Assessing the accuracy of health facility typology in representing the availability of health services: a case study in Mali.

Introduction: Using health facility types as a measure of service availability is a common approach in international standards for health system policy and planning. However, this proxy may not accurately reflect the actual availability of specific health services.

Objective: This study aims to evaluate the reliability of health facility typology as an indicator of specific health service availability and explore whether certain facility types consistently provide particular services.

Mental Health Consultations in Immigration Detention: What Can We Learn From Clinical Records?

Knowledge on mental health consultations in immigration detention and characteristics of people receiving consultations is scarce. Based on a sample of 230 adult men in immigration detention in Switzerland, we aimed to: (1) Quantify the proportion of persons receiving mental health consultations during detention; and (2) Identify socio-demographic and clinical characteristics associated with mental health consultations. Retrospective observational study with a cross-sectional design.

Inappropriate proton-pump inhibitor prescribing in primary care - an observational study with quality circles.

Introduction: Proton-pump inhibitors (PPIs) should be deprescribed when an indication is lacking or the dose is too high. Academic and media reports have tried to raise awareness and thereby reduce the inappropriate prescribing of PPIs. However, pharmacoepidemiologic studies have shown an unchanged frequency of such inappropriate prescribing over time.

Digitally transformed home office impacts on job satisfaction, job stress and job productivity. COVID-19 findings.

In these times of successive lockdown periods due to the health crisis induced by COVID-19, this paper investigates how the usages of collaborative and communication digital tools (groupware, workflow, instant messaging and web conference) are related to the evolution of teleworkers' subjective well-being (job satisfaction, job stress) and job productivity comparing during and before the first lockdown in spring 2020. Using a sample of 438 employees working for firms located in Luxembourg, this analysis enables, first, to highlight different profiles of teleworkers regarding the evolution of usages of these tools during the lockdown compared to before and the frequency of use during. Second, the analysis highlights that these profiles are linked to the evolution of job satisfaction, job stress and job productivity.

Changes to the Aqueous Humor Proteome during Glaucoma.

Purpose: To investigate the aqueous humor proteome in patients with glaucoma and a control group.

Method: Aqueous humor was obtained from five human donors diagnosed with primary open angle glaucoma (POAG) and five age- and sex-matched controls undergoing cataract surgery. Quantitative proteome analysis of the aqueous humor by hyper reaction monitoring mass spectrometry (HRM-MS) based on SWATH technology was performed.

Ebola virus disease in West Africa--the first 9 months of the epidemic and forward projections.

Background: On March 23, 2014, the World Health Organization (WHO) was notified of an outbreak of Ebola virus disease (EVD) in Guinea. On August 8, the WHO declared the epidemic to be a "public health emergency of international concern."

Methods: By September 14, 2014, a total of 4507 probable and confirmed cases, including 2296 deaths from EVD (Zaire species) had been reported from five countries in West Africa--Guinea, Liberia, Nigeria, Senegal, and Sierra Leone.

Immunohistochemical analysis of estrogen receptors in the urethra of sexually intact, ovariectomized, and estrogen-substituted ovariectomized sheep.

Introduction And Hypothesis: Urinary incontinence is prevalent in postmenopausal women and spayed dogs and is associated with decreased estrogen plasma concentrations. The objective of the study was to investigate the expression of estrogen receptors (ER) in the urethra of sexually intact, ovariectomized, and estrogen-substituted ovariectomized ewes.

Methods: Paraffin cross-sections from each urethral quarter were immunohistochemically analyzed.

Single particle tracking of alpha7 nicotinic AChR in hippocampal neurons reveals regulated confinement at glutamatergic and GABAergic perisynaptic sites.

Alpha7 neuronal nicotinic acetylcholine receptors (alpha7-nAChR) form Ca(2+)-permeable homopentameric channels modulating cortical network activity and cognitive processing. They are located pre- and postsynaptically and are highly abundant in hippocampal GABAergic interneurons. It is unclear how alpha7-nAChRs are positioned in specific membrane microdomains, particularly in cultured neurons which are devoid of cholinergic synapses.

Effect on behavior of dental treatment rendered under conscious sedation and general anesthesia in pediatric patients.

Purpose: The purpose of this study was to determine if there were differences in the amount of time it took to exhibit positive behavior following dental treatment under general anesthesia (GA) vs conscious sedation (CS).

Methods: This retrospective study examined charts of a pediatric dental office between 1999 to 2003. Patients presenting before 36 months old for an initial exam who were diagnosed with early childhood caries were included in the study.

Efficient transfection of DNA or shRNA vectors into neurons using magnetofection.

Efficient and long-lasting transfection of primary neurons is an essential tool for addressing many questions in current neuroscience using functional gene analysis. Neurons are sensitive to cytotoxicity and difficult to transfect with most methods. We provide a protocol for transfection of cDNA and RNA interference (short hairpin RNA (shRNA)) vectors, using magnetofection, into rat hippocampal neurons (embryonic day 18/19) cultured for several hours to 21 d in vitro.

Transformation of D-(-)-ribose into a natural product-like scaffold via a Lewis acid catalyzed intramolecular hetero-Diels-Alder reaction.

Starting from D-(-)-ribose, a tricyclic natural product-like scaffold suitable for combinatorial derivatization was synthesized via an intramolecular hetero-Diels-Alder reaction. Lithium perchlorate was found to enhance the reaction rate and, at the same time, had a pronounced influence on the chemoselectivity of the reaction. The stereochemical course of the reaction, however, was not influenced by the Lewis acid.

Tyrosine phosphatases such as SHP-2 act in a balance with Src-family kinases in stabilization of postsynaptic clusters of acetylcholine receptors.

Background: Development of neural networks requires that synapses are formed, eliminated and stabilized. At the neuromuscular junction (NMJ), agrin/MuSK signaling, by triggering downstream pathways, causes clustering and phosphorylation of postsynaptic acetylcholine receptors (AChRs). Postnatally, AChR aggregates are stabilized by molecular pathways that are poorly characterized.

PICK1 interacts with alpha7 neuronal nicotinic acetylcholine receptors and controls their clustering.

Central to synaptic function are protein scaffolds associated with neurotransmitter receptors. Alpha7 neuronal nicotinic acetylcholine receptors (nAChRs) modulate network activity, neuronal survival and cognitive processes in the CNS, but protein scaffolds that interact with these receptors are unknown. Here we show that the PDZ-domain containing protein PICK1 binds to alpha7 nAChRs and plays a role in their clustering.

Regulation of nicotinic acetylcholine receptors by tyrosine kinases in the peripheral and central nervous system: same players, different roles.

Nicotinic acetylcholine receptors (nAChRs) exist in many subtypes and are found in the peripheral and central nervous system where they mediate or modulate synaptic transmission. We review how tyrosine phosphorylation and kinases regulate muscle and neuronal nAChRs. Interestingly, although some of the same kinase players interact with the various receptor subtypes, the functional consequences are different.

Diverse molecular mechanisms involved in AChR deficiency due to rapsyn mutations.

Congenital myasthenic syndromes are inherited disorders of neuromuscular transmission characterized by fatigable muscle weakness. Autosomal recessive acetylcholine receptor (AChR) deficiency syndromes, in which levels of this receptor at the neuromuscular junction are severely reduced, may be caused by mutations within genes encoding the AChR or the AChR-clustering protein, rapsyn. Most patients have mutations within the rapsyn coding region and are either homozygous for N88K or heteroallelic for N88K and a second mutation.

Cholesterol and lipid microdomains stabilize the postsynapse at the neuromuscular junction.

Stabilization and maturation of synapses are important for development and function of the nervous system. Previous studies have implicated cholesterol-rich lipid microdomains in synapse stabilization, but the underlying mechanisms remain unclear. We found that cholesterol stabilizes clusters of synaptic acetylcholine receptors (AChRs) in denervated muscle in vivo and in nerve-muscle explants.

The incommensurately modulated structure of a tricyclic natural-product-like compound of empirical formula C22H20O3.

3,4-Diphenyl-2a,5a,6,7,8,8a,8b-heptahydro-furo[4,3,2-de]chromen-2-one (1) was prepared as part of a project aimed at the synthesis of polycyclic natural-product-like scaffolds. X-ray analysis of crystals grown from ethanol revealed an incommensurately modulated structure. Data include main and satellite reflections up to second order.

Src-family kinases stabilize the neuromuscular synapse in vivo via protein interactions, phosphorylation, and cytoskeletal linkage of acetylcholine receptors.

Postnatal stabilization and maturation of the postsynaptic membrane are important for development and function of the neuromuscular junction (NMJ), but the underlying mechanisms remain poorly characterized. We examined the role of Src-family kinases (SFKs) in vivo. Electroporation of kinase-inactive Src constructs into soleus muscles of adult mice caused NMJ disassembly: acetylcholine receptor (AChR)-rich areas became fragmented; the topology of nerve terminal, AChRs, and synaptic nuclei was disturbed; and occasionally nerves started to sprout.

Alpha7 neuronal nicotinic acetylcholine receptors are negatively regulated by tyrosine phosphorylation and Src-family kinases.

Nicotine, a component of tobacco, is highly addictive but possesses beneficial properties such as cognitive improvements and memory maintenance. Involved in these processes is the neuronal nicotinic acetylcholine receptor (nAChR) alpha7, whose activation triggers depolarization, intracellular signaling cascades, and synaptic plasticity underlying addiction and cognition. It is therefore important to investigate intracellular mechanisms by which a cell regulates alpha7 nAChR activity.

Natural product-like libraries based on non-aromatic, polycyclic motifs.

Diversity-oriented synthesis is an intriguing approach for creating structurally diverse compounds that cover the pharmaceutically relevant chemical space in an optimal way. On the other hand, an over-proportionally large number of drugs or lead structures originate from compounds isolated from natural sources. Thus, not surprisingly, an increasing number of combinatorial libraries are based on motifs resembling natural products.

A single pulse of agrin triggers a pathway that acts to cluster acetylcholine receptors.

Agrin triggers signaling mechanisms of high temporal and spatial specificity to achieve phosphorylation, clustering, and stabilization of postsynaptic acetylcholine receptors (AChRs). Agrin transiently activates the kinase MuSK; MuSK activation has largely vanished when AChR clusters appear. Thus, a tyrosine kinase cascade acts downstream from MuSK, as illustrated by the agrin-evoked long-lasting activation of Src family kinases (SFKs) and their requirement for AChR cluster stabilization.

The postsynaptic submembrane machinery at the neuromuscular junction: requirement for rapsyn and the utrophin/dystrophin-associated complex.

Neuromuscular synapse formation is brought about by a complex bi-directional exchange of information between the innervating motor neuron and its target skeletal muscle fiber. Agrin, a heparin sulfate proteoglycan, is released from the motor nerve terminal to activate its muscle-specific kinase (MuSK) receptor that leads to a second messenger cascade requiring rapsyn to ultimately bring about AChR clustering in the muscle membrane. Rapsyn performs many functions in skeletal muscle.