimination requires a better understanding of the epidemiology and clinical evolution of HAT. In addition to the classical clinical evolution of HAT, asymptomatic carriers and spontaneous cure have been reported in West Africa. A genetic component to human susceptibility to HAT has been suggested to explain these newly observed responses to infection. In order to test for genetic associations with infection response, genetic polymorphism in 17 genes were tested (APOL1, IL1B, IL4, IL4R, IL6, IL8, IL12B, IL12RB1, IL10, TNFA, INFG, MIF, HLA-G, HLA-A, HP, HPR and CFH)...
October 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29073144/the-socio-economic-burden-of-human-african-trypanosomiasis-and-the-coping-strategies-of-households-in-the-south-western-kenya-foci
#14
Salome A Bukachi, Simiyu Wandibba, Isaac K Nyamongo
INTRODUCTION: Human African Trypanosomiasis (HAT), a disease caused by protozoan parasites transmitted by tsetse flies, is an important neglected tropical disease endemic in remote regions of sub-Saharan Africa. Although the determination of the burden of HAT has been based on incidence, mortality and morbidity rates, the true burden of HAT goes beyond these metrics. This study sought to establish the socio-economic burden that households with HAT faced and the coping strategies they employed to deal with the increased burden...
October 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29072286/sleeping-sickness-can-now-be-cured-with-pills
#15
Amy Maxmen
No abstract text is available yet for this article.
October 18, 2017: Nature
https://www.readbyqxmd.com/read/29065822/privileged-structures-in-the-design-of-potential-drug-candidates-for-neglected-diseases
#16
Ana Cristina Lima Leite, José Wanderlan Pontes Espíndola, Marcos Veríssimo de Oliveira Cardoso, Gevanio Bezerra de Oliveira Filho
Privileged motifs are recurring in a wide range of biologically active compounds that reach different pharmaceutical targets and pathways and could represent a suitable start point to access potential candidates in the neglected diseases field. The current therapies to treat these diseases are based in drugs that lack of the desired effectiveness, affordable methods of synthesis and allow a way to emergence of resistant strains. Due the lack of financial return, only few pharmaceutical companies have been investing in research for new therapeutics for neglected diseases (ND)...
October 23, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29063677/transporters-of-trypanosoma-brucei-phylogeny-physiology-pharmacology
#17
REVIEW
Remo S Schmidt, Juan P Macêdo, Michael E Steinmann, Amaia González Salgado, Peter Bütikofer, Erwin Sigel, Doris Rentsch, Pascal Mäser
Trypanosoma brucei comprise the causative agents of sleeping sickness, T. b. gambiense and T. b. rhodesiense, as well as the livestock-pathogenic T. b. brucei. The parasites are transmitted by the tsetse fly and occur exclusively in sub-Saharan Africa. T. brucei are not only lethal pathogens, but have also become model organisms for molecular parasitology. We focus here on membrane transport proteins of T. brucei, their contribution to homeostasis and metabolism in the context of a parasitic lifestyle, and their pharmacological role as potential drug targets or routes of drug entry...
October 24, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29062898/essential-assembly-factor-rpf2-forms-novel-interactions-within-the-5s-rnp-in-trypanosoma-brucei
#18
Anyango D Kamina, Daniel Jaremko, Linda Christen, Noreen Williams
Ribosome biogenesis is a highly complex and conserved cellular process that is responsible for making ribosomes. During this process, there are several assembly steps that function as regulators to ensure proper ribosome formation. One of these steps is the assembly of the 5S ribonucleoprotein particle (5S RNP) in the central protuberance of the 60S ribosomal subunit. In eukaryotes, the 5S RNP is composed of 5S rRNA, ribosomal proteins L5 and L11, and assembly factors Rpf2 and Rrs1. Our laboratory previously showed that in Trypanosoma brucei, the 5S RNP is composed of 5S rRNA, L5, and trypanosome-specific RNA binding proteins P34 and P37...
September 2017: MSphere
https://www.readbyqxmd.com/read/29059176/candidate-genes-based-investigation-of-susceptibility-to-human-african-trypanosomiasis-in-c%C3%A3-te-d-ivoire
#19
Bernardin Ahouty, Mathurin Koffi, Hamidou Ilboudo, Gustave Simo, Enock Matovu, Julius Mulindwa, Christiane Hertz-Fowler, Bruno Bucheton, Issa Sidibé, Vincent Jamonneau, Annette MacLeod, Harry Noyes, Simon-Pierre N'Guetta
Human African Trypanosomiasis (HAT) or sleeping sickness is a Neglected Tropical Disease. Long regarded as an invariably fatal disease, there is increasing evidence that infection by T. b. gambiense can result in a wide range of clinical outcomes, including latent infections, which are long lasting infections with no parasites detectable by microscopy. The determinants of this clinical diversity are not well understood but could be due in part to parasite or host genetic diversity in multiple genes, or their interactions...
October 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29051618/development-and-validation-of-a-risk-prediction-model-for-work-disability-multicohort-study
#20
Jaakko Airaksinen, Markus Jokela, Marianna Virtanen, Tuula Oksanen, Jaana Pentti, Jussi Vahtera, Markku Koskenvuo, Ichiro Kawachi, G David Batty, Mika Kivimäki
Work disability affects quality of life, earnings, and opportunities to contribute to society. Work characteristics, lifestyle and sociodemographic factors have been associated with the risk of work disability, but few multifactorial algorithms exist to identify individuals at risk of future work disability. We developed and validated a parsimonious multifactorial score for the prediction of work disability using individual-level data from 65,775 public-sector employees (development cohort) and 13,527 employed adults from a general population sample (validation cohort), both linked to records of work disability...
October 19, 2017: Scientific Reports
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