Perceptions, attitudes, and willingness of healthcare and frontline workers to participate in an Ebola vaccine trial in Uganda.

Background: Understanding the knowledge, perception and attitudes towards Ebola vaccines is an important factor in ensuring future use of these vaccines. A qualitative methods study embedded in an Ebola vaccine immunogenicity and safety trial (NCT04028349) was conducted to explore the knowledge and perceptions of healthcare (HCWs) and frontline workers (FLWs), about Ebola vaccines and their willingness to participate or recommend participation in Uganda.

Method: We carried out focus group discussions and semi-structured interviews before and after vaccination, with 70 HCWs and FLWs who consented to participate in the trial, and in the qualitative component, from August to September 2019.

Practices and challenges related to antibiotic use in paediatric treatment in hospitals and health centres in Niger and Uganda: a mixed methods study.

Background: Antibiotic resistance is a significant public health problem and is responsible for high mortality in children and new-borns. Strengthening the rational use of antibiotics and improving the quality and access to existing antibiotics are important factors in the fight against antibiotic resistance. This study aims to provide knowledge on the use of antibiotics in children in resource-limited countries in order to identify problems and possible avenues for improvement of antibiotics use.

Juvenile CLN3 disease is a lysosomal cholesterol storage disorder: similarities with Niemann-Pick type C disease.

Background: The most common form of neuronal ceroid lipofuscinosis (NCL) is juvenile CLN3 disease (JNCL), a currently incurable neurodegenerative disorder caused by mutations in the CLN3 gene. Based on our previous work and on the premise that CLN3 affects the trafficking of the cation-independent mannose-6 phosphate receptor and its ligand NPC2, we hypothesised that dysfunction of CLN3 leads to the aberrant accumulation of cholesterol in the late endosomes/lysosomes (LE/Lys) of JNCL patients' brains.

Methods: An immunopurification strategy was used to isolate intact LE/Lys from frozen autopsy brain samples.

Lysosomal phospholipase A2 contributes to the biosynthesis of the atypical late endosome lipid bis(monoacylglycero)phosphate.

The late endosome/lysosome (LE/Lys) lipid bis(monoacylglycero)phosphate (BMP) plays major roles in cargo sorting and degradation, regulation of cholesterol and intercellular communication and has been linked to viral infection and neurodegeneration. Although BMP was initially described over fifty years ago, the enzymes regulating its synthesis remain unknown. The first step in the BMP biosynthetic pathway is the conversion of phosphatidylglycerol (PG) into lysophosphatidylglycerol (LPG) by a phospholipase A2 (PLA2) enzyme.

Triplication of in Alzheimer's Disease Pathology in Down Syndrome.

Down Syndrome (DS), caused by triplication of human chromosome 21 (Hsa21) is the most common form of intellectual disability worldwide. Recent progress in healthcare has resulted in a dramatic increase in the lifespan of individuals with DS. Unfortunately, most will develop Alzheimer's disease like dementia (DS-AD) as they age.

Specific Mutations in the Cholesterol-Binding Site of APP Alter Its Processing and Favor the Production of Shorter, Less Toxic Aβ Peptides.

Excess brain cholesterol is strongly implicated in the pathogenesis of Alzheimer's disease (AD). Here we evaluated how the presence of a cholesterol-binding site (CBS) in the transmembrane and juxtamembrane regions of the amyloid precursor protein (APP) regulates its processing. We generated nine point mutations in the APP gene, changing the charge and/or hydrophobicity of the amino-acids which were previously shown as part of the CBS.

An exploratory qualitative study of caregivers' knowledge, perceptions and practices related to hospital hygiene in rural Niger.

Background: The risk of healthcare-associated infections is exacerbated by poor hygiene practices in health care facilities and can contribute to increased patient morbidity and mortality. In low-income settings, caregivers play a key role in maintaining proper hygiene during inpatient stays. We aimed to explore caregivers' knowledge, perceptions and practices related to hospital hygiene in a rural, sub-Saharan African setting.

Development of a patient rated scale for mental health global state for use during humanitarian interventions.

Objective: We present the results of a cross-cultural validation of the Mental Health Global State (MHGS) scale for adults and adolescents (<14 years old).

Methods: We performed two independent studies using mixed methods among 103 patients in Hebron, Occupied Palestinian Territories and 106 in Cauca, Colombia. The MHGS was analyzed psychometrically, sensitivity and specificity, ability to detect clinically meaningful change, compared to the Clinical Global Impression-Severity scale (CGI-S).

Intrahousehold management and use of nutritional supplements during the hunger gap in Maradi region, Niger: a qualitative study.

Background: Nutritional supplements are used for preventing and treating childhood malnutrition. While there is a growing body of evidence on product efficacy, less emphasis has been placed on how they are perceived and used at the household level. Here, we report on the intrahousehold management of three different supplements (Ready to Use Supplementary food (RUSF), medium quantity lipid-based nutrient supplements (LNS-MQ) and Super Cereal Plus (SC+)) in the region of Maradi (Niger).

Hand hygiene compliance and environmental contamination with gram-negative bacilli in a rural hospital in Madarounfa, Niger.

Background: Healthcare-associated infections pose a major, yet often preventable risk to patient safety. Poor hand hygiene among healthcare personnel and unsanitary hospital environments may contribute to this risk in low-income settings. We aimed to describe hand hygiene behaviour and environmental contamination by season in a rural, sub-Saharan African hospital setting.

A screening tool for psychological difficulties in children aged 6 to 36 months: cross-cultural validation in Kenya, Cambodia and Uganda.

Background: In low-resource settings, the lack of mental health professionals and cross-culturally validated screening instruments complicates mental health care delivery. This is especially the case for very young children. Here, we aimed to develop and cross-culturally validate a simple and rapid tool, the PSYCa 6-36, that can be administered by non-professionals to screen for psychological difficulties among children aged six to 36 months.

Excess Synaptojanin 1 Contributes to Place Cell Dysfunction and Memory Deficits in the Aging Hippocampus in Three Types of Alzheimer's Disease.

The phosphoinositide phosphatase synaptojanin 1 (SYNJ1) is a key regulator of synaptic function. We first tested whether SYNJ1 contributes to phenotypic variations in familial Alzheimer's disease (FAD) and show that SYNJ1 polymorphisms are associated with age of onset in both early- and late-onset human FAD cohorts. We then interrogated whether SYNJ1 levels could directly affect memory.

Cell Size and Growth Rate Are Modulated by TORC2-Dependent Signals.

The size of all cells, from bacteria to vertebrates, is proportional to the growth rate set by nutrient availability, but the underlying mechanisms are unknown. Here, we show that nutrients modulate cell size and growth rate via the TORC2 signaling network in budding yeast. An important function of the TORC2 network is to modulate synthesis of ceramide lipids, which play roles in signaling.

The gender, social and cultural influences on the management and use of unconditional cash transfers in Niger: a qualitative study.

Objective: The current qualitative study aimed to identify gender, social and cultural influences on the management and use of unconditional cash transfers as part of a prospective intervention study in Niger.

Design: In February to March 2012, focus group discussions and semi-structured individual interviews were conducted with female caregivers of children aged 6 to 23 months who received unconditional cash transfers. Discussion and interview transcripts were analysed using content thematic analysis.

Arf6 controls retromer traffic and intracellular cholesterol distribution via a phosphoinositide-based mechanism.

Small GTPases play a critical role in membrane traffic. Among them, Arf6 mediates transport to and from the plasma membrane, as well as phosphoinositide signalling and cholesterol homeostasis. Here we delineate the molecular basis for the link between Arf6 and cholesterol homeostasis using an inducible knockout (KO) model of mouse embryonic fibroblasts (MEFs).

Maternal perception of emotional difficulties of preschool children in rural Niger.

Mental health care for infants and young children is often greatly limited in low-resource settings. The purpose of this study was to describe maternal perception of emotional difficulties of preschool children in a rural area of Niger (Maradi). In this context, both mental health awareness and services were scarce.

[Trauma and resilience among children 3 to 6 years old in three neighborhoods of Port-au-Prince after the 2010 earthquake in Haiti].

Unlabelled: The paper describes an action research for indicative assessment of psychological problems of young children following the 2010 earthquake in Haiti, and the interest of using the Creole version of the questionnaire PSYCa 3-6. The survey took place in Port-au-Prince, and the evaluators were trained to a proper standardized administration of the questionnaire.

Background: The mental health needs of young children in natural disaster contexts often remain unaddressed.

CYP46A1 inhibition, brain cholesterol accumulation and neurodegeneration pave the way for Alzheimer's disease.

Abnormalities in neuronal cholesterol homeostasis have been suspected or observed in several neurodegenerative disorders including Alzheimer's disease, Parkinson's disease and Huntington's disease. However, it has not been demonstrated whether an increased abundance of cholesterol in neurons in vivo contributes to neurodegeneration. To address this issue, we used RNA interference methodology to inhibit the expression of cholesterol 24-hydroxylase, encoded by the Cyp46a1 gene, in the hippocampus of normal mice.

Inhibiting cholesterol degradation induces neuronal sclerosis and epileptic activity in mouse hippocampus.

Elevations in neuronal cholesterol have been associated with several degenerative diseases. An enhanced excitability and synchronous firing in surviving neurons are among the sequels of neuronal death in these diseases and also in some epileptic syndromes. Here, we attempted to increase neuronal cholesterol levels, using a short hairpin RNA to suppress expression of the enzyme cytochrome P450 family 46, subfamily A, polypeptide 1 gene (CYP46A1).

Increasing membrane cholesterol of neurons in culture recapitulates Alzheimer's disease early phenotypes.

Background: It is suspected that excess of brain cholesterol plays a role in Alzheimer's disease (AD). Membrane-associated cholesterol was shown to be increased in the brain of individuals with sporadic AD and to correlate with the severity of the disease. We hypothesized that an increase of membrane cholesterol could trigger sporadic AD early phenotypes.

Reasons for defaulting from drug-resistant tuberculosis treatment in Armenia: a quantitative and qualitative study.

Setting: Armenia, a country with a high prevalence of drug-resistant tuberculosis (DR-TB).

Objective: To identify factors related to default from DR-TB treatment in Yerevan.

Design: Using a retrospective cohort design, we compared defaulters with patients who were cured, completed or failed treatment.

Homodimerization of amyloid precursor protein at the plasma membrane: a homoFRET study by time-resolved fluorescence anisotropy imaging.

Classical FRET (Förster Resonance Energy Transfer) using two fluorescent labels (one for the donor and another one for the acceptor) is not efficient for studying the homodimerization of a protein as only half of the homodimers formed can be identified by this technique. We thus resorted to homoFRET detected by time-resolved Fluorescence Anisotropy IMaging (tr-FAIM). To specifically image the plasma membrane of living cells, an original combination of tr-FAIM and Total Internal Reflection Fluorescence Lifetime Imaging Microscope (TIRFLIM) was implemented.

Time-of-flight secondary ion mass spectrometry (TOF-SIMS) imaging reveals cholesterol overload in the cerebral cortex of Alzheimer disease patients.

Although cholesterol has been involved in the pathophysiology of Alzheimer disease (AD), its distribution in the cerebral cortex over the course of AD is unknown. We describe an original method to quantify cholesterol distribution using time-of-flight secondary ion mass spectrometry imaging. Cholesterol was unevenly distributed along the cortical thickness, being more abundant close to the white matter, in both control and AD cases.