Attention deficit hyperactivity disorder (ADHD) is a diagnosis that describes children and adults who experience significant difficulty with sustained attention and impulse control.In the context of this post, ocular disorders consist of:Amblyopia - more commonly known as “lazy eye” Heterotropia - a deviation of the visual axis of one eye. The most common example is strabismus There have been anecdotal observations that ADHD is more commonly diagnosed in children and adults with ocular disorders. The intent of this post is to collect evidence that either supports or refutes the hypothesis that the incidence and/or prevalence of ADHD is higher in people with ocular disorders.
Since its discovery, the SARS-CoV-2 virus has created a global pandemic of COVID-19. As of August 2 2, 2021, more than 198 million infections were reported worldwide. Typical symptoms include fatigue, fever, cough, and anosmia or dysgeusia. Outbreak management has been hindered by high transmission rates and limitations in testing capacity. Effective public health tools are needed for rapid and early detection. The current diagnostic standard is quantitative real-time polymerase chain reaction (qRT-PCR), but its cost and long turnaround times limit its utility for widespread surveillance. Lack of surveillance has caused severe societal disruption. Rapid antigen tests that permit new cases to isolate immediately can be important surveillance tools. 3 A longitudinal comparison between antigen tests performed at home and qRT-PCR has not previously been performed, to our knowledge. Here, we describe implementation of high-frequency testing using inexpensive, at-home, semiquantitative, direct antigen rapid tests (DARTs) and compare their performance with that of qRT-PCR on self-collected nasal specimens.
Several lines of study suggest that peripheral metabolism of amyloid beta (Aß) is associated with risk for Alzheimer disease (AD). In blood, greater than 90% of Aß is complexed as an apolipoprotein, raising the possibility of a lipoprotein-mediated axis for AD risk. In this study, we report that genetic modification of C57BL/6J mice engineered to synthesise human Aß only in liver (hepatocyte-specific human amyloid (HSHA) strain) has marked neurodegeneration concomitant with capillary dysfunction, parenchymal extravasation of lipoprotein-Aß, and neurovascular inflammation. Moreover, the HSHA mice showed impaired performance in the passive avoidance test, suggesting impairment in hippocampal-dependent learning. Transmission electron microscopy shows marked neurovascular disruption in HSHA mice. This study provides causal evidence of a lipoprotein-Aß /capillary axis for onset and progression of a neurodegenerative process.
Earlier diagnosis of Alzheimer’s disease requires biomarkers sensitive to associated structural and functional changes. While considerable progress has been made in the development of structural biomarkers, functional biomarkers of early cognitive change, unconfounded by effort, practice and level of education, are still needed. We present Fastball, a new EEG method for the passive and objective measurement of recognition memory, that requires no behavioural memory response or comprehension of the task . Younger adults, older adults and Alzheimer’s disease patients (n = 20 per group) completed the Fastball task, lasting just under 3 min. Participants passively viewed rapidly presented images and EEG assessed their automatic ability to differentiate between images based on previous exposure, i.e. old/new. Participants were not instructed to attend to previously seen images and provided no behavioural response. Following the Fastball task, participants completed a two-alternative forced choice (2AFC) task to measure their explicit behavioural recognition of previously seen stimuli. Fastball EEG detected significantly impaired recognition memory in Alzheimer’s disease compared to healthy older adults (P
Several biomarkers of healthy aging have been proposed in recent years, including the epigenetic clocks, based on DNA methylation (DNAm) measures, which are getting increasingly accurate in predicting the individual biological age. The recently developed “next-generation clock” DNAmGrimAge outperforms “first-generation clocks” in predicting longevity and the onset of many age-related pathological conditions and diseases. Additionally, the total number of stochastic epigenetic mutations (SEMs), also known as the epigenetic mutation load (EML), has been proposed as a complementary DNAm-based biomarker of healthy aging. A fundamental biological property of epigenetic, and in particular DNAm modifications, is the potential reversibility of the effect, raising questions about the possible slowdown of epigenetic aging by modifying one's lifestyle. Here, we investigated whether improved dietary habits and increased physical activity have favorable effects on aging biomarkers in healthy postmenopausal women. The study sample consists of 219 women from the “Diet, Physical Activity, and Mammography” (DAMA) study: a 24-month randomized factorial intervention trial with DNAm measured twice, at baseline and the end of the trial. Women who participated in the dietary intervention had a significant slowing of the DNAmGrimAge clock, whereas increasing physical activity led to a significant reduction of SEMs in crucial cancer-related pathways. Our study provides strong evidence of a causal association between lifestyle modification and slowing down of DNAm aging biomarkers. This randomized trial elucidates the causal relationship between lifestyle and healthy aging-related epigenetic mechanisms.
Highlights •Bcl11a is expressed in a subset of murine and human dopaminergic neurons •Bcl11a+ dopaminergic neurons form a highly specific subcircuit in mouse •Bcl11a+ substantia nigra neurons are particularly vulnerable to neurodegeneration •Bcl11a inactivation increases vulnerability and impairs motor behavior in mice Summary Midbrain dopaminergic (mDA) neurons are diverse in their projection targets, effect on behavior, and susceptibility to neurodegeneration. Little is known about the molecular mechanisms establishing this diversity during development. We show that the transcription factor BCL11A is expressed in a subset of mDA neurons in the developing and adult murine brain and in a subpopulation of pluripotent-stem-cell-derived human mDA neurons. By combining intersectional labeling and viral-mediated tracing, we demonstrate that Bcl11a-expressing mDA neurons form a highly specific subcircuit within the murine dopaminergic system. In the substantia nigra, the Bcl11a-expressing mDA subset is particularly vulnerable to neurodegeneration upon α-synuclein overexpression or oxidative stress. Inactivation of Bcl11a in murine mDA neurons increases this susceptibility further, alters the distribution of mDA neurons, and results in deficits in skilled motor behavior. In summary, BCL11A defines mDA subpopulations with highly distinctive characteristics and is required for establishing and maintaining their normal physiology.
Loneliness is a painful condition associated with increased risk for premature mortality. The formation of new, positive social relationships can alleviate feelings of loneliness, but requires rapid trustworthiness decisions during initial encounters and it is still unclear how loneliness hinders interpersonal trust. Here, a multimodal approach including behavioral, psychophysiological, hormonal, and neuroimaging measurements is used to probe a trust-based mechanism underlying impaired social interactions in loneliness. Pre-stratified healthy individuals with high loneliness scores (n = 42 out of a screened sample of 3678 adults) show reduced oxytocinergic and affective responsiveness to a positive conversation, report less interpersonal trust, and prefer larger social distances compared to controls (n = 40). Moreover, lonely individuals are rated as less trustworthy compared to controls and identified by the blinded confederate better than chance. During initial trust decisions, lonely individuals exhibit attenuated limbic and striatal activation and blunted functional connectivity between the anterior insula and occipitoparietal regions, which correlates with the diminished affective responsiveness to the positive social interaction. This neural response pattern is not mediated by loneliness-associated psychological symptoms. Thus, the results indicate compromised integration of trust-related information as a shared neurobiological component in loneliness, yielding a reciprocally reinforced trust bias in social dyads.
Highlights •Relative to mouse counterparts, primate connections are sparse •Primate excitatory neurons receive fewer excitatory and inhibitory inputs •Primate inhibitory neurons have fewer somatic inputs but equivalent shaft inputs •Across species, inhibitory axons have similar innervation properties Summary Detailing how primate and mouse neurons differ is critical for creating generalized models of how neurons process information. We reconstruct 15,748 synapses in adult Rhesus macaques and mice and ask how connectivity differs on identified cell types in layer 2/3 of primary visual cortex. Primate excitatory and inhibitory neurons receive 2–5 times fewer excitatory and inhibitory synapses than similar mouse neurons. Primate excitatory neurons have lower excitatory-to-inhibitory (E/I) ratios than mouse but similar E/I ratios in inhibitory neurons. In both species, properties of inhibitory axons such as synapse size and frequency are unchanged, and inhibitory innervation of excitatory neurons is local and specific. Using artificial recurrent neural networks (RNNs) optimized for different cognitive tasks, we find that penalizing networks for creating and maintaining synapses, as opposed to neuronal firing, reduces the number of connections per node as the number of nodes increases, similar to primate neurons compared with mice.
Intermetallic nanocrystals are a large family of emerging materials with extensive applications in many fields. Yet, a generalized synthetic method for intermetallic nanocrystals is lacking. Here, we report the development of a colloidal synthesis method based on amalgamation of monometallic nanocrystal seeds with low–melting point metals. We use this approach to achieve crystalline and compositionally uniform intermetallic nanocrystals of Au-Ga, Ag-Ga, Cu-Ga, Ni-Ga, Pd-Ga, Pd-In, and Pd-Zn compounds. We demonstrate both compositional tunability across the phase spaces (e.g., AuGa2, AuGa, Au7Ga2, and Ga-doped Au), size tunability (e.g., 14.0-, 7.6-, and 3.8-nm AuGa2), and size uniformity (e.g., 5.4% size deviations). This approach makes it possible to systematically achieve size- and composition-controlled intermetallic nanocrystals, opening up a multitude of possibilities for these materials. Seed amalgamation reaction unlocks a large family of intermetallic nanocrystals with excellent size and composition control. Seed amalgamation reaction unlocks a large family of intermetallic nanocrystals with excellent size and composition control.