Lipid droplet dynamics are essential for the development of the malaria parasite Plasmodium falciparum.

Lipid droplets (LDs) are organelles that are central to lipid and energy homeostasis across all eukaryotes. In the malaria-causing parasite Plasmodium falciparum the roles of LDs in lipid acquisition from its host cells and their metabolism are poorly understood, despite the high demand for lipids in parasite membrane synthesis. We systematically characterised LD size, composition and dynamics across the disease-causing blood infection. Applying split fluorescence emission analysis and three-dimensional (3D) focused ion beam-scanning electron microscopy (FIB-SEM), we observed a decrease in LD size in late schizont stages. LD contraction likely signifies a switch from lipid accumulation to lipid utilisation in preparation for parasite egress from host red blood cells. We demonstrate connections between LDs and several parasite organelles, pointing to potential functional interactions. Chemical inhibition of triacylglyerol (TAG) synthesis or breakdown revealed essential LD functions for schizogony and in counteracting lipid toxicity. The dynamics of lipid synthesis, storage and utilisation in P. falciparum LDs might provide a target for new anti-malarial intervention strategies.

Antibiotic-induced intestinal microbiota depletion can attenuate the acute kidney injury to chronic kidney disease transition via NADPH oxidase 2 and trimethylamine-N-oxide inhibition.

Intestinal microbiota and their metabolites affect systemic inflammation and kidney disease outcomes. Here, we investigated the key metabolites associated with the acute kidney injury (AKI)-to chronic kidney disease (CKD) transition and the effect of antibiotic-induced microbiota depletion (AIMD) on this transition. In 61 patients with AKI, 59 plasma metabolites were assessed to determine the risk of AKI-to-CKD transition. An AKI-to-CKD transition murine model was established four weeks after unilateral ischemia-reperfusion injury (IRI) to determine the effects of AIMD on the gut microbiome, metabolites, and pathological responses related to CKD transition. Human proximal tubular epithelial cells were challenged with CKD transition-related metabolites, and inhibitory effects of NADPH oxidase 2 (NOX2) signals were tested. Based on clinical metabolomics, plasma trimethylamine N-oxide (TMAO) was associated with a significantly increased risk for AKI-to-CKD transition [adjusted odds ratio 4.389 (95% confidence interval 1.106-17.416)]. In vivo, AIMD inhibited a unilateral IRI-induced increase in TMAO, along with a decrease in apoptosis, inflammation, and fibrosis. The expression of NOX2 and oxidative stress decreased after AIMD. In vitro, TMAO induced fibrosis with NOX2 activation and oxidative stress. NOX2 inhibition successfully attenuated apoptosis, inflammation, and fibrosis with suppression of G2/M arrest. NOX2 inhibition (in vivo) showed improvement in pathological changes with a decrease in oxidative stress without changes in TMAO levels. Thus, TMAO is a key metabolite associated with the AKI-to-CKD transition, and NOX2 activation was identified as a key regulator of TMAO-related AKI-to-CKD transition both in vivo and in vitro.

Enhanced phagocytosis associated with multinucleated microglia via Pyk2 inhibition in an acute ß-amyloid infusion model.

Multinucleated microglia have been observed in contexts associated with infection, inflammation, and aging. Though commonly linked to pathological conditions, the larger cell size of multinucleated microglia might enhance their phagocytic functions, potentially aiding in the clearance of brain debris and suggesting a reassessment of their pathological significance. To assess the phagocytic capacity of multinucleated microglia and its implications for brain debris clearance, we induced their formation by inhibiting Pyk2 activity using the pharmacological inhibitor PF-431396, which triggers cytokinesis regression. Multinucleated microglia demonstrate enhanced phagocytic function, as evidenced by their increased capacity to engulf ß-amyloid (Aß) oligomers. Concurrently, the phosphorylation of Pyk2, induced by Aß peptide, was diminished upon treatment with a Pyk2 inhibitor (Pyk2-Inh, PF-431396). Furthermore, the increased expression of Lamp1, a lysosomal marker, with Pyk2-inh treatment, suggests an enhancement in proteolytic activity. In vivo, we generated an acute Alzheimer's disease (AD) model by infusing Aß into the brains of Iba-1 EGFP transgenic (Tg) mice. The administration of the Pyk2-Inh led to an increased migration of microglia toward amyloid deposits in the brains of Iba-1 EGFP Tg mice, accompanied by morphological activation, suggesting a heightened affinity for Aß. In human microglia, lipopolysaccharide (LPS)-induced inflammatory responses showed that inhibition of Pyk2 signaling significantly reduced the transcription and protein expression of pro-inflammatory markers. These results suggest that Pyk2 inhibition can modulate microglial functions, potentially reducing neuroinflammation and aiding in the clearance of neurodegenerative disease markers. This highlights Pyk2 as a promising target for therapeutic intervention in neurodegenerative diseases.

Sustaining Surface Lithiophilicity of Ultrathin Li-Alloy Coating Layers on Current Collector for Zero-Excess Li-Metal Batteries.

Zero-excess Li-metal batteries (ZE-LMBs) have emerged as the ultimate battery platform, offering an exceptionally high energy density. However, the absence of Li-hosting materials results in uncontrolled dendritic Li deposition on the Cu current collector, leading to chronic loss of Li inventory and severe electrolyte decomposition, limiting its full utilization upon cycling. This study presents the application of ultrathin (≈50 nm) coatings comprising six metallic layers (Cu, Ag, Au, Pt, W, and Fe) on Cu substrates in order to provide insights into the design of Li-depositing current collectors for stable ZE-LMB operation. In contrast to non-alloy Cu, W, and Fe coatings, Ag, Au, and Pt coatings can enhance surface lithiophilicity, effectively suppressing Li dendrite growth, thereby improving Li reversibility. Considering the distinct Li-alloying behaviors, particularly solid-solution and/or intermetallic phase formation, Pt-coated Cu current collectors maintain surface lithiophilicity over repeated Li plating/stripping cycles by preserving the original coating layer, thereby attaining better cycling performance of ZE-LMBs. This highlights the importance of selecting suitable Li-alloy metals to sustain surface lithiophilicity throughout cycling to regulate dendrite-less Li plating and improve the electrochemical stability of ZE-LMBs.

Interplay of Mediterranean-diet adherence, genetic factors, and metabolic dysfunction-associated steatotic liver disease risk in Korea.

BACKGROUNDS: Metabolic dysfunction-associated steatotic liver disease (MASLD) has gained attention owing to its severe complications. This study aimed to explore the interaction between Mediterranean-diet (MD) adherence, genetic factors, and MASLD risk in a Korean population. METHODS: In total, 33,133 individuals aged 40 years and older from the Korean Genome and Epidemiology Study (KoGES) were analyzed. Participants were assessed for MASLD based on criteria and MD adherence measured by the Korean version of the Mediterranean-Diet Adherence Screener (K-MEDAS). Individuals were categorized into two groups based on their MD adherence: high adherence (K-MEDAS > 6) and low adherence (K-MEDAS < 5). Single nucleotide polymorphism (SNP) genotypes were obtained using the Korea Biobank array. Logistic regression was used to examine the single-marker variants for genetic associations with MASLD prevalence. RESULTS: Individuals were categorized into MASLD (10,018 [30.2%]) and non-MASLD (23,115 [69.8%]) groups. A significant interaction was observed between the rs780094 glucokinase regulatory protein (GCKR) gene and K-MEDAS on MASLD (p < 10 - 2 ). Of individuals with K-MEDAS > 6, those carrying the minor allele (C) of the GCKR gene rs780094 exhibited a lower risk of MASLD compared to those without the allele (odds ratio [OR] = 0.88 [0.85-0.91], p-value = 5.54e-13). CONCLUSION: The study identified a significant interaction involving the rs780094 variant near the GCKR gene, with carriers of the minor allele exhibiting a lower MASLD risk among those adhering well to the MD. Dietary habits influence the MASLD risk associated with the rs780094 allele, emphasizing the need for personalized nutrition recommendations.

Clinical feature, GALC variant spectrum, and genotype-phenotype correlation in Korean Krabbe disease patients: Multicenter experience over 13 years.

Krabbe disease (KD) is an autosomal recessive neurodegenerative disorder caused by deficiency of the galactocerebrosidase (GALC) due to variants in the GALC gene. Here, we provide the first and the largest comprehensive analysis of clinical and genetic characteristics, and genotype-phenotype correlations of KD in Korean in comparison with other ethnic groups. From June 2010 to June 2023, 10 patients were diagnosed with KD through sequencing of GALC. Clinical features, and results of GALC sequencing, biochemical test, neuroimaging, and neurophysiologic test were obtained from medical records. An additional nine previously reported Korean KD patients were included for review. In Korean KD patients, the median age of onset was 2 years (3 months-34 years) and the most common phenotype was adult-onset (33%, 6/18) KD, followed by infantile KD (28%, 5/18). The most frequent variants were c.683_694delinsCTC (23%) and c.1901T>C (23%), while the 30-kb deletion was absent. Having two heterozygous pathogenic missense variants was associated with later-onset phenotype. Clinical features were similar to those of other ethnic groups. In Korean KD patients, the most common phenotype was the adult-onset type and the GALC variant spectrum was different from that of the Caucasian population. This study would further our understanding of KD.

Assessing social cognition in patients with schizophrenia and healthy controls using the reading the mind in the eyes test (RMET): a systematic review and meta-regression.

The reading the mind in the eyes test (RMET) - which assesses the theory of mind component of social cognition - is often used to compare social cognition between patients with schizophrenia and healthy controls. There is, however, no systematic review integrating the results of these studies. We identified 198 studies published before July 2020 that administered RMET to patients with schizophrenia or healthy controls from three English-language and two Chinese-language databases. These studies included 41 separate samples of patients with schizophrenia (total n = 1836) and 197 separate samples of healthy controls (total n = 23 675). The pooled RMET score was 19.76 (95% CI 18.91-20.60) in patients and 25.53 (95% CI 25.19-25.87) in controls (z = 12.41, p < 0.001). After excluding small-sample outlier studies, this difference in RMET performance was greater in studies using non-English v. English versions of RMET (Chi [Q] = 8.54, p < 0.001). Meta-regression analyses found a negative association of age with RMET score and a positive association of years of schooling with RMET score in both patients and controls. A secondary meta-analysis using a spline construction of 180 healthy control samples identified a non-monotonic relationship between age and RMET score - RMET scores increased with age before 31 and decreased with age after 31. These results indicate that patients with schizophrenia have substantial deficits in theory of mind compared with healthy controls, supporting the construct validity of RMET as a measure of social cognition. The different results for English versus non-English versions of RMET and the non-monotonic relationship between age and RMET score highlight the importance of the language of administration of RMET and the possibility that the relationship of aging with theory of mind is different from the relationship of aging with other types of cognitive functioning.

Optimal Insertion Depth of Central Venous Catheter through the Right Internal Jugular Vein, Verified by Transesophageal Echocardiography: A Prospective Observational Study.

This prospective observational study investigated the optimal insertion depth of the central venous catheter through the right internal jugular vein using transesophageal echocardiography. After tracheal intubation, the anesthesiologist inserted a probe for esophageal echocardiography into the patient's esophagus. The investigators placed the catheter tip 2 cm above the superior edge of the crista terminalis with echocardiography, which was defined as the optimal point. We measured the inserted length of the catheter. Pearson correlation tests were performed with the measured optimal depth and some patient parameters. We made a new formula for placing the catheter at the optimal position. A total of 89 subjects were enrolled in this trial. The correlation coefficient between the measured optimal depth and the patient's parameters was the highest for patient height (0.703, p < 0.001). We made a new formula of 'height (cm)/10 - 1.5 cm'. The accuracy rate of this formula for the optimal zone was 71.9% (95% confidence interval; 62.4 - 81.4%), which was the highest among the previous formulas or guidelines when we compared. In conclusion, the central venous catheter tip was evaluated with transesophageal echocardiography, and we could make a new formula of 'height (cm)/10 - 1.5', which seemed to be better than other previous guidelines.

Establishing Conditions for Blood Smear Drying and Staining on Sysmex SP-50 for Leukocyte Differential Count.

BACKGROUND: The purpose of this study was to determine the staining conditions and appropriate fan1 start time (FAN1ST) for Sysmex SP-50 to produce blood smears (BS) that reflect the true lymphocyte morphology of patient samples. METHODS: Using different start times of fan1, we obtained a set of 84 blood smear slides from 21 blood samples and measured 10,920 lymphocyte areas, which were then converted to compare lymphocyte sizes. We also performed a leukocyte differential count using Sysmex DI-60 on 202 blood smear slides prepared before and after the change in staining conditions and compared the results. RESULTS: The mean lymphocyte sizes at FAN1ST 0 second, 5 seconds, 10 seconds, and 30 seconds were 12.55 µm, 12.14 µm, 11.27 µm, and 10.50 µm, respectively. The mean differences in the preclassification of neutrophils, lymphocytes, monocytes, eosinophils, and basophils in DI-60, according to the SP-50 staining conditions, were 0.88, -1.58, -0.24, 0.37, and 0.07, respectively. CONCLUSIONS: Wright-Giemsa staining of blood smears prepared on the SP-50 showed that changing the pH of the concentrated phosphate buffer to 6.6 and adjusting the staining time did not affect the results of the leukocyte differential count. However, since fan1 was used to dry the blood smear on the SP-50 and the lymphocyte size gradually decreased as the start time was delayed, it was necessary to set a start time for fan1 that did not affect the lymphocyte size.

Genotype-phenotype correlations in children with Gitelman syndrome.

BACKGROUND: This study aimed to analyze genotype-phenotype correlations in children with Gitelman syndrome (GS). METHODS: This multicenter retrospective study included 50 Korean children diagnosed with SLC12A3 variants in one or both alleles and the typical laboratory findings of GS. Genetic testing was performed using the Sanger sequencing except for one patient. RESULTS: The median age at the diagnosis was 10.5 years (interquartile range, 6.8;14.1), and 41 patients were followed up for a median duration of 5.4 years (interquartile range, 4.1;9.6). A total of 30 different SLC12A3 variants were identified. Of the patients, 34 (68%) had biallelic variants, and 16 (32%) had monoallelic variants on examination. Among the patients with biallelic variants, those (n = 12) with the truncating variants in one or both alleles had lower serum chloride levels (92.2 ± 3.2 vs. 96.5 ± 3.8 mMol/L, P = 0.002) at onset, as well as lower serum potassium levels (3.0 ± 0.4 vs. 3.4 ± 0.3 mMol/L, P = 0.016), and lower serum chloride levels (96.1 ± 1.9 vs. 98.3 ± 3.0 mMol/L, P = 0.049) during follow-up than those without truncating variants (n = 22). Patients with monoallelic variants on examination showed similar phenotypes and treatment responsiveness to those with biallelic variants. CONCLUSIONS: Patients with GS who had truncating variants in one or both alleles had more severe electrolyte abnormalities than those without truncating variants. Patients with GS who had monoallelic SLC12A3 variants on examination had almost the same phenotypes, response to treatment, and long-term prognosis as those with biallelic variants.

Using propensity score matching analysis to compare between cardiometabolic risk factors and physical activity type in Korean adults: findings from a nationwide population-based survey.

PURPOSE: We aimed to assess the effects of different exercise modalities on cardiometabolic risk factors within a comprehensive, representative sample of the Korean population. METHODS: We categorized 13,971 adult participants into aerobic exercise (AE), resistance exercise (RE), combined aerobic and resistance exercise (TE), insufficient exercise, and inactive groups. Multivariable regressions were conducted to compare the incidence of chronic diseases across the groups before and after propensity score matching (PSM). RESULTS: The TE and RE groups had significantly lower waist circumference (WC), mean blood pressure (BP), glucose and insulin-related indices, and white blood cell count (WBC) measures, with TE showing the most significant differences. The TE group had significantly lower triglyceride levels and higher high-density lipoprotein-cholesterol levels. Post-PSM, the TE group had the lowest risk for metabolic syndrome, hypertension, and diabetes, closely followed by the RE group when compared with the inactive group. In a subgroup analysis, RE consistently exhibited benefits including lower body mass index, WC, BP, total cholesterol, glucose and insulin-related indices, and WBC count when compared with AE. RE may be associated with reduced incidence of cardiometabolic diseases compared to AE alone. CONCLUSION: TE appears to be associated with significant reduction in cardiometabolic risk in Korean adults. RE possibly provides a more favorable cardiometabolic effect than AE.

A randomized comparison of three intubation techniques/tube materials for nasotracheal intubation.

PURPOSE: We sought to compare three intubation methods using different intubation techniques/tube materials for tube advancement from the nasal cavity into the oral cavity during nasotracheal intubation. METHODS: We conducted a randomized clinical trial with adult patients scheduled to undergo elective surgery requiring nasotracheal intubation for general anesthesia. Participants were randomly allocated to a polyvinyl chloride (PVC) tube group (group P), PVC tube attached to a rubber catheter group (group PR), or velvet-soft PVC tube group (group V). Tracheal intubation was then performed based on group allocation. The primary outcome was the first-attempt success rate of tube advancement into the oral cavity; secondary outcomes included the time required for tube advancement into the oral cavity, total intubation time, and the incidence of epistaxis. RESULTS: A total of 149 patients were included in the study. The first-attempt success rate in group V (90%) was significantly higher than that in group P (58%) (odds ratio, 6.5; 95% confidence interval [CI], 2.2 to 19.2), but similar to that in group PR (100%). The mean (standard deviation) time required for tube advancement into the oral cavity was significantly shorter in group V (16 [13] sec) than in group PR [40 (10) sec; 95% CI of mean difference, 17 to 30] and group P (26 [16] sec; 95% CI of mean difference, 3 to 16). Total intubation time was longest in group PR. Epistaxis occurred the least in group V. CONCLUSIONS: Among the three intubation techniques/tube materials for nasotracheal intubation, the velvet-soft PVC tube provided the highest first-attempt success rate, most expeditious advancement into the oral cavity, and lowest incidence of epistaxis. STUDY REGISTRATION: ClinicalTrials.gov (NCT04695444); first submitted 30 December 2020.

RéSUMé: OBJECTIF: Nous avons cherché à comparer trois méthodes d'intubation utilisant différentes techniques d'intubation / matériaux de sondes pour l'avancement de la sonde de la cavité nasale dans la cavité buccale pendant l'intubation nasotrachéale. MéTHODE: Des patient·es devant recevoir une intubation nasotrachéale ont été réparti·es au hasard dans un groupe avec sondes en polychlorure de vinyle (PVC) (groupe P), un groupe avec sondes en PVC attachées à un cathéter en caoutchouc (groupe PR) ou un groupe avec sondes en PVC doux comme du velours (groupe V). L'intubation trachéale a ensuite été réalisée en fonction de l'affectation du groupe. Le critère d'évaluation principal était le taux de réussite de la première tentative d'avancement de la sonde dans la cavité buccale; les critères d'évaluation secondaires comprenaient le temps nécessaire à l'avancement de la sonde dans la cavité buccale, la durée totale de l'intubation et l'incidence d'épistaxis. RéSULTATS: Au total, 149 patient·es ont été inclus·es dans l'étude. Le taux de réussite de l'intubation à la première tentative était significativement plus élevé dans le groupe V (90 %) que dans le groupe P (58 %) (rapport de cotes, 6,5; intervalle de confiance à 95 % [IC], 2,2 à 19,2), mais similaire à celui du groupe PR (100 %). Le temps moyen (écart type) nécessaire pour l'avancement de la sonde dans la cavité buccale était significativement plus court dans le groupe V (16 [13] sec) que dans le groupe PR (40 [10] sec; IC 95 % de la différence moyenne, 17 à 30) et dans le groupe P (26 [16] sec; IC 95 % de la différence moyenne, 3 à 16). La durée totale d'intubation était la plus longue dans le groupe PR. C'est dans le groupe V que l'épistaxis a été la moins fréquente. CONCLUSION: Parmi les trois techniques d'intubation/matériaux de sonde pour l'intubation nasotrachéale, le tube en PVC doux comme du velours a fourni le taux de réussite de première tentative le plus élevé, l'avancement le plus rapide dans la cavité buccale et l'incidence d'épistaxis la plus faible. ENREGISTREMENT DE L'éTUDE: ClinicalTrials.gov (NCT04695444); première soumission le 30 décembre 2020.

Implications of Childhood Autism Spectrum Disorder for Maternal Employment: United States vs. Norway.

OBJECTIVES: A country's social welfare system may play an important role in maternal employment. This study compared the labor market participation of mothers of children within the United States (U.S.) and Norway to examine whether the child's age and severity of the ASD affected mothers' employment differently between the two countries. METHODS: The 2019 National Survey of Children's Health was used for the U.S. analysis, and the 2019 administrative register data were used for the Norwegian analysis. A logit model was used to analyze the impact of a child's age and ASD severity on maternal employment in the U.S. and Norway. We presented the results as average marginal effects obtained from the logistic regression analyses. RESULTS: After adjusting for mothers' sociodemographic variables and the child's age, U.S. mothers of children with mild ASD and moderate/severe ASD had respectively 12 and 25% points lower probability of being employed than U.S. mothers of children without special health care needs. In Norway, mothers of children with moderate/severe ASD had a 13% points lower probability of employment than mothers without special health care needs. The probability of being employed for mothers caring for a child with ASD was significantly greater as the child got older in both countries. CONCLUSIONS FOR PRACTICE: The employment gap was more substantial in the U.S. than in Norway. A general high employment participation rate among women and an elaborated welfare state and policy package seem to benefit employment among mothers of children with ASD in Norway.

Tetrahydrocannabinol and dopamine D1 receptor.

Dopamine is a hormone that is released by the adrenal gland and influences motor control and motivation. Dopamine is known to have 5 receptors which are D1, D2, D3, D4 and D5, which are further categorized into 2 families: D1 family and D2 family. The D1 family is known to play a role in motivation and motor control whereas the D2 family is known to affect attention and sleep. THC, a type of cannabinoid, can lead to feelings of euphoria, anxiety, fear, distrust, or panic. THC is known to affect dopamine in regions such as the anterior cingulate cortex (ACC), and plays a role in fundamental cognitive processes. Although there is a vast amount of research between the relationship of THC on dopamine, there continues to be limited research in relation to THC on dopamine receptors. The D1 receptor plays a role in several essential functions, such as memory, attention, impulse control, regulation of renal function, and locomotion. Accordingly, this review is intended to summarize the relationship between THC and D1 receptors, highlighting key gaps in the literature and avenues for future research.

Integrative detection of genome-wide translation using iRibo.

Ribosome profiling is a sequencing technique that provides a global picture of translation across a genome. Here, we present iRibo, a software program for integrating any number of ribosome profiling samples to obtain sensitive inference of annotated or unannotated translated open reading frames. We describe the process of using iRibo to generate a species' translatome from a set of ribosome profiling samples using S. cerevisiae as an example. For complete details on the use and execution of this protocol, please refer to Wacholder et al. (2023).1.

Symptom and Technology Management Intervention Usefulness for Caregivers of Children With Tracheostomies and Feeding Tubes.

BACKGROUND: Caregivers of children who require medical technology of tracheostomies and feeding tubes provide intensive and specialized care at home. They have extensive training in the hospital prior to their child's discharge; however, there is limited education about their child's care once they are at home. The Creating Opportunities for Personal Empowerment: Symptom and Technology Management Resources intervention focused on commonly experienced symptoms and technology used at home by caregivers. OBJECTIVE: We present the findings from the intervention exit interviews to gain insight about the intervention from caregiver perspectives, notably their perceptions of usefulness, ease of use, and acceptability. METHODS: A qualitative descriptive design was used to examine caregivers' perceptions of the intervention in exit interviews. These interviews were conducted upon completion of the intervention as part of feasibility testing. RESULTS: Sixteen caregivers completed the study and participated in exit interviews. Caregivers described the themes of the best that you can do, a reminder that I am doing it the right way, and I wish I had these when my child first had the tracheostomy and feeding tube. Caregivers also provided feedback about the intervention's usefulness and suggestions for further refinement and future adaptations of the intervention. CONCLUSIONS: Caregivers provided valuable insights about the intervention, describing its usefulness to them, the potential for usefulness for other caregivers of these children, and their experiences with care of their children at home. Future plans include efficacy testing and modifications to enhance the intervention based on caregiver feedback.

Non-Insulin-Based Indices of Insulin Resistance for Predicting Incident Albuminuria: A Nationwide Population-Based Study.

Background: Studies have shown that incident albuminuria is associated with insulin resistance (IR); however, an IR marker that best predicts the prevalence of albuminuria has not yet been established. This study explored the association between IR and incident albuminuria using various IR indices, including the homeostasis model assessment of IR (HOMA-IR), metabolic score for IR (METS-IR), and triglyceride-glucose (TyG) index, and compared their predictive abilities for the prevalence of albuminuria. Methods: A total of 4,982 Korean adults from the 2019 Korea National Health and Nutritional Examination Survey were analyzed. The odds of albuminuria were determined using the quartiles of the IR indices. Receiver operating characteristic (ROC) curves were used to calculate the area under the ROC curve and predictability. The cutoff values for albuminuria detection were also computed. Results: An increase in the quartiles of all three IR indices was associated with incident albuminuria, even after full adjustment for covariates (HOMA-IR: odds ratio [OR], 1.906; 95% confidence interval [CI], 1.311-2.772; P=0.006; METS-IR: OR, 2.236; 95% CI, 1.353-3.694; P=0.002; TyG index: OR, 1.757; 95% CI, 1.213-2.544; P=0.003). The area under the ROC curve for incident albuminuria based on the HOMA-IR, METS-IR, and TyG indices was 0.594 (95% CI, 0.568-0.619), 0.633 (95% CI, 0.607-0.659), and 0.631 (95% CI, 0.606-0.656), respectively. The optimal cutoff values for predicting albuminuria were 2.38, 35.38, and 8.72 for the HOMA-IR, METS-IR, and TyG indices, respectively. Conclusion: The METS-IR and TyG indices outperformed HOMA-IR in predicting incident albuminuria.

Secular trends in dietary energy, carbohydrate, fat, and protein intake among Korean adults, 2010-2020 KHANES.

OBJECTIVES: The composition and balance of macronutrient intake play key roles in promoting a longer lifespan. In this study, we aimed to investigate the secular trends in carbohydrate, fat, and protein intakes in South Koreans from 2010 to 2020. METHODS: We examined the dietary nutritional intake of South Koreans using data from the Korean National Health and Nutrition Examination Survey. A total of 60,190 adults aged ≥19 y who completed the 24-h dietary recall interviews in a single day on all survey periods were included in this study. The outcomes included changes in macronutrient intake according to subgroups, such as age; sex; and the presence of diabetes, dyslipidemia, stroke, or heart disease, as well as energy intake from macronutrients. RESULTS: The study population showed a significant decrease in total energy intake from 2010 to 2020, with a corresponding decrease in the percentage of energy intake from carbohydrates (p-values for trend < 0.001). Conversely, the proportions of energy intake from proteins and fats increased during the same period (p < 0.001). Subgroup analyses revealed variations in macronutrient intake trends according to age, sex, obesity status, and underlying diseases. The analysis of trends in energy intake from various fat subtypes, total sugar, and fiber revealed a decrease in the energy intake percentage of total sugar from 2016 to 2020 and an increase in the energy intake percentage of all fat subtypes and fiber from 2013 to 2020. CONCLUSIONS: In the past 10 y, the dietary patterns in Korea have shifted toward the consumption of high-fat and high-protein diets with reduced carbohydrate intake.

Age at menopause and risk of metabolic dysfunction-associated fatty liver disease: A 14-year cohort study.

BACKGROUNDS & AIMS: Menopause, characterized by a sudden decline in estrogen levels, has significant effects on women's health, especially when it occurs early. This study aimed to investigate the associations between menopausal age and incidence of metabolic dysfunction-associated fatty liver disease (MAFLD) using a large cohort and a long-term follow-up. METHODS: Menopausal age was categorized into four groups (G1-4 [<40, 40-44, 45-49, and ≥50 years, respectively]). Cox proportional hazards regression analysis was used to assess the risk of developing MAFLD during the follow-up period according to the menopausal age categories. RESULTS: A total of 1,888 participants were included in the final analysis and followed for a median period of 12.3 years. The unadjusted hazard ratios (95 % CIs) for the incidence of new-onset MAFLD were 1.11 (0.93-1.32), 1.15 (0.90-1.47), and 1.52 (1.12-2.07) in G3, G2, and G1, respectively, compared with that in G4. After adjusting for confounders, the hazard ratio (95 % CIs) for the incidence of new-onset MAFLD was 1.40 (1.00-1.95) in G1 compared with that in G4. CONCLUSION: The risk of developing MAFLD was higher in women with premature menopause (<40 years) than in those with menopause aged ≥50 years.

Association between carbohydrate to protein or fat ratio and mortality: A prospective cohort study.

BACKGROUND & AIMS: The effect of dietary macronutrient balance on longevity and metabolic health remains a subject of considerable interest. We aimed to investigate the association of carbohydrate-to-protein and carbohydrate-to-fat ratios with all-cause and cardiovascular mortalities. METHODS: In this population-based study, data from the Korean Genome and Epidemiology Study were integrated with those from national data sources, including mortality records from the Korea National Statistical Office. The primary outcomes were all-cause and cardiovascular mortalities. Carbohydrate-to-protein and carbohydrate-to-fat ratios were evaluated based on dietary habits assessed through a food frequency questionnaire. Harrell's C-index was employed to determine optimal cut-off points for carbohydrate-to-protein and carbohydrate-to-fat ratios. Cox proportional hazards regression models were used to assess associations. RESULTS: A total of 143,050 participants aged ≥40 years were included in the analyses. Compared with individuals with non-elevated carbohydrate-to-protein ratios (<5.2), those with elevated carbohydrate-to-protein ratios (>9.9) exhibited a higher all-cause mortality (hazard ratio 1.09, 95% confidence interval 1.01-1.17); however, no correlation between carbohydrate-to-protein ratio and cardiovascular mortality (hazard ratio 1.13, 95% confidence interval 0.96-1.32) was observed. Compared with those with non-elevated carbohydrate-to-fat ratios (<5.1), those with higher carbohydrate-to-fat ratios (>7.1) exhibited increased all-cause (hazard ratio 1.08, 95% confidence interval 1.00-1.16) and cardiovascular (hazard ratio 1.27, 95% confidence interval 1.06-1.52) mortalities. CONCLUSIONS: Our findings regarding macronutrient ratios and their association with mortality suggest that reducing excessive carbohydrate intake and increasing the consumption of protein and fats may have beneficial effects on longevity and cardiovascular health. Further studies are needed to understand the underlying mechanisms of these effects.