Food functionality research as a new national project in special reference to improvement of cognitive and locomotive abilities.

In Japan, where a super-aging society is realized, we are most concerned about healthy longevity, which would ascertain the wellness of people by improving their quality of life (QOL). In 2014, the Cabinet Office proposed a strategic innovation promotion programme, launching a national project for the development of the agricultural-forestry-fisheries food products with new functionalities for the next generation. In addition to focusing on a conventional prevention of lifestyle-associated metabolic syndromes, the project targets the scientific evidence of the activation of brain cognitive ability and the improvement of bodily locomotive function. The project also involves the analysis of the foods-sports interrelation of chronic importance, and the development of devices for the verification of QOL-associated maintenance of homeostasis. In this review, we provide an overview of these studies, with special reference to cognition as a case of the gut-brain axis which the author is particularly interested in.

Development of functional agricultural products utilizing the new health claim labeling system in Japan.

In April 2015, Consumer Affairs Agency of Japan launched a new food labeling system known as "Foods with Function Claims (FFC)." Under this system, the food industry independently evaluates scientific evidence on foods and describes their functional properties. As of May 23, 2017, 1023 FFC containing 8 fresh foods have been launched. Meanwhile, to clarify the health-promoting effects of agricultural products, National Agriculture and Food Research Organization (NARO) implemented the "Research Project on Development of Agricultural Products" and demonstrated the risk reduction of osteoporosis of ß-cryptoxanthin rich Satsuma mandarins and the anti-allergic effect of the O-methylated catechin rich tea cultivar Benifuuki. These foods were subsequently released as FFC. Moreover, NARO elucidated the health-promoting effects of various functional agricultural products (ß-glucan rich barley, ß-conglycinin rich soybean, quercetin rich onion, etc.) and a healthy boxed lunch. This review focuses on new food labeling system or research examining functional aspects of agricultural products.

Accuracy of salivary biomarkers in the diagnosis of periodontal status and coronary heart disease.

Inflammatory illnesses, such as periodontitis and atherosclerotic coronary heart disease (ASCHD), trigger the production of pro-inflammatory mediators. The aim of this study was to assess the accuracy of using salivary interleukin-1ß (IL-1ß), interleukin-18 (IL-18), and gasdermin D (GSDMD) in discerning patients with periodontitis with and without ASCHD from healthy individuals, and to assess their correlation with clinical periodontal parameters and low-density lipoprotein (LDL) levels. The study involved 120 participants: 30 were healthy subjects (control group, C), 30 had generalized periodontitis (group P), 30 had ASCHD and clinically healthy periodontium (group AS-C), and 30 had ASCHD and generalized periodontitis (group AS-P). Saliva and blood samples were collected, and periodontal characteristics such as plaque index, bleeding on probing, probing pocket depth, and clinical attachment loss were examined. IL-1ß, IL-18, and GSDMD levels from saliva were determined using ELISA. LDL levels were determined from the blood samples. Groups P, AS-C, and AS-P had higher levels of salivary IL-1ß, IL-18, and GSDMD than group C. The receiver operating characteristic (ROC) curves of all biomarkers showed high diagnostic accuracy, with a significant positive correlation with the clinical parameters and LDL levels. The observed correlations between the studied pro-inflammatory mediators and disease severity suggest that these biomarkers could serve as indicators of disease progression in conditions such as periodontitis and ASCHD.

Impact of Healthy Lifestyle in Patients With Familial Hypercholesterolemia.

Background: Pathogenic mutations are associated with poor outcomes in patients with familial hypercholesterolemia (FH). However, data on the effects of a healthy lifestyle on FH phenotypes are limited. Objectives: The authors investigated the interaction between a healthy lifestyle and FH mutation with prognosis in patients with FH. Methods: We investigated the associations of the interaction between genotypes and lifestyle, with the occurrence of major adverse cardiac events (MACE), such as cardiovascular-related mortality, myocardial infarction, unstable angina, and coronary artery revascularization, in patients with FH. We assessed their lifestyle based on 4 questionnaires (healthy dietary pattern, regular exercise, not smoking, and absence of obesity). The Cox proportional hazards model was used to assess the risk for MACE. Results: The median follow-up duration was 12.6 (IQR: 9.5-17.9) years. During the follow-up duration, 179 MACE were observed. Independent of classic risk factors, FH mutation and lifestyle score were significantly associated with MACE (HR: 2.73; 95% CI: 1.03-4.43; P = 0.02; and HR: 0.69, 95% CI: 0.40-0.98, P = 0.033, respectively). The estimated risk of coronary artery disease by 75 years of age varied according to lifestyle, ranging from 21.0% among noncarriers with a favorable lifestyle to 32.1% among noncarriers with an unfavorable lifestyle and ranging from 29.0% among carriers with a favorable lifestyle to 55.4% among carriers with an unfavorable lifestyle. Conclusions: A healthy lifestyle was associated with reduced risk for MACE among patients with FH with or without genetic diagnosis.

Low-density lipoprotein balances T cell metabolism and enhances response to anti-PD-1 blockade in a HCT116 spheroid model.

Introduction: The discovery of immune checkpoints and the development of their specific inhibitors was acclaimed as a major breakthrough in cancer therapy. However, only a limited patient cohort shows sufficient response to therapy. Hence, there is a need for identifying new checkpoints and predictive biomarkers with the objective of overcoming immune escape and resistance to treatment. Having been associated with both, treatment response and failure, LDL seems to be a double-edged sword in anti-PD1 immunotherapy. Being embedded into complex metabolic conditions, the impact of LDL on distinct immune cells has not been sufficiently addressed. Revealing the effects of LDL on T cell performance in tumor immunity may enable individual treatment adjustments in order to enhance the response to routinely administered immunotherapies in different patient populations. The object of this work was to investigate the effect of LDL on T cell activation and tumor immunity in-vitro. Methods: Experiments were performed with different LDL dosages (LDLlow = 50 µg/ml and LDLhigh = 200 µg/ml) referring to medium control. T cell phenotype, cytokines and metabolism were analyzed. The functional relevance of our findings was studied in a HCT116 spheroid model in the context of anti-PD-1 blockade. Results: The key points of our findings showed that LDLhigh skewed the CD4+ T cell subset into a central memory-like phenotype, enhanced the expression of the co-stimulatory marker CD154 (CD40L) and significantly reduced secretion of IL-10. The exhaustion markers PD-1 and LAG-3 were downregulated on both T cell subsets and phenotypical changes were associated with a balanced T cell metabolism, in particular with a significant decrease of reactive oxygen species (ROS). T cell transfer into a HCT116 spheroid model resulted in a significant reduction of the spheroid viability in presence of an anti-PD-1 antibody combined with LDLhigh. Discussion: Further research needs to be conducted to fully understand the impact of LDL on T cells in tumor immunity and moreover, to also unravel LDL effects on other lymphocytes and myeloid cells for improving anti-PD-1 immunotherapy. The reason for improved response might be a resilient, less exhausted phenotype with balanced ROS levels.

Serum biomarkers to predict hemorrhagic transformation and ischemic stroke outcomes in a prospective cohort study.

Ischemic stroke (IS) remains one of the most frequent causes of death and disability worldwide. Identifying possible prognosis factors for IS outcomes, including hemorrhagic transformation (HT), could improve patients' recovery. This study aimed to investigate the potential prognosis role of non-specific laboratory data at admission and baseline MMP-2 and MMP-9 serum levels in predicting HT risk, discharge, and 3-month follow-up status of IS patients. Data from 150 successive acute cerebral infarction patients were analyzed in a prospective cohort study. The active group included patients who developed HT during hospitalization (55 persons). There were no significant differences in age, gender distribution, time to admission, or time to blood sample collection for MMPs measurement between patients in the active and control groups. IS patients from the active group had a significantly higher rate of AF (atrial fibrillation) in the past (p=0.003), while differences in other factors such as diabetes, hypertension, myocardial infarction, previous stroke, obesity, smoking, and alcohol were not significant. Admission NIHSS score and mRS (modified Rankin Scale) values (at discharge and 90 days) were significantly worse in the active group (p<0.001). Among the analyzed admission laboratory factors (glycemia, lipid profile, coagulation panel, inflammatory reaction parameters, MMP-2, MMP-9), INR presented an inverse correlation, with lower values in the HT cohort (univariate analysis - p=0.01, OR=0.11; multivariate analysis - p=0.03, OR=0.09). Further research on larger cohorts is warranted to determine the specific laboratory biomarkers for predicting hemorrhagic transformation and ischemic stroke outcomes.

Nonarteritic Anterior Ischemic Optic Neuropathy: Cystic Change in the Inner Nuclear Layer Caused by Edema and Retrograde Maculopathy.

Purpose: Microcystic macular edema (MME), also known as retrograde maculopathy (RM), is associated with severe optic atrophy because of a range of causes. However, similar changes have also been described in primary retinal pathology and the pathogenesis of MME is debated. Design: A retrospective observational case series. Participants: Patients with nonarteritic ischemic optic neuropathy. Methods: A retrospective observational case series was performed at the University Hospital of Liège, Belgium. The medical records of patients who were referred to our Neuro-ophthalmology department with a diagnosis of nonarteritic anterior ischemic optic neuropathy (NA-AION), between 2014 and 2021, were reviewed. Main Outcome Measures: Ganglion cell complex thickness, acute and chronic inner nuclear change. Results: In a cohort of 34 patients (mean age: 60 ± 12.5 years; 65.6% men) with NA-AION, we identified a transient microcystic change in the inner nuclear layer (INL) associated with optic disc swelling in 19 eyes at presentation. This early change was associated with a transudate of intraretinal and subretinal fluid originating from the optic disc. Among patients who had shown this transient change 3 subsequently developed MME, which remained fixed during the period of observation (range, 12-34 months). No MME was observed in patients without an early INL transient change. Microcystic macular edema was observed in patients with severe ganglion cell complex thinning at 6 months: mean (± SD) loss in superior hemimacula (-28.2 ± 5.2 µm [-33.3%, range, -22.3 to -30.3 µm]) and in inferior hemimacula (-30.7 ± 5.6 µm [-31.0%, range, -24.3 to 34.8 µm]). Conclusions: Our study has revealed 2 causes of INL cystic change in the same patients experiencing NA-AION, 1 reversible and the other likely permanent. This finding highlights the distinction between genuine edema related to transudation of fluid (in this case secondary to ischemic optic disc swelling) and the phenomenon observed in RM that is related to the degree of retinal nerve fiber layer/ganglion cell complex thinning. Cystic change in the INL is associated with severe optic atrophy (MME). However, similar changes have been described in retinal pathology and the pathogenesis of MME is debated.

The Burden of Uncontrolled Cardiovascular Risk Factors in Men With Prostate Cancer: A RADICAL-PC Analysis.

Background: Cardiovascular disease (CVD) incidence is higher in men with prostate cancer (PC) than without. Objectives: We describe the rate and correlates of poor cardiovascular risk factor control among men with PC. Methods: We prospectively characterized 2,811 consecutive men (mean age 68 ± 8 years) with PC from 24 sites in Canada, Israel, Brazil, and Australia. We defined poor overall risk factor control as ≥3 of the following: suboptimal low-density lipoprotein cholesterol (>2 mmol/L if Framingham Risk Score [FRS] ≥15 and ≥3.5 mmol/L if FRS <15), current smoker, physical inactivity (<600 MET min/wk), suboptimal blood pressure (BP) (≥140/90 mm Hg if no other risk factors, systolic BP ≥120 mm Hg if known CVD or FRS ≥15, and ≥130/80 mm Hg if diabetic), and waist:hip ratio >0.9. Results: Among participants (9% with metastatic PC and 23% with pre-existing CVD), 99% had ≥1 uncontrolled cardiovascular risk factor, and 51% had poor overall risk factor control. Not taking a statin (odds ratio [OR]: 2.55; 95% CI: 2.00-3.26), physical frailty (OR: 2.37; 95% CI: 1.51-3.71), need for BP drugs (OR: 2.36; 95% CI: 1.84-3.03), and age (OR per 10-year increase: 1.34; 95% CI: 1.14-1.59) were associated with poor overall risk factor control after adjustment for education, PC characteristics, androgen deprivation therapy, depression, and Eastern Cooperative Oncology Group functional status. Conclusions: Poor control of modifiable cardiovascular risk factors is common in men with PC, highlighting the large gap in care and the need for improved interventions to optimize cardiovascular risk management in this population.

Acute and subchronic toxicity profile of methanol extract of leaves of Fimbristylis miliacea (L.) Vahl.

Ethnopharmacological relevance: Fimbristylis miliacea (L.) Vahl (Cyperaceae) is a grass like herb habitually breeds as weed in paddy fields and mostly disseminated in tropical or sub-tropical countries of south and south-east Asia, northern Australia, and west Africa. The plant has been traditionally used to treat fever as a form of poultice. However, no scientific study regarding its toxicity profile has been testified. Aim of the study: The study has been carried out to determine the potential toxicity of the methanol extract from leaves of the Fimbristylis miliacea, employing the technique of acute and subchronic oral administration in mice. Materials and methods: In the acute toxicity study according to OECD guideline 425, oral administration of FM methanol extract at single doses of 2000 and 5000 mg/kg in both sexes of Swiss albino mice was performed. Toxic symptoms, abnormal behavior, changes in body weight, and mortality were observed for 14 consecutive days. In subchronic toxicity study according to OECD guideline 407, plant extract was administered orally at doses of 100, 500, 1000, and 2000 mg/kg daily for 28 days. The general toxic symptoms, abnormal behavior, changes in body weight were observed daily. Biochemical analysis of serum, and histopathological examination of liver were performed at the end of the study. Results: No mortality, abnormal behavior and urination, changes in sleep, food intake, adverse effect, and non-linearity in body weight have been recorded during acute toxicity study at the doses of 2000 and 5000 mg/kg. Also, in subchronic toxicity study, FM extract produced no mortality or any kind of adverse effects in regards of general behavior, body weight, urination, sleeping routine, and food intake. In case of analysis of thirteen different biochemical parameters, concentrations of aspartate transaminase (AST) and glucose were altered significantly in male and female mice in both acute and subchronic study. Total cholesterol and triglycerides at 5000 mg/kg.bw were changed in male mice in acute toxicity study. On the other hand, female mice had altered triglycerides in subchronic test. All other critical parameters were found unaffected. In subchronic test, histopathological examination of liver demonstrated cellular necrosis at 2000 mg/kg.bw in both male and female mice while minor necrosis was observed at 1000 mg/kg.bw. Thus, the no observed adverse effect level (NOAEL) can be assumed around 1000 mg/kg.bw. Conclusion: The present study suggests that treatment with FM extract does not reveal significant toxicity.

Screening for Coronary Artery Disease in Cancer Survivors: JACC: CardioOncology State-of-the-Art Review.

Coronary artery disease (CAD) is an important contributor to the cardiovascular burden in cancer survivors. This review identifies features that could help guide decisions about the benefit of screening to assess the risk or presence of subclinical CAD. Screening may be appropriate in selected survivors based on risk factors and inflammatory burden. In cancer survivors who have undergone genetic testing, polygenic risk scores and clonal hematopoiesis markers may become useful CAD risk prediction tools in the future. The type of cancer (especially breast, hematological, gastrointestinal, and genitourinary) and the nature of treatment (radiotherapy, platinum agents, fluorouracil, hormonal therapy, tyrosine kinase inhibitors, endothelial growth factor inhibitors, and immune checkpoint inhibitors) are also important in determining risk. Therapeutic implications of positive screening include lifestyle and atherosclerosis interventions, and in specific instances, revascularization may be indicated.

Neuroprotective effects of pravastatin in cerebral venous infarction in a rat model.

Objectives: Pravastatin sodium is reported to have multiple beneficial effects in cerebral atherosclerosis and neuronal injury; however, the preventive effects on cerebral venous ischemia are still unknown. Herein, we aimed to examine the neuroprotective effects of transoral prior administration of pravastatin sodium against cerebral cortical venous ischemia with suppression of apoptosis. Methods: Thirty 8-week-old male Wistar rats were divided equally into two study groups (n = 15 vs. n = 15); the pravastatin group was fed 1% pravastatin sodium with their usual diet for 2 weeks, while the control group only received the usual diet. Two-vein occlusion (2VO) model was applied for this study, and two adjacent cortical veins in each animal were permanently occluded photochemically with rose bengal dye. During photo-thrombosis, regional changes of the cerebral blood flow (CBF) in area of the venous ischemia were recorded. At 48-h after 2VO, animals were euthanized using perfusion fixation, and we histologically measured ratios of infarcted area to contralateral hemisphere, and counted Bax- and Bcl-2-positive cells in the penumbra to investigate the implications for apoptosis. Results: The ratio of infarcted area was significantly decreased in the pravastatin group compared to the control group (P < 0.01). The number of Bax-positive cells also decreased significantly in the pravastatin group (P < 0.01). In contrast, immunolabeling for Bcl-2 was essentially negative in all areas in both groups. There were also no significant differences in regional CBF changes after 2VO between the two groups (P = 0.13). Conclusions: Pre-emptive administration of pravastatin sodium mixed in the food has neuroprotective effects against cerebral cortical venous ischemia with suppression of apoptosis associated with inhibition of Bax expression but has little influence on regional CBF.

Coronary Flow Reserve, Inflammation, and Myocardial Strain: The CIRT-CFR Trial.

Inflammation is a key determinant of cardiovascular outcomes, but its role in heart failure is uncertain. In patients with cardiometabolic disease enrolled in the prospective, multicenter ancillary study of CIRT (Cardiovascular Inflammation Reduction Trial), CIRT-CFR (Coronary Flow Reserve to Assess Cardiovascular Inflammation), impaired coronary flow reserve was independently associated with increased inflammation and myocardial strain despite well-controlled lipid, glycemic, and hemodynamic profiles. Inflammation modified the relationship between CFR and myocardial strain, disrupting the association between cardiac blood flow and function. Future studies are needed to investigate whether an early inflammation-mediated reduction in CFR capturing microvascular ischemia may lead to heart failure in patients with cardiometabolic disease. (Cardiovascular Inflammation Reduction Trial [CIRT]; NCT01594333; Coronary Flow Reserve to Assess Cardiovascular Inflammation [CIRT-CFR]; NCT02786134).

Hydroxytyrosol attenuates ethanol-induced liver injury by ameliorating steatosis, oxidative stress and hepatic inflammation by interfering STAT3/iNOS pathway.

Objective: Hydroxytyrosol (HT) is a polyphenol with a wide range of biological activities. Excessive drinking can lead to oxidative stress and inflammation in the liver, which usually develop into alcohol liver disease (ALD). At present, there is no specific drug to treat ALD. In this paper, the protection effect of HT on ALD and the underline mechanism were studied.Methods: HepG2 cells were exposed to ethanol in vitro and C57BL/6J mice were fed with a Lieber-DeCarli ethanol liquid diet in vivo.Results: triglyceride (TG) level in serum and the expression of fatty acid synthase (FASN) were reduced significantly by the treatment with HT The acetaldehyde dehydrogenase (ALDH) activity was increased, the serum level of malondialdehyde (MDA) was decreased, catalase (CAT) and glutathione (GSH) were increased, suggesting that HT may reduce its oxidative damage to the body by promoting alcohol metabolism. Furthermore, according to the mRNA levels of tnf-α, il-6 and il-1ß, HT inhibited ethanol-induced inflammation significantly. The anti-inflammatory mechanism of HT may be related to suppress the STAT3/iNOS pathway.Dissussion: Our study showed that HT could ameliorate ethanol-induced hepatic steatosis, oxidative stress and inflammation and provide a new candidate for the prevention and treatment of ALD.

Emerging Pharmacotherapies in Alcohol-Associated Hepatitis.

The incidence of alcoholic-associated hepatitis (AH) is increasing. The treatment options for severe AH (sAH) are scarce and limited to corticosteroid therapy which showed limited mortality benefit in short-term use only. Therefore, there is a dire need for developing safe and effective therapies for patients with sAH and to improve their high mortality rates.This review article focuses on the current novel therapeutics targeting various mechanisms in the pathogenesis of alcohol-related hepatitis. Anti-inflammatory agents such as IL-1 inhibitor, Pan-caspase inhibitor, Apoptosis signal-regulating kinase-1, and CCL2 inhibitors are under investigation. Other group of agents include gut-liver axis modulators, hepatic regeneration, antioxidants, and Epigenic modulators. We describe the ongoing clinical trials of some of the new agents for alcohol-related hepatitis. Conclusion: A combination of therapies was investigated, possibly providing a synergistic effect of drugs with different mechanisms. Multiple clinical trials of novel therapies in AH remain ongoing. Their result could potentially make a difference in the clinical course of the disease. DUR-928 and granulocyte colony-stimulating factor had promising results and further trials are ongoing to evaluate their efficacy in the large patient sample.

PPAR agonists for the treatment of primary biliary cholangitis: Old and new tales.

Introduction: Primary biliary cholangitis (PBC) is an autoimmune liver disease involving the small intrahepatic bile ducts; when untreated or undertreated, it may evolve to liver fibrosis and cirrhosis. Ursodeoxycholic Acid (UDCA) is the standard of care treatment, Obeticholic Acid (OCA) has been approved as second-line therapy for those non responder or intolerant to UDCA. However, due to moderate rate of UDCA-non responders and to warnings recently issued against OCA use in patients with cirrhosis, further therapies are needed.Areas covered. Deep investigations into the pathogenesis of PBC is leading to proposal of new therapeutic agents, among which peroxisome proliferator-activated receptor (PPAR) ligands seem to be highly promising given the preliminary, positive results in Phase 2 and 3 trials. Bezafibrate, the most evaluated, is currently used in clinical practice in combination with UDCA in referral centers. We herein describe completed and ongoing trials involving PPAR agonists use in PBC, analyzing pits and falls. Expert opinion: Testing new therapeutic opportunities in PBC is challenging due to its low prevalence and slow progression. However, new drugs including PPAR agonists, are currently under investigation and should be considered for at-risk PBC patients.

Gastric Xanthomatosis Secondary to Lipoprotein X in Primary Biliary Cholangitis.

Primary biliary cholangitis (PBC) is a rare autoimmune disease characterized by intralobular bile duct destruction. Patients typically present with generalized symptoms including fatigue and pruritis, and less commonly, manifestations of lipid deposition including xanthomas and xanthelasmas. We report a case of a 31-year-old female with PBC-associated cirrhosis who had cutaneous xanthelasmas and diffuse gastric xanthomas secondary to hyperlipidemia and lipoprotein X that completely resolved following liver transplantation. While gastric xanthomas have been reported in patients with PBC previously, to our knowledge, this is the first case report of diffuse gastric xanthomas secondary to PBC reported to resolve following liver transplantation, suggesting that liver transplantation is curative for gastric xanthomatosis in patients with PBC-related cirrhosis.

Secular trends in serum lipid profiles in young adults in Norway, 2001-19.

Background: Lower prevalence of major cardiovascular disease (CVD) risk factors, such as dyslipidemia, hypertension and smoking, can explain a substantial part of the decline in CVD mortality and incidence for the past decades in Western countries. However, some studies have indicated less favorable trends in risk factors in recent years. We have assessed time trends in lipid profiles among young adults in Norway measured between 2001 and 2019. Methods: Samples of serum lipids analyzed at one large medical laboratory in Oslo, Norway, mainly requisitioned by primary care physicians, were analyzed cross-sectionally to estimate year-to-year trends among men and women aged 18-49 years. We also assessed the lipid distributions and proportions with adverse lipid levels. Results: In total, more than 2,6 million blood samples, comprising more than 1 million individuals (mean age 37.7 years) from all regions of Norway were included. All measures improved among all age groups in both women and men, especially in total and non-HDL cholesterol (-0.22 and -0.25 mmol/l per decade, respectively). There were downward shifts in the population distribution of total, non-HDL-C and LDL-C. The overall prevalences of total cholesterol ≥5.0 mmol/l and non-HDL-C ≥3.9 mmol/l similarly decreased, from ∼63 to 46% and from ∼52 to 34%, respectively. More than 1/3 had elevated levels of total and/or non-HDL-C in 2019. Conclusion: In a large proportion of the Norwegian population aged 18-49 years old, the lipid profiles improved during the last two decades. As the use of lipid-lowering medications is low in this age group, this likely reflects favorable secular trends.

When LDL Cholesterol Is Not LDL Cholesterol: LpX, A Clinical Lesson.

LpX is a lipoprotein formed in cholestatic conditions and often erroneously reported as LDL-C. A low ApoB level can support the diagnosis of LpX. Treatment should not automatically focus on lowering serum lipid levels, but primarily on resolving the cause of cholestasis. (Level of Difficulty: Advanced.).

Diabetes care and its predictors among persons experiencing homelessness compared with domiciled adults with diabetes in New York City; An observational study.

Background: There is a dearth of data regarding diabetes control among patients experiencing homelessness. Methods: We retrospectively collected type 2 diabetes-related measurements, sociodemographic, and clinical indicators from medical records of all incoming adults with diabetes (n = 418; homeless: 356 and domiciled: 58) seen in shelter-clinics in New York City in 2019. The outcomes were the rates of inadequately managed diabetes and associated factors. Findings: Bivariate analysis showed that patients experiencing homelessness (63% Black; 32% Hispanic) 134/304 (43⋅9%) were more likely than domiciled patients 13/57 (22·8%) to have inadequately managed diabetes (OR 2⋅67, CI 1·38-5·16, p = 0⋅003). The average HbA1c among homeless (8·4%, SD± 2·6) was higher than that of domiciled persons (7·3%, SD± 1·8, p = 0·002). In logistic regression, domiciled status (OR 0⋅ 42, CI 0·21 - 0·84, p = 0·013), older age (OR 0·97, CI 0·95 - 0·99, p = 0·004), and non-Hispanic/Latino ethnicity were associated with well-managed diabetes. Among persons experiencing homelessness, non-Hispanic/Latino (OR 0·61, CI 0·37-0·99, p = 0·047) and older age (0·96, CI 0·94-0·99, p = 0·003) were associated with well-managed diabetes. In linear regression, mental illness (-0·11, p = 0·048) and older age (-0·15, p = 0·010) were associated with lower HbA1c, suggesting better support in respective shelters. There was no statistically significant association between inadequately managed diabetes with several traditional risk factors including substance or alcohol use disorder, health insurance, or other chronic diseases. Interpretation: Interventions at shelters or shelter-clinics should target subgroups in addition to addressing traditional risk factors to improve diabetes control. mHealth strategies could be considered to improve engagement, care delivery, and medication taking. Ultimately, homelessness itself needs to be addressed. Funding: There are no funding sources to declare.

Triglyceride glucose index: A new biomarker in predicting cardiovascular risk.

Introduction: Insulin resistance can be assessed by the Triglyceride-Glucose Index (TyG), a simple, low-cost, and easy-to-apply method. Objective: To assess the predictive capacity of the TyG index about cardiovascular risk and identify its cutoff point in a population at cardiometabolic risk. Methods: Cross-sectional study with 264 individuals at cardiometabolic risk (54.9% women, age: 43.1 ± 16.3 years). Demographic, anthropometric, clinical-laboratory, and lifestyle data were collected. The TyG index was determined using the formula Ln [fasting triglycerides (mg/dL) × fasting plasma glucose (mg (dL)/2]. The ten-year cardiovascular risk was assessed by the Framingham risk score (FRS). The receiver operating characteristic curve (ROC) was used to define the cutoff point for the TyG index, and the associations were tested by Poisson regression. Results: ROC curve analysis indicated an area under the curve of 0.678 (95% CI = 0.618-0.734; p < 0.001), with a cutoff of 9.04 (sensitivity = 62.5%, specificity = 66.7%, positive predictive value = 29.4% and negative predictive value = 88.9%). Elevated TyG values ​​(≥9.04) were positively associated with cardiometabolic risk factors (total cholesterol, LDL, VLDL, uric acid, alanine aminotransferase, aspartate aminotransferase, waist-hip ratio, systolic blood pressure, HOMA-IR, smoking, metabolic syndrome, diabetes, and hepatic steatosis). After adjustment for confounding factors, individuals with high TyG showed an increase of 69% (RP = 1.69; 95%CI = 1.03-2.78) in the prevalence of intermediate/high risk by FRS, compared to those with low TyG. Conclusion: The TyG index showed a good predictive capacity for cardiovascular risk in ten years assessed by the FRS.