BACKGROUND/OBJECTIVES: Supplementation of nicotinamide adenine dinucleotide (NAD) precursors has been investigated for its potential to counteract age-related physiological decline. While decreased NAD + level is associated with conditions such as obesity and dyslipidemia, few studies have explored its metabolic impact in relatively young animals.Here, we hypothesized that nicotinamide mononucleotide (NMN) could alleviate highfat diet-induced metabolic stress in young mice and sought to elucidate the underlying mechanisms.MATERIALS/METHODS: We first conducted a secondary analysis of hepatic transcriptome datasets from multiple NMN intervention studies to identify target pathways. Next, 11-weekold lean and obese C57BL/6N mice administrated NMN (500 mg/kg/day) for 1 mon were analyzed for metabolic parameters and gene expression for the target pathways. In vitro study using AML12 cell line was then conducted to confirm the effects of NMN. Additionally, transcriptomic data from liver-specific nicotinamide phosphoribosyltransferase (NAMPT)-deficient mice were analyzed to examine the relationship between NAD + metabolism, endoplasmic reticulum (ER) stress, and circadian rhythm. RESULTS: The secondary analysis of hepatic transcriptome datasets revealed potential target pathways related to circadian regulation and hepatic ER stress. In mouse study, short-term NMN administration significantly decreased body weight and fat mass. NMN also alleviated hepatic ER stress response in vivo and in vitro. Additional analysis revealed that the mice with diet-induced metabolic stress or NAMPT deficiency led to phase shifts of the hepatic circadian core clock oscillation by advancing the peak time, while time-restricted feeding shifted the opposite, indicating the metabolic regulation of the circadian phase. CONCLUSION Short-term NMN administration effectively attenuated obese condition in young mice and mitigated hepatic ER stress. The altered ER stress was regulated by NAMPT, potentially through the phase shift of the hepatic circadian rhythm.

PURPOSE: Respiratory syncytial virus (RSV) and human rhinovirus (hRV) are the most common causes of child respiratory viral infections. We aimed to investigate epidemiological and clinical characteristics of RSV and hRV single infections and coinfections. METHODS: Nasopharyngeal aspirates of hospitalized children aged <5 years were tested using multiplex reverse transcription polymerase chain reaction (RT-PCR) from October 2014 to April 2017. Their medical records were retrospectively reviewed. RESULTS: RSV or hRV was detected in 384 patients who divided into 3 groups: patients with RSV (R group, n=258); patients with hRV (H group, n=99); and patients with both (RH group, n=27). The R group (median age, 6 months) consisted of 248 (96.1%) patients with lower respiratory tract infection (LRTI), and 14 (5.4%) needed oxygen inhalation. Infants aged <12 months (63.2%) had respiratory difficulty and were supplied oxygen more often. The H group (median age, 16 months) consisted of 56 (56.6%) patients with LRTI, 4 (4%) required oxygen inhalation, and 1 (1.0%) required mechanical ventilation. Infants (40.4%) showed longer hospitalization compared to patients aged ≥12 months (5 vs. 4 days, P<0.05). The RH group consisted of 24 (88.9%) patients with LRTI, and 2 (7.4%) needed oxygen inhalation. Hospitalization days and oxygen inhalation and mechanical ventilation rates did not differ between single infections (R and H groups) and coinfections (RH group). CONCLUSIONS: RSV was detected more often in younger patients and showed higher LRTI rates compared to hRV. Single infections and coinfections of RSV and hRV showed no difference in severity.
Child ; Child, Hospitalized ; Coinfection ; Epidemiology ; Hospitalization ; Humans ; Infant ; Inhalation ; Korea ; Medical Records ; Multiplex Polymerase Chain Reaction ; Oxygen ; Polymerase Chain Reaction ; Respiration, Artificial ; Respiratory Syncytial Viruses ; Respiratory Tract Infections ; Retrospective Studies ; Reverse Transcription ; Rhinovirus

Background: Little is known regarding the functional outcome and quality of life of neuro-ICU survivors. In Korea, the neuro-ICU concept was introduced relatively late and data about long term outcome and predictors concerning functional outcome is scarce. The main objective of this study was to analyze functional outcome and mortality, and to determine prognostic predictors for the outcome in patients admitted to Korean neuro-ICUs. Methods: Consecutive adult (≥ 15-years-of-age) patients admitted to a neuro-ICU due to various causes including ischemic or hemorrhagic stroke, and other neurological or neurosurgical problems such as traumatic brain injury, seizure, or drug intoxication during an 18-month period from July 2008 through December 2009 were included. Demographic and clinical variables were compared between groups stratifi ed based on 6-month modifi ed Rankin scale score. Results: Of 555 patients, there were signifi cant differences in age (P=0.013), sex (P=0.02), hospital stay (P<0.01), neuro-ICU stay (P<0.01), admission diagnosis (P=0.001), intubation (P<0.01), mechanical ventilation (P<0.01), tracheostomy (P<0.01), comorbid conditions such as atrial fi brillation (P<0.01), cardiac complication (P<0.01) and pulmonary complication (P<0.01), a high Therapeutic Intervention Scoring System (TISS-28) score (P<0.01), and a high Acute Physiology and chronic health evaluation (APACHE) II score (P<0.01) between favorable and unfavorable outcome groups. The overall mortality rate was 15.0% (n=83). In multivariable logistic regression analysis, age, sex, high TISS-28, high APACHE II score, intubation, and cardiac complication were independent predictors of unfavorable outcome. Conclusion: The identifi ed predictors for functional outcomes in Korean neuro-ICU patients will be an important aid in diagnosing and treating neuro-ICU patients.

BACKGROUND: Small proportions of all the elderly stroke patients receive recombinant tissue plasminogen activator (r-tPA) therapy, although old age is not a proven contraindication to intravenous thrombolytic therapy for acute ischemic stroke. The purpose of this study was to identify reasons for exclusion from r-tPA therapy and factors associated with the decision of r-tPA use in elderly patients with acute ischemic stroke. METHODS: From the acute stroke registries of 22 domestic university hospitals taking the r-tPA therapy from January 2007 to May 2010, we extracted data of all acute ischemic stroke patients who were aged 80 or over and arrived within onset 3 hours. For all patients, we assessed the eligibility of r-tPA therapy using National Institute of Neurological Disorders and Stroke (NINDS) r-tPA trial criteria. For eligible patients, we compared all clinical variables between patients who were treated with r-tPA and those who were not, and analyzed potential factors related to the decision of r-tPA use. RESULTS: A total of 494 patients were included in this study. 255 patients (51.6%) were excluded by NINDS r-tPA trial criteria and the major reasons for exclusion were minor neurological deficit (53.7%) and clinical improvement (17.3%). Among 239 patients who were eligible for r-tPA, 162 (32.8%) patients received r-tPA and 77 (15.6%) did not. Multivariable analysis showed that younger age, shorter time-delay from onset to admission, non-smoker, no history of prior stroke, good pre-stroke functional status and severe initial neurological deficit were independently associated with the decision of r-tPA use in the elderly stroke patients predictors for r-tPA treatment. CONCLUSION: In very elderly patients, mild neurological deficit on arrival and rapid clinical improvement in neurological symptoms were the main reasons for exclusion from thrombolytic therapy.
Aged ; Hospitals, University ; Humans ; National Institute of Neurological Disorders and Stroke ; Registries ; Stroke ; Thrombolytic Therapy ; Tissue Plasminogen Activator