Insulin sensitization causes accelerated sinus nodal dysfunction through autophagic dysregulation in hypertensive mice

Insulin sensitizers, while effective in glucose-lowering for diabetes control, are linked to an increased risk of heart disease through mechanisms that are not well understood. In this study, we investigated the molecular mechanisms underlying the effects of insulin sensitization on cardiac sinus node dysfunction. We used pharmacologic or genetic approaches to enhance insulin sensitivity, by treating with pioglitazone or rosiglitazone, or through phosphatase and tensin homolog (PTEN) deletion in cardiomyocytes respectively. We employed an angiotensin II (Ang II)-induced hypertensive animal model which causes sinus node dysfunction and accumulation of oxidized calcium/calmodulin-dependent protein kinase II (CaMKII), which also serves as a biomarker for this defect. While neither PTEN deficiency nor insulin sensitizers caused sinus node dysfunction in normotensive mice, both accelerated the onset of sinus node dysfunction and CaMKII oxidation in hypertensive mice.These abnormalities were accompanied by a significant defect in autophagy as revealed by unc-51 like autophagy activating kinase 1 (ULK1) signaling. Indeed, mice deficient in ulk1 in cardiomyocytes and the sinus node also showed early onset of slow atrial impulse conduction with frequent sinus pauses and upregulated CaMKII oxidation following Ang II infusion similar to that seen with PTEN deficiency, or treatment with insulin sensitizers. To further elucidate the role of autophagy in sinus node dysfunction, we treated mice with a peptide D-Tat-beclin1 that enhanced autophagy, which significantly abrogated the frequent sinus pauses and accumulation of oxidized CaMKII induced by insulin sensitizers treatment, or PTEN deficiency in hypertensive animals. Together, these findings provide clear evidence of the detrimental cardiac effects of insulin sensitization that occurs through failure of autophagy-mediated proteolytic clearance.

Impact of the Health Insurance Coverage Policy on Oral Anticoagulant Prescription among Patients with Atrial Fibrillation in Korea from 2014 to 2016

BACKGROUND: To evaluate oral anticoagulant (OAC) utilization in patients with atrial fibrillation after the changes in the health insurance coverage policy in July 2015. METHODS: We used the Health Insurance Review and Assessment Service-National Patient Samples (HIRA-NPS) between 2014 and 2016. The HIRA-NPS, including approximately 1.4 million individuals, is a stratified random sample of 3% of the entire Korean population using 16 age groups and 2 sex groups. The HIRA-NPS comprises personal and medical information such as surgical or medical treatment provided, diagnoses, age, sex, region of medical institution, and clinician characteristics. The studied drugs included non-vitamin K antagonist OACs (NOACs) such as apixaban, dabigatran, edoxaban, and rivaroxaban, and were compared with warfarin. We analyzed drug utilization pattern under three aspects: person, time, and place. RESULTS: The number of patients with atrial fibrillation who were prescribed OACs was 3,114, 3,954, and 4,828; and the proportions of prescribed NOACs to total OACs were 5.1%, 36.2%, and 60.8% in 2014, 2015, and 2016, respectively. The growth rate of OACs prescription increased from 61.4 patients/quarter before June 2015 to 147.7 patients/quarter thereafter. These changes were predominantly in elderly individuals aged more than 70 years. The proportion of NOACs to OACs showed significant regional difference. CONCLUSION: The change of health insurance coverage policy substantially influenced OACs prescription pattern in whole Korean region. But the impact has been significantly different among regions and age groups, which provides the evidence for developing standard clinical practice guideline on OACs use.

Protective effects of kaempferol against cardiac sinus node dysfunction via CaMKII deoxidization / 대한해부학회지

Kaempferol exerts cardioprotective actions through incompletely understood mechanisms. This study investigated the molecular mechanisms underlying the cardioprotective effects of kaempferol in sinus node dysfunction (SND) heart. Here, we demonstrate that angiotensin II (Ang II) infusion causes SND through oxidized calmodulin kinase II (CaMKII). In contrast to this, kaempferol protects sinus node against Ang II-induced SND. Ang II evoked apoptosis with caspase-3 activation in sinus nodal cells. However, kaempferol lowered the CaMKII oxidization and the sinus nodal cell death. To block the CaMKII oxidization, gene of p47phox, a cytosolic subunit of NADPH oxidase, was deleted using Cas9 KO plasmid. In the absence of p47phox, sinus nodal cells were highly resistance to Ang II-induced apoptosis, suggesting that oxidized-CaMKII contributed to sinus nodal cell death. In Langendorff heart from Ang II infused mice, kaempferol preserved normal impulse formation at right atrium. These data suggested that kaempferol protects sinus node via inhibition of CaMKII oxidization and may be useful for preventing SND in high risk patients.

The Impacts of Cognitive Function, Disease Severity, and Disability on Ability to Perform Activities of Daily Living after Stroke / 재활간호학회지

PURPOSE: This study aimed to examine influence of cognitive function, disease severity and disability on ability to perform activity of daily living (ADL) after ischemic stroke. METHODS: A total of 88 patients with ischemic stroke were recruited from January 1, 2008 to December 31, 2012 and assessed with the standardized cognitive test battery and self-reports about disease severity, disability, and ADL. To analyze the data, ANOVA, Pearson correlation coefficients and multiple regression were conducted using SPSS/WIN program. RESULTS: Significant correlations were found between ADL and visuospatial function, visual memory, executive function, and disability (r=.29~.38). Executive function and disability explained 17.3% of total variability in ADL performance after ischemic stroke. CONCLUSION: Executive function may be a promising target for cognitive rehabilitation after ischemic stroke. Thus, effective therapeutic interventions such as cognitive training for stroke patients should be considered to improve their ability to perform ADL.

Effects on Blood Flow Velocity, Wound Healing and Pain in Hand Microsurgery Patients Following Heating on Non-affected Side

PURPOSE: The purpose of this study was to identify the effects of heating on the non-affected hand on blood flow velocity, wound healing, and pain for hand microsurgery patients. METHODS: This study was designed using the nonequivalent control group pretest-posttest design. Thirty-nine patients were assigned either to the experimental group (20 patients) or control group (19 patients). Data were analyzed with chi2-test, Fisher's exact test, t-test, and repeated measure ANOVA using SPSS/WIN 17.0 program. RESULTS: After treatment in this program, blood flow velocity (F=5.13, p=.008) and wound healing (F=4.11, p=.020) improved significantly in the experimental group compared to the control group. But there was no significant improvement in pain in the experimental group compared to the control group (F=2.40, p=.097). CONCLUSION: Based upon these results, the non-affected side hand heating was recommended as an independent nursing intervention for the patients who need improvement in blood flow velocity and wound healing such as patients who have microsurgery. As the heating was effective even when applied on the non-affected side, it is the applicable to patients who cannot tolerate any therapy on affected side.