BACKGROUND AND PURPOSE: The present study was designed to investigate whether 24 h of SD negatively affects the attention and working memory and increases the serum concentrations of stress hormones, glucose, and inflammatory markers. METHODS: The acute effects of sleep deprivation (SD) on cognition and the stress hormones were evaluated in six healthy volunteers (all men, age 23-27 years). All were good sleepers, had no history of medical or neuropsychiatric diseases, and were not taking any kind of medication. All of the volunteers were subjected to the Continuous Performance Test (CPT) for attention and working memory of cognition and blood tests both before and after 24 h of SD. Electroencephalographic monitoring was performed during the study to confirm the wakefulness of the subjects. RESULTS: SD significantly elevated the serum concentrations of stress hormones (cortisol, epinephrine, and norepinephrine), but serum levels of glucose and inflammatory markers were not changed compared to baseline. For easier steps of the CPT the subjects performed well in giving correct responses after SD; the correct response scores decreased only at the most difficult step of the CPT. However, the subjects performed consistently poor for the error responses at all steps after SD. There was no correlation between the CPT scores and stress hormone levels. CONCLUSIONS: The 24 h of SD significantly heightened the levels of stress hormones and lowered attention and working memory. The acute SD condition seems to render the subject more susceptible to making errors.
Cognition ; Epinephrine ; Glucose ; Hematologic Tests ; Humans ; Male ; Memory, Short-Term ; Sleep Deprivation ; Wakefulness

OBJECTIVE: Early treatment choice is critical in first-episode schizophrenia-spectrum disorders. The purpose of this study was to describe prescribing trends of antipsychotics use in patients with first-episode schizophrenia in 2005 and 2010, respectively. METHODS: We reviewed the medical records of newly treated patients with schizophrenia from a university psychiatric hospital in 2005 (n=47) and 2010 (n=52). We defined patients as receiving a high antipsychotic dose if their ratio of prescribed daily dose (PDD) to defined daily dose (DDD) was greater than 1.5. RESULTS: The rates of high-dose antipsychotic prescription were 61.7% and 53.8% in 2005 and 2010, respectively. The rates of antipsychotic polypharmacy were 34.6% in 2005 and 34.0% in 2010. The most common first-prescribed antipsychotics were (in descending order of prescription frequency) olanzapine, risperidone, aripiprazole, and haloperidol in 2005 and risperidone, quetiapine, paliperidone, and olanzapine in 2010. High-dose antipsychotics were significantly associated with antipsychotic poly-pharmacy (odds ratio=23.97; p<0.01). More individuals were treated with mood stabilizers in 2010 than in 2005 (p=0.003). CONCLUSION: The practice of prescribing high-dose antipsychotics and associated antipsychotic polypharmacy were common even for initial treatment of first-episode schizophrenia in 2005 and 2010. In 2010, the list of the most common first-prescribed antipsychotics changed, and the use of mood stabilizers increased in non-affective schizophrenia.
Antimanic Agents ; Antipsychotic Agents ; Haloperidol ; Hospitals, Psychiatric ; Humans ; Medical Records ; Polypharmacy ; Prescriptions ; Risperidone ; Schizophrenia* ; Aripiprazole ; Quetiapine Fumarate

BACKGROUND AND PURPOSE: Differences in hippocampal volume (HV) were compared between chronic primary insomniacs (PIs) and good sleepers (GSs), and the relationship between HV and memory function in PIs was investigated to clarify the effect of chronic sleep deprivation on brain structure and cognition. METHODS: Twenty PIs (mean age, 50 years; 18 females) and 20 age-, gender-, and education-matched GSs were enrolled. Brain magnetic resonance imaging (MRI) was performed on a 1.5-T MRI scanner. Left and right HV and intracranial volume (ICV) were measured manually. Nighttime polysomnography and neuropsychological testing were also applied to all subjects. Group differences in HV were analyzed and the relationships between HV and sleep questionnaire data, nighttime polysomnography, and neuropsychological findings were evaluated. RESULTS: Compared to GSs, PIs exhibited significantly increased sleep latency and arousal index and a decreased percentage of REM sleep in nighttime polysomnography, as well as impaired verbal and visual memory, and frontal lobe function. Absolute HV and ICV did not differ significantly between PIs and GSs. In the PIs, right and left HVs were negatively correlated with the duration of insomnia and the arousal index, and positively correlated with the recognition of visual memory. In addition, free recall in verbal memory was positively correlated with left HV in PIs. CONCLUSIONS: These findings suggest that chronic sleep deprivation impairs memory and frontal lobe function, and that a long duration of insomnia and poor sleep quality contribute to a bilateral reduction in HV.
Arousal ; Brain ; Cognition ; Frontal Lobe ; Hippocampus ; Humans ; Magnetic Resonance Imaging ; Memory ; Neuropsychological Tests ; Polysomnography ; Sleep Deprivation ; Sleep Initiation and Maintenance Disorders ; Sleep, REM ; Surveys and Questionnaires

Composite biological and synthetic grafts with progenitor cells offer an alternative approach to auto- or allografts for fracture repair. This study was conducted to evaluate osteogenesis of autologous serum-derived albumin (ASA) scaffolds seeded with canine adipose tissue-derived mesenchymal stem cells (Ad-MSCs) in a canine segmental bone defect model. ASA scaffold was prepared with canine serum using cross-linking and freeze-drying procedures. Beta-tricalcium phosphate (beta-TCP) was mixed at the cross-linking stage. Ad-MSCs were seeded into the scaffold and incubated for one day before implantation. After 16 weeks, the grafts were harvested for histological analysis. The dogs were divided into five groups: control, ASA scaffolds with and without Ad-MSCs, and ASA scaffolds including beta-TCP with and without Ad-MSCs. ASA scaffolds with Ad-MSCs had a significantly larger area of increased opacity at the proximal and distal host cortex-implant interfaces in radiographs 16 weeks after implantation compared to the groups with beta-TCP (p < 0.05). Histomorphometric analysis showed that ASA scaffolds with Ad-MSCs had significantly greater new bone formation than other groups (p < 0.05). These results suggest that Ad-MSCs seeded into ASA scaffolds enhanced osteogenesis in the bone defect model, but that beta-TCP in the ASA scaffold might prevent penetration of the cells required for bone healing.
Allografts ; Animals ; Dogs ; Mesenchymal Stromal Cells* ; Osteogenesis* ; Stem Cells ; Transplants

Background: and Purpose Excess or insufficient sleep, irregular sleep-wake patterns, and an extreme early or late chronotypes adversely impact physical and mental health. Changes in sleep characteristics should therefore be tracked, and factors that contribute to poor sleep should be identified. We investigated the changes in sleep patterns among South Korean adults during 2009–2018. Methods: Using data of a representative sample of South Korean adults from the 2009 (n= 2,658, 48.5% males; age=44.5±15.0 years old [mean±standard deviation], age range=19–86 years) and 2018 (n=2,389, 49.1% males; age=47.9±16.3 years, age range=19–92 years) Korean Headache-Sleep Study, we explored changes in sleep timing, sleep duration, chronotype, and social jetlag (SJL). Logistic regression analysis was used to examine the association between average sleep duration and depression. Results: From 2009 to 2018, bedtimes were advanced by 10 and 25 min on workdays and free days, respectively. Meanwhile, wake-up times were advanced by 13 min and delayed by 12 min on workdays and free days, respectively. The average sleep duration significantly decreased from 7.45 h to 7.13 h. The prevalence of short sleep duration (<7 h) increased, whereas that of long sleep duration (≥8 h) decreased. A circadian preference toward eveningness and SJL increased. The prevalence of depression increased from 4.6% to 8.4%, and there were significant reverse J-shaped and U-shaped associations between average sleep duration and depression in 2009 and 2018, respectively. Conclusions Changes in sleep patterns and the association between sleep duration and depressive mood were determined from a representative sample of the South Korean adult population. Interventions to modify sleep behaviors might improve public health.

Interleukin-1 receptor-associated kinase 4 (IRAK4) is a pivotal enzyme in the Toll-like receptor (TLR)/MYD88 dependent signaling pathway, which is highly activated in rheumatoid arthritis tissues and activated B cell-like diffuse large B-cell lymphoma (ABC-DLBCL). Inflammatory responses followed by IRAK4 activation promote B-cell proliferation and aggressiveness of lymphoma. Moreover, proviral integration site for Moloney murine leukemia virus 1 (PIM1) functions as an anti-apoptotic kinase in propagation of ABC-DLBCL with ibrutinib resistance. We developed a dual IRAK4/PIM1 inhibitor KIC-0101 that potently suppresses the NF-κB pathway and proinflammatory cytokine induction in vitro and in vivo. In rheumatoid arthritis mouse models, treatment with KIC-0101 significantly ameliorated cartilage damage and inflammation. KIC-0101 inhibited the nuclear translocation of NF-κB and activation of JAK/STAT pathway in ABC-DLBCLs. In addition, KIC-0101 exhibited an anti-tumor effect on ibrutinib-resistant cells by synergistic dual suppression of TLR/MYD88-mediated NF-κB pathway and PIM1 kinase. Our results suggest that KIC-0101 is a promising drug candidate for autoimmune diseases and ibrutinib-resistant B-cell lymphomas.