Associations of chronotype and insomnia with menstrual problems in newly employed nurses at university hospitals in the Republic of Korea.

Background: Dysmenorrhea and menstrual cycle changes occur in women working shifts. Circadian rhythm disruption and sleep disturbances associated with shift work leads to health problems. We identified chronotypes and the occurrence of insomnia among newly employed university hospital nurses and investigated the association of these factors with menstrual problems. Methods: We conducted pre-placement health examinations for shift workers using self-reported questionnaires between 2018 and 2020. A total of 463 nurses were included in the study. Sociodemographic data, shift work experience, and information on insomnia were collected from health examination data. In addition, details regarding chronotype, dysmenorrhea, irregular and abnormal menstrual cycles, amenorrhea, and contraceptive use were obtained from the questionnaire. Multiple logistic regression analysis was performed to study the association between chronotype, insomnia, and menstrual problems after controlling for age, body mass index, contraceptive use, amenorrhea, and prior shift work. Results: The prevalence rates of dysmenorrhea, irregular menstrual cycles, and longer menstrual cycles were 23.8%, 14.9%, and 4.1%, respectively. The risk of dysmenorrhea increased in the evening-type (odds ratio [OR]: 3.209; 95% confidence interval [CI]: 1.685-6.113) and those with insomnia (OR: 1.871; 95% CI: 1.074-3.261). Additionally, the risk of an irregular menstrual cycle (OR: 2.698; 95% CI: 1.167-6.237) increased in the evening-type, and the risk of a longer menstrual cycle (OR: 4.008; 95% CI: 1.354-11.864) increased in individuals with insomnia. Conclusions: Our findings suggest that dysmenorrhea is promoted in the evening-type and insomnia individuals. There may be an increased risk of irregular menstrual cycles among evening-type nurses and an increased risk of longer menstrual cycles among those with insomnia. Therefore, factors such as evening-type and insomnia should be considered for the prevention of menstrual problems in women performing shift work.

Preserved Muscle Strength Despite Muscle Mass Loss After Bariatric Metabolic Surgery: a Systematic Review and Meta-analysis.

BACKGROUND: Contrary to the previously known concept of muscle mass decrease following bariatric metabolic surgery, changes in muscle strength have been poorly investigated in systematic reviews. In this meta-analysis, we evaluated changes in handgrip strength (HGS) and lean mass (LM) after undergoing bariatric metabolic surgery. METHODS: A systematic literature review using the PubMed, Embase, and Cochrane Library databases was conducted in November 2022. Longitudinal studies reporting HGS change after bariatric metabolic surgery were eligible. Pooled estimates for changes in HGS, body mass index (BMI), LM, and fat mass (FM) were calculated. Changes from baseline to the point closest to 6 months postoperatively were analyzed in trials with multiple follow-up examinations. The risk of bias was assessed using the Joanna Briggs Institute critical appraisal checklist. RESULTS: Three randomized controlled trials and seven prospective cohort studies involving 301 patients were included. Follow-up evaluations were conducted 6 months postoperatively in all trials except for two, whose follow-up visits were at 18 weeks and 12 months, respectively. Pooled analysis showed reduced BMI (- 10.8 kg/m2; 95% confidence interval: - 11.6 to - 9.9 kg/m2), LM (- 7.4 kg; - 9.3 to - 5.4 kg), and FM (- 22.3 kg; - 25.1 to - 19.6 kg) after bariatric metabolic surgery, whereas the change in HGS was not statistically significant (- 0.46 kg; - 1.76 to 0.84 kg). CONCLUSION: Despite the decreased body composition parameters, including muscle mass, strength was not impaired after bariatric metabolic surgery; this indicates that bariatric metabolic surgery is an effective weight management intervention that does not compromise strength.

Taste Bud-Inspired Single-Drop Multitaste Sensing for Comprehensive Flavor Analysis with Deep Learning Algorithms.

The electronic tongue (E-tongue) system has emerged as a significant innovation, aiming to replicate the complexity of human taste perception. In spite of the advancements in E-tongue technologies, two primary challenges remain to be addressed. First, evaluating the actual taste is complex due to interactions between taste and substances, such as synergistic and suppressive effects. Second, ensuring reliable outcomes in dynamic conditions, particularly when faced with high deviation error data, presents a significant challenge. The present study introduces a bioinspired artificial E-tongue system that mimics the gustatory system by integrating multiple arrays of taste sensors to emulate taste buds in the human tongue and incorporating a customized deep-learning algorithm for taste interpretation. The developed E-tongue system is capable of detecting four distinct tastes in a single drop of dietary compounds, such as saltiness, sourness, astringency, and sweetness, demonstrating notable reversibility and selectivity. The taste profiles of six different wines are obtained by the E-tongue system and demonstrated similarities in taste trends between the E-tongue system and user reviews from online, although some disparities still exist. To mitigate these disparities, a prototype-based classifier with soft voting is devised and implemented for the artificial E-tongue system. The artificial E-tongue system achieved a high classification accuracy of ∼95% in distinguishing among six different wines and ∼90% accuracy even in an environment where more than 1/3 of the data contained errors. Moreover, by harnessing the capabilities of deep learning technology, a recommendation system was demonstrated to enhance the user experience.

Association Between Insulin Resistance and Myosteatosis Measured by Abdominal Computed Tomography.

CONTEXT: Ectopic fat deposition in skeletal muscle, termed myosteatosis, is a key factor in developing insulin resistance. OBJECTIVE: This work aimed to evaluate the association between insulin resistance and myosteatosis in a large Asian population. METHODS: A total of 18 251 participants who had abdominal computed tomography were included in this cross-sectional study. Patients were categorized into 4 groups according to quartiles of Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). The total abdominal muscle area (TAMA) at the L3 vertebral level was segmented into normal-attenuation muscle area (NAMA), low-attenuation muscle area (LAMA), and intermuscular adipose tissue (IMAT). The absolute values of TAMA, NAMA, LAMA, and IMAT and the ratios of NAMA/BMI, LAMA/BMI, and NAMA/TAMA were used as myosteatosis indices. RESULTS: The absolute values of TAMA, NAMA, LAMA, and IMAT appeared to increase with higher HOMA-IR levels, and LAMA/BMI showed a similar upward trend. Meanwhile, the NAMA/BMI and NAMA/TAMA index showed downward trends. As HOMA-IR levels increased, the odds ratios (ORs) of the highest quartile of NAMA/BMI and NAMA/TAMA index decreased and that of LAMA/BMI increased. Compared with the lowest HOMA-IR group, the adjusted ORs (95% CI) in the highest HOMA-IR group for the lowest NAMA/TAMA quartile were 0.414 (0.364-0.471) in men and 0.464 (0.384-0.562) in women. HOMA-IR showed a negative correlation with NAMA/BMI (r = -0.233 for men and r = -0.265 for women), and NAMA/TAMA index (r = -0.211 for men and r = -0.214 for women), and a positive correlation with LAMA/BMI (r = 0.160 for men and r = 0.119 for women); P was less than .001 for all. CONCLUSION: In this study, a higher HOMA-IR level was significantly associated with a high risk of myosteatosis.

Association between Body Mass Index and Mortality in Type 1 Diabetes Mellitus: A Systematic Review and Meta-Analysis.

Background: The association between body mass index (BMI) and mortality in patients with type 1 diabetes mellitus (T1DM) has been poorly examined and has never been systematically reviewed. This meta-analysis investigated the all-cause mortality risk for each BMI category among patients with T1DM. Methods: A systematic literature review of the PubMed, Embase, and Cochrane Library databases was performed in July 2022. Cohort studies comparing the mortality risk between BMI categories among patients with T1DM were eligible. Pooled hazard ratios (HRs) for all-cause mortality among underweight (BMI <18.5 kg/m2), overweight (BMI, 25 to <30 kg/m2), and obese (BMI ≥30 kg/m2) individuals were calculated in reference to the normal-weight group (BMI, 18.5 to <25 kg/m2). The Newcastle-Ottawa Scale was used to assess the risk of bias. Results: Three prospective studies involving 23,407 adults were included. The underweight group was shown to have a 3.4 times greater risk of mortality than the normal-weight group (95% confidence interval [CI], 1.67 to 6.85). Meanwhile, there was no significant difference in mortality risk between the normal-weight group and the overweight group (HR, 0.90; 95% CI, 0.66 to 1.22) or the obese group (HR, 1.36; 95% CI, 0.86 to 2.15), possibly due to the heterogeneous results of these BMI categories among the included studies. Conclusion: Underweight patients with T1DM had a significantly greater risk of all-cause mortality than their normal-weight counterparts. Overweight and obese patients showed heterogeneous risks across the studies. Further prospective studies on patients with T1DM are required to establish weight management guidelines.

Association between sarcopenic obesity and poor muscle quality based on muscle quality map and abdominal computed tomography.

OBJECTIVE: This study evaluated whether sarcopenic obesity is closely associated with muscle quality using abdominal computed tomography. METHODS: This cross-sectional study included 13,612 participants who underwent abdominal computed tomography. The cross-sectional area of the skeletal muscle was measured at the L3 level (total abdominal muscle area [TAMA]) and segmented into normal attenuation muscle area (NAMA, +30 to +150 Hounsfield units), low attenuation muscle area (-29 to +29 Hounsfield units), and intramuscular adipose tissue (-190 to -30 Hounsfield units). The NAMA/TAMA index was calculated by dividing NAMA by TAMA and multiplying by 100, and the lowest quartile of NAMA/TAMA index was defined as myosteatosis (<73.56 in men and <66.97 in women). Sarcopenia was defined using BMI-adjusted appendicular skeletal muscle mass. RESULTS: The prevalence of myosteatosis was found to be significantly higher in participants with sarcopenic obesity (17.9% vs. 54.2%, p < 0.001) than the control group without sarcopenia or obesity. Compared with the control group, the odds ratio (95% CI) for having myosteatosis was 3.70 (2.87-4.76) for participants with sarcopenic obesity after adjusting for age, sex, smoking, drinking, exercise, hypertension, diabetes, low-density lipoprotein cholesterol, and high-sensitivity C-reactive protein. CONCLUSIONS: Sarcopenic obesity is significantly associated with myosteatosis, which is representative of poor muscle quality.

Circulating blood eNAMPT drives the circadian rhythms in locomotor activity and energy expenditure.

Nicotinamide adenine dinucleotide (NAD+) is an essential cofactor of critical enzymes including protein deacetylase sirtuins/SIRTs and its levels in mammalian cells rely on the nicotinamide phosphoribosyltransferase (NAMPT)-mediated salvage pathway. Intracellular NAMPT (iNAMPT) is secreted and found in the blood as extracellular NAMPT (eNAMPT). In the liver, the iNAMPT-NAD+ axis oscillates in a circadian manner and regulates the cellular clockwork. Here we show that the hypothalamic NAD+ levels show a distinct circadian fluctuation with a nocturnal rise in lean mice. This rhythm is in phase with that of plasma eNAMPT levels but not with that of hypothalamic iNAMPT levels. Chemical and genetic blockade of eNAMPT profoundly inhibit the nighttime elevations in hypothalamic NAD+ levels as well as those in locomotor activity (LMA) and energy expenditure (EE). Conversely, elevation of plasma eNAMPT by NAMPT administration increases hypothalamic NAD+ levels and stimulates LMA and EE via the hypothalamic NAD+-SIRT-FOXO1-melanocortin pathway. Notably, obese animals display a markedly blunted circadian oscillation in blood eNAMPT-hypothalamic NAD+-FOXO1 axis as well as LMA and EE. Our findings indicate that the eNAMPT regulation of hypothalamic NAD+ biosynthesis underlies circadian physiology and that this system can be significantly disrupted by obesity.

Sarcopenia in youth.

Recent research has revealed causes other than aging that may induce sarcopenia in young people, contrary to the long-studied age-dependent reduction in muscular mass and function. The risk of sarcopenia begins in early adulthood, resulting in exaggerated muscle dysfunction in later life. Despite its clinical significance, research on youth-onset sarcopenia is still in its infancy. Due to a paucity of epidemiologic data and standardized criteria for sarcopenia in youth, determining the prevalence of sarcopenia in the young population remains challenging. Based on the evidence, >1 in every 10 young adults of most ethnicities is estimated to have sarcopenia. This review summarizes the possible etiologies of sarcopenia in young populations, including metabolic syndrome, physical inactivity, inadequate nutrition, inherent and perinatal factors, vitamin D deficiency, endocrinopathy, an imbalance of gut microbiota, neuromuscular diseases, organ failure, malignancy, and other inflammatory disorders. This is the first review of the current knowledge on the importance, prevalence, diagnosis, and causes of sarcopenia in youth.

Development of Spleen Targeting H2S Donor Loaded Liposome for the Effective Systemic Immunomodulation and Treatment of Inflammatory Bowel Disease.

Nanoparticles are primarily taken up by immune cells after systemic administration. Thus, they are considered an ideal drug delivery vehicle for immunomodulation. Because the spleen is the largest lymphatic organ and regulates the systemic immune system, there have been studies to develop spleen targeting nanoparticles for immunomodulation of cancer and immunological disorders. Inflammatory bowel disease (IBD) includes disorders involving chronic inflammation in the gastrointestinal tract and is considered incurable despite a variety of treatment options. Hydrogen sulfide (H2S) is one of the gasotransmitters that carries out anti-inflammatory functions and has shown promising immunomodulatory effects in various inflammatory diseases including IBD. Herein, we developed a delicately tuned H2S donor delivering liposome for spleen targeting (ST-H2S lipo) and studied its therapeutic effects in a dextran sulfate sodium (DSS) induced colitis model. We identified the ideal PEG type and ratio of liposome for a high stability, loading efficiency, and spleen targeting effect. In the treatment of the DSS-induced colitis model, we found that ST-H2S lipo and conventional long-circulating liposomes loaded with H2S donors (LC-H2S lipo) reduced the severity of colitis, whereas unloaded H2S donors did not. Furthermore, the therapeutic effect of ST-H2S lipo was superior to that of LC-H2S lipo due to its better systemic immunomodulatory effect than that of LC-H2S lipo. Our findings demonstrate that spleen targeting H2S lipo may have therapeutic potential for IBD.

Association between hypertension and myosteatosis evaluated by abdominal computed tomography.

Few studies have examined the relationship between myosteatosis and hypertension, and no studies have enrolled an Asian population. Existing studies also found discordant results, possibly due to the use of conventional myosteatosis indices that are not sufficiently reliable and representative. Therefore, we investigated the association between myosteatosis and hypertension in Asian individuals using novel, objective computed tomography (CT) markers. The total abdominal muscle area (TAMA) was determined from abdominal CT scans taken at the L3 level. Based on the mean CT attenuation, the TAMA was divided into intramuscular adipose tissue and skeletal muscle area (SMA), which was further segmented into normal attenuation muscle area (NAMA) and low attenuation muscle area (LAMA). Among SMA/body mass index (BMI), NAMA/BMI, LAMA/BMI, and the NAMA/TAMA index, NAMA/BMI was chosen through receiver operating characteristic curves as the best predictive marker for hypertension. The hypertension risk for each quartile of NAMA/BMI was calculated by logistic regression analysis. Among the 19,766 participants, 40.3% of men and 23.8% of women had hypertension. People with hypertension showed unhealthier myosteatosis profiles than normotensive controls. Similarly, a lower NAMA/BMI was significantly associated with a greater hypertension risk. The lowest quartile group of NAMA/BMI exhibited 2.3- and 2.6-fold higher risks of hypertension than the highest quartile in men and women, respectively. In conclusion, advanced myosteatosis assessed by abdominal CT was significantly correlated with a higher risk of hypertension. Improving myosteatosis may be a new approach for preventing cardiovascular diseases, including hypertension. Advanced myosteatosis measured by abdominal CT taken at the L3 level was significantly correlated with a higher risk of hypertension even after adjusting for health behaviors, intake of lipid-lowering drugs, plasma lipid levels, and other ectopic fat distribution.

Association of serum gamma-glutamyl transferase with myosteatosis assessed by muscle quality mapping using abdominal computed tomography.

PURPOSE: Myosteatosis, which is associated with a variety of cardiometabolic illnesses, represents muscle quality, an important aspect of sarcopenia. A new laboratory marker for myosteatosis has been required to more readily identify it. We investigated whether serum gamma-glutamyl transferase (GGT) levels are associated with myosteatosis measured by computed tomography (CT). METHODS: The total abdominal muscle area (TAMA) of 13,452 subjects was measured at the L3 level with abdominal CT. TAMA was segmented into intramuscular adipose tissue and skeletal muscle area (SMA), which was further classified into normal attenuation muscle area (NAMA) and low attenuation muscle area (LAMA). The following variables were adopted as indicators of myosteatosis: SMA/body mass index (BMI), NAMA/BMI, LAMA/BMI, and NAMA/TAMA. Logistic regression analysis was used to examine the odds ratio (OR) of each GGT quartile for the highest quartile of myosteatosis indices in each sex. RESULTS: The mean age and serum GGT levels were 53.7 years and 32.8 IU/L (standard deviation [SD], 37.6), respectively, in men, and 53.2 years and 18.4 IU/L (SD, 19.8) in women. In both sexes, the ORs of all myosteatosis indices differed significantly between GGT quartiles. Indices of good- and poor-quality muscle were negatively and positively correlated with GGT levels, respectively. CONCLUSION: Higher GGT levels were significantly associated with advanced myosteatosis defined by reliable CT indices. This result opens the possibility for using GGT as a cost-effective indicator of myosteatosis. Further prospective research on changes to GGT levels with myosteatosis alleviation will validate GGT as a monitoring marker.

Relationship between chronotype and depressive symptoms among newly hired hospital nurses in the Republic of Korea.

Background: This study was conducted to examine the relationship between chronotype and depressive symptoms to provide grounded knowledge in establishing nurses' health promotion strategies. Methods: The subjects of this study were 493 newly hired nurses working in 2 general hospitals within the university from September 2018 to September 2020. Sociodemographic and work-related characteristics were collected from a medical examination database and a self-reported questionnaire. These included sex, age, marital status, living situation, education level, alcohol consumption, physical activity, prior work experience before 3 months, workplace, and departments. To analyze the associations between the chronotype and depressive symptoms, multiple logistic regression analyses were performed to calculate odds ratios (ORs). Results: Among participants, 9.1% had depressive symptoms and 16.4% had insomnia. The subjects are divided into morningness (30.2%), intermediate (48.7%), and eveningness (21.1%). The multiple logistic regression analysis controlling for age, living status, education level, alcohol consumption, physical activity, workplace, prior work experience before 3 months, and insomnia, revealed that the OR of depressive symptoms in the eveningness group was 3.71 (95% confidence interval [CI]: 1.50-9.18) compared to the morningness group, and the R2 value was 0.151. It also can be confirmed that insomnia symptoms have a statistically significant effect on depressive symptoms (OR: 2.16, 95% CI: 1.03-4.52). Conclusions: Our findings suggest that evening-type nurses are more likely to have depression than morning-type nurses. We should consider interventions in a high-risk group such as the evening type nurses to reduce depressive symptoms in nurses.

Lipid nanoparticles for delivery of RNA therapeutics: Current status and the role of in vivo imaging.

Lipid nanoparticles (LNPs) have been one of the most successful nano-delivery vehicles that enable efficient delivery of cytotoxic chemotherapy agents, antibiotics, and nucleic acid therapeutics. During the coronavirus disease (COVID-19) pandemic, LNP-based COVID-19 messenger RNA (mRNA) vaccines from Pfizer/BioNTech and Moderna have been successfully developed, resulting in global sales of $37 billion and $17.7 billion, respectively, in 2021. Based on this success, the development of multiple LNP-based RNA therapeutics is gaining momentum due to its potential in vaccines and therapeutics for various genetic diseases and cancers. Furthermore, imaging techniques can be utilized to evaluate the pharmacokinetics and pharmacodynamics (PK/PD) effects, which helps target discovery and accelerates the development of LNP-based mRNA therapies. A thorough introduction and explanation of the components of LNPs and its functions along with various production methods of formulating LNPs are provided in this review. Furthermore, recent advances in LNP-based RNA therapeutics in clinics and clinical trials are explored. Additionally, the evaluation of PK/PD of LNPs for RNA delivery and the current and potential roles in developing LNP-based mRNA pharmaceutics through imaging techniques will be discussed.

Self-Assembled DNA-Protein Hybrid Nanospheres: Biocompatible Nano-Drug-Carriers for Targeted Cancer Therapy.

We developed hybrid nanospheres comprised of two of the most important biomolecules in nature, DNA and proteins, which have excellent biocompatibility, high drug payload capacity, in vivo imaging ability, and in vitro/in vivo cancer targeting capability. The synthesis can be done in a facile one-pot assembly system that includes three steps: step-growth polymerization of two DNA oligomers, addition of streptavidin to assemble spherical hybrid nanostructures, and functionalization of hybrid nanospheres with biotinylated aptamers. To test the feasibility of cancer targeting and drug-loading capacity of the hybrid nanospheres, MUC1-specific aptamers (MA3) were conjugated to nanosphere surfaces (apt-nanospheres), and doxorubicin (Dox) was loaded into nanospheres by DNA intercalation. The successful construction of nanospheres and apt-nanospheres was confirmed by agarose gel electrophoresis and dynamic light scattering (DLS). Their uniform spherical morphology was confirmed by transmission electron microscopy (TEM). Fluorescence spectra of nanospheres demonstrated high Dox-loading capability and slow-release characteristics. In vitro MUC1-specific binding of the apt-nanospheres was confirmed by flow cytometry and confocal microscopy. Dox-loaded apt-nanospheres significantly increased cytotoxicity of the MUC1-positive cancer cells due to aptamer-mediated selective internalization, as shown via cell viability assays. Apt-nanospheres could also be imaged in vivo through the synthesis of hybrid nanospheres using fluorescent dye-conjugated DNA strands. Finally, in vivo specific targeting ability of apt-nanospheres was confirmed in a MUC1-positive 4T1 tumor-bearing mouse model, whereas apt-nanospheres did not cause any sign of systemic toxicity in normal mice. Taken together, our self-assembled DNA-streptavidin hybrid nanospheres show promise as a biocompatible cancer targeting material for contemporary nanomedical technology.

Free Versus Fixed-Ratio Combination of Basal Insulin and GLP-1 Receptor Agonists in Type 2 Diabetes Uncontrolled With GLP-1 Receptor Agonists: A Systematic Review and Indirect Treatment Comparison.

Introduction: This study evaluates the efficacy and safety of the free up-titration of basal insulin and fixed-ratio combination (FRC) of basal insulin and glucagon-like peptide-1 receptor agonists (GLP-1RAs) in type 2 diabetes mellitus (T2DM) patients inadequately controlled with GLP-1RA. Methods: With the use of a systematic literature review of PubMed, Embase, Web of Science, and the Cochrane Library databases through July 2021, randomized controlled trials that compared the free up-titration or FRC with remaining on GLP-1RA in T2DM patients uncontrolled with GLP-1RA were included. A comparison of adding basal insulin to maintaining GLP-1RA and an indirect comparison between the two strategies were conducted on the change in HbA1c, fasting plasma glucose (FPG), target achievement [HbA1c < 7.0%], and the risk of confirmed hypoglycemia. The Cochrane Collaboration's tool was used to assess the risk of bias. Results: Two free up-titration and two FRC trials involving 1,612 participants, all lasting 26 weeks, were included. Both approaches significantly lowered HbA1c levels (weighted mean difference [WMD] -0.75%, 95% CI -0.97 to -0.53) but increased hypoglycemic risk [risk ratio (RR) 7.59, 95% CI 3.35-17.17] compared to the unchanged GLP-1RA. No significant differences were discovered between the two methods regarding the decrease in HbA1c (WMD 0.08%, 95% CI -1.07% to 1.23%), FPG (WMD -2.29 mg/dl, 95% CI -45.07 to 40.49 mg/dl), target achievement (RR 1.03, 95% CI 0.50-2.14), and hypoglycemic risk (RR 0.32, 95% CI 0.03-3.59). Conclusion: In patients who failed to reach target HbA1c levels despite the GLP-1RA treatment, both strategies of adding basal insulin, free up-titration and FRC, are comparable options are comparable options.

Age-Related Associations of Low-Density Lipoprotein Cholesterol and Atherosclerotic Cardiovascular Disease: A Nationwide Population-Based Cohort Study.

Background The relationship between low-density lipoprotein cholesterol (LDL-C) and atherosclerotic cardiovascular disease (ASCVD) according to age remains undetermined. Thus, this study aimed to investigate the age-related association of LDL-C and ASCVD. Methods and Results Data from the Korean NHIS-HEALS (National Health Insurance Service-National Health Screening Cohort) were analyzed. Individuals previously diagnosed with cardiovascular disease or taking lipid-lowering drugs were excluded. Age-specific association between LDL-C and ASCVD was calculated using adjusted Cox proportional hazards models. During a median follow-up of 6.44 years for 285 119 adults, ASCVD developed in 8996 (3.2%). All age groups showed positive associations between LDL-C and ASCVD risk, mostly with statistical significance from LDL-C of 160 mg/dL onward. ASCVD risk did not differ significantly between the age groups (P for interaction=0.489). Correspondingly, subgroup analysis in type 2 diabetes exhibited no difference in the age-specific association of LDL-C and ASCVD (P for interaction=0.784). Conclusions The study demonstrated that people aged ≥75 years with higher LDL-C at baseline still presented increased ASCVD risk, which was not significantly different from the younger groups. These findings support the importance of managing LDL-C for the prevention of primary ASCVD in the growing elderly population.

M1 Macrophage-Derived Exosome-Mimetic Nanovesicles with an Enhanced Cancer Targeting Ability.

Extracellular vesicles (EVs) have been found to be effective therapeutic drug delivery vehicles in a wide range of human diseases, including cancer and neurodegenerative diseases. Proinflammatory (M1) macrophages can modulate the suppressive immune environment of tumor tissues to be more inflammatory and have been considered as candidates for cancer immunotherapy. Furthermore, macrophage-derived exosome-mimetic nanovesicles (MNVs) could effectively induce antitumor response and enhance the efficacy of immune checkpoint inhibitors in a recent paper. However, multiple studies indicate that EVs were rapidly cleared by the reticuloendothelial system, and therefore, their tumor targeting efficiencies were limited. Herein, we developed a simple surface modification method of MNVs using polyethylene glycol (PEG) to enhance the in vivo tumor targeting efficiency. PEG-MNVs had 7-fold higher blood circulation than bare MNVs in the animal tumor model. Also, MNVs had a 25-fold higher protein amount than exosomes. Overall, the nanovesicle preparation strategies presented in this study may expedite the clinical translation of EV-based therapeutics in various diseases.

The Upcoming Weekly Tides (Semaglutide vs. Tirzepatide) against Obesity: STEP or SURPASS?

The rapidly increasing prevalence of obesity and obesity-associated morbidity is causing an ever-increasing global burden. Beyond lifestyle modifications, pharmacological approaches to losing body weight to achieve a decrease in cardiometabolic complications are in the spotlight. Pre-existing anti-obesity medications (AOMs) approved for long-term prescription use showed a weight reduction of around 5% more than placebo. In contrast to the modest efficacy of pre-existing AOMs, two newly developed, weekly-administered injectable drugs, semaglutide and tirzepatide, exhibited outstanding weight-loss effects in a series of multinational randomized phase III trials. Considering that these two peptides are the most promising candidates for the upcoming battle in the anti-obesity market, comparison of their efficacy and safety is essential. This review summarizes the body weight reduction efficacy, glycemic control, and safety of semaglutide up to a 2.4-mg dose and tirzepatide up to a 15-mg dose, focusing on the Semaglutide Treatment Effect in People with Obesity (STEP) 2, SURPASS-1, and SURPASS-2 trials, the subjects of which were all patients with type 2 diabetes mellitus.

The Role of Anti-Inflammatory Adipokines in Cardiometabolic Disorders: Moving beyond Adiponectin.

The global burden of obesity has multiplied owing to its rapidly growing prevalence and obesity-related morbidity and mortality. In addition to the classic role of depositing extra energy, adipose tissue actively interferes with the metabolic balance by means of secreting bioactive compounds called adipokines. While most adipokines give rise to inflammatory conditions, the others with anti-inflammatory properties have been the novel focus of attention for the amelioration of cardiometabolic complications. This review compiles the current evidence on the roles of anti-inflammatory adipokines, namely, adiponectin, vaspin, the C1q/TNF-related protein (CTRP) family, secreted frizzled-related protein 5 (SFRP5), and omentin-1 on cardiometabolic health. Further investigations on the mechanism of action and prospective human trials may pave the way to their clinical application as innovative biomarkers and therapeutic targets for cardiovascular and metabolic disorders.