Entomological drivers of uneven malaria transmission in urban lowland areas in Bouaké, Côte d'Ivoire.

BACKGROUND: The use of urban lowlands for agriculture contributes to the food security of city- dwellers, but promotes malaria transmission. The objective of the study was to characterize the entomological drivers of malaria transmission in two lowlands (N'Gattakro and Odiennekourani) in the city of Bouaké, Côte d'Ivoire. METHODS: The human landing catch technique was used to capture mosquitoes in houses located at the edge of two lowlands in Bouaké from February to December 2019. Cultivated surfaces were calculated monthly in both lowlands for each crop type (rice and market gardening) using images acquired by a drone. The different mosquito species were identified morphologically and by PCR analysis for the Anopheles gambiae complex. Anopheles infection by Plasmodium parasites was assessed by quantitative PCR. Mosquito diversity, biting behaviour and rhythmicity, and malaria transmission were determined in each lowland and compared. RESULTS: Anopheles gambiae sensu lato (s.l.) was predominant in N'Gattakro and Culex quinquefasciatus in Odiennekourani. Four Anopheles species were identified: An. gambiae s.l. and Anopheles funestus s.l. in both lowlands, Anopheles pharoensis in N'Gattakro, and Anopheles ziemanni in Odiennekourani. Within the An. gambiae complex, three species were caught: An. gambiae sensu stricto (s.s.), Anopheles coluzzii, and Anopheles arabiensis for the first time in Côte d'Ivoire (30.1%, 69.9% and 0% in N'Gattakro, and 45.1%, 52.6% and 2.4% in Odiennekourani, respectively). Anopheles gambiae s.l. species exhibited a significant exophagic behaviour in N'Gattakro (77.1% of outdoor bites versus 52.2% in Odiennekourani). In N'Gattakro, 12.6% of captures occurred before bedtime (09.00 pm) and after waking up (05.00 am), 15.1% in Odiennekourani. The mean human biting rate was higher in N'Gattakro than in Odiennekourani (61.6 versus 15.5 bites per person per night). Overall, Anopheles infection rate was 0.68%, with 0.539 and 0.029 infected bites per person per night in N'Gattakro and Odiennekourani, respectively. CONCLUSION: The risk of malaria in urban agricultural lowland areas is uneven. The role of agricultural developments and irrigation patterns in the production of larval habitat should be explored. The exophagic behaviour of Anopheles vectors raises the question of the residual transmission that needs to be assessed to implement appropriate control strategies.

Facteurs pronostiques des pneumopathies acquises sous ventilation mécanique en réanimation polyvalente du CHU d'Angre (RCI) / Prognostic factors for pneumopathy acquired under mechanical ventilation in multi-purpose resuscitation at the Angre CHU (RCI)

Objectifs : Identifier les facteurs de mauvais pronostic des pneumopathies acquises sous ventilation mécanique(PAVM) afin d'améliorer leur prise en charge.Patients et methode : Etude prospective, descriptive et analytique portant sur les patients admis en réanimation du CHU d'Angré du 1er novembre 2019 au 31 juillet 2021 et ayant présenté une PAVM.Resultats : Nous avons colligé 43 patients sur 625 admissions soit 6,88%. L'âge moyen était de 49,06 ans. Le sex ratio était de 0,38. Le principal motif d'admission était le coma avec 88,37%. L'HTA et le diabète étaient les principaux antécédents .Les PAVM précoces représentaient 53,49%. Le Klebsiella pneumoniae était le principal germe. Les patients intubés à l'admission représentaient 79,07%. La durée moyenne de ventilation était de 26,95 jours et la durée moyenne d'hospitalisation était de 30,8140 jours. Une antibiothérapie probabiliste a été réalisée chez 75,76% des patients. La mortalité était de 76,74%. Les facteurs de mortalité étaient une durée de ventilation mécanique supérieure à 15 jours et l'âge supérieur à 50 ans.Conclusion :La mortalité secondaire au PAVM demeure élevée. L'identification des deux facteurs pronostiques devrait améliorer la prise en charge ultérieure de tous nouveaux cas

Objectives: To identify the factors of poor prognosis of ventilator-associated lung disease (VAP) in order to improve their management. Patients and method: Prospective, descriptive and analytical study of patients admitted to intensive care at the Angré University Hospital from November 1, 2019 to July 31, 2021 and having presented VAP.Results: We collected 43 patients out of 625 admissions, i.e. 6.88%. The average age was 49.06 years. The sex ratio was 0.38. The main reason for admission was coma with 88.37%. Hypertension and diabetes were the main antecedents. Early VAP accounted for 53.49%. Klebsiella pneumoniae was the main germ. Patients intubated on admission accounted for 79.07%. The average duration of ventilation was 26.95 days and the average duration of hospitalization was 30.8140 days. Probabilistic antibiotic therapy was performed in 75.76% of patients. Mortality was 76.74%. The mortality factors were duration of mechanical ventilation greater than 15 days and age greater than 50 years.Conclusion:Secondary mortality from VAP remains high. The identification of the two prognostic factors should improve the subsequent management of all new cases.

Facteurs de morbidité du syndrome de mal-être post-rachianesthésie / Morbidity factors of post-spinal anesthesia disease syndrome

La pratique de la rachianesthésie est motivée par la qualité de l'analgésie post-opératoire qu'elle procure. Cependant, la rachianesthésie reste comme tout acte médical associée à certains accidents. Méthodes : C'est une étude prospective, descriptive et analytique qui s'est déroulée sur une période d'un (01) mois allant du 07 Mai 2022 au 07 Juin 2022 au CHU d'Angré. Résultats : la rachianesthésie a été réalisée dans 188 des cas, soit un taux de 60% de l'ensemble des interventions. Le sexe ratio était de 0,13 et l'âge moyen était de 33 ± 10 ans. L'antécédent le plus retrouvé était l'HTA. La bupivacaine était le seul anesthésique local utilisé avec comme adjuvant la morphine, le fentanyl ou l'association morphine -fentanyl. Les incidents peropératoires étaient dominés par les troubles hémodynamiques à type d'hypotension artérielle (98,7%) et de bradycardie. Les patients ayant présenté un syndrome de mal être post opératoire représentaient 70,8% de notre effectif. Le Syndrome de Mal Etre post opératoires était dominé par les nausées et vomissements suivis des prurits. Tous les patients ayant présenté un syndrome de mal être post rachianesthésie n'avaient pas bénéficié de prise en charge. La survenue du syndrome de mal être post rachianesthésie était statistiquement associé à la présence de la morphine comme adjuvant (p=0,016). Conclusion : La rachianesthésie est une remarquable technique d'anesthésie. Néanmoins la fréquence des évènements per et post opératoires survenant au décours de cette technique n'est pas négligeable, car ils sont la source d'inconforts notables

Fetal Alcohol Spectrum Disorder and Iron Homeostasis.

Prenatal alcohol exposure results in a spectrum of behavioral, cognitive, and morphological abnormalities collectively referred to as fetal alcohol spectrum disorder (FASD). FASD presents with significant phenotypic variability and may be modified by gestational variables such as maternal nutritional status. Iron serves a critical function in the development of and processes within central nervous system (CNS) structures. Gestational iron deficiency alters CNS development and may contribute to neurodevelopmental impairment in FASD. This review explores the relationship between iron deficiency and fetal alcohol spectrum disorder as described in small animal and human studies. Consideration is given to the pathophysiologic mechanisms linking iron homeostasis and prenatal alcohol exposure. Existing data suggest that iron deficiency contributes to the severity of FASD and provide a mechanistic explanation linking these two conditions.

First detection of the malaria vector Anopheles arabiensis in Côte d'Ivoire: urbanization in question.

BACKGROUND: Previous studies have revealed high malaria transmission in Bouaké, Côte d'Ivoire. The sociopolitical crisis in the country and the resulting environmental changes have raised the need to update existing knowledge on mosquito vector species and malaria transmission. METHODS: Adult mosquitoes were caught using the human landing catch (HLC) sampling method in Bouaké. They were collected in six districts representative of the diversity in urban landscapes. Sampling points were selected along the water network crossing the city and monitored from 2020 to 2021 to detect the presence of anopheline larvae. PCR techniques were used to ascertain the species of the Anopheles gambiae complex, Plasmodium falciparum sporozoite infection in a subset of Anopheles vectors, and insecticide resistance mechanisms in Anopheles arabiensis only. RESULTS: A total of 4599 Anopheles mosquitoes were collected and then identified. Anopheles gambiae sensu lato (s.l.) made up the majority of the whole collection (99%) while Anopheles funestus (0.7%), Anopheles ziemanni (0.2%), Anopheles pharoensis (0.2%) represented the remaining proportion of collection. Among the Anopheles gambiae complex, three species were identified namely An. gambiae sensu stricto (45.9%), Anopheles coluzzii (52.2%), and Anopheles arabiensis (1.9%). The first two species had already been collected in Bouaké, however this is the first time that An. arabiensis is reported in Côte d'Ivoire. Anopheles arabiensis was also collected during the larval surveys in a similar proportion (1.1%) in the same areas as the adults. CONCLUSIONS: This study detected the presence of An. arabiensis for the first time in Côte d'Ivoire. This species was found quite far from its usual geographic area and its expansion could be linked to the urbanization process. Although no An. arabiensis was found to be infected by Plasmodium sp., its role in malaria transmission in Bouaké has to be explored, particularly since its exophagic behaviour raises the issue of control measures and the use of insecticide-impregnated nets. The spread of this species in Côte d'Ivoire should be assessed through further research in additional towns in the country.

HIV-1 gp120-Induced Endolysosome de-Acidification Leads to Efflux of Endolysosome Iron, and Increases in Mitochondrial Iron and Reactive Oxygen Species.

The HIV-1 coat protein gp120 continues to be implicated in the pathogenesis of HIV-1 associated neurocognitive disorder (HAND); a condition known to affect ~50% of people living with HIV-1 (PLWH). Autopsy brain tissues of HAND individuals display morphological changes to mitochondria and endolysosomes, and HIV-1 gp120 causes mitochondrial dysfunction including increased levels of reactive oxygen species (ROS) and de-acidification of endolysosomes. Ferrous iron is linked directly to ROS production, ferrous iron is contained in and released from endolysosomes, and PLWH have elevated iron and ROS levels. Based on those findings, we tested the hypothesis that HIV-1 gp120-induced endolysosome de-acidification and subsequent iron efflux from endolysosomes is responsible for increased levels of ROS. In U87MG glioblastoma cells, HIV-1 gp120 de-acidified endolysosomes, reduced endolysosome iron levels, increased levels of cytosolic and mitochondrial iron, and increased levels of cytosolic and mitochondrial ROS. These effects were all attenuated significantly by the endolysosome-specific iron chelator deferoxamine, by inhibitors of endolysosome-resident two-pore channels and divalent metal transporter-1 (DMT-1), and by inhibitors of mitochondria-resident DMT-1 and mitochondrial permeability transition pores. These results suggest that oxidative stress commonly observed with HIV-1 gp120 is downstream of its ability to de-acidify endolysosomes, to increase the release of iron from endolysosomes, and to increase the uptake of iron into mitochondria. Thus, endolysosomes might represent early and upstream targets for therapeutic strategies against HAND.

Guilt and Burnout in Medical Students.

THEORY: Burnout is prevalent among medical students and is correlated with negative feelings, behaviors, and outcomes. Empathy is a desired trait for medical students that has been correlated with reduced burnout. The concept of guilt is closely related to concern about the well-being of others; therefore, feelings of guilt may be associated with empathy. Excessive guilt poses an increased risk for internalized distress, symptoms such as anhedonia, and may be related to burnout. The relationship between pathogenic guilt and burnout in medical students is unknown. HYPOTHESIS: We hypothesize that pathogenic guilt is present and related to both burnout and empathy in medical students. METHODS: We conducted a cross-sectional survey study of all students in one medical school. Data were collected in February 2020. The Oldenburg Burnout Inventory (OBLI), Toronto Empathy Questionnaire (TEQ), and Interpersonal Guilt Questionaire-67 (IGQ-67) were used. A modified version of IGQ-67 was used to measure four subscales of pathogenic guilt: survival guilt, separation guilt, omnipotence guilt, and self-hate guilt. Data analyses for this study including screening, evaluation of assumptions, descriptive statistics, reliabilities, one-way ANOVA, and correlation coefficients, were conducted using SPSS version 26. RESULTS: Of 300, 168 (56.0%) students participated in the study. Survival, omnipotence, and self-hate classes of pathogenic guilt were positively correlated with burnout. Empathy was correlated with two classes of pathogenic guilt: survival and omnipotence. Empathy was inversely related to burnout (disengagement). CONCLUSIONS: Pathogenic guilt may be a contributor to burnout in medical students. Guilt should be a target of prevention and treatment in burnout in medical students.Supplemental data for this article is available online at https://doi.org/10.1080/10401334.2021.1891544.

[Prognostic factors for pneumopathy acquired under mechanical ventilation in multi-purpose resuscitation at the Angre CHU (RCI)]. / Facteurs pronostiques des pneumopathies acquises sous ventilation mecanique en reanimation polyvalente du CHU D'Angre (RCI).

OBJECTIVES: To identify the factors of poor prognosis of ventilator-associated lung disease (VAP) in order to improve their management. PATIENTS AND METHOD: Prospective, descriptive and analytical study of patients admitted to intensive care at the Angré University Hospital from November 1, 2019 to July 31, 2021 and having presented VAP. RESULTS: We collected 43 patients out of 625 admissions, i.e. 6.88%. The average age was 49.06 years. The sex ratio was 0.38. The main reason for admission was coma with 88.37%. Hypertension and diabetes were the main antecedents. Early VAP accounted for 53.49%. Klebsiella pneumoniae was the main germ. Patients intubated on admission accounted for 79.07%. The average duration of ventilation was 26.95 days and the average duration of hospitalization was 30.8140 days. Probabilistic antibiotic therapy was performed in 75.76% of patients. Mortality was 76.74%. The mortality factors were duration of mechanical ventilation greater than 15 days and age greater than 50 years. CONCLUSION: Secondary mortality from VAP remains high. The identification of the two prognostic factors should improve the subsequent management of all new cases.

OBJECTIFS: Identifier les facteurs de mauvais pronostic des pneumopathies acquises sous ventilation mécanique(PAVM) afin d'améliorer leur prise en charge. PATIENTS ET METHODE: Etude prospective, descriptive et analytique portant sur les patients admis en réanimation du CHU d'Angré du 1er novembre 2019 au 31 juillet 2021 et ayant présenté une PAVM. RESULTATS: Nous avons colligé 43 patients sur 625 admissions soit 6,88%. L'âge moyen était de 49,06 ans. Le sex ratio était de 0,38. Le principal motif d'admission était le coma avec 88,37%. L'HTA et le diabète étaient les principaux antécédents .Les PAVM précoces représentaient 53,49%. Le Klebsiella pneumoniae était le principal germe. Les patients intubés à l'admission représentaient 79,07%. La durée moyenne de ventilation était de 26,95 jours et la durée moyenne d'hospitalisation était de 30,8140 jours. Une antibiothérapie probabiliste a été réalisée chez 75,76% des patients. La mortalité était de 76,74%. Les facteurs de mortalité étaient une durée de ventilation mécanique supérieure à 15 jours et l'âge supérieur à 50 ans. CONCLUSION: La mortalité secondaire au PAVM demeure élevée. L'identification des deux facteurs pronostiques devrait améliorer la prise en charge ultérieure de tous nouveaux cas.

Lysosomal Stress Response (LSR): Physiological Importance and Pathological Relevance.

Extensive work has characterized endoplasmic reticulum (ER) and mitochondrial stress responses. In contrast, very little has been published about stress responses in lysosomes; subcellular acidic organelles that are physiologically important and are of pathological relevance. The greater lysosomal system is dynamic and is comprised of endosomes, lysosomes, multivesicular bodies, autophagosomes, and autophagolysosomes. They are important regulators of cellular physiology, they represent about 5% of the total cellular volume, they are heterogeneous in their sizes and distribution patterns, they are electron dense, and their subcellular positioning within cells varies in response to stimuli, insults and pH. These organelles are also integral to the pathogenesis of lysosomal storage diseases and it is increasingly recognized that lysosomes play important roles in the pathogenesis of such diverse conditions as neurodegenerative disorders and cancer. The purpose of this review is to focus attention on lysosomal stress responses (LSR), compare LSR with better characterized stress responses in ER and mitochondria, and form a framework for future characterizations of LSR. We synthesized data into the concept of LSR and present it here such that the definition of LSR can be modified as new knowledge is added and specific therapeutics are developed.

Antiretroviral Drugs Promote Amyloidogenesis by De-Acidifying Endolysosomes.

Antiretroviral therapeutics (ART) have effectively increased the long-term survival of HIV-1 infected individuals. However, the prevalence of HIV-1 associated neurocognitive disorders (HAND) has increased and so too have clinical manifestations and pathological features of Alzheimer's disease (AD) in people living with HIV-1/AIDS. Although underlying mechanisms are not clear, chronic exposure to ART drugs has been implicated in the development of AD-like symptoms and pathology. ART drugs are categorized according to their mechanism of action in controlling HIV-1 levels. All ART drugs are organic compounds that can be classified as being either weak acids or weak bases, and these physicochemical properties may be of central importance to ART drug-induced AD-like pathology because weak bases accumulate in endolysosomes, weak bases can de-acidify endolysosomes where amyloidogenesis occurs, and endolysosome de-acidification increases amyloid beta (Aß) protein production and decreases Aß degradation. Here, we investigated the effects of ART drugs on endolysosome pH and Aß levels in rat primary cultured neurons. ART drugs that de-acidified endolysosomes increased Aß levels, whereas those that acidified endolysosomes decreased Aß levels. Acidification of endolysosomes with the mucolipin transient receptor potential (TRPML) channel agonist ML-SA1 blocked ART drug-induced increases in Aß levels. Further, ART drug-induced endolysosome de-acidification increased endolysosome sizes; effects that were blocked by ML-SA1-induced endolysosome acidification. These results suggest that ART drug-induced endolysosome de-acidification plays an important role in ART drug-induced amyloidogenesis and that endolysosome acidification might attenuate AD-like pathology in HIV-1 positive people taking ART drugs that de-acidify endolysosomes. Graphical Abstract.

Two-pore channels regulate Tat endolysosome escape and Tat-mediated HIV-1 LTR transactivation.

HIV-1 Tat is essential for HIV-1 replication and appears to play an important role in the pathogenesis of HIV-associated neurological complications. Secreted from infected or transfected cells, Tat has the extraordinary ability to cross the plasma membrane. In the brain, Tat can be taken up by CNS cells via receptor-mediated endocytosis. Following endocytosis and its internalization into endolysosomes, Tat must be released in order for it to activate the HIV-1 LTR promoter and facilitate HIV-1 viral replication in the nucleus. However, the underlying mechanisms whereby Tat escapes endolysosomes remain unclear. Because Tat disrupts intracellular calcium homeostasis, we investigated the involvement of calcium in Tat endolysosome escape and subsequent LTR transactivation. We demonstrated that chelating endolysosome calcium with high-affinity rhodamine-dextran or chelating cytosolic calcium with BAPTA-AM attenuated Tat endolysosome escape and LTR transactivation. Significantly, we demonstrated that pharmacologically blocking and knocking down the endolysosome-resident two-pore channels (TPCs) attenuated Tat endolysosome escape and LTR transactivation. This calcium-mediated effect appears to be selective for TPCs because knocking down TRPML1 calcium channels was without effect. Our findings suggest that calcium released from TPCs is involved in Tat endolysosome escape and subsequent LTR transactivation. TPCs might represent a novel therapeutic target against HIV-1 infection and HIV-associated neurological complications.

Readily Releasable Stores of Calcium in Neuronal Endolysosomes: Physiological and Pathophysiological Relevance.

Neurons are long-lived post-mitotic cells that possess an elaborate system of endosomes and lysosomes (endolysosomes) for protein quality control. Relatively recently, endolysosomes were recognized to contain high concentrations (400-600 µM) of readily releasable calcium. The release of calcium from this acidic organelle store contributes to calcium-dependent processes of fundamental physiological importance to neurons including neurotransmitter release, membrane excitability, neurite outgrowth, synaptic remodeling, and cell viability. Pathologically, disturbances of endolysosome structure and/or function have been noted in a variety of neurodegenerative disorders including Alzheimer's disease (AD) and HIV-1 associated neurocognitive disorder (HAND). And, dysregulation of intracellular calcium has been implicated in the neuropathogenesis of these same neurological disorders. Thus, it is important to better understand mechanisms by which calcium is released from endolysosomes as well as the consequences of such release to inter-organellar signaling, physiological functions of neurons, and possible pathological consequences. In doing so, a path forward towards new therapeutic modalities might be facilitated.

Multi-Fold Enhancement in Compressive Properties of Polystyrene Foam Using Pre-delaminated Stearate Functionalized Layer Double Hydroxides.

Developing an environmentally benign styrene foam is a critical environmental need. Supercritical CO2 use in foams has proven to be a valuable path. Adding fillers to increase bubble nucleation has been pursued concurrently. A prominent filler used is high surface area fillers, such as smectic clays. However, all studies to date show a limit of 152% in compressive moduli and 260% in the compressive stress. The values, even with such gains, limit structural application. A seminal work in 1987 by Suh and Cotton proved that carbonyl linkages in calcium carbonates and CO2 interact and impact nucleation efficiency and performance in supercritical CO2 foams. In this paper, a high surface area clay (layer double hydroxides) which begins in an exfoliated state, then functionalized with a long chain alkyl carboxylate (stearic acid) is synthesized. The result is a remarkable multi-fold improvement to the compressive properties in comparison to polystyrene (PS); a 268% and 512% increase in compressive modulus and strength, respectively. Using a pre-delaminated approach, the higher surface area was achieved in the clays. The presence of the stearate improved the interactions between the clay galleries and PS through hydrophobic-hydrophobic interactions. The glass transition temperature of the nanocomposites was observed to shift to higher values after foaming. The results point to a new path to increase performance using a pre-delaminated clay with functional groups for environmentally benign foams.

BK channels regulate extracellular Tat-mediated HIV-1 LTR transactivation.

HIV-1 Tat is essential for HIV-1 replication and plays an important role in latent HIV-1 infection, HIV-1 associated neurological complication, and other HIV-1 comorbidities. Secreted from HIV-1 infected or transfected cells, Tat can be up-taken into cells by receptor-mediated endocytosis and internalized into endolysosomes. To reach nucleus where it can facilitate HIV-1 viral replication, exogenous Tat has to escape the degradation by endolysosomes. Because of findings that endolysosome de-acidification with, for example, the weak-base anti-malarial drug chloroquine prevents exogenous Tat degradation and enhances the amount of Tat available to activate HIV-1 LTR, we hypothesize that acidifying endolysosomes may enhance Tat degradation in endolysosomes and restrict LTR transactivation. Here, we determined the involvement of endolysosome-resident transient receptor potential mucolipin 1 channel (TRPML1) and the big conductance Ca2+-activated potassium (BK) channel in regulating endolysosome pH, as well as Tat-mediated HIV-1 LTR transactivation in U87MG cells stably integrated with HIV-1 LTR luciferase reporter. Activating TRPML1 channels with ML-SA1 acidified endolysosomes and restricted Tat-mediated HIV-1 LTR transactivation. These effects of ML-SA1 appeared to be mediated through activation of BK channels, because the effects of ML-SA1 on Tat-mediated HIV-1 LTR transactivation were blocked using pharmacological inhibitors or shRNA knock-down of BK channels. On the other hand, activating TRPML1 and BK channels enhanced cellular degradation of exogenous Tat. These results suggest that acidifying endolysosomes by activating TRPML1 or BK channels may provide therapeutic benefit against latent HIV-1 infection, HIV-1 associated neurocognitive disorders, and other HIV-1 comorbidities.

Effects of silica nanoparticles on endolysosome function in primary cultured neurons 1.

Silica nanoparticles (SiNPs) have been used as vehicles for drug delivery, molecular detection, and cellular manipulations in nanoneuromedicine. SiNPs may cause adverse effects in the brain including neurotoxicity, neuroinflammation, neurodegeneration, and enhancing levels of amyloid beta (Aß) protein-all pathological hallmarks of Alzheimer's disease. Therefore, the extent to which SiNPs influence Aß generation and the underlying mechanisms by which this occurs deserve investigation. Our studies were focused on the effects of SiNPs on endolysosomes which uptake, traffic, and mediate the actions of SiNPs. These organelles are also where amyloidogenesis largely originates. We found that SiNPs, in primary cultured hippocampal neurons, accumulated in endolysosomes and caused a rapid and persistent deacidification of endolysosomes. SiNPs significantly reduced endolysosome calcium stores as indicated by a significant reduction in the ability of the lysosomotropic agent glycyl-l-phenylalanine 2-naphthylamide (GPN) to release calcium from endolysosomes. SiNPs increased Aß1-40 secretion, whereas 2 agents that acidified endolysosomes, ML-SA1 and CGS21680, blocked SiNP-induced deacidification and increased generation of Aß1-40. Our findings suggest that SiNP-induced deacidification of and calcium release from endolysosomes might be mechanistically linked to increased amyloidogenesis. The use of SiNPs might not be the best nanomaterial for therapeutic strategies against Alzheimer's disease and other neurological disorders linked to endolysosome dysfunction.

Acidifying Endolysosomes Prevented Low-Density Lipoprotein-Induced Amyloidogenesis.

Cholesterol dyshomeostasis has been linked to the pathogenesis of sporadic Alzheimer's disease (AD). In furthering the understanding of mechanisms by which increased levels of circulating cholesterol augments the risk of developing sporadic AD, others and we have reported that low-density lipoprotein (LDL) enters brain parenchyma by disrupting the blood-brain barrier and that endolysosome de-acidification plays a role in LDL-induced amyloidogenesis in neurons. Here, we tested the hypothesis that endolysosome de-acidification was central to amyloid-ß (Aß) generation and that acidifying endolysosomes protects against LDL-induced increases in Aß levels in neurons. We demonstrated that LDL, but not HDL, de-acidified endolysosomes and increased intraneuronal and secreted levels of Aß. ML-SA1, an agonist of endolysosome-resident TRPML1 channels, acidified endolysosomes, and TRPML1 knockdown attenuated ML-SA1-induced endolysosome acidification. ML-SA1 blocked LDL-induced increases in intraneuronal and secreted levels of Aß as well as Aß accumulation in endolysosomes, prevented BACE1 accumulation in endolysosomes, and decreased BACE1 activity levels. LDL downregulated TRPML1 protein levels, and TRPML1 knockdown worsens LDL-induced increases in Aß. Our findings suggest that endolysosome acidification by activating TRPML1 may represent a protective strategy against sporadic AD.

[Use of the Xpert® MTB/RIF test in routine screening of new cases of pulmonary tuberculosis in an endemic area]. / Test Xpert® MTB/RIF et dépistage des nouveaux cas de tuberculose pulmonaire en routine dans une zone de haute endémicité tuberculeuse.

BACKGROUND: Developed initially for the diagnosis of multidrug-resistant tuberculosis, the Xpert® MTB/RIF test has shown to be useful for the diagnosis of tuberculosis, especially among HIV-infected subjects. The objective of the study was to determine the contribution of the Xpert® MTB/RIF test for routine pulmonary tuberculosis diagnosis in an endemic area. METHODOLOGY: We undertook a prospective study among patients presenting with cough and sputum. The sputum was submitted to microscopic examination, to the Xpert® MTB/RIF test and cultured by the Mycobacteria growth indicator tube (MGIT) technique. The study compared cases of pulmonary tuberculosis confirmed by a positive sputum culture and cases with cough but negative sputum culture. RESULTS: In multivariate analysis, the factors associated with positive cultures were the following: male gender, cough for more than 2 weeks, loss of weight and fever. The estimated clinical suspicion score consisted of 4 signs each having a coefficient of 1. The sensitivity of each clinical sign varied between 79 and 94%. In 348 cases of negative microscopic examination (composed of 295 cases with score<4 and 53 cases with score=4), the predictive positive value of the Xpert® MTB/RIF was 80% for a score equal to 4 and 40.9% for a score<4. In cases of negative microscopic examination of the sputum, the Xpert® MRT/RIF test should be undertaken if the score=4. CONCLUSION: The diagnosis of tuberculosis in endemic zones could be improved by using the Xpert® MTB/RIF.

Water-responsive mechanically adaptive nanocomposites based on styrene-butadiene rubber and cellulose nanocrystals--processing matters.

Biomimetic, stimuli-responsive polymer nanocomposites based on a hydrophobic styrene-butadiene rubber (SBR) matrix and rigid, rod-like cellulose nanocrystals (CNCs) isolated from cotton were prepared by three different approaches, and their properties were studied and related to the composition, processing history, and exposure to water as a stimulus. The first processing approach involved mixing an aqueous SBR latex with aqueous CNC dispersions, and films were subsequently formed by solution-casting. The second method utilized the first protocol, but films were additionally compression-molded. The third method involved the formation of a CNC organogel via a solvent exchange with acetone, followed by infusing this gel, in which the CNCs form a percolating network with solutions of SBR in tetrahydrofuran. The thermomechanical properties of the materials were established by dynamic mechanical thermal analysis (DMTA). In the dry state, all nanocomposites show much higher tensile storage moduli, E', than the neat SBR or the SBR latex. E' increases with the CNC content and depends strongly on the processing method, which appears to influence the morphology of the SBR nanocomposites produced. The highest E' values were observed for the solution cast samples involving an SBR latex, where E' increased from 3 MPa for the neat SBR to ca. 740 MPa for the nanocomposite containing 20% v/v CNCs. Upon submersion in deionized water, a dramatic reduction of E' was observed, for example from 740 to 5 MPa for the solution-cast nanocomposite containing 20% v/v CNCs. This change is interpreted as a disengagement of the percolating CNC network, on account of modest aqueous swelling and competitive hydrogen bonding of water molecules with the CNCs. It is shown that the method of preparation also influenced the swelling behavior and kinetics of modulus switching, consistent with different arrangements of the CNCs, which serve as channels for water absorption and transport within the hydrophobic SBR matrix.

[Prevalence of ketotic hypoglycaemia among schoolchildren in the village of Ahoué in Côte-d'Ivoire]. / Prévalence de l'hypoglycémie cétosique chez les enfants d'âge scolaire dans le village d'Ahoué en Côte-d'Ivoire.

To determine the prevalence of ketotic hypoglycemia among schoolchildren, a descriptive cross-sectional study was conducted in preschools and schools in rural areas that involved 102 schoolchildren, from 4 to 7 years old, comprised 51 girls and 51 boys. Index WHZ was used to evaluate the children's nutritional status. The sampling was obtained by a drop of capillary blood in the pulp of the finger. The determination of glucose was realized by glucose oxidase method using an ultra sensitive and fast (One Touch Ultra) glucometer, and ketonuria was detected by dipstick "Ketodiastix." The clinical results revealed that most of children had a normal birth weight with an average of 2.885 g, a good Apgar's score superior to 7, and then the nutritional index WHZ revealed 3% of severe malnutrition and 34% of moderate malnutrition. Ten children (9.8%) had a hypoglycemia with a median of 0.51 g/l and extreme values going from 0.42 to 0.59 g/l. Seven children had a hypoglycemia associated with ketonuria. The prevalence of ketotic hypoglycemia was 7% in this study, and more frequent in the children between 4 and 5 years with 57% of cases in this age group. Thus, this condition, found in Western countries is a reality in Côte d'Ivoire, where the diathesis of malnutrition (37% of the population of the study) is a favorable factor. Therefore, it is useful to prevent protein-energy malnutrition by a balanced food by avoiding fasting before school by diet management.

The microbiology of Ghanaian cocoa fermentations analysed using culture-dependent and culture-independent methods.

Export of cocoa beans is of great economic importance in Ghana and several other tropical countries. Raw cocoa has an astringent unpleasant taste and a spontaneous fermentation is the first step in a process leading to cocoa beans with the characteristic cocoa flavour and taste. The microbiology of Ghanaian cocoa fermentations was investigated using culture-dependent and culture-independent methods. Samples were collected at 12 hour intervals during 96-144 hour tray and traditional heap fermentations. Yeast, Lactic Acid Bacteria (LAB), Acetic Acid Bacteria (AAB) and Bacillus spp. were enumerated on suitable substrates and identified using phenotypic and molecular methods. The yeast and bacterial micro-populations involved in the cocoa fermentation were further investigated using the culture-independent method Denaturing Gradient Gel Electrophopresis (DGGE). A microbiological succession was observed during the fermentations. At the onset of fermentation yeasts were the dominating microorganisms. Lactic Acid Bacteria became dominant after 12-24 h of fermentation and remained predominant throughout the fermentations with AAB reaching high counts in the mid phase of fermentation. Bacillus spp. were only detected during heap fermentations where they reached high numbers during the later stages of fermentation. Hanseniaspora guilliermondii was the predominant yeast during the initial phase and Pichia membranifaciens during the later phases of fermentation. A number of other yeast species including three putatively undescribed species were isolated during the fermentations. Lactobacillus fermentum was the dominant LAB in most samples. Several other LAB including Lactobacillus plantarum, Leuconostoc pseudomesenteroides, Leuconostoc pseudoficulneum, Pediocococcus acidilactici and a putatively undescribed LAB species were detected during the fermentations. Acetobacter syzygii, Acetobacter pasteurianus and Acetobacter tropicalis were the predominant AAB in all investigated fermentations. During the later stages of heap fermentation Bacillus licheniformis and occasionally other Bacillus spp. were detected in high numbers. In general the culture-based findings were confirmed using DGGE. However, DGGE indicated that Lc. pseudoficulneum plays a more important role during the fermentation of cocoa than expected from the culture-based findings as it yielded a strong band in most DGGE fingerprints. Cluster analysis of the DGGE fingerprints revealed that the DGGE fingerprints clustered according to fermentation site. Within each fermentation site the profiles clustered according to fermentation time. The DGGE method seems to offer a relatively fast and reliable tool for studying yeast and bacterial dynamics during cocoa fermentations.