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We have measured the synaptic properties of a magnetic Josephson junction (MJJ) consisting of a barrier of amorphous Ge containing size-selected Fe nanoclusters between two Nb electrodes. We show that the critical current of the device varies with the magnetic order of the clusters and that the magnetic order can be tuned in a quasi-analog way with short electrical pulses of 16 pJ applied through the device. This is the first demonstration of critical current tuning via magnetic order in a nano-clustered MJJ in a material system other than SiMn. This result eliminates the need for a postdeposition annealing step for synaptic MJJs in neuromorphic applications and opens new options to optimize materials, which has the potential to improve the performance of the MJJs and provide a better understanding of the physics of the device. [ABSTRACT FROM AUTHOR]

Zinc is an essential nutrient--it is stored during periods of excess to promote detoxification and released during periods of deficiency to sustain function. Lysosome-related organelles (LROs) are an evolutionarily conserved site of zinc storage, but mechanisms that control the directional zinc flow necessary for homeostasis are not well understood. In Caenorhabditis elegans intestinal cells, the CDF-2 transporter stores zinc in LROs during excess. Here, we identify ZIPT-2.3 as the transporter that releases zinc during deficiency; ZIPT-2.3 transports zinc, localizes to the membrane of LROs in intestinal cells, and is necessary for zinc release from LROs and survival during zinc deficiency. In zinc excess and deficiency, the expression levels of CDF-2 and ZIPT-2.3 are reciprocally regulated at the level of mRNA and protein, establishing a fundamental mechanism for directional flow to promote homeostasis. To elucidate how the ratio of CDF-2 and ZIPT-2.3 is altered, we used super-resolution microscopy to demonstrate that LROs are composed of a spherical acidified compartment and a hemispherical expansion compartment. The expansion compartment increases in volume during zinc excess and deficiency. These results identify the expansion compartment as an unexpected structural feature of LROs that facilitates rapid transitions in the composition of zinc transporters to mediate homeostasis, likely minimizing the disturbance to the acidified compartment. [ABSTRACT FROM AUTHOR]

Objective: To determine the association between brain MRI abnormalities and incident epilepsy in older adults. Methods: Men and women (ages 45–64 years) from the Atherosclerosis Risk in Communities study were followed up from 1987 to 2018 with brain MRI performed between 2011 and 2013. We identified cases of incident late‐onset epilepsy (LOE) with onset of seizures occurring after the acquisition of brain MRI. We evaluated the relative pattern of cortical thickness, subcortical volume, and white matter integrity among participants with incident LOE after MRI in comparison with participants without seizures. We examined the association between MRI abnormalities and incident LOE using Cox proportional hazards regression. Models were adjusted for demographics, hypertension, diabetes, smoking, stroke, and dementia status. Results: Among 1251 participants with brain MRI data, 27 (2.2%) developed LOE after MRI over a median of 6.4 years (25–75 percentile 5.8–6.9) of follow‐up. Participants with incident LOE after MRI had higher levels of cortical thinning and white matter microstructural abnormalities before seizure onset compared to those without seizures. In longitudinal analyses, greater number of abnormalities was associated with incident LOE after controlling for demographic factors, risk factors for cardiovascular disease, stroke, and dementia (gray matter: hazard ratio [HR]: 2.3, 95% confidence interval [CI]: 1.0–4.9; white matter diffusivity: HR: 3.0, 95% CI: 1.2–7.3). Interpretation: This study demonstrates considerable gray and white matter pathology among individuals with LOE, which is present prior to the onset of seizures and provides important insights into the role of neurodegeneration, both of gray and white matter, and the risk of LOE. [ABSTRACT FROM AUTHOR]

The renin-angiotensin-aldosterone system (RAAS) plays a wellcharacterized role regulating blood pressure in mammals. Pharmacological and genetic manipulation of the RAAS has been shown to extend lifespan in Caenorhabditis elegans, Drosophila and rodents, but its mechanism is not well defined. Here, we investigate the angiotensin-converting enzyme (ACE) inhibitor drug captopril, which extends lifespan inworms andmice. To investigate themechanism, we performed a forward genetic screen for captopril-hypersensitive mutants. We identified a missense mutation that causes a partial loss of function of the daf-2 receptor tyrosine kinase gene, a powerful regulator of aging. The homologous mutation in the human insulin receptor causes Donohue syndrome, establishing thesemutant worms as an invertebrate model of this disease. Captopril functions in C. elegans by inhibiting ACN-1, the worm homolog of ACE. Reducing the activity of acn-1 via captopril or RNA interference promoted dauer larvae formation, suggesting that acn-1 is a daf gene. Captoprilmediated lifespan extension was abrogated by daf-16(lf) and daf-12(lf) mutations. Our results indicate that captopril and acn-1 influence lifespan by modulating dauer formation pathways. We speculate that this represents a conserved mechanism of lifespan control. [ABSTRACT FROM AUTHOR]

Remote voice recording and acoustic analysis allow for comprehensive voice assessment and outcome tracking without the requirements of travel to the clinic, in-person visit, or expensive equipment. This paper delineates the process and considerations for implementing remote voice recording and acoustic analysis in a high-volume university voice clinic. Clinical Focus. Acoustic voice recordings were attempted on 108 unique patients over a 6-month period using a remote voice recording phone application. Development of the clinical process including determining normative data in which to compare acoustic results, clinician training, and clinical application is described. The treating Speech Language Pathologists (SLPs) were surveyed 2 months after implementation to assess ease of application, identify challenges and assess implementation of potential solutions. Of 108 unique patients, 83 patients were successful in completing the process of synchronous remote acoustic voice recording in conjunction with their SLP clinician. The process of downloading the application, setting up, and obtaining voice recordings was most commonly 10-20 minutes according to the 8 SLPs surveyed. Challenges and helpful techniques were identified. Remote acoustic voice recordings have allowed SLPs to continue to complete a comprehensive voice evaluation in a telepractice model. Given emerging knowledge about the viability of remote voice recordings, the success in obtaining acoustic data remotely, and the accessibility of a low-cost app for SLPs makes remote voice recordings a viable option to facilitate remote clinical care and research investigation. [ABSTRACT FROM AUTHOR]

Stroke is a leading cause of disability for persons with stroke (PWS). Difficulty coping with long-term stress for PWS and their caregivers (CG) contributes to their poor health. Variations of chronic-disease self-management programs (CDSMPs) have reduced long-term stress in PWS and CGs. CDSMPs include training for decision-making, problem-solving, resource utilization, peer support, developing a patient–provider relationship, and environmental support. This study examined whether a user-designed stroke camp addressed CDSMP domains, used consistent activities, and decreased stress in PWS and CG. This open cohort survey study followed STROBE guidelines and assessed stress at four timepoints: 1 week before camp, immediately before camp, immediately after camp, and 1 month after camp. Mixed-model analysis examined changes in stress from the two baseline time points to the two post-camp time points. The research team reviewed documents and survey responses to assess activities described in camp documents and CDSMP domains across camps. PWS and CG who attended a camp in 2019. The PWS sample (n = 40) included50% males, aged 1-41-years post stroke, 60% with ischemic, one-third with aphasia, and 37.5% with moderate-severe impairment. CG sample (n = 24) was 60.8% female, aged 65.5 years, and had 7.4 years CG experience. Stress decreased significantly in PWS (Cohen's d = −0.61) and CGs (Cohen's d = −0.87) from pre- to post-camp. Activities addressing all but one CDSMP domains were evident across camps. Stroke camp is a novel model that addresses CDSMP domains, which may reduce stress in PWS and CG. Larger, controlled studies are warranted. [ABSTRACT FROM AUTHOR]

Although human females appear be at a higher risk of concussion and suffer worse outcomes than males, underlying mechanisms remain unclear. With increasing recognition that damage to white matter axons is a key pathologic substrate of concussion, we used a clinically relevant swine model of concussion to explore potential sex differences in the extent of axonal pathologies. At 24 h post-injury, female swine displayed a greater number of swollen axonal profiles and more widespread loss of axonal sodium channels than males. Axon degeneration for both sexes appeared to be related to individual axon architecture, reflected by a selective loss of small caliber axons after concussion. However, female brains had a higher percentage of small caliber axons, leading to more extensive axon loss after injury compared to males. Accordingly, sexual dimorphism in axonal size is associated with more extensive axonal pathology in females after concussion, which may contribute to worse outcomes. [ABSTRACT FROM AUTHOR]

Summary: Longitudinal studies observed that individuals suffering from insomnia disorder have a higher vulnerability to develop symptoms of psychopathology compared with good sleepers. Particularly, insomnia disorder has been associated with an increased risk for depression. Previous studies indicate relatively stable effects; however, replication is needed as the last meta‐analysis on the topic has been published 4 years ago. We conducted a replication of a previous systematic review and meta‐analysis evaluating the longitudinal association between insomnia disorder and psychopathology, including original works published between 2018 and 2022. Literature search was conducted from April 2018 to August 2022 using key words identifying longitudinal studies that evaluate individuals with insomnia disorder compared with good sleepers at baseline, and the onset of all possible mental disorders at long‐term follow‐up. Only one work was added to the previous sample of studies published in 2019 looking at the longitudinal association between insomnia disorder and depression. Meta‐analytic results confirmed the previous observation, with an even higher observed effect for the link between insomnia and depression. This again recognizes insomnia disorder as a possible transdiagnostic process in psychopathology, with consequent important clinical implications. Nevertheless, more longitudinal studies are needed evaluating the link between insomnia disorder and mental disorders. [ABSTRACT FROM AUTHOR]