In the early stages of retinal development, a form of correlated activity known as retinal waves causes periodic depolarizations of immature retinal ganglion cells (RGCs). Retinal waves are crucial for refining visual maps in the brain's retinofugal targets and for the development of retinal circuits underlying feature detection, such as direction selectivity. Yet, how waves alter gene expression in immature RGCs is poorly understood, particularly at the level of the many distinct types of RGCs that underlie the retina's ability to encode diverse visual features.
View Article and Find Full Text PDFContext: Subclinical thyroid dysfunction (ScTD) comprising subclinical hypothyroidism (SHypo) and subclinical hyperthyroidism (SHyper) has been associated with increased risk for cardiovascular events.
Objective: To assess associations between ScTD and cardiovascular risk factors (cvRFs) according to age and sex.
Design And Setting: Pooled individual participant data analysis of large prospective cohort studies from the Thyroid Studies Collaboration.
Patterns of spontaneous neuronal activity instruct the refinement of developing brain circuits.
View Article and Find Full Text PDFBackground: Early identification of child abuse is critical to prevent death and disability. Studies suggest implicit bias of providers may lead to overrepresentation of minority and impoverished children in child abuse reporting. At our institution, universal screening for sexual and physical abuse for all children under 18 years of age was implemented in 2016.
View Article and Find Full Text PDFAn organizational feature of neural circuits is the specificity of synaptic connections. A striking example is the direction-selective (DS) circuit of the retina. There are multiple subtypes of DS retinal ganglion cells (DSGCs) that prefer motion along one of four preferred directions.
View Article and Find Full Text PDFNeurotransmitter release relies on the regulated fusion of synaptic vesicles (SVs) that are tightly packed within the presynaptic bouton of neurons. The mechanism by which SVs are clustered at the presynapse, while preserving their ability to dynamically recycle to support neuronal communication, remains unknown. Synapsin 2a (Syn2a) tetramerization has been suggested as a potential clustering mechanism.
View Article and Find Full Text PDFBackground: Electronic nicotine-delivery systems - also called e-cigarettes - are used by some tobacco smokers to assist with quitting. Evidence regarding the efficacy and safety of these systems is needed.
Methods: In this open-label, controlled trial, we randomly assigned adults who were smoking at least five tobacco cigarettes per day and who wanted to set a quit date to an intervention group, which received free e-cigarettes and e-liquids, standard-of-care smoking-cessation counseling, and optional (not free) nicotine-replacement therapy, or to a control group, which received standard counseling and a voucher, which they could use for any purpose, including nicotine-replacement therapy.
Prior to the onset of vision, neurons in the developing mammalian retina spontaneously fire in correlated activity patterns known as retinal waves. Experimental evidence suggests that retinal waves strongly influence the emergence of sensory representations before visual experience. We aim to model this early stage of functional development by using movies of neurally active developing retinas as pre-training data for neural networks.
View Article and Find Full Text PDFVision begins in the retina, which extracts salient features from the environment and encodes them in the spike trains of retinal ganglion cells (RGCs), the output neurons of the eye. RGC axons innervate diverse brain areas (>50 in mice) to support perception, guide behavior, and mediate influences of light on physiology and internal states. In recent years, complete lists of RGC types (∼45 in mice) have been compiled, detailed maps of their dendritic connections drawn, and their light responses surveyed at scale.
View Article and Find Full Text PDFBackground And Aims: People with familial hypercholesterolaemia are 13 times more likely to develop cardiovascular disease than the general population. However, familial hypercholesterolaemia remains largely underdiagnosed. Tendon xanthoma is a specific clinical feature of familial hypercholesterolaemia and its presence alone implies a probable diagnosis of familial hypercholesterolaemia according to the Dutch Lipid Clinic Network Score (DLCNS).
View Article and Find Full Text PDFBackground: Statin therapy in multimorbid older individuals with polypharmacy is controversial, particularly in primary prevention of cardiovascular disease. Thereby, physicians must weigh potential benefits against potential side effects, drug-drug interactions, and limited life expectancy.
Aim: To assess the prevalence and determinants of potentially inappropriate statin therapy in multimorbid older patients.
Photoisomerization of azobenzenes from their stable isomer to the metastable state is the basis of numerous applications of these molecules. However, this reaction typically requires ultraviolet light, which limits applicability. In this study, we introduce disequilibration by sensitization under confinement (DESC), a supramolecular approach to induce the -to- isomerization by using light of a desired color, including red.
View Article and Find Full Text PDFDuring nervous system development, neurons choose synaptic partners with remarkable specificity; however, the cell-cell recognition mechanisms governing rejection of inappropriate partners remain enigmatic. Here, we show that mouse retinal neurons avoid inappropriate partners by using the FLRT2-uncoordinated-5 (UNC5) receptor-ligand system. Within the inner plexiform layer (IPL), FLRT2 is expressed by direction-selective (DS) circuit neurons, whereas UNC5C/D are expressed by non-DS neurons projecting to adjacent IPL sublayers.
View Article and Find Full Text PDFObjective: To assess how inadequate reporting of cointerventions influences estimated treatment effects in recent cardiovascular trials.
Methods: Medline/Embase were systematically searched from January 1, 2011 to July 1, 2021 for trials evaluating pharmacologic interventions on clinical cardiovascular outcomes published in 5 high-impact journals. Information on adequate vs inadequate reporting of cointerventions, blinding, risk of bias due to deviations of intended interventions (low vs high/some concerns), funding (nonindustry vs industry), design (superiority vs noninferiority), and results were assessed by 2 reviewers.
Background: In multimorbid older patients with type 2 diabetes mellitus (T2DM), the intensity of glucose-lowering medication (GLM) should be focused on attaining a suitable level of glycated hemoglobin (HbA ) while avoiding side effects. We aimed at identifying patients with overtreatment of T2DM as well as associated risk factors.
Methods: In a secondary analysis of a multicenter study of multimorbid older patients, we evaluated HbA levels among patients with T2DM.
Spontaneous activity is a hallmark of developing neural systems. In the retina, spontaneous activity comes in the form of retinal waves, comprised of three stages persisting from embryonic day 16 (E16) to eye opening at postnatal day 14 (P14). Though postnatal retinal waves have been well characterized, little is known about the spatiotemporal properties or the mechanisms mediating embryonic retinal waves, designated stage 1 waves.
View Article and Find Full Text PDFBackground: loss of skeletal muscle function, strength and mass is common in older adults, with important socioeconomic impacts. Subclinical hypothyroidism is common with increasing age and has been associated with reduced muscle strength. Yet, no randomized placebo-controlled trial (RCT) has investigated whether treatment of subclinical hypothyroidism affects muscle function and mass.
View Article and Find Full Text PDFBackground: Fasting is frequently imposed before extubation in patients in intensive care units, with the aim to reduce risk of aspiration. This unevaluated practice might delay extubation, increase workload, and reduce caloric intake. We aimed to compare continued enteral nutrition until extubation with fasting before extubation in patients in the intensive care unit.
View Article and Find Full Text PDFMolecular confinement effects can profoundly alter the physicochemical properties of the confined species. A plethora of organic molecules were encapsulated within the cavities of supramolecular hosts, and the impact of the cavity size and polarity was widely investigated. However, the extent to which the properties of the confined guests can be affected by the symmetry of the cage─which dictates the shape of the cavity─remains to be understood.
View Article and Find Full Text PDFIntroduction: Multimorbidity and polypharmacy are risk factors for drug-related hospital admissions (DRAs) in the ageing population. DRAs caused by medication errors (MEs) are considered potentially preventable. The STOPP/START criteria were developed to detect potential MEs in older people.
View Article and Find Full Text PDFDevelopmental language disorder (DLD) and dyslexia are common but under-identified conditions that affect children's ability to read and comprehend text. Universal screening is a promising solution for improving under-identification of DLD and dyslexia, however, we lack evidence for how to effectively implement and sustain screening procedures in schools. In the current study, we solicited input from educators in the U.
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