There are unmet needs for pharmacologic agents beyond current medications, such as statins, to effectively lower low-density lipoprotein cholesterol levels to target goals, especially in patients with very high or extremely high risk. Pharmacological targeting of mRNA represents an emerging, innovative approach with the potential to expand upon current therapies. In RNA-targeted therapeutics, a novel approach is the use of chemically modified oligonucleotides to inhibit the production of target proteins at their sites of gene coding. There are two main classes of RNA-targeted therapeutics: single-stranded antisense oligonucleotides (ASOs) and double-stranded small inhibiting RNAs. ASOs are synthetic molecules with a length of 15–30 nucleotides that are designed specifically to bind to a target mRNA in a sequence-specific manner. Using these agents to inhibit the translation of key regulatory proteins, such as apolipoprotein CIII, apolipoprotein(a), and angiopoietinlike protein 3, has demonstrated treatment efficacy for dyslipidemia. Many cardiovascular outcome trials with ASOs are ongoing. As clinicians, we must carefully monitor the longterm safety and efficacy of this new modality through large clinical trials in the future.

Statins are the cornerstone of the prevention and treatment of atherosclerotic cardiovascular disease (ASCVD). However, even under optimal statin therapy, a significant residual ASCVD risk remains. Therefore, there has been an unmet clinical need for novel lipid-lowering agents that can target low-density lipoprotein cholesterol (LDL-C) and other atherogenic particles. During the past decade, several drugs have been developed for the treatment of dyslipidemia. Inclisiran, a small interfering RNA that targets proprotein convertase subtilisin/kexin type 9 (PCSK9), shows comparable effects to that of PCSK9 monoclonal antibodies. Bempedoic acid, an ATP citrate lyase inhibitor, is a valuable treatment option for the patients with statin intolerance. Pemafibrate, the first selective peroxisome proliferator-activated receptor alpha modulator, showed a favorable benefit-risk balance but the large clinical phase 3 trial (Pemafibrate to Reduce Cardiovascular OutcoMes by Reducing Triglycerides IN patiENts With diabe- Tes [PROMINENT]) was recently stopped due to the underperformance from interim analysis. High dose icosapent ethyl, a modified eicosapentaenoic acid preparation, shows cardiovascular benefits. Evinacumab, an angiopoietin-like 3 (ANGPTL3) monoclonal antibody, reduces plasma LDL-C levels in patients with refractory hypercholesterolemia. Novel antisense oligonucleotides targeting apolipoprotein C3 (apoC3), ANGPTL3, and lipoprotein(a) have significantly attenuated the levels of their target molecules with beneficial effects on associated dyslipidemias. Apolipoprotein A1 (apoA1) is considered as a potential treatment to exploit the athero-protective effects of high-density lipoprotein cholesterol (HDL-C), but solid clinical evidence is necessary. In this review, we discuss the mode of action and clinical outcomes of these novel lipid-lowering agents beyond statins.

Objectives: ：Based on the fact that cognitive functions decline known as comorbid symptoms of depression can precede depression, this study seeks to observe the effects of depressive symptoms and anxiety symptoms on cognitive function in healthy subjects. Methods: ：To recruit 50 general populations to evaluate cognitive and clinical symptoms and to find out the effects of clinical symptoms on cognitive functions, Pearson correlation and multivariate regression were conducted. Correlation analysis of subdomain cognitive function was conducted for reliability analysis. Results: ：Trail making test-B that evaluates the execution function correlates with depressive symptoms (r=0.300, p=0.03) and age (r=0.323, p=0.02). Depressive symptoms (β=0.304, p=0.03) and age (β=0.335, p=0.01) were significantly related to Trail making test -B (Adjusted R2 =0.148). Subjective cognitive tests correlates with anxiety symptoms (r=0.434, p=0.002). In the correlation between cognitive functional items, Subjective cognitive tests was found to be correlated with other test except Spotter. Conclusions ：In this study, depressive symptoms contribute independently to executive functions in addition to demographic characteristics such as age and duration of education. Given that cognitive decline is a common long-term clinical outcome in depression, we expect active early intervention and evaluation of cognitive function to be helpful.

To achieve an esthetic restoration, visualized information considering the facial aspect of patient is required. As for the reasons of esthetic failure, it could be explained by lack of communication and information such as horizontal, vertical and esthetic line. Therefore, it is important to deliver that the visualized information to dental technicians or other dentists for the success of esthetic treatment. This case report presents the process of visualizing esthetic information and designing the restoration using a digital diagnostic tool; Digital Smile Design.
Dental Technicians ; Dentists ; Humans

A 49-year-old man visited the emergency room of Korea University Ansan Hospital with hematochezia starting the day before the visit. Recently, he was on anti-platelet medication due to hypertension. The patient had no definite symptoms other than hematochezia. Digital rectal exam was positive and laboratory tests showed severe anemia. Sigmoidoscopy was initiated and almost no fecal material was observed in the intestinal tract, allowing insertion into the cecum. Active bleeding from the appendiceal opening was noted. On abdominal CT, contrast enhancement was observed at the tip of the appendix. Under suspicion of acute appendicitis, we consulted with a surgeon. The patient underwent appendectomy with partial cecal resection. Pathologic examination revealed a diagnosis of appendix bleeding due to acute suppurative appendicitis. The patient had no further bleeding after surgery and was discharged in a stable state. Careful observation by the endoscopist is necessary for accurate diagnosis of lower gastrointestinal hemorrhage. Appendiceal hemorrhage is very rarely reported, but it has various pathophysiologies. CT scan is useful when appendiceal hemorrhage is confirmed by endoscopic findings. Surgical treatment was needed in almost all cases reported worldwide. If bleeding from the appendix is confirmed, surgical treatment should be considered for both therapeutic and diagnostic purposes.
Anemia ; Appendectomy ; Appendicitis* ; Appendix ; Cecum ; Colonoscopy ; Diagnosis ; Emergency Service, Hospital ; Gastrointestinal Hemorrhage* ; Gyeonggi-do ; Hemorrhage ; Humans ; Hypertension ; Korea ; Middle Aged ; Sigmoidoscopy ; Tomography, X-Ray Computed

Here we present an autopsy case of chronic traumatic encephalopathy (CTE) in a 36-year-old man. He had a history of febrile seizures at the age of four and was severely demented at age 10 when he was admitted to a mental hospital. He had suffered repetitive self-harm, such as frequent banging of the head on the wall in his hospital record, but he had no clear history between the ages of four and ten. Autopsy revealed global cerebral atrophy, including the basal ganglia, thalamus, hippocampus, amygdala, mammilary bodies and lateral geniculate bodies. This case showed typical pathological features of CTE. Phosphorylated tau (p-tau)-positive neurofibrillary tangles (NFTs) and neuropil threads (NT) we are widely distributed in the brain, especially in the depth of the cerebral sulci. NFT and NT were also found in the basal ganglia, thalamus, amygdala and brainstem. Scanty β-amyloid deposits were found in the motor and sensory cortices, but α-synuclein was completely negative in the brain. This example showed that CTE can occur in young ages and that even children can experience CTE dementia.
Adult ; Amygdala ; Atrophy ; Autopsy* ; Basal Ganglia ; Brain ; Brain Injuries ; Brain Injury, Chronic* ; Brain Stem ; Child* ; Dementia ; Geniculate Bodies ; Head ; Hippocampus ; Hospital Records ; Hospitals, Psychiatric ; Humans ; Neurofibrillary Tangles ; Neuropil Threads ; Pathology ; Seizures, Febrile ; Thalamus