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Aim: This study aims to describe dental treatment provided to healthy and medically compromised patients treated under general anesthesia (GA) over a four-year period., Materials and Methods: A total of 97 patients who received dental treatment under GA at the Saint Joseph University, Lebanon, from 2016 to 2019 were included in the study. The study population was analyzed according to the patient's age, medical status, and type of treatment done accordingly., Results: The mean age of the patients was 9.15 ± 8.84 years. About 58.8% were aged below 6 years (primary dentition) and 48.5% had medical problems. Dental procedures performed were mostly extractions (4.00 ± 4.15 per patient) followed by resin composite restorations (3.66 ± 3.02 per patient). The mean number of pulpotomies per patient ( p <0.001) and stainless steel crowns ( p <0.001) were significantly higher in primary dentition, whereas in permanent dentition, the mean number of endodontic treatments per patient ( p = 0.016) was significantly larger. Also, there was a significant difference between the type of treatment done on healthy and medically compromised patients ( p <0.001)., Conclusion: Better emphasis on oral health education and preventive strategies for children and special need patients is essential., Clinical Significance: Dental GA is a reliable treatment for young uncooperative children and medically compromised patients. A multidisciplinary treatment plan must be conducted to ensure optimal oral healthcare and avoid unnecessary extractions.

Technical lignins produced as a by-product in biorefinery processes represent a potential source of renewable carbon. In consideration of the possibilities of the industrial transformation of this substrate into various valuable bio-based molecules, the biological deconstruction of a technical soda lignin by filamentous fungi was investigated. The ability of three basidiomycetes ( Polyporus brumalis , Pycnoporus sanguineus and Leiotrametes menziesii ) to modify this material, the resultant structural and chemical changes, and the secreted proteins during growth on this substrate were investigated. The three fungi could grow on the technical lignin alone, and the growth rate increased when the media were supplemented with glucose or maltose. The proteomic analysis of the culture supernatants after three days of growth revealed the secretion of numerous Carbohydrate-Active Enzymes (CAZymes). The secretomic profiles varied widely between the strains and the presence of technical lignin alone triggered the early secretion of many lignin-acting oxidoreductases. The secretomes were notably rich in glycoside hydrolases and H 2 O 2 -producing auxiliary activity enzymes with copper radical oxidases being induced on lignin for all strains. The lignin treatment by fungi modified both the soluble and insoluble lignin fractions. A significant decrease in the amount of soluble higher molar mass compounds was observed in the case of P. sanguineus . This strain was also responsible for the modification of the lower molar mass compounds of the lignin insoluble fraction and a 40% decrease in the thioacidolysis yield. The similarity in the activities of P. sanguineus and P. brumalis in modifying the functional groups of the technical lignin were observed, the results suggest that the lignin has undergone structural changes, or at least changes in its composition, and pave the route for the utilization of filamentous fungi to functionalize technical lignins and produce the enzymes of interest for biorefinery applications.

Introduction: According to the taxonomy of the International Association for the Study of Pain (IASP 2011), neuropathic pain (NeuP) is defined as " pain caused by a lesion or disease of the somatosensory nervous system ". NeuP is currently well-defined clinically, despite a high degree of etiological variation, and it has become a significant public health problem. This work aimed to study the situation regarding NeuP in current practice in Mali, as well as to analyze the therapeutic environment of the patients., Methodology: This was a retrospective and cross-sectional study, carried out in two phases: (1) compilation of the files of patients according to the ICD-11, over a period of 24 months (2) a second prospective phase regarding the Knowledge, Attitudes, and Practices (KAP) of general practitioners and neurologists in regard to NeuP. The focus of the first phase of the study was the files of the patients who had undergone a consultation at the Gabriel Touré UHC. The second phase of the study focused on the general practitioners (Community Health Centers (comHC) of Bamako) and neurologists (Malian or not)., Results: Over the period of the study, 7840 patients were seen in consultation in the Department of Neurology, of whom 903 for NeuP, thus amounting to a NeuP frequency of 11.5%. Women accounted for 58.9% (532/903), with a sex ratio of 1.4. Using a comparative normal law, the difference in frequency was statistically significant between males and females ( p  < 10 -7 ) and between two age groups (p 〈10 -3 ). The 49-58 years of age group was represented the most. Diabetic NeuP (21%), lumbar radiculopathies (14%), HIV/AIDS NeuP (13%), and post-stroke NeuP (11%) were the most represented. The survey among the carers revealed: a need for training, a low level of compliance with the therapeutic guidelines, and the use of traditional medicine by the patients., Discussion/conclusion: This work confirms that NeuP is encountered frequently in current practice, and its optimal management will involve specific training of carers and improvement of access to the medications recommended in this indication. In light of this issue, we revisit the debate regarding the concept of essential medications and the relevance of taking into account effective medications for the treatment of NeuP., (© 2021 The Author(s).)

Objective: Interest in automatic associations of exercise and physical activity as potential contributors to behavior is rising. However, the measurement of these associations presents a challenge, since the reliability and validity of behavioral tests (despite their widespread usage) is unsatisfactory by most accounts. As a possible alternative, an electroencephalographic (EEG) index (i.e., P3b amplitude) was examined in the present study., Design: We used a mixed-factor design, with one group of insufficiently and one group of sufficiently physically active participants being compared across different experimental conditions., Methods: Thirty-seven insufficiently and thirty-six sufficiently active participants viewed exercise-related images presented within series of negative, neutral, or positive images and rated all images as negative (unpleasant) or positive (pleasant) while EEG recordings were obtained. The amplitude of the P3b component of the EEG-derived event-related potential, time-locked to the onset of exercise images in each context (series), was extracted as the dependent variable., Results: Insufficiently active participants rated the exercise-related images as neutral-to-positive, whereas sufficiently active participants rated the images as positive. However, all participants exhibited the smallest P3b amplitude when the images were presented in the neutral context, suggesting that the images were registering as neutral., Conclusion: Exercise-related images may evoke neutral automatic associations, but these associations may differ from how individuals reflectively rate the same images. P3b amplitude may be useful in detecting such discrepancies and potentially a promising (evidence-based) option for assessing automatic associations of exercise stimuli., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: Diabetic polyneuropathy (DPN) with or without neuropathic pain is a frequent complication of diabetes. This work aimed to determine the prevalence of diabetic polyneuropathy, to describe its epidemiological aspects, and to analyze the therapeutic itinerary of patients with DPN., Methods: This was a cross-sectional, descriptive study performed synchronously over six months at two major follow-up sites for patients with diabetes in Mali. DPN was diagnosed based on the Michigan Neuropathy Screening Instrument (MNSI). The neuropathic nature of the pain and the quality of life of patients were evaluated by the DN4 and the ED-5D scale, respectively. We used three (3) different questionnaires to collect data from patients (one at inclusion and another during the follow-up consultation) and from the caregivers of patients with DPN., Results: We included 252 patients with diabetes, and DPN was found to have a healthcare facility-based prevalence of 69.8% (176/252). The sex ratio was approximately three females for every male patient. The patients were mostly 31 to 60 years of age, 83% had type 2 diabetes, and 86.9% had neuropathic pain Approximately half of the patients (48.3%) had autonomic neuropathy and they reported moderate to intense pain, which was mainly described as a burning sensation. The patients exhibited impaired exteroceptive and proprioceptive sensations in 51.7% of cases. The patients smoked tobacco in 3.4% of cases, while 36.6% of the patients were obese and had dyslipidemia. The caregivers clearly indicated that appropriate medications were not readily accessible or available for their patients with DPN., Conclusion: The healthcare facility-based prevalence of DPN with or without neuropathic pain was high in our cohort. These inexpensive and easy-to-use tools (MNSI, DN4) can be used to adequately diagnose DPN in the African context. In Mali, screening and early treatment of patients at risk of DPN should allow for a reduction of the burden of the disease, while caregivers need to be adequately trained to manage DPN., Competing Interests: The authors have declared that no competing interests exist.

Objective: Having learners practice a motor skill with the expectation of teaching it (versus an expectation of being tested on it) has been revealed to enhance skill learning. However, this improvement in skill performance is lost when the skill must be performed under psychological pressure due to 'choking under pressure.' The present study will investigate whether this choking effect is caused by an accrual of declarative knowledge during skill practice and could be prevented if a technique (analogy instructions) to minimize the accrual of declarative knowledge during practice is employed., Design: We will use a 2 (Expectation: teach/test) x 2 (Instruction: analogy/explicit) x 2 (Posttest: high-pressure/low-pressure) mixed-factor design, with repeated measures on the last factor., Methods: A minimum of 148 participants will be quasi-randomly assigned (based on sex) to one of four groups. Participants in the teach/analogy and teach/explicit groups will practice golf putting with the expectation of teaching putting to another participant, and analogy instructions or explicit instructions, respectively. Participants in the test/analogy and test/explicit groups will practice golf putting with the expectation of being tested on their putting, and analogy instructions or explicit instructions, respectively. The next day all participants will complete low- and high-pressure putting posttests, with their putting accuracy serving as the dependent variable., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 Elsevier Ltd. All rights reserved.)

Delirium is a syndrome characterized by acute brain failure resulting in neurocognitive disturbances affecting attention, awareness, and cognition. It is highly prevalent among critically ill patients and is associated with increased morbidity and mortality. A core domain of delirium is represented by behavioral disturbances in sleep-wake cycle probably related to circadian rhythm disruption. The relationship between sleep, circadian rhythm and intensive care unit (ICU)-acquired delirium is complex and likely bidirectional. In this review, we explore the proposed pathophysiological mechanisms of sleep disruption and circadian dysrhythmia as possible contributing factors in transitioning to delirium in the ICU and highlight some of the most relevant caveats for understanding the relationship between these complex phenomena. Specifically, we will (1) review the physiological consequences of poor sleep quality and efficiency; (2) explore how the neural substrate underlying the circadian clock functions may be disrupted in delirium; (3) discuss the role of sedative drugs as contributors to delirium and chrono-disruption; and, (4) describe the association between abnormal sleep-pathological wakefulness, circadian dysrhythmia, delirium and critical illness. Opportunities to improve sleep and readjust circadian rhythmicity to realign the circadian clock may exist as therapeutic targets in both the prevention and treatment of delirium in the ICU. Further research is required to better define these conditions and understand the underlying physiologic relationship to develop effective prevention and therapeutic strategies., (Copyright © 2020 Daou, Telias, Younes, Brochard and Wilcox.)

Elastomeric chains are widely used by orthodontists for incisor retraction and space closure. However, force degradation and permanent deformation are expected to occur., Objectives: The present study was designed to compare the force degradation of closed, open, grey and transparent power chains from four orthodontic companies (American orthodontics® (AO®), Dentsply®, Ormco® and Rocky Mountain Orthodontics® (RMO®)) over time., Materials and Methods: Universal testing machine was used to measure the force of the power chains elongated to 25mm at 0hours, and after storage in artificial saliva at 24hours, 1 week, 2 weeks, 3 weeks, and 4 weeks. A Tukey's honestly significant difference test was performed., Results: Most of the power chains showed less than 30% of force decay at 24hours of elongation. The AO® transparent open elastomeric chains presented the lowest percentage of force remaining at almost all times: 24hours (58.9%), 1 week (67.7%), 2 weeks (43.2%), 3 weeks (72.4%), and 4 weeks (63%). Most of the power chains had an increase of force measured after 2 weeks of storage in artificial saliva. Three of the sixteen groups (Ormco® grey open, RMO® grey and transparent closed) displayed an increase in the force at 4 weeks of elongation compared to the force registered at 0hours., Conclusion: The results indicated that the force generated by elastomeric chains at 4 weeks remains optimal for a physiologic tooth movement., (Copyright © 2020 CEO. Published by Elsevier Masson SAS. All rights reserved.)

Background: Multiple sclerosis (MS) is the most common immune-mediated inflammatory demyelinating disease of the central nervous system. Multiple brain and spinal tumors have been linked to MS, but a causal relationship between the two has not been determined. Here, we report a case of spinal meningioma in a patient with MS and review literature discussing the possible connection between these two disease entities., Case Description: A 58-year-old female with MS presented with a 1-year history of progressively worsening back pain in conjunction with worsening right upper and lower extremity weakness. The patient was diagnosed with MS 19 months prior and had multiple known demyelinating plaques in her cervical spine. New MRI revealed an intradural extramedullary thoracic tumor with characteristics consistent with meningioma. She underwent T6- T8 laminectomies for tumor resection and pathology confirmed the radiological diagnosis. At 3-month follow- up, the patient reported complete resolution of her back pain and persistence of weakness-related gait issues., Conclusion: CNS neoplasms including meningioma should be considered in MS patients presenting with newly onset neurological symptoms not entirely consistent with demyelinating disease. Both disease processes should be addressed with appropriate long-term follow-up., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Surgical Neurology International.)

Reward positivity (RewP) is an EEG component reflecting reward-prediction errors. Using multilevel models, we measured single-trial RewP amplitude from trial-to-trial, while reward and prediction varied during learning. Sixty participants completed a category-learning task in either engaging or sterile conditions with the RewP time-locked to feedback. Sequential analysis of single-trial RewP showed its relationship to current and previous accuracy, and the probability of changing one's response to subsequent stimuli. Simulations show these effects can be explained in detail by the dynamics of participants' expectations according to principles of reinforcement learning. The single-trial RewP findings were consistent with previous literature linking RewP to reward-prediction error under reinforcement-learning theory. In contrast, the aggregate RewP was unrelated to the engagement manipulation or to delayed retention performance. Thus the present results provide a detailed computational account how RewP relates to acute adaptation, but suggest RewP plays little role in long-term learning., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Introduction: This study aimed to describe the epidemiological, clinical and evolutionary profile of patients treated for tuberculosis at the Regional Hospital of Maradi., Methods: We conducted a retrospective, descriptive and analytical study of data from the medical records of patients treated for tuberculosis from 1 st January 2015 to 31 st December 2017., Results: A total of 595 patients were followed (406 men, 68.24%, and 189 women, 31.76%) with a prevalence of 27,71%. The average age of patients was 42.3 ranging from 13 months to 85 years; 70.5% of these patients were from urban areas. Merchants represented 36.9% of the cases. Bacterial test was positive in 64.7% of cases. Functional signs included: coughing (99.5%), fever (79.5%), and chest pain. Pulmonary tuberculosis represented 78.7% of cases. Therapy was effective in 81.28% of cases. HIV prevalence was 13.6%, lethality 10.42% (40.4% of patients died from TB/HIV co-infection)., Conclusion: Tuberculosis is a scourge in low-income countries, with 10.42% of deaths. HIV/AIDS infection has negatively contributed to these deaths during the study period. The search for comorbidities in any patient with tuberculosis should be systematic in order to improve their global management., Competing Interests: Les auteurs ne déclarent aucun conflit d'intérêts.

When practicing a motor skill, learners who are expecting to teach it to another person exhibit superior gains in skill execution and declarative knowledge. Since skills acquired with large gains in declarative knowledge are highly susceptible to decrement under psychological pressure, it is possible the advantage of expecting to teach is lost when performing the learned skill under pressure. To test this hypothesis, we had 40 participants practice golf putting with the expectation of teaching (teach group) and 42 participants practice with the expectation of being tested (test group). The next day, all participants performed low- and high-pressure posttests. The teach group outperformed the test group under low pressure but not high pressure, where the teach group's performance declined to that of the test group. Further, the teach group reported using more declarative knowledge during the posttests than the test group, but declarative knowledge use did not mediate the performance decline from low- to high-pressure posttest. Taken together, results suggest expecting to teach benefits skill learning, but this advantage is lost when performing the skill under high pressure. However, whether skill breakdown under high pressure is caused by an increase in declarative knowledge use remains an open question. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

: Two laccase-encoding genes from the marine-derived fungus Pestalotiopsis sp. have been cloned in Aspergillus niger for heterologous production, and the recombinant enzymes have been characterized to study their physicochemical properties, their ability to decolorize textile dyes for potential biotechnological applications, and their activity in the presence of sea salt. The optimal pH and temperature of Ps Lac1 and Ps Lac2 differed in relation to the substrates tested, and both enzymes were shown to be extremely stable at temperatures up to 50 °C, retaining 100% activity after 3 h at 50 °C. Both enzymes were stable between pH 4-6. Different substrate specificities were exhibited, and the lowest K m and highest catalytic efficiency values were obtained against syringaldazine and 2,6-dimethoxyphenol (DMP) for Ps Lac1 and Ps Lac2, respectively. The industrially important dyes-Acid Yellow, Bromo Cresol Purple, Nitrosulfonazo III, and Reactive Black 5-were more efficiently decolorized by Ps Lac1 in the presence of the redox mediator 1-hydroxybenzotriazole (HBT). Activities were compared in saline conditions, and Ps Lac2 seemed more adapted to the presence of sea salt than Ps Lac1. The overall surface charges of the predicted Ps Lac three-dimensional models showed large negatively charged surfaces for Ps Lac2, as found in proteins for marine organisms, and more balanced solvent exposed charges for Ps Lac1, as seen in proteins from terrestrial organisms.

Background: 5-Hydroxymethylfurfural (HMF), a major residual component of a lignocellulosic bio-refinery process, can be transformed into fundamental building blocks for green chemistry via oxidation. While chemical methods are well established, interest is also being directed into the enzymatic oxidation of HMF into the bio-plastic precursor 2,5-furandicarboxylic acid (FDCA)., Results: We demonstrate that three glyoxal oxidases ( Pci GLOX) isoenzymes from the Basidiomycete fungus Pycnoporus cinnabarinus were able to oxidize HMF, with Pci GLOX2 and Pci GLOX3 being the most efficient. The major reaction product obtained with the three isoenzymes was 5-hydroxymethyl-2-furancarboxylic (HMFCA), a precursor in polyesters and pharmaceuticals production, and very little subsequent conversion of this compound was observed. However, small concentrations of FDCA, a substitute for terephthalic acid in the production of polyesters, were also obtained. The oxidation of HMF was significantly boosted in the presence of catalase for Pci GLOX2, leading to 70% HMFCA yield. The highest conversion percentages were observed on 2,5-furandicarboxaldehyde (DFF), a minor product from the reaction of Pci GLOX on HMF. To bypass HMFCA accumulation and exploit the efficiency of Pci GLOX in oxidizing DFF and 5-formyl-2-furan carboxylic acid (FFCA) towards FDCA production, HMF was oxidized in a cascade reaction with an aryl alcohol oxidase ( Uma AAO). After 2 h of reaction, Uma AAO completely oxidized HMF to DFF and further to FFCA, with FDCA only being detected when Pci GLOX3 was added to the reaction. The maximum yield of 16% FDCA was obtained 24 h after the addition of Pci GLOX3 in the presence of catalase., Conclusions: At least two conversion pathways for HMF oxidation can be considered for Pci GLOX; however, the highest selectivity was seen towards the production of the valuable polyester precursor HMFCA. The three isoenzymes showed differences in their catalytic efficiencies and substrate specificities when reacted with HMF derivatives., Competing Interests: The authors declare that they have no competing interests.

Past research has revealed practicing and studying a motor skill with the expectation of teaching it to another person increases the amount of time participants spend preparing for movement during practice trials of the skill. However, it is unknown whether the increased motor preparation time explains the benefit of expecting to teach on motor learning. To address this question, we had participants practice golf putting with the expectation of teaching the skill to another participant the following day or the expectation of being tested on the skill the following day. We limited the motor preparation time for half of the participants who expected to teach and half of the participants who expected to test, and allowed the remaining participants to take as much motor preparation time as they liked. All participants were tested on their putting the next day. We predicted that participants who expected to teach would exhibit superior posttest performance, but this benefit would be exclusive to those participants who also practiced with unlimited motor preparation. Although the current data did not support this hypothesis, we also conducted an exploratory analysis in which we aggregated data from two prior experiments. This cumulative analysis suggested that expecting to teach does indeed enhance motor learning, but not through motor preparation during practice., (Copyright © 2018. Published by Elsevier B.V.)

Objectives: The aim of this in vitro study was to assess the dentinal tubule penetration of three different sealers, AH Plus, BC Sealer and a novel tricalcium silicate sealer (NTS)., Materials and Methods: Ninety-six human maxillary central incisors were divided into three experimental groups (n = 32) and were filled with gutta-percha using a single-cone technique in conjunction with one of the three sealers: AH Plus, BC Sealer or NTS. The roots in each group were cross-sectioned at 1 and 5 mm from the root apex, and the surfaces were examined under confocal laser scanning microscopy (CLSM). The sealer penetration depths were measured at their maximum depths and at four circumferential depths (12, 3, 6 and 9 o'clock) and were evaluated using ImageJ software (ImageJ, NIH)., Results: The maximum and mean penetration depths were significantly higher at 5 mm compared to 1 mm from the apex in the AH Plus (p < 0.001), BC Sealer (p < 0.001) and NTS groups (p < 0.001). No significant difference was observed between the groups at 1 mm for both parameters. The maximum and mean penetration depths were significantly lower at 5 mm for AH Plus compared with the other two groups (p = 0.012)., Conclusions: Within the study limitations, the BC Sealer and NTS demonstrated better tubule penetration results than the AH Plus sealer., Clinical Relevance: Although no study has confirmed a relationship between the penetration depth of root canal sealers and the prevention of apical periodontitis, dentinal tubule sealer penetration may improve obturation quality.

Statement of Problem: Data for the color stability of dual-polymerized and light-polymerized resin cements used in esthetic dentistry are lacking., Purpose: The purpose of this in vitro study was to evaluate the color stability of 4 types of composite resin cements after water aging., Material and Methods: Specimens (n=30) of each resin cement (Variolink Esthetic LC, RelyX Ultimate DC, Nexus 3 DC, Nexus 3 LC) were prepared. The shade selected was Light+ for Variolink Esthetic, B 0.5 for RelyX Ultimate, and White for both Nexus 3 DC and LC. All 120 specimens were aged by water for 30 days at 37°C under dark conditions, using a thermocycling machine. The specimens' color characteristics (L*, luminosity; a*, red-green; b*, yellow-blue) and color differences (ΔE) were measured with a spectrophotometer before day 0, after day 1, and after 30 days of immersion. Statistical analysis used ANOVA and Tukey post hoc tests (α=.05)., Results: Considering ΔE<3.3 as clinically acceptable, results showed significant color variations for all cements (RelyX Ultimate=3.69; Nexus 3 LC=3.76; Nexus 3 DC=5.34), except for Variolink Esthetic (0.88). However, this variation was significantly less when day 1 was considered the baseline measurement, showing clinically acceptable ΔE values for all types of cement., Conclusions: Water aging had a significant effect on color stability; most color variations occurred in the first 24 hours of polymerization, with relatively nonsignificant variations afterwards., (Copyright © 2018 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

This study assessed whether a multi-ingredient energy supplement (MIES) could enhance cerebral-cortical activation and cognitive performance during an attention-switching task. Cerebral-cortical activation was recorded in 24 young adults (12 males, 12 females; 22.8 ± 3.8 yrs) via electroencephalography (EEG) both at rest and during the attention-switching task before (pretest) and 30 min after (posttest) consumption of a single serving of a MIES (MIES-1), two servings of a MIES (MIES-2), or a placebo (PL) in a double-blinded, randomized crossover experimental design. EEG upper-alpha power was assessed at rest and during the task, wherein d' (Z[hit rate]-Z[false alarm rate]) and median reaction time (RT) for correct responses to targets on attention-hold and attention-switch trials were analyzed. For both d' and RT, the Session (MIES-1, MIES-2, PL) × Time (pretest, posttest) interaction approached statistical significance (p = .07, η 2 p = 0.106). Exploring these interactions with linear contrasts, a significant linear effect of supplement dose on the linear effect of time was observed (ps ≤.034), suggesting the pretest-to-posttest improvement in sensitivity to task target stimuli (d') and RT increased as a function of supplement dose. With respect to upper-alpha power, the Session × Time interaction was significant (p < .001, η 2 p = 0.422). Exploring this interaction with linear contrasts, a significant linear effect of supplement dose on the linear effect of time was observed (p < .001), suggesting pretest-to-posttest increases in cerebral-cortical activation were a function of supplement dose. In conclusion, our findings suggest that MIES can increase cerebral-cortical activation and RT during task performance while increasing sensitivity to target stimuli in a dose-dependent manner.

Purpose: The aim of this study was to compare and evaluate the retention of two new attachment systems used for implant-supported overdentures subjected to insertion-removal cycles., Materials and Methods: Twenty custom-manufactured polyvinyl chloride models mimicking implant-retained over-dentureresin blocks were fabricated and divided into two groups (n = 10): group 1 ('Kerator' attachment) and group 2 ('EMI' attachment). Each model received two parallel implants (JD evolution®) 20 mm apart and was subjected to cyclic retention forces of 10, 100, 1000, 5000, 10000 and 14600 cycles using a universal testing machine in a 0.9% sodium chloride water solution at 22° C. Data were analyzed using one-way analysis of variance; the level of significance was set at a < 0.05., Results: The 'Kerator' and 'EMI' attachment systems reported a significant decrease in retention (64 and 56.6% respectively) after 14600 insertion-removal cycles (p < 0.001). The 'EMI' attachment showed significant higher loss of retention than the 'Kerator' attachment all along the 14600 cycles (p < 0.05) except for cycles 100 and 5000 (p > 0.05)., Conclusion: Within the limitations of this in vitro study, both attachments reported satisfactory retentive values during the 14600 cycles, the 'Kerator' attachment showed better retention than the new 'EMI' attachment. The initial retentive force of both attachments has gradually decreased., Clinical Significance: Both attachment systems evaluated in this study can be used in clinical practice for implant-supported overdentures.

Recent evidence suggests practicing a motor skill with the expectation of teaching it enhances learning by increasing information processing during motor preparation. However, the specific motor preparatory processes remain unknown. The present study sought to address this shortcoming by employing EEG to assess participants' motor preparatory processes while they completed a golf putting pretest, and then practiced putting with the expectation of (a) teaching another participant how to putt the next day (teach group, n = 30), or (b) being tested on their putting the next day (test group, n = 30). Participants' EEG during the 3-s prior to and 1-s after initiating putter movement was analyzed. All participants completed posttests 1 day after the practice session. The teach group exhibited better posttest performance (superior learning) relative to the test group, but no group differences in motor preparatory processing (EEG) emerged. However, participants in both groups exhibited linear decreases in both theta power at frontal midline and upper-alpha power over motor areas during putt initiation. These results suggest a decrease in working memory and action monitoring (frontal midline theta), and an increase in motor programming (motor upper-alpha) during putt initiation. Further, participants in both groups exhibited increased frontal midline theta from pretest to practice, but decreases in both upper motor-alpha and upper-alpha coherence between left/right temporal and motor planning regions. These results suggest participants utilized working memory and action monitoring to a greater extent during practice relative to pretest, while refining their motor programming and verbal-analytic/visuospatial involvement in motor programming., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Trametes versicolor is a wood-inhabiting agaricomycete known for its ability to cause strong white-rot decay on hardwood and for its high tolerance of phenolic compounds. The goal of the present work was to gain insights into the molecular biology and biochemistry of the heme-including class II and dye-decolorizing peroxidases secreted by this fungus. Proteomic analysis of the secretome of T. versicolor BRFM 1218 grown on oak wood revealed a set of 200 secreted proteins, among which were the dye-decolorizing peroxidase Tv DyP1 and the versatile peroxidase Tv VP2. Both peroxidases were heterologously produced in Escherichia coli , biochemically characterized, and tested for the ability to oxidize complex substrates. Both peroxidases were found to be active against several substrates under acidic conditions, and Tv DyP1 was very stable over a relatively large pH range of 2.0 to 6.0, while Tv VP2 was more stable at pH 5.0 to 6.0 only. The thermostability of both enzymes was also tested, and Tv DyP1 was globally found to be more stable than Tv VP2. After 180 min of incubation at temperatures ranging from 30 to 50°C, the activity of Tv VP2 drastically decreased, with 10 to 30% of the initial activity retained. Under the same conditions, Tv DyP1 retained 20 to 80% of its enzyme activity. The two proteins were catalytically characterized, and Tv VP2 was shown to accept a wider range of reducing substrates than Tv DyP1. Furthermore, both enzymes were found to be active against two flavonoids, quercetin and catechin, found in oak wood, with Tv VP2 displaying more rapid oxidation of the two compounds. They were tested for the ability to decolorize five industrial dyes, and Tv VP2 presented a greater ability to oxidize and decolorize the dye substrates than Tv DyP1. IMPORTANCE Trametes versicolor is a wood-inhabiting agaricomycete known for its ability to cause strong white-rot decay on hardwood and for its high tolerance of phenolic compounds. Among white-rot fungi, the basidiomycete T. versicolor has been extensively studied for its ability to degrade wood, specifically lignin, thanks to an extracellular oxidative enzymatic system. The corresponding oxidative system was previously studied in several works for classical lignin and manganese peroxidases, and in this study, two new components of the oxidative system of T. versicolor , one dye-decolorizing peroxidase and one versatile peroxidase, were biochemically characterized in depth and compared to other fungal peroxidases., (Copyright © 2018 American Society for Microbiology.)

Objective: Minimal invasive endodontics preserve coronal and radicular tooth structure to increase the fracture resistance of teeth. The aim of this study was to assess the influence of final preparation taper on the fracture resistance of maxillary premolars., Materials and Methods: Sixty maxillary premolars were selected and divided into 2 groups: 30 were shaped with a final apical diameter 30 and a 4% taper and 30 with 6% taper using iRaCe ® instrument (FKG dentaire, Switzerland). All root canals were irrigated with sodium hypochlorite and final rinse with ethylenediaminetetraacetic acid. All canals were filled with gutta-percha single-cone filling technique and AHPlus ® sealer (Dentsply- Maillefer, Baillagues, Switzerland) and access cavity restored with resin composite. Roots were wax coated, placed in an acrylic mold and loaded to compressive strength fracture in a mechanical material testing machine recording the maximum load at fracture and fracture pattern (favorable/restorable or unfavorable/unrestorable). Fracture loads were compared statistically, and data examined with Student t -test with a level of significance set at P ≤ 0.05., Results: No statistically significant difference was registered between the 4% taper of preparation (270.47 ± 90.9 N) and 6% taper of preparation (244.73 ± 120.3 N) regarding the fracture resistance of the endodontically treated premolars tested ( P = 0.541), while more favorable restorable fractures were registered in the 4% taper group., Conclusions: Continuous 4% preparation taper did not enhance the fracture resistance of endodontically treated maxillary premolars when compared to a 6% taper root canal preparation. More fractures were registered in the 4% taper group., Competing Interests: There are no conflicts of interest.

Introduction: The brachial plexus consists of the ventral twigs of the last four cervical nerves and the first thoracic nerve. It ensures the motor and sensitive innervations of the thoracic limb., Aim: Our goal was to describe the brachial plexus of the cervical region to the middle third of the arm., Methodology: We conducted a prospective study at the anatomy Laboratory of the Faculty of Medicine and Dentistry in Bamako from September 2016 to October 2017. We dissected the brachial plexus (PB) of 13 fresh adult corpses on both sides. The inclusion criteria were: Fresh adult corpses with cervical regions and brachial without scarring. The injected or scar-carrying corpses were not included in the cervical and brachial regions., Results: Twenty-six brachial plexus of which 18 bp in men and 8 bp in women were dissected. The average age of the subjects was 42 years (extreme: 18 and 70 years). We noted nerve block variations in 3.8%, fascicular in 3.8% and late terminal in 73.1%. The involvement of the anterior branch of the fourth spinal nerve (C4) was found in 46.2%., Conclusion: The brachial plexus is the seat of many anatomical variations whose knowledge is indispensable to treat its lesions., (Le comitée de rédaction se réserve le droit de revoyer aux auteurs avant toute soumission à l'avis des lecteurs les manuscrits qui ne seraient pas conformes à ces modalités de présentation. En outre il leur conseille de sonserver un examplaire du manuscrit, des figures et des tableaux.)

In areas of seasonal malaria transmission, the incidence rate of malaria infection is presumed to be near zero at the end of the dry season. Asymptomatic individuals may constitute a major parasite reservoir during this time. We conducted a longitudinal analysis of the spatio-temporal distribution of clinical malaria and asymptomatic parasitemia over time in a Malian town to highlight these malaria transmission dynamics. For a cohort of 300 rural children followed over 2009-2014, periodicity and phase shift between malaria and rainfall were determined by spectral analysis. Spatial risk clusters of clinical episodes or carriage were identified. A nested-case-control study was conducted to assess the parasite carriage factors. Malaria infection persisted over the entire year with seasonal peaks. High transmission periods began 2-3 months after the rains began. A cluster with a low risk of clinical malaria in the town center persisted in high and low transmission periods. Throughout 2009-2014, cluster locations did not vary from year to year. Asymptomatic and gametocyte carriage were persistent, even during low transmission periods. For high transmission periods, the ratio of asymptomatic to clinical cases was approximately 0.5, but was five times higher during low transmission periods. Clinical episodes at previous high transmission periods were a protective factor for asymptomatic carriage, but carrying parasites without symptoms at a previous high transmission period was a risk factor for asymptomatic carriage. Stable malaria transmission was associated with sustained asymptomatic carriage during dry seasons. Control strategies should target persistent low-level parasitemia clusters to interrupt transmission.

The reflective⁻impulsive model (RIM) has been employed to explain various health behaviors. The present study used RIM to predict a spontaneous physical activity behavior. Specifically, 107 participants (75 females; M age = 20.6 years, SD = 1.92 years) completed measures of (1) reflections about spontaneous physical activity, as indexed by self-report questionnaire; (2) impulse toward physical activity, as indexed by the manikin task; and (3) (state) self-control, as indexed by the Stroop task. The dependent variable was whether participants took the stairs or the elevator to the study laboratory. Results revealed reflections toward spontaneous physical activity positively predicted stair-taking. Further, a significant impulse toward physical activity × self-control interaction was observed. This interaction revealed that participants with high self-control who had a high impulse toward PA were more likely to take the stairs than their counterparts with a low impulse toward PA, whereas the opposite was the case for participants with low self-control. However, the impulse × self-control interaction was not significant when employing a self-report measure of trait self-control. Thus, RIM may be a good framework with which to consider spontaneous physical activity, but careful consideration must be given when examining variables within RIM (e.g., the boundary condition of self-control)., Competing Interests: The authors declare no conflict of interest.

Introduction: The aim of this study was to evaluate the prevalence of musculoskeletal disorders and identify their associated factors among a group of Lebanese dentists., Materials and Methods: A total of 314 Lebanese, dentists completed an anonymous questionnaire that focused on occupational health problems. This study was approved by the ethics committee of Saint-Joseph University of Beirut, Lebanon. The statistical analyses were performed using SPSS for windows. The alpha error was set to 0.05., Results: The mean age of the participants was 39.2 (±11.66) years. The results showed that 61.5% of the surveyed dentists complained of spinal pain: 31.6% of cervical pain, 22.3% of lumbar pain and 13.0% of dorsal pain. Moreover, the pain was continuous in 20.7% and, occasional in 65.8%. Our statistics showed that 7.6% had a problem with the carpal tunnel. A total of 22.3% suffered from tendinitis and 9.2% from arthritis of shoulder, elbow, wrist and hand. The frequency of headaches was 30.6%. Concerning sports activity, 49.7% practiced it occasionally and 3.6% did so frequently., Conclusions: The occurrence of musculoskeletal pain in the upper extremities is a serious concern that affects Lebanese dentists. Most of them often complained of tendinitis and headaches because they do not practice sports; thus, encouraging them to practice sports may reduce or solve such health problems. Issuing brochures that include exercises to perform and hiring trained assistants could help reduce the risk of musculoskeletal disorders. Finally, these occupational health problems should be highlighted at all clinical and research symposia to increase awareness.

H 2 O 2 has been found to be required for the activity of the main microbial enzymes responsible for lignin oxidative cleavage, peroxidases. Along with other small radicals, it is implicated in the early attack of plant biomass by fungi. Among the few extracellular H 2 O 2 -generating enzymes known are the glyoxal oxidases (GLOX). GLOX is a copper-containing enzyme, sharing high similarity at the level of active site structure and chemistry with galactose oxidase. Genes encoding GLOX enzymes are widely distributed among wood-degrading fungi especially white-rot degraders, plant pathogenic and symbiotic fungi. GLOX has also been identified in plants. Although widely distributed, only few examples of characterized GLOX exist. The first characterized fungal GLOX was isolated from Phanerochaete chrysosporium. The GLOX from Utilago maydis has a role in filamentous growth and pathogenicity. More recently, two other glyoxal oxidases from the fungus Pycnoporus cinnabarinus were also characterized. In plants, GLOX from Vitis pseudoreticulata was found to be implicated in grapevine defence mechanisms. Fungal GLOX were found to be activated by peroxidases in vitro suggesting a synergistic and regulatory relationship between these enzymes. The substrates oxidized by GLOX are mainly aldehydes generated during lignin and carbohydrates degradation. The reactions catalysed by this enzyme such as the oxidation of toxic molecules and the production of valuable compounds (organic acids) makes GLOX a promising target for biotechnological applications. This aspect on GLOX remains new and needs to be investigated.

Background: Encoded by the var gene family, highly variable Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP1) proteins mediate tissue-specific cytoadherence of infected erythrocytes, resulting in immune evasion and severe malaria disease. Sequencing and assembling the 40-60 var gene complement for individual infections has been notoriously difficult, impeding molecular epidemiological studies and the assessment of particular var elements as subunit vaccine candidates., Methods: We developed and validated a novel algorithm, Exon-Targeted Hybrid Assembly (ETHA), to perform targeted assembly of var gene sequences, based on a combination of Pacific Biosciences and Illumina data., Results: Using ETHA, we characterized the repertoire of var genes in 12 samples from uncomplicated malaria infections in children from a single Malian village and showed them to be as genetically diverse as vars from isolates from around the globe. The gene var2csa, a member of the var family associated with placental malaria pathogenesis, was present in each genome, as were vars previously associated with severe malaria., Conclusion: ETHA, a tool to discover novel var sequences from clinical samples, will aid the understanding of malaria pathogenesis and inform the design of malaria vaccines based on PfEMP1. ETHA is available at: https://sourceforge.net/projects/etha/ .

The blood-stage malaria vaccine FMP2.1/AS02A, comprised of recombinant Plasmodium falciparum apical membrane antigen 1 (AMA1) and the adjuvant system AS02A, had strain-specific efficacy against clinical malaria caused by P. falciparum with the vaccine strain 3D7 AMA1 sequence. To evaluate a potential correlate of protection, we measured the ability of participant sera to inhibit growth of 3D7 and FVO strains in vitro using high-throughput growth inhibition assay (GIA) testing. Sera from 400 children randomized to receive either malaria vaccine or a control rabies vaccine were assessed at baseline and over two annual malaria transmission seasons after immunization. Baseline GIA against vaccine strain 3D7 and FVO strain was similar in both groups, but more children in the malaria vaccine group than in the control group had 3D7 and FVO GIA activity ≥15% 30 days after the last vaccination (day 90) (49% vs. 16%, p<0.0001; and 71.8% vs. 60.4%, p = 0.02). From baseline to day 90, 3D7 GIA in the vaccine group was 7.4 times the mean increase in the control group (p<0.0001). In AMA1 vaccinees, 3D7 GIA activity subsequently returned to baseline one year after vaccination (day 364) and did not correlate with efficacy in the extended efficacy time period to day 730. In Cox proportional hazards regression models with time-varying covariates, there was a slight suggestion of an association between 3D7 GIA activity and increased risk of clinical malaria between day 90 and day 240. We conclude that vaccination with this AMA1-based malaria vaccine increased inhibition of parasite growth, but this increase was not associated with allele-specific efficacy in the first malaria season. These results provide a framework for testing functional immune correlates of protection against clinical malaria in field trials, and will help to guide similar analyses for next-generation malaria vaccines. Clinical trials registry: This clinical trial was registered on clinicaltrials.gov, registry number NCT00460525.

Introduction: Geophagy or soil eating is mostly described in pregnant women from Sub-Saharan Africa, South America. Here, we report 12 cases of geophagy associated with severe anemia in non-pregnant Nigerian women., Results/case Reports: The median age at diagnosis was 34.5 years. The socioeconomic level was average for all patients. The median hemoglobin level at admission was 6.9g/dL (3.3-8.6), median corpuscular volume was 78.3fL (63-106) and median serum ferritin was 9.2ng/mL (3.6-11.2). The reasons of this practice were "desire" (5/12) and tradition (4/12). All patients received psychotherapy and supplementation with intravenous iron., Conclusion: Geophagy is an underestimated practice in developed countries and in non-pregnant women. It can be the cause of severe iron deficiency and must be discussed in patients with anemia, including non-pregnant patients, and in Africa as well as in migration areas, where the practice can be exported., (Copyright © 2016 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.)

Recent research has revealed that having learners study and practice a motor skill with the expectation of having to teach it enhances motor learning. However, the mechanisms underlying this effect remain unknown. We attempted to replicate this effect and elucidate the mechanisms underlying it. Thus, participants studied golf putting instructions and practiced putting either with the expectation of having to teach another participant how to putt or the expectation of being tested on their putting. During this acquisition phase, participants' motivation, anxiety, and information processing (the duration they took preparing each putt) were indexed as possible mechanisms underlying a motor learning effect. One day and seven days after the acquisition phase, learning was assessed by testing all participants on their golf putting. Results revealed that expecting to teach enhanced motor learning, replicating the original finding. Moreover, expecting to teach increased the duration participants took preparing each putt, which was correlated with superior motor learning. Thus, results suggest expecting to teach enhances motor learning by increasing information processing during practice., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: The safety and immunogenicity of PfAMA1, adjuvanted with Alhydrogel(®) was assessed in malaria-experienced Malian adults. The malaria vaccine, PfAMA1-FVO [25-545] is a recombinant protein Pichia pastoris-expressed AMA-1 from Plasmodium falciparum FVO clone adsorbed to Alhydrogel(®), the control vaccine was tetanus toxoid produced from formaldehyde detoxified and purified tetanus toxin., Methods: A double blind randomized controlled phase 1 study enrolled and followed 40 healthy adults aged 18-55 years in Bandiagara, Mali, West Africa, a rural setting with intense seasonal transmission of P. falciparum malaria. Volunteers were randomized to receive either 50 µg of malaria vaccine or the control vaccine. Three doses of vaccine were given on Days 0, 28 and 56, and participants were followed for 1 year. Solicited symptoms were assessed for seven days and unsolicited symptoms for 28 days after each vaccination. Serious adverse events were assessed throughout the study. The titres of anti-AMA-1 antibodies were measured by ELISA and P. falciparum growth inhibition assays were performed., Results: Commonest local solicited adverse events were the injection site pain and swelling more frequent in the PfAMA1 group. No vaccine related serious adverse events were reported. A significant 3.5-fold increase of anti-AMA-1 IgG antibodies was observed in malaria vaccine recipients four weeks after the third immunization compared to the control group., Conclusion: The PfAMA1 showed a good safety profile. Most adverse events reported were of mild to moderate intensity. In addition, the vaccine induced a significant though short-lived increase in the anti-AMA1 IgG titres. Registered on www.clinicaltrials.gov with the number NCT00431808.

Unlabelled: The genome of the white rot fungus Pycnoporus cinnabarinus includes a large number of genes encoding enzymes implicated in lignin degradation. Among these, three genes are predicted to encode glyoxal oxidase, an enzyme previously isolated from Phanerochaete chrysosporium The glyoxal oxidase of P. chrysosporium is physiologically coupled to lignin-oxidizing peroxidases via generation of extracellular H2O2 and utilizes an array of aldehydes and α-hydroxycarbonyls as the substrates. Two of the predicted glyoxal oxidases of P. cinnabarinus, GLOX1 (PciGLOX1) and GLOX2 (PciGLOX2), were heterologously produced in Aspergillus niger strain D15#26 (pyrG negative) and purified using immobilized metal ion affinity chromatography, yielding 59 and 5 mg of protein for PciGLOX1 and PciGLOX2, respectively. Both proteins were approximately 60 kDa in size and N-glycosylated. The optimum temperature for the activity of these enzymes was 50°C, and the optimum pH was 6. The enzymes retained most of their activity after incubation at 50°C for 4 h. The highest relative activity and the highest catalytic efficiency of both enzymes occurred with glyoxylic acid as the substrate. The two P. cinnabarinus enzymes generally exhibited similar substrate preferences, but PciGLOX2 showed a broader substrate specificity and was significantly more active on 3-phenylpropionaldehyde., Importance: This study addresses the poorly understood role of how fungal peroxidases obtain an in situ supply of hydrogen peroxide to enable them to oxidize a variety of organic and inorganic compounds. This cooperative activity is intrinsic in the living organism to control the amount of toxic H2O2 in its environment, thus providing a feed-on-demand scenario, and can be used biotechnologically to supply a cheap source of peroxide for the peroxidase reaction. The secretion of multiple glyoxal oxidases by filamentous fungi as part of a lignocellulolytic mechanism suggests a controlled system, especially as these enzymes utilize fungal metabolites as the substrates. Two glyoxal oxidases have been isolated and characterized to date, and the differentiation of the substrate specificity of the two enzymes produced by Pycnoporus cinnabarinus illustrates the alternative mechanisms existing in a single fungus, together with the utilization of these enzymes to prepare platform chemicals for industry., (Copyright © 2016 Daou et al.)

Based on Plasmodium falciparum (Pf) apical membrane antigen 1 (AMA1) from strain 3D7, the malaria vaccine candidate FMP2.1/AS02A showed strain-specific efficacy in a Phase 2 clinical trial in 400 Malian children randomized to 3 doses of the AMA1 vaccine candidate or control rabies vaccine on days 0, 30 and 60. A subset of 10 Pf(-) (i.e., no clinical malaria episodes) AMA1 recipients, 11 Pf(+) (clinical malaria episodes with parasites with 3D7 or Fab9-type AMA1 cluster 1 loop [c1L]) AMA1 recipients, and 10 controls were randomly chosen for analysis. Peripheral blood mononuclear cells (PBMCs) isolated on days 0, 90 and 150 were stimulated with full-length 3D7 AMA1 and c1L from strains 3D7 (c3D7) and Fab9 (cFab9). Production of IFN-γ, TNF-α, IL-2, and/or IL-17A was analyzed by flow cytometry. Among AMA1 recipients, 18/21 evaluable samples stimulated with AMA1 demonstrated increased IFN-γ, TNF-α, and IL-2 derived from CD4(+) T cells by day 150 compared to 0/10 in the control group (p<0.0001). Among AMA1 vaccines, CD4(+) cells expressing both TNF-α and IL-2 were increased in Pf(-) children compared to Pf(+) children. When PBMCs were stimulated with c3D7 and cFab9 separately, 4/18 AMA1 recipients with an AMA1-specific CD4(+) response had a significant response to one or both c1L. This suggests that recognition of the AMA1 antigen is not dependent upon c1L alone. In summary, AMA1-specific T cell responses were notably increased in children immunized with an AMA1-based vaccine candidate. The role of CD4(+)TNF-α(+)IL-2(+)-expressing T cells in vaccine-induced strain-specific protection against clinical malaria requires further exploration. Clinicaltrials.gov Identifier: NCT00460525., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objectives: In Niger, 65% of hepatocarcinoma and 75% of cirrhosis cases were due to hepatitis B virus (HBV). We studied the genotypic characteristics of HBsAg in chronically HBV-infected patients in Niamey., Methods: We studied prospectively HBV genotypic patterns among hospitalized patients with HBV infection in the National Hospital of Niamey, Niger. Patients were screened for hepatitis B surface antigen (HBsAg) and HBV genotyping was performed on the HBsAg-positive patients., Results: In this study, we have confirmed the predominance of the HBV genotype E (HBV-E) in Niger and have identified 2 recombinant forms including HBV-E/D and HBV-A3/E reported previously among blood donors in Niger and Ghana, respectively. Amino acid substitutions found in HBV sequences obtained here included P120T, S143L, G145A and A194T. These substitutions were characterized as being associated with modified antigenicity and, notably, with impaired serological detection of HBsAg, while the A194T variant was found to have a controversial role in reduced susceptibility to tenofovir., Conclusions: We have identified two recombinant HBV forms and rare genotypic patterns in Niger that may affect hepatitis B surface antigen antigenicity, and improve current knowledge of epidemiological, clinical and virological patterns of hepatitis B in this country., (Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Malaria is a major public health problem in Niger. The Global Fund to fight AIDS, Tuberculosis, and Malaria launched, in 2011, an initiative entitled "Affordable Medicines Facility - Malaria" or AMFm which aims to make artemisinin-based combination therapies (ACT) more available, more accessible and to eliminate the development of artemisinin resistance. It is in this context that we have conducted a randomized comparative double open-arm study of the efficacy and safety of artemether-lumefantrine (AL) and artesunate-amodiaquine (AM) in Gaya., The objective of the study is to evaluate and then to compare the efficiency and tolerance to these two combinations. The study was modeled with the WHO 2003, 28 days protocol., 370 febrile patients were examined. 159 patients were included, where 79 (49.4%) were put in the AL arm and 81 (50.6%) were placed in the AM arm. The adequate clinical and parasitological response was 94.8% and 97.1% respectively for AL and AM. There was no statistical significant difference in efficiency between the two therapies (P=0.4) . This difference in adverse effects was not statistically significant (P=0.18) . Artemether-lumefantrine and artesunate-amodiaquine are two combinations with comparable efficacies and safety., (Le comitée de rédaction se réserve le droit de revoyer aux auteurs avant toute soumission à l'avis des lecteurs les manuscrits qui ne seraient pas conformes à ces modalités de présentation. En outre il leur conseille de sonserver un examplaire du manuscrit, des figures et des tableaux.)

A longitudinal study was conducted in a low endemic area in northern Tanzania to examine the influence of the α-thalassaemia trait on malaria incidence and antibody responses to malaria apical membrane antigen-1 (AMA-1) and merozoite surface protein1-19 (MSP-119). Out of 394 children genotyped for α-thalassaemia trait, 4.1% (16 of 394) and 30.7% (121 of 394) were homozygous and heterozygous, respectively. During the 1 year follow-up, four incidents of malaria cases were detected without an evident association with α-thalassaemia. Being heterozygous or homozygous for α-thalassaemia was associated with an increased prevalence of antibodies to AMA-1 [odds ratio (OR): 1.83, 95% confidence interval (CI): 1.07-3.12, p = 0.027] and MSP-1 (OR: 2.04, 95% CI: 1.16-3.60, p = 0.013) after adjustment for age and reported bednet use. The observed association between α-thalassaemia and malaria antibody responses may reflect longer-term differences in antigen exposure or differences in antibody acquisition upon exposure in this low endemic setting., (© The Author [2015]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Naturally acquired immunity to clinical malaria is thought to be mainly antibody-mediated, but reports on antigen targets are contradictory. Recognition of multiple antigens may be crucial for protection. In this study, the magnitude of antibody responses and their temporal stability was assessed for a panel of malaria antigens in relation to protection against clinical Plasmodium falciparum malaria., Methods: Malian children aged two to 14 years were enrolled in a longitudinal study and followed up by passive and active case detection for seven months. Plasma was collected at enrolment and at the beginning, in the middle and after the end of the transmission season. Antibody titres to the P. falciparum-antigens apical membrane protein (AMA)-1, merozoite surface protein (MSP)-1₁₉, MSP-3, glutamine-rich protein (GLURP-R0) and circumsporozoite antigen (CSP) were assessed by enzyme-linked immunosorbent assay (ELISA) for 99 children with plasma available at all time points. Parasite carriage was determined by microscopy and nested PCR., Results: Antibody titres to all antigens, except MSP-1₁₉, and the number of antigens recognized increased with age. After malaria exposure, antibody titres increased in children that had low titres at baseline, but decreased in those with high baseline responses. No significant differences were found between antibody titers for individual antigens between children remaining symptomatic or asymptomatic after exposure, after adjustment for age. Instead, children remaining asymptomatic following parasite exposure had a broader repertoire of antigen recognition., Conclusions: The present study provides immune-epidemiological evidence from a limited cohort of Malian children that strong recognition of multiple antigens, rather than antibody titres for individual antigens, is associated with protection from clinical malaria.

Background: The recent decline in malaria incidence in many African countries has been attributed to the provision of prompt and effective anti-malarial treatment using artemisinin-based combination therapy (ACT) and to the widespread distribution of long-lasting, insecticide-treated bed nets (LLINs). At a malaria vaccine-testing site in Bandiagara, Mali, ACT was introduced in 2004, and LLINs have been distributed free of charge since 2007 to infants after they complete the Expanded Programme of Immunization (EPI) schedule and to pregnant women receiving antenatal care. These strategies may have an impact on malaria incidence., Methods: To document malaria incidence, a cohort of 400 children aged 0 to 14 years was followed for three to four years up to July 2013. Monthly cross-sectional surveys were done to measure the prevalence of malaria infection and anaemia. Clinical disease was measured both actively and passively through continuous availability of primary medical care. Measured outcomes included asymptomatic Plasmodium infection, anaemia and clinical malaria episodes., Results: The incidence rate of clinical malaria varied significantly from June 2009 to July 2013 without a clear downward trend. A sharp seasonality in malaria illness incidence was observed with higher clinical malaria incidence rates during the rainy season. Parasite and anaemia point prevalence also showed seasonal variation with much higher prevalence rates during rainy seasons compared to dry seasons., Conclusions: Despite the scaling up of malaria prevention and treatment, including the widespread use of bed nets, better diagnosis and wider availability of ACT, malaria incidence did not decrease in Bandiagara during the study period.

Erythrocyte G6PD deficiency is the most common worldwide enzymopathy. The aim of this study was to determine erythrocyte G6PD deficiency in 3 ethnic groups of Mali and to investigate whether erythrocyte G6PD deficiency was associated to the observed protection against malaria seen in Fulani ethnic group. The study was conducted in two different areas of Mali: in the Sahel region of Mopti where Fulani and Dogon live as sympatric ethnic groups and in the Sudanese savannah area where lives mostly the Malinke ethnic group. The study was conducted in 2007 in Koro and in 2008 in Naguilabougou. It included a total 90 Dogon, 42 Fulani and 80 Malinke ethnic groups. Malaria was diagnosed using microscopic examination after Giemsa-staining of thick and thin blood smear. G6PD deficiency (A-(376/202)) samples were identified using RFLP (Restriction Fragment Length Polymorphism) assay and analysis of PCR-amplified DNA amplicon. G6PD deficiency (A-(376/202)) rate was 11.1%, 2.4%, and 13.3% in Dogon, Fulani, and Malinke ethnic group respectively. Heterozygous state for G6PD (A-(376/202)) was found in 7.8% in Dogon; 2.4% in Fulani and 9.3% in Malinke ethnic groups while hemizygous state was found at the frequency of 2.2% in Dogon and 4% in Malinke. No homozygous state was found in our study population.We conclude that G6PD deficiency is not differing significantly between the three ethnic groups, Fulani, Dogon and Malinke.

Background: The FMP2.1/AS02A candidate malaria vaccine was tested in a Phase 2 study in Mali. Based on results from the first eight months of follow-up, the vaccine appeared well-tolerated and immunogenic. It had no significant efficacy based on the primary endpoint, clinical malaria, but marginal efficacy against clinical malaria in secondary analyses, and high allele-specific efficacy. Extended follow-up was conducted to evaluate extended safety, immunogenicity and efficacy., Methods: A randomized, double-blinded trial of safety, immunogenicity and efficacy of the candidate Plasmodium falciparum apical membrane antigen 1 (AMA1) vaccine FMP2.1/AS02A was conducted in Bandiagara, Mali. Children aged 1-6 years were randomized in a 1∶1 ratio to receive FMP2.1/AS02A or control rabies vaccine on days 0, 30 and 60. Using active and passive surveillance, clinical malaria and adverse events as well as antibodies against P. falciparum AMA1 were monitored for 24 months after the first vaccination, spanning two malaria seasons., Findings: 400 children were enrolled. Serious adverse events occurred in nine participants in the FMP2.1/AS02A group and three in the control group; none was considered related to study vaccination. After two years, anti-AMA1 immune responses remained significantly higher in the FMP2.1/AS02A group than in the control group. For the entire 24-month follow-up period, vaccine efficacy was 7.6% (p = 0.51) against first clinical malaria episodes and 9.9% (p = 0.19) against all malaria episodes. For the final 16-month follow-up period, vaccine efficacy was 0.9% (p = 0.98) against all malaria episodes. Allele-specific efficacy seen in the first malaria season did not extend into the second season of follow-up., Interpretation: Allele-specific vaccine efficacy was not sustained in the second malaria season, despite continued high levels of anti-AMA1 antibodies. This study presents an opportunity to evaluate correlates of partial protection against clinical malaria that waned during the second malaria season., Trial Registration: Clinicaltrials.gov NCT00460525 NCT00460525.

Background: Heterogeneous patterns of malaria transmission are thought to be driven by factors including host genetics, distance to mosquito breeding sites, housing construction, and socio-behavioural characteristics. Evaluation of local transmission epidemiology to characterize malaria risk is essential for planning malaria control and elimination programmes. The use of geographical information systems (GIS) techniques has been a major asset to this approach. To assess time and space distribution of malaria disease in Bandiagara, Mali, within a transmission season, data were used from an ongoing malaria incidence study that enrolled 300 participants aged under six years old"., Methods: Children's households were georeferenced using a handheld global position system. Clinical malaria was defined as a positive blood slide for Plasmodium falciparum asexual stages associated with at least one of the following signs: headache, body aches, fever, chills and weakness. Daily rainfall was measured at the local weather station.Landscape features of Bandiagara were obtained from satellite images and field survey. QGIS™ software was used to map malaria cases, affected and non-affected children, and the number of malaria episodes per child in each block of Bandiagara. Clusters of high or low risk were identified under SaTScan(®) software according to a Bernoulli model., Results: From June 2009 to May 2010, 296 clinical malaria cases were recorded. Though clearly temporally related to the rains, Plasmodium falciparum occurrence persisted late in the dry season. Two "hot spots" of malaria transmission also found, notably along the Yamé River, characterized by higher than expected numbers of malaria cases, and high numbers of clinical episodes per child. Conversely, the north-eastern sector of the town had fewer cases despite its proximity to a large body of standing water which was mosquito habitat., Conclusion: These results confirm the existence of a marked spatial heterogeneity of malaria transmission in Bandiagara, providing support for implementation of targeted interventions.

Fulani of Mali are known for their lower susceptibility to Plasmodium falciparum malaria than their neighbours, the Dogon, despite similar transmission conditions. However, the mechanisms underlying these differences are poorly understood, particularly those concerning antigenspecific immune responses. The Apical Membrane Antigen 1 (AMA1) and the Merozoite Surface Antigen 1 (MSP1) are two malaria vaccine candidates, which play a pivotal role during the invasion of parasites into erythrocytes, and in the case of AMA1, of hepatocytes. Therefore, we analyzed the level of anti-AMA1 and anti-MSP1 antibodies (FVO and 3D7 alleles), by using ELISA (Enzyme Linked Immuno Sorbent Assay) to investigate whether there are differences between the two ethnic groups. Our results show that the splenic rate, the level of anti-AMA1 and anti-MSP1 were significantly higher in Fulani compared to Dogon; while the parasite rate was lower in Fulani group compared to Dogon. Our results suggest that the lower susceptibility of Fulani to malaria could be due to the higher specific humoral responses against AMA1 and MSP 1 in Fulani's ethnic group compared to Dogon.

In Africa, malaria is responsible for 25-40% of all outpatient visits and 20-50% of all hospitalizations. In malaria-endemic areas, individuals do not behave the same toward the outcome of clinical malaria. The aim of this study is to determine the prevalence of malaria in the locality among the different ethnic groups, evaluate the place of malaria among febrile illnesses, and assess the relationship between fever and parasite density of Plasmodium falciparum. Studies on susceptibility to malaria between the Fulani and Dogon groups in Mali were conducted in Mantéourou and the surrounding villages from 1998 to 2008. We carried out six cross-sectional studies during the malaria transmission and longitudinal surveys (July to December depending on the year) during the 10-year duration. In longitudinal studies, clinical data on malaria and other diseases frequently observed in the population were recorded. It appears from this work that malaria is the leading cause of febrile syndromes. We observed a significant reduction in malaria morbidity in the study population from 1998 to 2008. The pyrogenic threshold of parasitaemia was 1,000 parasites/mm(3) of blood in the Dogon and 5,000 parasites/mm(3) of blood in the Fulani.We have also found that high parasitical densities were not always associated with fever. Malaria morbidity was higher among the Dogon than in Fulani. The immunogenetic factors might account for this difference in susceptibility to malaria between Fulani and Dogon in the area under study. With regard to this study, it is important to take into account the ethnic origin of subjects when interpreting data of clinical and malarial vaccine trials.

Studies performed in Burkina Faso and Mali showed differences in susceptibility to malaria between the Fulani and other sympatric ethnic groups, the Mossi and Dogon. We carried out a longitudinal survey and three cross-sectional studies from 2003 to 2005 in order to assess the prevalence of anemia in Dogon and Fulani. The distribution of the study population by sex was comparable between the two ethnic groups (p = ns). The Fulani are mainly cattle breeders and the Dogons, farmers. They were exposed to similar entomological inoculation rates, and studies on "knowledge, attitude, and practices" showed no difference between the two ethnic groups. The cross-sectional studies were performed during the intense malaria transmission season (in September 2003 and 2005) and during the dry season (in March 2004). Longitudinal clinical follow-up studies were performed from August to December 2005 using the WHO 28 days in vivo test, after administration of a curative dose of antimalarial drugs to patients with mild malaria. During the cross-sectional studies, both Fulani men and women had significantly lower hemoglobin levels than their Dogon counterparts; this difference was most evident in the women (in 2005: 9.4 g/dl in Fulani vs 10.7 g/dl in Dogon, p = 0.0002). Clinical longitudinal follow-up data showed that Fulani children aged 10-14 years have lower hemoglobin levels than Dogon children. At day 0, the mean of hemoglobin level was 9.6 g/dl in Dogon children vs. 8.7 g/dl in Fulani children (p = 0.01). At day 28, after malaria treatment, we also observed a significant difference in hemoglobin levels in children (10.6 g/dl in Dogon vs 9.3 g/dl in Fulani, p < 0.001). A stronger association between anemia and spleen enlargement was found in the Fulani (53.2% with spleen enlargement) than in the Dogon (32.9%) [p = 0.005]. The Fulani suffer more from anemia than the Dogon, despite their lower susceptibility to malaria. The difference in anemia between Dogon and Fulani must be further investigated to determine possible factors involved in malaria susceptibility.

Polyparasitism is common in the developing world. We have previously demonstrated that schistosomiasis-positive (SP) Malian children have age-dependent protection from malaria compared to matched schistosomiasis-negative (SN) children. Evidence of durable immunologic memory to malaria antigens is conflicting, particularly in young children and the effect of concomitant schistomiasis upon acquisition of memory is unknown. We examined antigen-specific B memory cell (MBC) frequencies (expressed as percentage of total number of IgG-secreting cells) in 84 Malian children aged 4-14 to malaria blood-stage antigens, apical membrane antigen 1 (AMA-1) and merozoite surface protein 1 (MSP-1) and to schistosomal antigens, Soluble Worm Antigenic Preparation (SWAP) and Schistosoma Egg Antigen (SEA), at a time point during the malaria transmission season and a follow-up dry season visit. We demonstrate, for the first time, MBC responses to S. haematobium antigens in Malian children with urinary egg excretion and provide evidence of seasonal acquisition of immunologic memory, age-associated differences in MBC acquisition, and correlation with circulating S. haematobium antibody. Moreover, the presence of a parasitic co-infection resulted in older children, aged 9-14 years, with underlying S. haematobium infection having significantly more MBC response to malaria antigens (AMA1 and MSP1) than their age-matched SN counterparts. We conclude that detectable MBC response can be measured against both malaria and schistosomal antigens and that the presence of S. haematobium may be associated with enhanced MBC induction in an age-specific manner.

Background: Regulatory T cells (Tregs) suppress host immune responses and participate in immune homeostasis. In co-infection, secondary parasite infections may disrupt the immunologic responses induced by a pre-existing parasitic infection. We previously demonstrated that schistosomiasis-positive (SP) Malian children, aged 4-8 years, are protected against the acquisition of malaria compared to matched schistosomiasis-negative (SN) children., Methods and Findings: To determine if Tregs contribute to this protection, we performed immunologic and Treg depletion in vitro studies using PBMC acquired from children with and without S. haematobium infection followed longitudinally for the acquisition of malaria. Levels of Tregs were lower in children with dual infections compared to children with malaria alone (0.49 versus 1.37%, respectively, P = 0.004) but were similar months later, during a period with negligible malaria transmission. The increased levels of Tregs in SN subjects were associated with suppressed serum Th1 cytokine levels, as well as elevated parasitemia compared to co-infected counterparts., Conclusions: These results suggest that lower levels of Tregs in helminth-infected children correlate with altered circulating cytokine and parasitologic results which may play a partial role in mediating protection against falciparum malaria.

Background: Blood-stage malaria vaccines are intended to prevent clinical disease. The malaria vaccine FMP2.1/AS02(A), a recombinant protein based on apical membrane antigen 1 (AMA1) from the 3D7 strain of Plasmodium falciparum, has previously been shown to have immunogenicity and acceptable safety in Malian adults and children., Methods: In a double-blind, randomized trial, we immunized 400 Malian children with either the malaria vaccine or a control (rabies) vaccine and followed them for 6 months. The primary end point was clinical malaria, defined as fever and at least 2500 parasites per cubic millimeter of blood. A secondary end point was clinical malaria caused by parasites with the AMA1 DNA sequence found in the vaccine strain., Results: The cumulative incidence of the primary end point was 48.4% in the malaria-vaccine group and 54.4% in the control group; efficacy against the primary end point was 17.4% (hazard ratio for the primary end point, 0.83; 95% confidence interval [CI], 0.63 to 1.09; P=0.18). Efficacy against the first and subsequent episodes of clinical malaria, as defined on the basis of various parasite-density thresholds, was approximately 20%. Efficacy against clinical malaria caused by parasites with AMA1 corresponding to that of the vaccine strain was 64.3% (hazard ratio, 0.36; 95% CI, 0.08 to 0.86; P=0.03). Local reactions and fever after vaccination were more frequent with the malaria vaccine., Conclusions: On the basis of the primary end point, the malaria vaccine did not provide significant protection against clinical malaria, but on the basis of secondary results, it may have strain-specific efficacy. If this finding is confirmed, AMA1 might be useful in a multicomponent malaria vaccine. (Funded by the National Institute of Allergy and Infectious Diseases and others; ClinicalTrials.gov number, NCT00460525.).

Background: The full-length (L-) variant of caspase-12 is believed to predispose to sepsis. It has been replaced in the genome of most human populations by the (S-) variant, which leads to premature termination of translation. Strikingly, the L-allele is still widely prevalent in African populations, presumably due to a counterbalancing selective force specific to this continent, for which malaria is a prime candidate., Methods: We investigated associations between caspase-12 genotype and malarial parameters in three West-African populations, in studies encompassing immunological, clinical and obstetric data., Results: The caspase-12 L-allele was found at frequencies of 11-34%. Plasmodium falciparum-stimulated mononuclear cells from S/L heterozygote donors produced stronger interferon-gamma and interleukin-10 responses than S/S homozygotes (p = 0.011 and p = 0.023 in uninfected and infected donors respectively). Nevertheless, we found no association between caspase-12 genotype and either the presentation of severe malaria or individual clinical parameters in sick children. Amongst pregnant women, the caspase-12 genotype did not influence peripheral or placental malaria infection, or basic obstetric parameters. Interestingly, perinatal mortality was more frequent in children of both S/S and L/L than S/L mothers, independent of placental P. falciparum-infection., Conclusion: We find little clinical or epidemiological evidence that malaria has contributed to the persistence of functional caspase-12 in Africa, suggesting either that alternative selective forces are at work or that genetic drift underlies its current global distribution.