We examined the effects of empagliflozin, a selective inhibitor of Na+-glucose cotransporter 2, on mitochondrial quality control and autophagy in renal tubular cells in a diabetic environment in vivo and in vitro. Human renal proximal tubular cells (hRPTCs) were incubated under high-glucose conditions. Diabetes was induced with streptozotocin in male C57BL/6J mice. Improvements in mitochondrial biogenesis and balanced fusion-fission protein expression were noted in hRPTCs after treatment with empagliflozin in high-glucose media. Empagliflozin also increased autophagic activities in renal tubular cells in the high-glucose environment, which was accompanied with mammalian target of rapamycin inhibition. Moreover, reduced mitochondrial reactive oxygen species production and decreased apoptotic and fibrotic protein expression were observed in hRPTCs after treatment with empagliflozin, even in the hyperglycemic circumstance. Importantly, empagliflozin restored AMP-activated protein kinase-α phosphorylation and normalized levels of AMP-to-ATP ratios in hRPTCs subjected to a high-glucose environment, which suggests the way that empagliflozin is involved in mitochondrial quality control. Empagliflozin effectively suppressed Na+-glucose cotransporter 2 expression and ameliorated renal morphological changes in the kidneys of streptozotocin-induced diabetic mice. Electron microscopy analysis showed that mitochondrial fragmentation was decreased and 8-hydroxy-2′-deoxyguanosine content was low in renal tubular cells of empagliflozin treatment groups compared with those of the diabetic control group. We suggest one mechanism related to the renoprotective actions of empagliflozin, which reverse mitochondrial dynamics and autophagy.

Background: Community-acquired pneumonia (CAP) is one of the leading worldwide causes of childhood morbidity and mortality. Its disease burden varies by age and etiology and is time dependent. We aimed to investigate the annual and seasonal patterns in etiologies of pediatric CAP requiring hospitalization. Methods: We conducted a retrospective study in 30,994 children (aged 0-18 years) with CAP between 2010 and 2015 at 23 nationwide hospitals in South Korea. Mycoplasma pneumoniae (MP) pneumonia was clinically classified as macrolide-sensitive MP, macrolide-less effective MP (MLEP), and macrolide-refractory MP (MRMP) based on fever duration after initiation of macrolide treatment, regardless of the results of in vitro macrolide sensitivity tests. Results: MP and respiratory syncytial virus (RSV) were the two most commonly identified pathogens of CAP. With the two epidemics of MP pneumonia (2011 and 2015), the rates of clinical MLEP and MRMP pneumonia showed increasing trends of 36.4% of the total MP pneumonia. In children < 2 years of age, RSV (34.0%) was the most common cause of CAP, followed by MP (9.4%); however, MP was the most common cause of CAP in children aged 2-18 years of age (45.3%). Systemic corticosteroid was most commonly administered for MP pneumonia. The rate of hospitalization in intensive care units was the highest for RSV pneumonia, and ventilator care was most commonly needed in cases of adenovirus pneumonia.

The effect of aerobic exercise on physical function and mental health in various adult age groups (young-old, 65-74; old-old, 75-84; oldest-old, ≥ 85 years) is unclear. The aim of this study was to investigate the effects of the Kohzuki Exercise Program (KEP) on physical function and mental health in these age groups. The KEP consisted of 40-min supervised sessions 3 times per week for 6 months as follows: 5 min of warm-up, 30 min of lower limb aerobic exercise, and 5 min of cool-down. A total of 50 participants (22 young-old, 20 old-old, and 8 oldest-old) who participated in the KEP completed at least 88% of the sessions. In statistical analysis, 3 (group: oldest-old, old-old, young-old) × 2 (time: baseline and after 6 months) analyses of variance were used to determine if there were significant main and interaction effects. Significant interactions were probed using the post-hoc paired t test. The Short Physical Performance Battery (SPPB) score showed significant group × time interactions after 6 months (p = 0.031). In the post-hoc test, oldest-old (p < 0.001), old-old (p < 0.001), and young-old (p < 0.01) groups had significantly better physical function after 6 months. However, none of the mental health measures showed group × time interactions at 6-month. Our results suggest that a 6-month KEP led to improved physical function in oldest-old, old-old, and young-old adults. The KEP was effective for oldest-old adults in particular. The KEP exhibits good adherence, making it suitable for a wide age range in society.

Abstract. The action of fluoxetine, a serotonin reuptake inhibitor, on the cloned neuronal rat Kv3.1 channels stably expressed in Chinese hamster ovary cells was investigated using the whole-cell patch-clamp technique. Fluoxetine reduced Kv3.1 whole-cell currents in a reversible, concentration-dependent manner, with an IC 50 value and a Hill coefficient of 13.4 µM and 1.4, respectively. Fluoxetine accelerated the decay rate of inactivation of Kv3.1 currents without modifying the kinetics of current activation. The inhibition increased steeply between 0 and +30 mV, which corresponded with the voltage range for channel opening. In the voltage range positive to +30 mV, inhibition displayed a weak voltage dependence, consistent with an electrical distance δ of 0.38. The binding (k +1 ) and dissociation (k −1 ) rate constants for fluoxetine-induced block of Kv3.1 were 5.7 µM