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https://www.readbyqxmd.com/read/29337878/tetrasubstituted-imidazolium-salts-as-potent-antiparasitic-agents-against-african-and-american-trypanosomiases
#1
Ouldouz Ghashghaei, Nicola Kielland, Marc Revés, Martin C Taylor, John M Kelly, Ornella Di Pietro, Diego Muñoz-Torrero, Belén Pérez, Rodolfo Lavilla
Imidazolium salts are privileged compounds in organic chemistry, and have valuable biological properties. Recent studies show that symmetric imidazolium salts with bulky moieties can display antiparasitic activity against T. cruzi. After developing a facile methodology for the synthesis of tetrasubstituted imidazolium salts from propargylamines and isocyanides, we screened a small library of these adducts against the causative agents of African and American trypanosomiases. These compounds display nanomolar activity against T...
January 16, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29302035/sleeping-sickness-is-a-circadian-disorder
#2
Filipa Rijo-Ferreira, Tânia Carvalho, Cristina Afonso, Margarida Sanches-Vaz, Rui M Costa, Luísa M Figueiredo, Joseph S Takahashi
Sleeping sickness is a fatal disease caused by Trypanosoma brucei, a unicellular parasite that lives in the bloodstream and interstitial spaces of peripheral tissues and the brain. Patients have altered sleep/wake cycles, body temperature, and endocrine profiles, but the underlying causes are unknown. Here, we show that the robust circadian rhythms of mice become phase advanced upon infection, with abnormal activity occurring during the rest phase. This advanced phase is caused by shortening of the circadian period both at the behavioral level as well as at the tissue and cell level...
January 4, 2018: Nature Communications
https://www.readbyqxmd.com/read/29282538/barometric-pressure-change-and-heart-rate-response-during-sleeping-at-%C3%A2-3000%C3%A2-m-altitude
#3
Masahiro Horiuchi, Junko Endo, Yoko Handa, Hiroshi Nose
We investigated effects of change in barometric pressure (P B) with climate change on heart rate (HR) during sleep at 3000 m altitude. Nineteen healthy adults (15 males and four females; mean age 32 years) participated in this study. We measured P B (barometry) and HR (electrocardiography) every minute during their overnight stay in a mountain lodge at ~ 3000 m. We also measured resting arterial oxygen saturation (SpO2) and evaluated symptoms of acute mountain sickness (AMS) by using the Lake Louise Questionnaire at 2305 and 3000 m, respectively...
December 27, 2017: International Journal of Biometeorology
https://www.readbyqxmd.com/read/29275007/fexinidazole-a-new-drug-for-african-sleeping-sickness-on-the-horizon
#4
Michael P Pollastri
Decades after the last new chemical entity was added to the pharmacopeia for human African trypanosomiasis (or sleeping sickness), orally dosed fexinidazole stands poised to replace the current treatment regimen for Trypanosoma brucei gambiense infections, following a positive Phase 2/3 clinical trial.
December 20, 2017: Trends in Parasitology
https://www.readbyqxmd.com/read/29246805/substrate-specificity-profiling-of-m32-metallocarboxypeptidases-from-trypanosoma-cruzi-and-trypanosoma-brucei
#5
Alejandra P Frasch, León A Bouvier, Florencia M Oppenheimer, Maria Aparecida Juliano, Luiz Juliano, Adriana K Carmona, Juan José Cazzulo, Gabriela T Niemirowicz
Metallocarboxypeptidases (MCPs) of the M32 family, while broadly distributed among prokaryotic organisms, have so far been only found in a few eukaryotes including trypanosomatids. Among these organisms are human and animal pathogens of medical relevance such as Trypanosoma brucei and Trypanosoma cruzi, the respective causative agents of sleeping sickness and Chagas disease. The M32 MCP orthologues found in these parasites share 72% protein sequence identity. They also present a cytosolic localization, a similar pattern of expression and a marked preference for Arg/Lys residues at P1'...
December 12, 2017: Molecular and Biochemical Parasitology
https://www.readbyqxmd.com/read/29243461/physicians-working-conditions-health-and-working-capacity
#6
Marko Elovainio, Marianna Virtanen, Tuula Oksanen
Changes in the working environment will also influence the work of physicians. The greatest of these changes on the Finnish scale, the SOTE reform (the reform in social welfare and public health services), still lies ahead. Labor shortage, on-call duties and patient record systems providing little support to work add to the burden. In surveys related to psychosocial working conditions, physicians' greatest work load factors have been rush, forced working pace and poor communication despite the fact that, on average, they consider their working conditions to be good, frequently better than those of other professional groups, and are committed to carry on with their work until retirement age...
2017: Duodecim; Lääketieteellinen Aikakauskirja
https://www.readbyqxmd.com/read/29232179/adenotonsillectomy-for-obstructive-sleep-apnea-in-children-with-complex-chronic-conditions
#7
Reshma Amin, Theresa Holler, Indra Narang, Sharon L Cushing, Evan J Propst, Suhail Al-Saleh
Objective To estimate the prevalence of persistent obstructive sleep apnea postadenotonsillectomy in children with complex chronic conditions. Study Design A retrospective cohort study. Setting The Hospital for Sick Children Sleep laboratory. Subjects Children ≤18 years of age who had moderate to severe obstructive sleep apnea and had polysomnography pre- and postadenotonsillectomy. Methods Medical and polysomnographic data were reviewed. The prevalence of persistent obstructive sleep apnea postadenotonsillectomy was determined for the following groups: no complex chronic conditions, single-system complex chronic conditions, and multisystem complex chronic conditions...
December 1, 2017: Otolaryngology—Head and Neck Surgery
https://www.readbyqxmd.com/read/29228986/addressing-vulnerability-building-resilience-community-based-adaptation-to-vector-borne-diseases-in-the-context-of-global-change
#8
REVIEW
Kevin Louis Bardosh, Sadie Ryan, Kris Ebi, Susan Welburn, Burton Singer
BACKGROUND: The threat of a rapidly changing planet - of coupled social, environmental and climatic change - pose new conceptual and practical challenges in responding to vector-borne diseases. These include non-linear and uncertain spatial-temporal change dynamics associated with climate, animals, land, water, food, settlement, conflict, ecology and human socio-cultural, economic and political-institutional systems. To date, research efforts have been dominated by disease modeling, which has provided limited practical advice to policymakers and practitioners in developing policies and programmes on the ground...
December 11, 2017: Infectious Diseases of Poverty
https://www.readbyqxmd.com/read/29213301/including-refugees-in-disease-elimination-challenges-observed-from-a-sleeping-sickness-programme-in-uganda
#9
Jennifer J Palmer, Okello Robert, Freddie Kansiime
Background: Ensuring equity between forcibly-displaced and host area populations is a key challenge for global elimination programmes. We studied Uganda's response to the recent refugee influx from South Sudan to identify key governance and operational lessons for national sleeping sickness programmes working with displaced populations today. A refugee policy which favours integration of primary healthcare services for refugee and host populations and the availability of rapid diagnostic tests (RDTs) to detect sleeping sickness at this health system level makes Uganda well-placed to include refugees in sleeping sickness surveillance...
2017: Conflict and Health
https://www.readbyqxmd.com/read/29212563/clinically-relevant-and-simple-immune-system-measure-is-related-to-symptom-burden-in-bipolar-disorder
#10
Ole Köhler-Forsberg, Louisa Sylvia, Thilo Deckersbach, Michael Joshua Ostacher, Melvin McInnis, Dan Iosifescu, Charles Bowden, Susan McElroy, Joseph Calabrese, Michael Thase, Richard Charles Shelton, Mauricio Tohen, James Kocsis, Edward Friedman, Terence Ketter, Andrew Alan Nierenberg
OBJECTIVE: Immunological theories, particularly the sickness syndrome theory, may explain psychopathology in mood disorders. However, no clinical trials have investigated the association between overall immune system markers with a wide range of specific symptoms including potential gender differences. METHODS: We included two similar clinical trials, the lithium treatment moderate-dose use study and clinical and health outcomes initiatives in comparative effectiveness for bipolar disorder study, enrolling 765 participants with bipolar disorder...
December 7, 2017: Acta Neuropsychiatrica
https://www.readbyqxmd.com/read/29210635/potential-drug-targets-in-the-pentose-phosphate-pathway-of-trypanosomatids
#11
Ines Loureiro, Joana Faria, Nuno Santarem, Terry K Smith, Joana Tavares, Anabela Cordeiro-da-Silva
The trypanosomatids, Trypanosoma brucei, Trypanosoma cruzi and Leishmania spp, are causative agents of important human diseases such African sleeping sickness, Chagas' disease and Leishmaniasis, respectively. The high impact of these diseases on human health and economy worldwide, the unsatisfactory available chemotherapeutic options and the absence of human effective vaccines, strongly justifies the search for new drugs. The pentose phosphate pathway has been proposed to be a viable strategy to defeat several infectious diseases, including those from trypanosomatids, as it includes an oxidative branch, important in the maintenance of cell redox homeostasis, and a non-oxidative branch in which ribose 5-phosphate and erythrose 4-phosphate, precursors of nucleic acids and aromatic amino acids, are produced...
December 5, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29199348/unhealthy-lifestyle-and-sleep-problems-as-risk-factors-for-increased-direct-employers-cost-of-short-term-sickness-absence
#12
Noora Kanerva, Olli Pietiläinen, Tea Lallukka, Ossi Rahkonen, Jouni Lahti
Objectives Unhealthy lifestyle (eg, smoking) as well as sleep problems are associated with increased risk of sickness absence, but the financial impact of these associations beyond risk ratios is not well known. We aimed to estimate the additive contribution of lifestyle and sleep problems (risk factors) to direct costs of short-term (<15 days) sickness absence. Methods The Helsinki Health Study is a longitudinal cohort of employees of the City of Helsinki, Finland (N=8960, response rate 67%). During 2000-2002 the participants were mailed a survey questionnaire that gathered information on their lifestyle and sleep...
December 4, 2017: Scandinavian Journal of Work, Environment & Health
https://www.readbyqxmd.com/read/29197735/novel-triazine-dimers-with-potent-antitrypanosomal-activity
#13
Muthusamy Venkatraj, Irene G Salado, Jan Heeres, Jurgen Joossens, Paul J Lewi, Guy Caljon, Louis Maes, Pieter Van der Veken, Koen Augustyns
Human African trypanosomiasis (HAT), also known as sleeping sickness is a parasitic disease transmitted by the bite of the 'Glossina' insect, commonly known as the tsetse fly. This disease affects mostly poor populations living in remote rural areas of Africa. Untreated, it is usually fatal. Currently, safe and effective treatments against this disease are lacking. Phenotypic screening of triazine non-nucleoside HIV-1 reverse transcriptase inhibitors (monomers) resulted in potent and selective antitrypanosomal compounds...
November 27, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29173252/chronic-kidney-disease-in-african-americans-puzzle-pieces-are-falling-into-place
#14
REVIEW
Joseph V Nally
Recent decades have seen great advances in the understanding of chronic kidney disease, spurred by standardizing disease definitions and large-scale patient surveillance. African Americans are disproportionately affected by the disease, and recently discovered genetic variants in APOL1 that protect against sleeping sickness in Africa provide an important explanation for the increased burden. Studies are now under way to determine if genetic testing of African American transplant donors and recipients is advisable...
November 2017: Cleveland Clinic Journal of Medicine
https://www.readbyqxmd.com/read/29172727/objective-versus-self-reported-sleep-quality-at-high-altitude
#15
Paul J Anderson, Christina M Wood-Wentz, Kent R Bailey, Bruce D Johnson
Anderson, Paul J., Christina M. Wood-Wentz, Kent R. Bailey, and Bruce D. Johnson. Objective versus self-reported sleep quality at high altitude. High Alt Med Biol. 16:000-000, 2017. BACKGROUND: Previous studies have found little relationship between polysomnography and a diagnosis of acute mountain sickness (AMS) using the Lake Louise Symptom Questionnaire (LLSQ). The correlation between sleep question responses on the LLSQ and polysomnography results has not been explored. We compared LLSQ sleep responses and polysomnography data from our previous study of workers rapidly transported to the South Pole...
November 27, 2017: High Altitude Medicine & Biology
https://www.readbyqxmd.com/read/29168449/barcoding-in-trypanosomes
#16
Rachel Hutchinson, Jamie R Stevens
Trypanosomes (genus Trypanosoma) are parasites of humans, and wild and domestic mammals, in which they cause several economically and socially important diseases, including sleeping sickness in Africa and Chagas disease in the Americas. Despite the development of numerous molecular diagnostics and increasing awareness of the importance of these neglected parasites, there is currently no universal genetic barcoding marker available for trypanosomes. In this review we provide an overview of the methods used for trypanosome detection and identification, discuss the potential application of different barcoding techniques and examine the requirements of the 'ideal' trypanosome genetic barcode...
November 23, 2017: Parasitology
https://www.readbyqxmd.com/read/29137663/patent-landscape-of-neglected-tropical-diseases-an-analysis-of-worldwide-patent-families
#17
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
#18
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
#19
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
#20
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
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