In recent years, next-generation sequencing (NGS)–based genetic testing has become crucial in cancer care. While its primary objective is to identify actionable genetic alterations to guide treatment decisions, its scope has broadened to encompass aiding in pathological diagnosis and exploring resistance mechanisms. With the ongoing expansion in NGS application and reliance, a compelling necessity arises for expert consensus on its application in solid cancers. To address this demand, the forthcoming recommendations not only provide pragmatic guidance for the clinical use of NGS but also systematically classify actionable genes based on specific cancer types. Additionally, these recommendations will incorporate expert perspectives on crucial biomarkers, ensuring informed decisions regarding circulating tumor DNA panel testing.

Background: and Purpose: The SoUth Korea study to PrEvent cognitive impaiRment and protect BRAIN health through lifestyle intervention (SUPERBRAIN) proved the feasibility of multidomain intervention for elderly people. One-quarter of the Korean population over 65 years of age has mild cognitive impairment (MCI). Digital health interventions may be costeffective and have fewer spatial constraints. We aim to examine the efficacy of a multidomain intervention through both face-to-face interactions and video communication platforms using a tablet personal computer (PC) application in MCI. Methods: Three hundred participants aged 60–85 years, with MCI and at least one modifiable dementia risk factor, will be recruited from 17 centers and randomly assigned in a 1:1 ratio to the multidomain intervention and the waiting-list control groups. Participants will receive the 24-week intervention through the tablet PC SUPERBRAIN application, which encompasses the following five elements: managing metabolic and vascular risk factors, cognitive training,physical exercise, nutritional guidance, and boosting motivation. Participants will attend the interventions at a facility every 1–2 weeks. They will also engage in one or two self-administered cognitive training sessions utilizing the tablet PC application at home each week. They will participate in twice or thrice weekly online exercise sessions at home via the ZOOM platform. The primary outcome will be the change in the total scale index score of the Repeatable Battery for the Assessment of Neuropsychological Status from baseline to study end. Conclusions This study will inform the effectiveness of a comprehensive multidomain intervention utilizing digital technologies in MCI.

In recent years, next-generation sequencing (NGS)–based genetic testing has become crucial in cancer care. While its primary objective is to identify actionable genetic alterations to guide treatment decisions, its scope has broadened to encompass aiding in pathological diagnosis and exploring resistance mechanisms. With the ongoing expansion in NGS application and reliance, a compelling necessity arises for expert consensus on its application in solid cancers. To address this demand, the forthcoming recommendations not only provide pragmatic guidance for the clinical use of NGS but also systematically classify actionable genes based on specific cancer types. Additionally, these recommendations will incorporate expert perspectives on crucial biomarkers, ensuring informed decisions regarding circulating tumor DNA panel testing.

Background: and PurposeThe prevalence of dementia is increasing in South Korea. Multidomain interventions may be useful for preventing dementia. Such programs need to be disseminated to elderly Koreans throughout the country. We have developed programs of the SoUth Korean study to PrEvent cognitive impaiRment and protect BRAIN health through lifestyle intervention in at-risk elderly people (SUPERBRAIN), which consists of a facility-based multidomain intervention (FMI) program and a home-based multidomain intervention (HMI) program suitable for elderly Koreans. We aim to determine the feasibility of the SUPERBRAIN programs before a large-scale randomized controlled trial. Methods: We will recruit 150 participants among those without dementia aged 60–79 years with at least 1 modifiable dementia risk factor. They will be randomly assigned in a 1:1:1 ratio to the FMI, HMI, and the waiting-list control arm. The 6-month multidomain intervention consists of management of metabolic and vascular risk factors, cognitive training and social activity, physical exercise, nutritional guidance, and motivational enhancement programs. The primary outcomes are adherence and retention rates and changes in the total scale index score of the Repeatable Battery for the Assessment of Neuropsychological Status from baseline to the study end. The main secondary outcomes are disability, depressive symptoms, quality of life, vascular risk factors, physical performance, nutritional assessment, and motivation questionnaire. There will be an exploratory evaluation of neurotrophic, neurodegeneration, and neuroinflammation factors, microbiome, telomere length, electroencephalography, and neuroimaging measures. Conclusions The results obtained will provide information on the applicability of these multidomain intervention programs to at-risk elderly people.

BACKGROUND: Postoperative sore throat (POST) is considered a usual complication after tracheal intubation, especially, thyroid surgery. Gabapentin is a widely studied multimodal perioperative drug, which can be used to treat acute postoperative pain. The primary endpoints of this study was a reduction of the incidence of POST at rest and during the swallowing movements after thyroid surgery. And the second endpoints was a reduction of the intensity of the POST after thyroid surgery. METHODS: Seventy-one patients that underwent elective thyroid surgery received either gabapentin (Neurontin(TM) 600 mg) or placebo, orally, one hour before anesthesia. The VAS scores and incidences of POST and adverse effects were determined at 1 hr, 6 hr, 12 hr, and 24 hr after surgery at rest and during swallowing movement. RESULTS: The gabapentin group (N = 36) showed a lower incidence of POST than the placebo group (N = 35) (47% vs. 78%, P = 0.038), and had significant lower VAS score at 6 and 24 hours after surgery in the resting state. However, during the movement, no intergroup differences were found in terms of the incidence of POST (83% vs. 91%, P = 0.305) or VAS score. Furthermore, no significant difference was observed between the two groups, in adverse effects. CONCLUSIONS: Gabapentin (Neurontin(TM) 600 mg) administered 1 hr before anesthesia reduced the intensity and incidence of POST during the resting state without a significant adverse event, during the 24 hr after thyroid surgery. However, gabapentin did not reduce the intensity and incidence of POST during the swallowing movement.
Amines ; Anesthesia ; Cyclohexanecarboxylic Acids ; Deglutition ; gamma-Aminobutyric Acid ; Humans ; Incidence ; Intubation ; Pain, Postoperative ; Pharyngitis ; Thyroid Gland ; Thyroid Neoplasms

OBJECTIVE: We investigated the norepinephrine transporter (NET) expression in normal and pre-eclamptic placentas and analyzed the invasion activity of trophoblastic cells based on norepinephrine (NE)-NET regulation. METHODS: NET and NE expression levels were examined by western blot and enzyme-linked immunosorbent assay, respectively. Trophoblast invasion activity, depending on NE-NET regulation, was determined by NET-small interfering RNA (siRNA) and NET transfection into the human extravillous trophoblast cells with or without NE treatment and invasion rates were analyzed by zymography and an invasion assay. RESULTS: NET mRNA was expressed at a low level in pre-eclamptic placentas compared with normal placentas and NE concentration in maternal plasma increased significantly in pre-eclamptic women compared to normal pregnant women (p<0.05). NET gene upregulation and NE treatment stimulated trophoblast cell invasion up to 2.5-fold (p<0.05) by stimulating matrix metalloproteinase-9 activity via the phosphoinositol-3-kinase/AKT signaling pathway, whereas NET-siRNA with NE treatment reduced invasion rates. CONCLUSION: NET expression is reduced by inadequate regulation of NE levels during placental development. This suggests that a complementary balance between NET and NE regulates trophoblast cell invasion activities during placental development.
Blotting, Western ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Matrix Metalloproteinase 9 ; Norepinephrine ; Norepinephrine Plasma Membrane Transport Proteins ; Placenta ; Placentation ; Plasma ; Pre-Eclampsia ; Pregnant Women ; RNA ; RNA, Messenger ; RNA, Small Interfering ; Transfection ; Trophoblasts ; Up-Regulation

We studied the sex different nicotine effect on evoked population spike amplitudes (ePSA) and connexin (Cx) expression in the hippocampus CA1 area of gerbils. Acute doses of nicotine bitartrate (0.5 mg/kg: NT-0.5) slightly reduced ePSA in males but markedly augmented that in females. Acute NT (5.0 mg/kg) markedly increased the ePSA in all gerbils. Unlike acute NT-0.5, repeated NT-0.5 injection (twice a day for 7 days) significantly increased the ePSA in males and slightly affected the NT-0.5 effect in females. The Cx36 and Cx43 expression levels as well as Cx expressing neuronal populations were significantly increased by repeated NT-0.5 in in both male and female gerbils, and particularly, Cx43 expression was somewhat prominent in females. These results demonstrated a sex difference with respect to the nicotine effect on hippocampal bisynaptic excitability, irrelevant to connexin expression.
Animals ; Connexins ; Connexin 43 ; Female ; Gerbillinae* ; Hippocampus ; Male ; Neurons* ; Nicotine* ; Sex Characteristics*

Oxidative stress plays various roles in the development and progression of IgA nephropathy, while bilirubin is known as a potent antioxidant. We therefore hypothesized that serum bilirubin would be associated with renal prognosis in IgA nephropathy. The study subjects comprised 1,458 adult patients with primary IgA nephropathy in Korea. We grouped patients according to the following quartile levels of bilirubin: <0.4 mg/dL (Q1), 0.4-0.5 mg/dL (Q2), 0.6-0.7 mg/dL (Q3), and >0.8 mg/dL (Q4). The outcome data were obtained from the Korean Registry of end-stage renal disease (ESRD). Eighty patients (5.5%) contracted ESRD during a mean follow-up period of 44.9 months. The ESRD incidences were 10.7% in Q1, 8.2% in Q2, 2.8% in Q3, and 2.8% in Q4 (p<0.001). The relative risk of ESRD compared to that in Q1 was 0.307 (95% confidence interval [CI], 0.126-0.751) in Q3 and 0.315 (95% CI, 0.130-0.765) in Q4. The differences of ESRD incidence were greater in subgroups of males and of patients aged 35 yr or more, with serum albumin 4.0 g/dL or more, with normotension, with eGFR 60 mL/min/1.73 m2 or more, and with proteinuria less then 3+ by dipstick test. In conclusion, higher bilirubin level was negatively associated with ESRD incidence in IgA nephropathy.
Adult ; Bilirubin/*blood ; Disease Progression ; Female ; Glomerular Filtration Rate ; Glomerulonephritis, IGA/*blood/complications ; Humans ; Hypertension/complications ; Incidence ; Kidney Failure, Chronic/*blood/complications ; Male ; Middle Aged ; Risk ; Risk Factors ; Treatment Outcome

BACKGROUND/AIMS: Behcet's disease (BD) is a systemic disorder associated with a characteristic vasculitis that can involve both veins and arteries of all sizes. Endothelial activation or injury is a characteristic feature of BD. Endothelial dysfunction is widely regarded as being the initial lesion in the development of atherosclerosis. The carotid artery intima-media thickness (IMT) is a widely accepted marker of subclinical atherosclerosis. We aimed to determine the carotid IMT in BD patients with using high-resolution B-mode Doppler ultrasonography. METHODS: We studied 40 patients (24 males, mean age: 39.1+/-8.5 years) who were diagnosed by the international diagnostic criteria of Behcet's disease and 20 healthy controls (13 males, mean age: 40.2+/-5.1 years), and the two groups were matched by age and gender. No subject in either group had a history of atherosclerosis or its complications. The clinical data, including the age of onset, the duration of disease, a history of medication, the activity score and the laboratory data were analyzed. RESULTS: The carotid IMT in the BD group was significantly higher than that in the control group (0.71+/-0.22 mm vs. 0.59+/-0.09 mm, respectively, p<0.01). Cardiac and major vessel involvements were not identified in the BD group. However, minor vascular involvements were documented in 2 patients with deep vein thrombosis, in 4 patients with superficial thrombophlebitis and in 2 patients with pseudoaneurysm. The carotid IMT in the patients with posterior uveitis or retinal vasculitis was higher than that of the patients without these findings (0.85+/-0.21 mm vs. 0.64+/-0.10 mm, respectively, p=0.007), but there was no difference of the IMT according to minor vascular involvement. CONCLUSIONS: Despite that there was no significant cardiovascular involvement in the BD patients, the carotid IMT was significantly higher in the BD patients as compared with the healthy controls.
Adult ; Behcet Syndrome/complications/diagnosis/*pathology ; Carotid Arteries/*pathology/ultrasonography ; Case-Control Studies ; Endothelium, Vascular/pathology ; Female ; Humans ; Male ; Prognosis ; Prospective Studies ; Risk Factors ; Tunica Intima/*pathology/ultrasonography ; Tunica Media/*pathology/ultrasonography ; Ultrasonography, Doppler ; Vasculitis/pathology

BACKGROUND AND OBJECTIVES: It is well known that atherosclerosis is characterized by chronic inflammation of an injured intima and the pathological processes are initiated by an accumulation of morphologically distinct, modified forms of low density lipoprotein (LDL)-cholesterol. However, it is not well known whether the level of modified LDL-cholesterol has clinical significance for the patients who underwent percutaneous coronary intervention (PCI). SUBJECTS AND METHODS: Eighty seven patients (mean age: 63.0 +/- 11.1 years, 58 men) who underwent PCI were enrolled. The patients with stable or unstable angina pectoris were classified as group I (n=44, mean age: 62.4 +/- 9.3 years), and the patients with acute myocardial infarction were classified as group II (n=43, mean age: 63.6 +/- 12.7 years). Modified LDL-cholesterol was expressed semiquantitatively by agarose gel electrophoresis with using the charge modification frequency (CMF). The clinical and coronary angiographic data was analyzed. RESULTS: The clinical diagnosis was stable angina in 13 patients, unstable angina in 31 patients, non-ST elevation myocardial infarction in 5 patients and ST elevation myocardial infarction in 38 patients. There were no significant differences of the CMF between two groups (3.0 +/- 7.9 vs. 2.1 +/- 10.9, respectively, p=0.671). The diameter stenosis was severe in the patients with a CMF greater than 10 (84.0 +/- 10.4% vs. 78.6 +/- 13.7%, respectively, p=0.047). The six-month major adverse cardio-vascular events (MACEs) had no relationship with the CMF in group I. However, in group II, the 6-month MACEs developed more frequently in the patients with a CMF higher than 10 {2 (28%) for group ll vs. 2 (5%) for group 1, p=0.031}. The patients with acute myocardial infarction and whose CMF was higher than 10 had in-stent restenosis observed on their follow-up coronary angiography (p=0.003). CONCLUSION: A higher level of modified LDL-cholesterol is associated with severe angiographic findings and a poor prognosis for patients with acute myocardial infarction.
Acute Coronary Syndrome ; Angina, Stable ; Angina, Unstable ; Atherosclerosis ; Constriction, Pathologic ; Coronary Angiography ; Electrophoresis, Agar Gel ; Fees and Charges ; Follow-Up Studies ; Humans ; Inflammation ; Lipoproteins ; Myocardial Infarction ; Pathologic Processes ; Percutaneous Coronary Intervention ; Prognosis