The Oral Antimalarial Drug Tafenoquine Shows Activity against Trypanosoma brucei

The protozoan parasite Trypanosoma brucei causes human African trypanosomiasis, or sleeping sickness, a neglected tropical disease that requires new, safer, and more effective treatments. Repurposing oral drugs could reduce both the time and cost involved in sleeping sickness drug discovery. Tafenoquine (TFQ) is an oral antimalarial drug belonging to the 8-aminoquinoline family which is currently in clinical phase III. We show here that TFQ efficiently kills different T. brucei spp. in the submicromolar concentration range. Our results suggest that TFQ accumulates into acidic compartments and induces a necrotic process involving cell membrane disintegration and loss of cytoplasmic content, leading to parasite death. Cell lysis is preceded by a wide and multitarget drug action, affecting the lysosome, mitochondria, and acidocalcisomes and inducing a depolarization of the mitochondrial membrane potential, elevation of intracellular Ca²⁺, and production of reactive oxygen species. This is the first report of an 8-aminoquinoline demonstrating significant in vitro activity against T. brucei.     

Tinnitus in children without hearing impairment

ObjectiveTinnitus is not an uncommon symptom in the pediatric population and, despite its incidence, is still an unrecognized problem, particularly in normal hearing children. As tinnitus is frequently described by adults without evidence of ear disease, reports of tinnitus can be obtained also from a group of children without otological pathology. The present review has been performed in order to emphasize the great importance to try to identify children suffering from tinnitus and to recognize the difference between the tinnitus characteristics in children with ear pathology and those one without otological problems.MethodsA review of the literature regarding the nature of pediatric tinnitus and the practical diagnostic approach to this symptom has been carried out.ResultsChildren rarely complain spontaneously of tinnitus but are able to describe it when questioned. In our experience the total percentage of children with tinnitus rises from 6.5% (tinnitus reported spontaneously), to 34% when children are specifically questioned.Most children, more than 50%, have normal hearing; in those with hearing impairment, no particular type or severity of hearing loss has been found.An important point that must be considered much more seriously is tinnitus sequela following head injuries to which children are particularly exposed during their daily activities.Due to the serious consequences that may be caused by tinnitus, it is of great importance to identify and analyze it, so as to minimize its damage, utilizing a protocol of study of pediatric tinnitus which allows to collect interesting informations about tinnitus characteristics.ConclusionsIn considering that tinnitus in children exists and may provoke serious consequences, even in absence of ear pathology, it is necessary to investigate and understand more about this symptom in children. From this viewpoint, it is very important to recognize the value of a global evaluation of a child suffering from tinnitus.There is no reason why such an important symptom well reported in adults should not be investigated in the pediatric population in which it seems to be as frequent as in the adult one.It is reasonable to believe that also in children tinnitus may have significant implications for medical and rehabilitative management.     

Proficiency test for gamma spectroscopic analysis with a simulated fission product reference spectrum.

Within the proficiency test programme for the radionuclide laboratories supporting the verification of the Comprehensive Nuclear-Test-Ban Treaty, a simulated gamma spectrum with the characteristics of an atmospheric nuclear test was used as reference material. The spectrum was produced by the MCNP-based Virtual Gamma Spectroscopy Laboratory (VGSL), using analysis results of a historical measurement of nuclear weapons debris as input. The method was found suitable for a proficiency test assessing laboratories' gamma spectroscopic analysis.     

Verifying the operational set-up of a radionuclide air-monitoring station.

A worldwide radionuclide network of 80 stations, part of the International Monitoring System, was designed to monitor compliance with the Comprehensive Nuclear-Test-Ban Treaty. After installation, the stations are certified to comply with the minimum requirements laid down by the Preparatory Commission of the Comprehensive Nuclear-Test-Ban Treaty Organization. Among the several certification tests carried out at each station, the verification of the radionuclide activity concentrations is a crucial one and is based on an independent testing of the airflow rate measurement system and of the gamma detector system, as well as on the assessment of the samples collected during parallel sampling and measured at radionuclide laboratories.     

Pharmaciens d'officine et dopage sportif : enquête sur les connaissances et les attitudes au niveau de la région de Dakar au Sénégal

Aim. – Evaluate the knowledge of retail pharmacists of doping in sport and to describe their attitude in front to this phenomenon.Methods. – We proceeded by a prospective self-reported survey by postal mail with 105 retail pharmacists in Dakar which contains 299 pharmacies.Results. – We have received 68 answers. Only 10% of pharmacists know doping definition. They are 66% who think that senegalese sportsmen use doping products. They feel concerned with the problem of doping (81%) and 19% of them said having been contacted during these last 12 months for advice on doping products. They consider that doping is a kind of drug addiction and a public health problem. They estimated to 95% that the most effectiveness means of prevention would be to talk about side effects of doping products with the support of doctors.Conclusion. – This study which has to be extended must bring us to do big preventing actions.     

Towards Semiconducting Graft Copolymers: Switching from ATRP to “Click” Approach

The synthesis of two polyconjugated graft copolymers based on a poly(fluorene‐phenylene) backbone and polystyrene side chains is described here. The two different approaches followed, ATRP growth of side chains from a preformed conjugated backbone and “click” connection of well‐defined polymeric chains to the backbone, led to different results in terms of solubility and material properties. While the ATRP method seems to be responsible of a partially cross‐linked and nonsoluble copolymer, the “click” approach provides a graft copolymer, which is completely soluble, showing atypical spectroscopic properties that are here elucidated.

     

Effectiveness of two home ergonomic programs in reducing pain and enhancing quality of life in informal caregivers of post-stroke patients: A pilot randomized controlled clinical trial

Background

Informal caregivers of post-stroke patients usually undergo high levels of pain and stress and have a reduced quality of life.

Validation of a New Arabic Version of the Neuropathic Pain Diagnostic Questionnaire (DN4)

The “Douleur Neuropathique 4 (DN4) questionnaire” was developed for screening neuropathic pain. The purpose of this work was to validate the DN4 questionnaire in the standard Arabic language. First, the questionnaire was translated and semantically adapted to Arabic according to the international guidelines for cross‐cultural adaptation. Second, a prospective observational study was performed to validate this questionnaire. A total of 195 patients with chronic pain (n = 99 with neuropathic pain and n = 96 without neuropathic pain) were enrolled in the study. The internal consistency Kuder–Richardson's Formula 20 for the whole DN4 questionnaire was 0.86 (P < 0.001) and the intraclass correlation coefficient 0.99 (95% CI: 0.99 to 1.00). The test–retest reliability kappa coefficient for each item ranged from 0.92 to 1.00. Using a receiver‐operating characteristic (ROC) curve analysis, the areas under the curve were 0.94 and 0.97 for the 7‐item DN4 and 10‐item DN4, respectively. A cut‐off score of 3 resulted in a sensitivity of 97.0% and a specificity of 82.3% for the 7‐item DN4, while a cut‐off score of 5 for the 10‐item DN4 resulted in a sensitivity of 93.0% and a specificity of 95.8%. Tingling, numbness, and hypoesthesia to touch and to pricking were the most discriminating pain items. The sensitivity and specificity of the 7‐item DN4 and 10‐item DN4 were not influenced by either pain severity or educational level. In conclusion, this new Arabic version DN4 questionnaire is a simple, reliable, and valid tool for discriminating between neuropathic and non‐neuropathic pain. It represents a useful tool in clinical setting and population‐based studies.     

Resistance to Targeted Therapies in Renal Cancer: The Importance of Changing the Mechanism of Action

Renal cell carcinoma (RCC) is a complex disease characterized by mutations in several genes. Loss of function of the von Hippel-Lindau (VHL) tumour suppressor gene is a very common finding in RCC and leads to up-regulation of hypoxia-inducible factor (HIF)-responsive genes accountable for angiogenesis and cell growth, such as platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF). Binding of these proteins to their cognate tyrosine kinase receptors on endothelial cells promotes angiogenesis. Promotion of angiogenesis is in part due to the activation of the phosphatidylinositol-3-kinase (PI3K)/AKT/mechanistic target of rapamycin (mTOR) pathway. Inhibition of this pathway decreases protein translation and inhibits both angiogenesis and tumour cell proliferation. Although tyrosine kinase inhibitors (TKIs) stand as the main first-line treatment option for advanced RCC, eventually all patients will become resistant to TKIs. Resistance can be overcome by using second-line treatments with different mechanisms of action, such as inhibitors of mTOR, c-MET, programmed death 1 (PD-1) receptor, or the combination of an mTOR inhibitor (mTORi) with a TKI. In this article, we briefly review current evidence regarding mechanisms of resistance in RCC and treatment strategies to overcome resistance with a special focus on the PI3K/AKT/mTOR pathway.

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