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1.
Association between the Composition of Drinking Water and Cognitive Function in the Elderly: A Systematic Review.
Wasick, A, Kim, Y
International journal of environmental research and public health. 2024;(3)
Abstract
The prevalence of dementia increases with nearly 10 million new cases each year, with Alzheimer's disease contributing to 60-70% of cases. Environmental factors such as drinking water have been evaluated to determine if a relationship exists between trace elements in drinking water and the risk of developing cognitive disorders in the elderly. The purpose of the current systematic review was to evaluate an association between the composition of drinking water and cognitive function in the elderly. In accordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines, a literature search was conducted using PubMed and CINAHL databases. A total of 10 studies were included in the current systematic review. Aluminum is the most commonly evaluated trace element in studies (n = 8), followed by silica (n = 5), calcium (n = 4), and fluoride (n = 4). Aluminum exposure showed an increased risk of cognitive decline in four studies, with no association reported in the other studies. Higher silica and pH levels were shown to be protective against a decline in cognitive function. A similar protective effect of calcium was found in two studies. Future research should measure multiple trace mineral levels in all water sources to evaluate the impact on cognitive function.
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2.
Hypertension effects of the COVID-19 lockdowns: Evidence from a repeated cross-sectional survey in Peru.
Sara, R, Radoias, V, Kim, Y
Economics and human biology. 2024;:101332
Abstract
Using data from Peru and a quasi-experimental approach, we document significant increases in arterial blood pressure and in the incidence of arterial hypertension caused by the restrictive measures employed by the Peruvian authorities during the COVID-19 pandemic. The effects are more pronounced for women, older respondents, and urban residents. The effects are statistically significant and high in magnitude relative to the pre-pandemic incidence of disease in the Peruvian population. A main channel of disease propagation seems to be the changes in dietary habits and physical activity imposed by the COVID-19 lockdowns, which affected several anthropometric measurements that are common risk factors for hypertension.
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3.
A 52-week efficacy and safety study of enavogliflozin versus dapagliflozin as an add-on to metformin in patients with type 2 diabetes mellitus: ENHANCE-M extension study.
Sohn, TS, Han, KA, Kim, Y, Lee, BW, Chon, S, Jeong, IK, Hong, EG, Son, JW, Na, J, Cho, JM, et al
Diabetes, obesity & metabolism. 2024
Abstract
AIM: To evaluate the long-term safety and efficacy of enavogliflozin 0.3 mg/day added to metformin in patients with type 2 diabetes mellitus. MATERIALS AND METHODS After 24 weeks of a randomized, double-blind treatment period with enavogliflozin 0.3 mg/day (n = 101) or dapagliflozin 10 mg/day (n = 99) added to metformin, all patients received enavogliflozin 0.3 mg/day plus metformin for an additional 28 weeks during the open-label extension period. RESULTS Eighty-two patients continued enavogliflozin (maintenance group), and 77 were switched from dapagliflozin to enavogliflozin (switch group). All adverse drug reactions (ADR) were mild in severity. In the maintenance group, ADRs (cystitis and vaginal infection) were reported in two patients (2.44%) during 52 weeks. In the switch group, ADR (hypoglycaemia) was reported in one patient (1.30%) during a 28-week open-label extension period. At week 52, glycated haemoglobin and fasting plasma glucose were significantly lower than at the baseline, by 0.85% and 29.08 mg/dl, respectively, in the maintenance group (p < .0001 for both), and by 0.81% and 32.77 mg/dl, respectively, in the switch group (p < .0001 for both). At week 52, 68.92% of patients from the maintenance group and 64.29% from the switch group achieved glycated haemoglobin <7%. A significant increase in the urine glucose-creatinine ratio was observed at week 52, by 58.81 g/g and 63.77 g/g in the maintenance and switch groups, respectively (p < .0001). CONCLUSIONS Enavogliflozin added to metformin was tolerated well for up to 52 weeks and provided continual glycaemic control in type 2 diabetes mellitus, along with a significant increase in the urine glucose-creatinine ratio.
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4.
tRNA engineering strategies for genetic code expansion.
Kim, Y, Cho, S, Kim, JC, Park, HS
Frontiers in genetics. 2024;:1373250
Abstract
The advancement of genetic code expansion (GCE) technology is attributed to the establishment of specific aminoacyl-tRNA synthetase/tRNA pairs. While earlier improvements mainly focused on aminoacyl-tRNA synthetases, recent studies have highlighted the importance of optimizing tRNA sequences to enhance both unnatural amino acid incorporation efficiency and orthogonality. Given the crucial role of tRNAs in the translation process and their substantial impact on overall GCE efficiency, ongoing efforts are dedicated to the development of tRNA engineering techniques. This review explores diverse tRNA engineering approaches and provides illustrative examples in the context of GCE, offering insights into the user-friendly implementation of GCE technology.
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5.
Outcomes of Various Classes of Oral Antidiabetic Drugs on Nonalcoholic Fatty Liver Disease.
Jang, H, Kim, Y, Lee, DH, Joo, SK, Koo, BK, Lim, S, Lee, W, Kim, W
JAMA internal medicine. 2024;(4):375-383
Abstract
IMPORTANCE Several oral antidiabetic drug (OAD) classes can potentially improve patient outcomes in nonalcoholic fatty liver disease (NAFLD) to varying degrees, but clinical data on which class is favored are lacking. OBJECTIVE To investigate which OAD is associated with the best patient outcomes in NAFLD and type 2 diabetes (T2D). DESIGN, SETTING, AND PARTICIPANTS This retrospective nonrandomized interventional cohort study used the National Health Information Database, which provided population-level data for Korea. This study involved patients with T2D and concomitant NAFLD. EXPOSURES Receiving either sodium-glucose cotransporter 2 (SGLT2) inhibitors, thiazolidinediones, dipeptidyl peptidase-4 (DPP-4) inhibitors, or sulfonylureas, each combined with metformin for 80% or more of 90 consecutive days. MAIN OUTCOMES AND MEASURES The main outcomes were NAFLD regression assessed by the fatty liver index and composite liver-related outcome (defined as liver-related hospitalization, liver-related mortality, liver transplant, and hepatocellular carcinoma) using the Fine-Gray model regarding competing risks. RESULTS In total, 80 178 patients (mean [SD] age, 58.5 [11.9] years; 43 007 [53.6%] male) were followed up for 219 941 person-years, with 4102 patients experiencing NAFLD regression. When compared with sulfonylureas, SGLT2 inhibitors (adjusted subdistribution hazard ratio [ASHR], 1.99 [95% CI, 1.75-2.27]), thiazolidinediones (ASHR, 1.70 [95% CI, 1.41-2.05]), and DPP-4 inhibitors (ASHR, 1.45 [95% CI, 1.31-1.59]) were associated with NAFLD regression. SGLT2 inhibitors were associated with a higher likelihood of NAFLD regression when compared with thiazolidinediones (ASHR, 1.40 [95% CI, 1.12-1.75]) and DPP-4 inhibitors (ASHR, 1.45 [95% CI, 1.30-1.62]). Only SGLT2 inhibitors (ASHR, 0.37 [95% CI, 0.17-0.82]), not thiazolidinediones or DPP-4 inhibitors, were significantly associated with lower incidence rates of adverse liver-related outcomes when compared with sulfonylureas. CONCLUSIONS AND RELEVANCE The results of this cohort study suggest that physicians may lean towards prescribing SGLT2 inhibitors as the preferred OAD for individuals with NAFLD and T2D, considering their potential benefits in NAFLD regression and lower incidences of adverse liver-related outcomes. This observational study should prompt future research to determine whether prescribing practices might merit reexamination.
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6.
Conformational coupling of the sialic acid TRAP transporter HiSiaQM with its substrate binding protein HiSiaP.
Peter, MF, Ruland, JA, Kim, Y, Hendricks, P, Schneberger, N, Siebrasse, JP, Thomas, GH, Kubitscheck, U, Hagelueken, G
Nature communications. 2024;(1):217
Abstract
The tripartite ATP-independent periplasmic (TRAP) transporters use an extra cytoplasmic substrate binding protein (SBP) to transport a wide variety of substrates in bacteria and archaea. The SBP can adopt an open- or closed state depending on the presence of substrate. The two transmembrane domains of TRAP transporters form a monomeric elevator whose function is strictly dependent on the presence of a sodium ion gradient. Insights from experimental structures, structural predictions and molecular modeling have suggested a conformational coupling between the membrane elevator and the substrate binding protein. Here, we use a disulfide engineering approach to lock the TRAP transporter HiSiaPQM from Haemophilus influenzae in different conformational states. The SBP, HiSiaP, is locked in its substrate-bound form and the transmembrane elevator, HiSiaQM, is locked in either its assumed inward- or outward-facing states. We characterize the disulfide-locked constructs and use single-molecule total internal reflection fluorescence (TIRF) microscopy to study their interactions. Our experiments demonstrate that the SBP and the transmembrane elevator are indeed conformationally coupled, meaning that the open and closed state of the SBP recognize specific conformational states of the transporter and vice versa.
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7.
Sorafenib for 9,923 Patients with Hepatocellular Carcinoma: An Analysis from National Health Insurance Claim Data in South Korea.
Han, S, Kim, DY, Lim, HY, Yoon, JH, Ryoo, BY, Kim, Y, Kim, K, Kim, BY, Yi, SY, Kim, DS, et al
Gut and liver. 2024;(1):116-124
Abstract
BACKGROUND/AIMS: Sorafenib is the standard of care in the management of advanced hepatocellular carcinoma (HCC). The purpose of this study was to investigate the characteristics, treatment patterns and outcomes of sorafenib among HCC patients in South Korea. METHODS This population-based retrospective, single-arm, observational study used the Korean National Health Insurance database to identify patients with HCC who received sorafenib between July 1, 2008, and December 31, 2014. A total of 9,923 patients were recruited in this study. RESULTS Among 9,923 patients, 6,669 patients (68.2%) received loco-regional therapy prior to sorafenib, and 1,565 patients (15.8%) received combination therapy with concomitant sorafenib; 2,591 patients (26.1%) received rescue therapy after sorafenib, and transarterial chemoembolization was the most common modality applied in 1,498 patients (15.1%). A total of 3,591 patients underwent rescue therapy after sorafenib, and the median overall survival was 14.5 months compared to 4.6 months in 7,332 patients who received supportive care after sorafenib. The mean duration of sorafenib administration in all patients was 105.7 days; 7,023 patients (70.8%) received an initial dose of 600 to 800 mg. The longest survival was shown in patients who received the recommended dose of 800 mg, subsequently reduced to 400 mg (15.0 months). The second longest survival was demonstrated in patients with a starting dose of 800 mg, followed by a dose reduction to 400-600 mg (9.6 months). CONCLUSIONS Real-life data show that the efficacy of sorafenib seems similar to that observed in clinical trials, suggesting that appropriate subsequent therapy after sorafenib might prolong patient survival.
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8.
Effect of MIND diet on cognitive function in elderly: a narrative review with emphasis on bioactive food ingredients.
Seo, Y, Gang, G, Kim, HK, Kim, Y, Kang, S, Kim, H, Lee, SG, Go, GW
Food science and biotechnology. 2024;(2):297-306
Abstract
As the world becomes a super-aged society, cognitive decline is public health problems that are increasing rapidly. A healthy diet has great potential for maintaining cognitive health. A diet that could delay the onset of neurodegenerative diseases has been developed: the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet, a hybrid form of the Mediterranean diet and the Dietary Approaches to Stop Hypertension (DASH) diet. In this review, the effects of the MIND diet on improving cognitive function, including memory, are summarized. In most studies, the higher the adherence to the MIND diet, the higher the cognitive function evaluation score, and the lower the incidence of dementia. This is because of the anti-inflammatory and antioxidant effects of the major nutritional components of the MIND diet: folate, carotenoids, polyphenols, and polyunsaturated fatty acids. Adherence to the MIND diet, containing various bioactive food ingredients, is related to cognitive improvement in the elderly population.
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9.
The Significance of N6-Methyladenosine RNA Methylation in Regulating the Hepatitis B Virus Life Cycle.
Moon, JS, Lee, W, Cho, YH, Kim, Y, Kim, GW
Journal of microbiology and biotechnology. 2024;(2):233-239
Abstract
N6-methyladenosine (m6A) RNA methylation has recently emerged as a significant co-transcriptional modification involved in regulating various RNA functions. It plays a vital function in numerous biological processes. Enzymes referred to as m6A methyltransferases, such as the methyltransferaselike (METTL) 3-METTL14-Wilms tumor 1 (WT1)-associated protein (WTAP) complex, are responsible for adding m6A modifications, while m6A demethylases, including fat mass and obesity-associated protein (FTO) and alkB homolog 5 (ALKBH5), can remove m6A methylation. The functions of m6A-methylated RNA are regulated through the recognition and interaction of m6A reader proteins. Recent research has shown that m6A methylation takes place at multiple sites within hepatitis B virus (HBV) RNAs, and the location of these modifications can differentially impact the HBV infection. The addition of m6A modifications to HBV RNA can influence its stability and translation, thereby affecting viral replication and pathogenesis. Furthermore, HBV infection can also alter the m6A modification pattern of host RNA, indicating the virus's ability to manipulate host cellular processes, including m6A modification. This manipulation aids in establishing chronic infection, promoting liver disease, and contributing to pathogenesis. A comprehensive understanding of the functional roles of m6A modification during HBV infection is crucial for developing innovative approaches to combat HBV-mediated liver disease. In this review, we explore the functions of m6A modification in HBV replication and its impact on the development of liver disease.
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10.
The Impact of Chronic Cannabis Use on Esophageal Motility in Patients Referred for Esophageal Manometry.
Ugwuegbu, O, Shibli, F, Kim, Y, Rangan, V, Kurin, M, Ayoub, F, Ganocy, S, Kavitt, R, Fass, R
Journal of clinical gastroenterology. 2024;(4):342-348
Abstract
BACKGROUND Tetrahydrocannabinol, the main psychoactive compound in cannabis, binds with high affinity to the cannabinoid 1 receptor. Small randomized controlled studies using conventional manometry have shown that the cannabinoid 1 receptor can modulate esophageal function, namely transient lower esophageal sphincter relaxation frequency and lower esophageal sphincter tone. The effect of cannabinoids on esophageal motility in patients referred for esophageal manometry has not been fully elucidated using high-resolution esophageal manometry (HREM). We aimed to characterize the clinical effect of chronic cannabis use on esophageal motility utilizing HREM. METHODS Patients who underwent HREM from 2009 to 2019 were identified at 4 academic medical centers. The study group consisted of patients with a noted history of chronic cannabis use, a diagnosis of cannabis-related disorder, or a positive urine toxicology screen. Age and gender-matched patients with no history of cannabis use were selected to form the control group. Data on HREM metrics based on the Chicago classification V3, and the prevalence of esophageal motility disorders were compared. Confounding effects of BMI and medications on esophageal motility were adjusted for. RESULTS Chronic cannabis use was found to be an independent negative predictor of weak swallows (β=-8.02, P =0.0109), but not a predictor of failed swallows ( P =0.6890). The prevalence of ineffective esophageal motility was significantly lower in chronic cannabis users compared with nonusers (OR=0.44, 95% CI 0.19-0.93, P =0.0384). There was no significant difference in the prevalence of other esophageal motility disorders between the 2 cohorts. In patients with dysphagia as their primary indication for HREM, chronic cannabis use was found to be independently associated with increased median integrated relaxation pressure (β=6.638, P =0.0153) and increased mean lower esophageal sphincter resting pressure (β=10.38, P =0.0084). CONCLUSIONS Chronic cannabis use is associated with decreased weak swallows and reduced prevalence of ineffective esophageal motility in patients referred for esophageal manometry. In patients referred for dysphagia, chronic cannabis use is associated with increased integrated relaxation pressure and lower esophageal sphincter resting pressure, though not to levels above the normal range.