Frequency and determinants of ocular trauma in the Kimpese Rural Health Zone, Kongo Central, Democratic Republic of Congo: Fréquence et Déterminants des traumatismes oculaires dans la Zone de santé de Kimpese, Kongo Central, RDC

Context and objective. Ocular trauma is very common and its etiological factors vary by region and age group. This study aims to describe the magnitude and determinants of ocular trauma complications in rural areas.  Methods. We conducted a retrospective study of patients admitted for ocular trauma at Kimpese Hospital between January 2014 and December 2016. Univariate logistic regression was used to assess the determinants of ocular trauma complications. The statistical significance level is p˂ 0.05.  Results. A total of 223 patients were included. The majority of participants were men (69.5%), over 18 years of age (70%), with poor visual acuity (57.8%) and bilateral ocular involvement (51.1%). Plant objects (44.8%) and metal objects (15.2%) were the most common traumatic agents. After treatment, an improvement in visual acuity was observed in 64.3% of patients with previously poor visual acuity (p < 0.001). The delay of care > 7 days [aOR: 2.286 (95% CI: 1.302-4.012), p=0.004] and the poor visual acuity on admission [aOR: 5.906 (95% CI: 3.231-10.796), p< 0.0001] emerged as determinants of the onset of complications. Conclusion. Awareness-raising efforts for early consultation after ocular trauma and integration of eye care at the primary level should be promoted for efficiency in care. Contexte et objectifs. Les traumatismes oculaires sont très fréquents et ses facteurs étiologiques varient selon les régions et les tranches d’âge. Cette étude a pour objectifs de décrire le fardeau et rechercher les déterminants des complications des traumatismes oculaires en milieu rural. Méthodes. Nous avons mené une étude documentaire sur les patients admis à l’hopital de Kimpese pour un traumatisme oculaire entre janvier 2014 et décembre 2016. La régression logistique univariée a été utilisée pour rechercher les déterminants des complications des traumatismes oculaires. Le seuil de signification statistique est p˂0.05. Résultats. La majorité des participants était des hommes (69,5%), de la tranche de plus de 18 ans (70 %), avec une mauvaise acuité visuelle (57,8%) et une atteinte oculaire bilatérale (51,1%). Les objets de nature végétale (44,8%) et les objets métalliques (15,2%) ont constitué les agents traumatiques les plus rencontrés. Après traitement, une amélioration de l’acuité visuelle a été constatée chez 64,3% des patients ayant précédemment une acuité visuelle mauvaise (p< 0,001). Le délai de prise en charge > 7 jours [ORa : 2 ,286 (IC 95% : 1,302-4,012), p= 0,004] et la mauvaise acuité visuelle à l’admission [ORa : 5,906 (IC 95%: 3,231-10,796), p < 0,0001] ont émergé comme déterminants de la survenue des complications. Conclusion. Les efforts de sensibilisation en faveur de la consultation précoce après les traumatismes oculaires et une intégration des soins oculaires au niveau primaire sont à promouvoir pour une efficience dans la prise en charge

Efficacy, safety, and dose of Pafuramidine, a new oral drug for treatment of first stage sleeping sickness, in a phase 2a clinical study and phase 2b randomized clinical studies

Sleeping sickness (human African trypanosomiasis [HAT]) is caused by protozoan parasites and characterized by a chronic progressive course, which may last up to several years before death. We conducted two Phase 2 studies to determine the efficacy and safety of oral pafuramidine in African patients with first stage HAT.; The Phase 2a study was an open-label, non-controlled, proof-of-concept study where 32 patients were treated with 100 mg of pafuramidine orally twice a day (BID) for 5 days at two trypanosomiasis reference centers (Angola and the Democratic Republic of the Congo [DRC]) between August 2001 and November 2004. The Phase 2b study compared pafuramidine in 41 patients versus standard pentamidine therapy in 40 patients. The Phase 2b study was open-label, parallel-group, controlled, randomized, and conducted at two sites in the DRC between April 2003 and February 2007. The Phase 2b study was then amended to add an open-label sequence (Phase 2b-2), where 30 patients received pafuramidine for 10 days. The primary efficacy endpoint was parasitologic cure at 24 hours (Phase 2a) or 3 months (Phase 2b) after treatment completion. The primary safety outcome was the rate of occurrence of World Health Organization Toxicity Scale Grade 3 or higher adverse events. All subjects provided written informed consent.; Pafuramidine for the treatment of first stage HAT was comparable in efficacy to pentamidine after 10 days of dosing. The cure rates 3 months post-treatment were 79% in the 5-day pafuramidine, 100% in the 7-day pentamidine, and 93% in the 10-day pafuramidine groups. In Phase 2b, the percentage of patients with at least 1 treatment-emergent adverse event was notably higher after pentamidine treatment (93%) than pafuramidine treatment for 5 days (25%) and 10 days (57%). These results support continuation of the development program for pafuramidine into Phase 3

Big Data Architectures and Concepts

Nowadays, the processing of big data has become a major preoccupation for businesses, not only for storage and processing but also for operational requirements such as speed, maintaining performance with scalability, reliability, availability, security, and cost control; ultimately enabling them to maximize their profits by using the new possibilities offered by Big Data. In this article, we will explore and exploit the concepts and architectures of Big Data, in particular through the Hadoop open-source framework, and see how it meets the needs set out above, in its cluster structure, its components, its Lambda and Kappa architectures, and so on. We are also going to deploy Hadoop in a virtualized Linux environment, with several nodes, under the Oracle Virtual Box virtualization software, and use the experimental method to compare the processing time of the MapReduce algorithm on two DataSets with successively one, two, and three and four Datanodes, and thus observe the gains in processing time with the increase in the number of nodes in the cluste

Fractionation of sialylated oligosaccharides, glycopeptides, and glycoproteins on immobilized elderberry (Sambucus nigra L.) bark lectin

A new plant lectin from elderberry (Sambucus nigra L.) bark, which was shown by immunochemical techniques to bind specifically to terminal Neu5Ac([alpha]2-6)Gal/GalNAc residues of glycoconjugates, was immobilized onto Sepharose 4B (SNA-Sepharose) and its carbohydrate binding properties was determined using a series of standard compounds. Oligosaccharides, glycopeptides, or glycoproteins containing terminal Neu5Ac([alpha]2-6)Gal/GalNAc sequences bound to SNA-Sepharose and were eluted with 50-100 m lactose, whereas those with Neu5Ac([alpha]2-3)Gal/GalNAc failed to bind to this column. Furthermore, the SNA-Sepharose column was capable of resolving two oligosaccharides/glycopeptides based on the number of Neu5Ac([alpha]2-6)Gal units present in each molecule. Application of this technique to two glycoproteins, fetuin and orosomucoid, revealed the presence of microheterogeneity. It was also shown that esterification of the carboxyl group of Neu5Ac units, or branching at the O-3 of the subterminal GalNAc (probably also Gal) destroyed the binding ability of the molecule.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26737/1/0000288.pd

Safety and efficacy of oral fexinidazole in children with gambiense human African trypanosomiasis: a multicentre, single-arm, open-label, phase 2-3 trial

BACKGROUND: Fexinidazole has been reported as an effective oral monotherapy against non-severe gambiense human African trypanosomiasis in a recent trial in adults. We aimed to assess the safety and efficacy of fexinidazole in children across all disease stages of gambiense human African trypanosomiasis. METHODS: We did a multicentre, single-arm, open-label, phase 2-3 trial at eight district hospitals in the Democratic Republic of the Congo. We recruited children with a Karnofsky score of more than 50, those aged 6 years to younger than 15 years, weighing 20 kg or more, and with confirmed gambiense human African trypanosomiasis (any stage). Children weighing 20 kg or more and less than 35 kg received oral fexinidazole of 1200 mg (two x 600 mg tablets) once per day for 4 days (days 1-4) followed by 600 mg (one x 600 mg tablet) once per day for 6 days (days 5-10). Children weighing 35 kg or more received oral fexinidazole of 1800 mg (three x 600 mg tablets) once per day for 4 days (days 1-4), followed by 1200 mg (two x 600 mg tablets) once per day for 6 days (days 5-10). The primary endpoint was fexinidazole treatment success rate 12 months after end of treatment. A rate greater than 80% was deemed acceptable and a target value of 92% was aimed for. Safety was assessed through routine monitoring. This study is completed and registered with ClinicalTrials.gov, number NCT02184689. FINDINGS: Between May 3, 2014, and Nov 22, 2016, we screened a total of 130 paediatric patients, of whom 125 (96%) received at least one dose of fexinidazole. All 125 patients (69 [55%] patients with stage 1, 19 [15%] with early stage 2, and 37 [30%] with late stage 2 gambiense human African trypanosomiasis) completed the 10-day treatment. Treatment success rate at 12 months was 97.6% (95% CI 93.1-99.5; 122 of 125 patients). The primary endpoint was met and the targeted value of 92% was exceeded. Treatment success at 12 months was elevated across all disease stages: 98.6% (95% CI 92.2-99.9; 68 of 69 patients) in stage 1, 94.7% (74.0-99.9; 18 of 19 patients) in early stage 2, and 97.3% (85.8-99.9; 36 of 37 patients) in late stage 2 gambiense human African trypanosomiasis. No new safety issues were observed beyond those found in adult trials. Overall, 116 (93%) of 125 patients reported 586 treatment-emergent adverse events, mainly mild or moderate. The most frequently reported treatment-emergent adverse events of interest during hospital admission were vomiting (86 [69%] of 125) and headache (41 [33%]). Seven (6%) of 125 patients had severe malaria, which was often accompanied by anaemia that was unrelated to fexinidazole. One patient died following dyspnoea and injury due to traumatic aggression 172 days after end of treatment, which was considered unrelated to fexinidazole or gambiense human African trypanosomiasis. INTERPRETATION: Oral fexinidazole is a safe and effective first-line treatment option across all gambiense human African trypanosomiasis disease stages in paediatric patients. FUNDING: Through the Drugs for Neglected Diseases initiative: the Bill & Melinda Gates Foundation (USA), the Republic and Canton of Geneva (Switzerland), the Dutch Ministry of Foreign Affairs (Netherlands), the Norwegian Agency for Development Cooperation (Norway), the Federal Ministry of Education and Research through KfW (Germany), the Brian Mercer Charitable Trust (UK), and other private foundations and individuals from the human African trypanosomiasis campaign. TRANSLATION: For the French translation of the abstract see Supplementary Materials section

High CD8+ T Cell Activation Marks a Less Differentiated HIV-1 Specific CD8+ T Cell Response that Is Not Altered by Suppression of Viral Replication

The relationship of elevated T cell activation to altered T cell differentiation profiles, each defining features of HIV-1 infection, has not been extensively explored. We hypothesized that anti-retroviral suppression of T cell activation levels would lead to alterations in the T cell differentiation of total and HIV-1 specific CD8+ T cell responses among recently HIV-1 infected adults.We performed a longitudinal study simultaneously measuring T cell activation and maturation markers on both total and antigen-specific T cells in recently infected adults: prior to treatment; after the initiation of HAART; and after treatment was halted. Prior to treatment, HIV-1 Gag-specific CD8+ T cells were predominantly of a highly activated, intermediate memory (CD27+CD28-) phenotype, while CMV pp65-specific CD8+ T cells showed a late memory (CD27-CD28-), low activation phenotype. Participants with the highest fraction of late memory (CD27-CD28-) HIV-1-specific CD8+ T cells had higher CD4+ T cell counts (rho = +0.74, p = 0.004). In turn, those with the highest fraction of intermediate memory (CD27+ CD28-) HIV-1 specific CD8+ T cells had high total CD8+ T cell activation (rho = +0.68, p = 0.01), indicating poorer long-term clinical outcomes. The HIV-1 specific T cell differentiation profile was not readily altered by suppression of T cell activation following HAART treatment.A more differentiated, less activated HIV-1 specific CD8+ T cell response may be clinically protective. Anti-retroviral treatment initiated two to four months after infection lowered T cell activation but had no effect on the differentiation profile of the HIV-1-specific response. Intervention during the first month of acute infection may be required to shift the differentiation phenotype of HIV-1 specific responses to a more clinically favorable profile

Vaccinating for natural killer cell effector functions

Vaccination has proved to be highly effective in reducing global mortality and eliminating infectious diseases. Building on this success will depend on the development of new and improved vaccines, new methods to determine efficacy and optimum dosing and new or refined adjuvant systems. NK cells are innate lymphoid cells that respond rapidly during primary infection but also have adaptive characteristics enabling them to integrate innate and acquired immune responses. NK cells are activated after vaccination against pathogens including influenza, yellow fever and tuberculosis, and their subsequent maturation, proliferation and effector function is dependent on myeloid accessory cell-derived cytokines such as IL-12, IL-18 and type I interferons. Activation of antigen-presenting cells by live attenuated or whole inactivated vaccines, or by the use of adjuvants, leads to enhanced and sustained NK cell activity, which in turn contributes to T cell recruitment and memory cell formation. This review explores the role of cytokine-activated NK cells as vaccine-induced effector cells and in recall responses and their potential contribution to vaccine and adjuvant development