Parkinson’s disease (PD) is a neurodegenerative disease caused by the death of dopaminergic neurons in the nigrostriatal pathway, leading to motor and non-motor dysfunctions, such as depression, olfactory dysfunction, and memory impairment. Although levodopa (L-dopa) has been the gold standard PD treatment for decades, it only relieves motor symptoms and has no effect on non-motor symptoms or disease progression. Prior studies have reported that 6-shogaol, the active ingredient in ginger, exerts a protective effect on dopaminergic neurons by suppressing neuroinflammation in PD mice. This study investigated whether cotreatment with 6-shogaol and L-dopa could attenuate both motor and non-motor symptoms and dopaminergic neuronal damage.Both 6-shogaol (20 mg/kg) and L-dopa (80 mg/kg) were orally administered to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid-induced PD model mice for 26 days. The experimental results showed that L-dopa alleviated motor symptoms, but had no significant effect on non-motor symptoms, loss of dopaminergic neuron, or neuroinflammation. However, when mice were treated with 6-shogaol alone or in combination with L-dopa, an amelioration in both motor and non-motor symptoms such as depressionlike behavior, olfactory dysfunction and memory impairment was observed. Moreover, 6-shogaol-only or co-treatment of 6-shogaol with L-dopa protected dopaminergic neurons in the striatum and reduced neuroinflammation in the striatum and substantia nigra.Overall, these results suggest that 6-shogaol can effectively complement L-dopa by improving non-motor dysfunction and restoring dopaminergic neurons via suppressing neuroinflammation.

Background: Reactive atrial-based anti-tachycardia pacing (rATP) in CIED (cardiovascular implantable electronic devices) is effective in atrial fibrillation (AF) suppression. Uninterrupted systemic anticoagulation is recommended when this algorithm is activated to avoid stroke, however, the use of a rATP algorithm in patients with a left atrial appendage (LAA) closure device has not been studied. We assessed the safety and feasibility of rATP algorithm to sup‑ press AF in patients with a LAA closure device over an extended period. Methods: Data from 55 consecutive patients who underwent a ­Watchman® implant at a tertiary care hospital between September 1, 2015, and January 30, 2020, who also had an in situ ­Medtronic® CIED (45 with and 10 with‑ out rATP capability) were retrospectively reviewed. Results: The 55-patient cohort was 60% male, 77 ± 8 years old, ­CHA2DS2 -VASc score 5 (4–6), HAS-BLED score 3 (3–4), LVEF 53 ± 14%, LA size 4.4 ± 0.7 cm and ventricular pacing burden of 73 (1.4–98.3)%. The CIEDs (20 ICDs and 35 pace‑ makers) antedated ­Watchman® implants by 915 ± 725 days. Post-implant, all patients discontinued anticoagulation.Twenty patients in the rhythm-control group with active rATP algorithm displayed no increase in yearly AF burden and were less likely to develop permanent/long-standing persistent AF (p = 0.002) when compared to 35 patients in the rate-control group with CIEDs inactive/incapable of rATP over a ≤ 5-year follow-up. The longest AF episode in the rhythm-control group lasted 204 (19–2520) h. There was no increase in stroke/thromboembolism and a significant reduction in major bleeding noted over ≤ 5 years pre- versus post-implant in the whole cohort (p = 0.005). Conclusion rATP algorithm use is safe and feasible in patients with a ­Watchman® device. Patients should be fore‑ warned of a surge in post-Watchman® implant AF burden.

Parkinson’s disease (PD) which has various pathological mechanisms, recently, it is attracting attention to the mechanism via microbiome-gut-brain axis. 6-Shogaol, a representative compound of ginger, have been known for improving PD phenotypes by reducing neuroinflammatory responses. In the present study, we investigated whether 6-shogaol and ginger attenuate degeneration induced by Proteus Mirabilis(P. mirabilis) on the intestine and brain, simultaneously. C57BL/6J mice received P. mirabilis for 5 days. Ginger (300 mg/kg) and 6-shogaol (10 mg/kg) were treated by gavage feeding for 22 days including the period of P. mirabilis treatment. Results showed that 6-shogaol and ginger improved motor dysfunction and dopaminergic neuronal death induced by P. mirabilis treatment. In addition, they suppressed P. mirabilis-induced intestinal barrier disruption, pro-inflammatory signals such as toll-like receptor and TNF-α, and intestinal α-synuclein aggregation. Moreover, ginger and 6-shogaol significantly inhibited neuroinflammation and α-synuclein in the brain. Taken together, 6-shogaol and ginger have the potential to ameliorate PD-like motor behavior and degeneration of dopaminergic neurons induced by P. mirabilis in mice. Here, these findings are meaningful in that they provide the first experimental evidence that 6-shogaol might attenuate PD via regulating gut-brain axis.

Long-term administration of levodopa (L-DOPA) to patients with Parkinson’s disease (PD) commonly results in involuntary dyskinetic movements, as is known for L-DOPA-induced dyskinesia (LID). 5-Hydroxytryptophan (5-HTP) has recently been shown to alleviate LID; however, no biochemical alterations to aberrant excitatory conditions have been revealed yet. In the present study, we aimed to confirm its anti-dyskinetic effect and to discover the unknown molecular mechanisms of action of 5-HTP in LID. We made an LID-induced mouse model through chronic L-DOPA treatment to 6-hydroxydopamine-induced hemi-parkinsonian mice and then administered 5-HTP 60 mg/kg for 15 days orally to LID-induced mice. In addition, we performed behavioral tests and analyzed the histological alterations in the lesioned part of the striatum (ST). Our results showed that 5-HTP significantly suppressed all types of dyskinetic movements (axial, limb, orolingual and locomotive) and its effects were similar to those of amantadine, the only approved drug by Food and Drug Administration. Moreover, 5-HTP did not affect the efficacy of L-DOPA on PD motor mani-festations. From a molecular perspective, 5-HTP treatment significantly decreased phosphorylated CREB and ΔFosB expression, commonly known as downstream factors, increased in LID conditions. Furthermore, we found that the effects of 5-HTP were not mediated by dopamine1 receptor (D1)/DARPP32/ERK signaling, but regulated by AKT/mTOR/S6K signaling, which showed different mechanisms with amantadine in the denervated ST. Taken together, 5-HTP alleviates LID by regulating the hyperactivated striatal AKT/mTOR/S6K and CREB/ΔFosB signaling.

In May 2023, the Committee of Clinical Practice Guidelines of the Korean Diabetes Association published the revised clinical practice guidelines for Korean adults with diabetes and prediabetes. We incorporated the latest clinical research findings through a comprehensive systematic literature review and applied them in a manner suitable for the Korean population. These guidelines are designed for all healthcare providers nationwide, including physicians, diabetes experts, and certified diabetes educators who manage patients with diabetes or individuals at risk of developing diabetes. Based on recent changes in international guidelines and the results of a Korean epidemiological study, the recommended age for diabetes screening has been lowered. In collaboration with the relevant Korean medical societies, recently revised guidelines for managing hypertension and dyslipidemia in patients with diabetes have been incorporated into this guideline. An abridgment containing practical information on patient education and systematic management in the clinic was published separately.

Background and Objectives: Moderate aortic stenosis (AS) confers a surprisingly adverse prognosis, approaching that of severe AS. The objective of this study was to describe the clinical course of patients with moderate AS with evidence of concomitant heart failure manifesting as elevated brain natriuretic peptide (BNP) levels. Methods: This is a single-center, retrospective cohort study of 332 patients with elevated BNP. 165 patients with moderate AS were compared with 167 controls with none-mild AS.The Median follow-up duration was 3.85 years. The primary outcome was a composite endpoint of all-cause hospitalizations and all-cause mortality. Results: BNP levels were 530 and 515 pg/mL in the study and the control groups, respectively. Moderate AS had significantly higher rates of primary composite endpoint in both univariate analysis (hazard ratio [HR], 1.50; 95% confidence interval [CI], 1.14–1.97; p=0.004) and adjusted analysis (HR, 1.45; 95% CI, 1.05–2.01; p=0.02). Moderate AS had 1.41 (95% CI, 1.18– 1.69; p<0.001) times more all-cause hospitalization per patient-year of follow-up compared to controls in the univariate model. After adjustment for significant covariates, moderate AS remained an independent predictor of all-cause hospitalizations (incidence rate ratio [IRR], 1.45; 95% CI, 1.18–1.79; p=0.005). Furthermore, moderate AS was significantly associated with higher all-cause hospitalization rates in both heart failure with reduced ejection fraction (IRR, 1.33; 95% CI, 1.02–1.75; p=0.038) and heart failure with preserved ejection fraction [IRR], 1.31; 95% CI, 1.03–1.67; p=0.026). Conclusions Moderate AS in conjunction with elevated BNP portends a significantly worse prognosis than those without moderate AS and should be followed closely.

Methods: Clinical and neuromonitoring data of 207 consecutive adult patients who underwent cervical spine surgeries at multiple surgical centers using bimodal IONM were analyzed. Signal changes were divided into three groups. Group 0 had transient signal changes in either MEPs or SSEPs, group 1 had sustained unimodal changes, and group 2 had sustained changes in both MEPs and SSEPs. The incidences of true neurological deficits in each group were recorded. Results: A total of 25% (52/207) had IONM signal alerts. Out of these signal drops, 96% (50/52) were considered to be false positives. Groups 0 and 1 had no incidence of neurological deficits, while group 2 had a 29% (2/7) rate of true neurological deficits. The sensitivities of both MEP and SSEP were 100%. SSEP had a specificity of 96.6%, while MEP had a lower specificity at 76.6%. C5 palsy rate was 6%, and there was no correlation with IONM signal alerts (p=0.73). Conclusions This study shows that we can better predict its clinical significance by dividing IONM signal drops into three groups. A sustained, bimodal (MEP and SSEP) signal drop had the highest risk of true neurological deficits and warrants a high level of caution. There were no clear risk factors for false-positive alerts but there was a trend toward patients with cervical myelopathy.

Methods: Clinical and neuromonitoring data of 207 consecutive adult patients who underwent cervical spine surgeries at multiple surgical centers using bimodal IONM were analyzed. Signal changes were divided into three groups. Group 0 had transient signal changes in either MEPs or SSEPs, group 1 had sustained unimodal changes, and group 2 had sustained changes in both MEPs and SSEPs. The incidences of true neurological deficits in each group were recorded. Results: A total of 25% (52/207) had IONM signal alerts. Out of these signal drops, 96% (50/52) were considered to be false positives. Groups 0 and 1 had no incidence of neurological deficits, while group 2 had a 29% (2/7) rate of true neurological deficits. The sensitivities of both MEP and SSEP were 100%. SSEP had a specificity of 96.6%, while MEP had a lower specificity at 76.6%. C5 palsy rate was 6%, and there was no correlation with IONM signal alerts (p=0.73). Conclusions This study shows that we can better predict its clinical significance by dividing IONM signal drops into three groups. A sustained, bimodal (MEP and SSEP) signal drop had the highest risk of true neurological deficits and warrants a high level of caution. There were no clear risk factors for false-positive alerts but there was a trend toward patients with cervical myelopathy.

Background: Right ventricular pacing (RVP) increases heart failure, AF, and death rates in pacemaker patients and ventricular arrhythmias (VAs) in defibrillator patients. However, the impact of RVP on VAs burden and its clinical significance in pacemaker patients with normal range LVEF of > 50–55% remains unknown. We sought to evaluate the relationship of RVP and VAs and its clinical impact in a pacemaker patient population. Methods: Records of 105 patients who underwent de novo dual-chamber pacemaker implant or a generator change (Medtronic™ or Boston Scientific™) for AV block and sinus node disease at a tertiary care center between September 1, 2015, and September 1, 2016, were retrospectively reviewed. Results: Data from 105 patients (51% females, mean age 76 ± 1 years, mean LVEF 61 ± 0.7%) without history of VAs (98.2%) were reviewed over 1044 ± 23 days. Dependent patients (100% RVP) exhibited the lowest VAs burden when compared to < 100% RVP (isolated PVCs, PVC runs of < 4 beats, and NSVT; p ≤ 0.001). Patients with < 1% RVP also exhibited low VA burden with intermediate RVP (1–99.9%) being most arrhythmogenic for PVC runs (p = 0.04) and for isolated PVCs (p = 0.006). Antiarrhythmics/beta and calcium channel blockers use and stress tests performed to evaluate VAs which were positive requiring intervention did not differ significantly. Burden of > 1/h of PVC runs and increasing PVC runs/h were significantly associated with hospitalization (p = 0.04) and all-cause mortality (p = 0.03), respectively. Conclusions In pacemaker patients with normal range LVEF (> 50–55%), 100% RVP is associated with the lowest burden of NSVT. Furthermore, patients with < 1% RVP also exhibit low VA burden; however, intermittent RVP seems to significantly correlate with non-sustained VAs.