Partial activation of SIK3 delays the onset of wakefulness and alleviates hypersomnia due to the lack of protein kinase A-phosphorylation site.

Study Objectives: Sleep/wakefulness is regulated by intracellular signaling pathways composed of protein kinases such as salt-inducible kinase 3 (Sik3). Sik3-deficiency in neurons decreases NREM sleep time and electroencephalogram (EEG) delta power during NREM sleep, while Sik3Slp mice lacking a protein kinase A (PKA)-phosphorylation site, S551, show hypersomnia phenotype. In this study, we examined how a phosphomimetic mutation of the 221st threonine residue (T221E), which provides a partial (weak) constitutive activity of the kinase, affects sleep/wakefulness and circadian behavior.

Attitudes toward subsequent primary cancer prevention among survivors of childhood, adolescent, and young adult (CAYA) cancer in Japan: results of a comprehensive questionnaire survey on long-term women's health after CAYA cancer.

Objective: Prevention of subsequent primary cancer (SPC) is crucial for cancer survivors, particularly those who developed the disease during childhood, adolescence, and young adulthood (CAYA). The aim of this study was to assess the current status of SPC prevention among female CAYA cancer survivors.

Methods: A survey regarding long-term health issues after cancer treatment was conducted using questionnaires that targeted women aged ≥20 years who had developed cancer before the age of 40 years.

Frailty Index Based on Common Laboratory Tests for Patients Starting Home-Based Medical Care.

Objectives: To determine whether a Frailty Index based on laboratory tests (FI-lab) is associated with clinical outcomes independently of a standard nonlaboratory Frailty Index (FI-clinical) in older patients starting home-based medical care.

Design: Secondary analysis of data from a multicenter prospective cohort study.

Setting And Participants: Patients aged ≥65 years who were starting home-based medical care services provided by doctors and nurses at Nagoya, Japan.

Objective physical function declines in the absence of subjective physical complaints among patients with amnestic mild cognitive impairments and mild alzheimer's disease.

Purpose: To examine the extent to which patients with amnestic mild cognitive impairment (aMCI) or Alzheimer's disease (AD) perceive their own physical decline.

Methods: This study included 4450 outpatients (1008 normal cognition [NC], 1605 aMCI, and 1837 mild AD) who attended an initial visit to a memory clinic between July 2010 and June 2021. Their physical function was assessed by the Timed Up and Go test, one-leg standing test, and grip strength.

Association of marital relationship with quality of life among older adults with mild cognitive impairment and mild dementia.

The marital relationship is associated with the quality of life among those with cognitive impairment, but sarcopenia status seems to play an important role in the association.

Independent mesenchymal progenitor pools respectively produce and maintain osteogenic and chondrogenic cells in zebrafish.

Skeletal tissues including cartilage and bones are characteristic features of vertebrates that are crucial for supporting body morphology and locomotion. Studies mainly in mice have shown that osteoblasts and chondroblasts are supplied from several progenitors like the sclerotome cells in the embryonic stage, osteo-chondroprogenitors in growing long bones, and skeletal stem cells of bone marrow in the postnatal period. However, the exact origins of progenitor cells, their lineage relationships, and their potential to differentiate into osteoblasts and chondroblasts from embryos to adult tissues are not well understood.

Lateral olfactory tract usher substance (LOTUS), an endogenous Nogo receptor antagonist, ameliorates disease progression in amyotrophic lateral sclerosis model mice.

Nogo-Nogo receptor 1 (NgR1) signaling is significantly implicated in neurodegeneration in amyotrophic lateral sclerosis (ALS). We previously showed that lateral olfactory tract usher substance (LOTUS) is an endogenous antagonist of NgR1 that prevents all myelin-associated inhibitors (MAIs), including Nogo, from binding to NgR1. Here we investigated the role of LOTUS in ALS pathogenesis by analyzing G93A-mutated human superoxide dismutase 1 (SOD1) transgenic (Tg) mice, as an ALS model, as well as newly generated LOTUS-overexpressing SOD1 Tg mice.

RNA Foci in Two bi-Allelic RFC1 Expansion Carriers.

Cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) is a late-onset, autosomal recessive neurodegenerative disorder caused by biallelic AAGGG/ACAGG repeat expansion (AAGGG-exp/ACAGG-exp) in RFC1. The recent identification of patients with CANVAS exhibiting compound heterozygosity for AAGGG-exp and truncating variants supports the loss-of-function of RFC1 in CANVAS patients. We investigated the pathological changes in 2 autopsied patients with CANVAS harboring biallelic ACAGG-exp and AAGGG-exp.

Stent Graft Placement for Injured Visceral Artery.

Injury of the visceral artery is a potentially fatal complication of iatrogenic procedures, trauma, and tumors. A stent graft can achieve rapid exclusion of the injured arterial portion and minimize the risk of ischemic complications by preserving arterial flow to organs. Although various types of stent grafts are available worldwide, Viabahn has only been approved for visceral arterial injury in Japan.

Relationship between cognitive function and phase angle measured with a bioelectrical impedance system.

Purpose: The purpose of this study was to investigate the relationship between cognitive function and phase angle (PhA), an indicator of muscle quality.

Methods: This cross-sectional study enrolled outpatients who visited a memory clinic at the Nagoya University hospital from January 2016 to June 2022. We enrolled 153 participants with body composition measurements.

Relationship Between Non-Cognitive Intrinsic Capacity and Activities of Daily Living According to Alzheimer's Disease Stage.

Background: Few studies have examined the relationship between non-cognitive factors and activities of daily living (ADL) according to Alzheimer's disease (AD) stage.

Objective: We aimed to identify the differences in non-cognitive factors according to AD stages and their involvement in basic and instrumental ADL performance by using intrinsic capacity (IC) in groups with cognition ranging from normal to moderate or severe AD.

Methods: We enrolled 6397 patients aged≥65 years who visited our memory clinic.

The association between early rehabilitation and ambulatory ability at discharge in patients with hip fractures at acute-phase rehabilitation wards: a survey of the Japan Association of Rehabilitation Database.

This study aimed to examine the effectiveness of early rehabilitation in patients with femoral neck fractures admitted to acute care settings in Japan using the data registered with the Japan Association of Rehabilitation Databases (JARD). We included data for 401 patients (out of 3088 patients) aged ≥ 65 years (85 males, 316 females) from nine hospitals who sustained a femoral neck fracture between July 2005 and September 2015. Using the number of days until surgery or the number of days until the start of rehabilitation or both as the explanatory variables, and the indoor mobility at discharge as the outcome variable, we calculated the adjusted rate ratio (ARR) and 95% confidence interval (CI) using Poisson regression analysis (age, sex, cognitive impairment, concurrent symptoms, and previous history of fracture adjusted as covariates).

Intrinsic capacity in acutely hospitalized older adults.

Objectives: We aimed to examine the association between intrinsic capacity (IC) and adverse outcomes of hospitalization.

Design: A prospective observational cohort study.

Setting And Participants: We recruited patients aged 65 years or older who were admitted to the geriatric ward of an acute hospital between Oct 2019 and Sep 2022.

Combined use of the Clinical Frailty Scale and laboratory tests in acutely hospitalized older patients.

Aims: To evaluate the Clinical Frailty Scale (CFS) and a Frailty Index based on laboratory tests (FI-lab) in terms of what each assesses about frailty and to determine the appropriateness of combined use of these two frailty scales.

Methods: This was a prospective observational cohort study in an acute geriatric ward of a university hospital. The FI-lab is the proportion of laboratory parameters that yield abnormal results from a total of 23.

Long-read sequencing revealing intragenic deletions in exome-negative spastic paraplegias.

Hereditary spastic paraplegias (HSPs) are a heterogeneous group of neurodegenerative disorders characterized by progressive spasticity and weakness in the lower extremities. To date, a total of 88 types of SPG are known. To diagnose HSP, multiple technologies, including microarray, direct sequencing, multiplex ligation-dependent probe amplification, and short-read next-generation sequencing, are often chosen based on the frequency of HSP subtypes.

Clinical significance of geriatric conditions in acute hospitalization.

Background: Geriatric conditions (GCs) are common in the elderly population, but their clinical significance in acute care is not well understood. In this study, we first investigated the cross-sectional associations of GCs with frailty and polypharmacy at the time of admission to an acute care geriatric ward. Then, to clarify the clinical significance of GCs in acute care, we prospectively examined the association of GCs with the incidence of hospital-acquired complications and consequences after discharge.

Kinase signalling in excitatory neurons regulates sleep quantity and depth.

Progress has been made in the elucidation of sleep and wakefulness regulation at the neurocircuit level. However, the intracellular signalling pathways that regulate sleep and the neuron groups in which these intracellular mechanisms work remain largely unknown. Here, using a forward genetics approach in mice, we identify histone deacetylase 4 (HDAC4) as a sleep-regulating molecule.

Association between changes in frailty during hospitalization in older adults and 3-month mortality after discharge.

Frailty is a dynamic status that can worsen or improve. However, changes in their frailty status that occur during hospitalization and their significance have not been comprehensively investigated. In this study, we explored the association between such changes and mortality 3 months after discharge in older adults hospitalized for acute care.

Relationship of creatinine cystatin C ratio with muscle mass and grip strength in memory clinic outpatients.

Objectives: The purpose of this study was to examine the relationship of the serum creatinine/cystatin C ratio (CCR) with hand grip strength (HGS), total body muscle mass, trunk muscle mass, and skeletal muscle mass index (SMI) in patients attending a memory clinic.

Design: This cross-sectional study enrolled outpatients of a memory clinic in Japan from October 2010 to July 2017.

Setting And Participants: We enrolled 1945 participants aged 60 years or older with measured skeletal muscle mass, HGS, and serum creatinine and serum cystatin C levels.

Anti-inflammatory effects of siponimod on astrocytes.

Siponimod, which is approved to treat active secondary progressive multiple sclerosis, acts as a functional antagonist of sphingosine-1-phosphate (S1P) receptor 1 (S1P) and an agonist of S1P. S1P antagonization, which inhibits lymphocyte egress from lymphoid tissues and subsequent infiltration into the central nervous system (CNS), is considered the main therapeutic mechanism of siponimod. In addition, siponimod's direct effects on CNS glial cells are another potential neuroprotective mechanism because siponimod can penetrate the blood-brain barrier and CNS glial cells express S1P receptors.

Electrolyte Engineering for Oxygen Evolution Reaction Over Non-Noble Metal Electrodes Achieving High Current Density in the Presence of Chloride Ion.

Direct seawater electrolysis potentially simplifies the electrolysis process and leads to a decrease in the cost of green hydrogen production. However, impurities present in the seawater, especially chloride ions (Cl ), cause corrosion of the electrode material, and its oxidation competes with the anodic oxygen evolution reaction (OER). By carefully tuning electrode substrate and electrolyte solutions, the CoFeO H /Ti electrode with high double-layer capacitance actively and stably electro-catalyzed the OER in potassium borate solutions at pH 9.

Muscle Evaluation and Hospital-Associated Disability in Acute Hospitalized Older Adults.

Objectives: We aimed to examine the association of muscle evaluation, including muscle ultrasound, with hospital-associated disability (HAD), focusing on ADL categories.

Design: A prospective observational cohort study.

Setting And Participants: We recruited patients aged 65 years or older who were admitted to the geriatric ward of an acute hospital between October 2019 and September 2021.