Higher Age Level Research Articles

Advanced glycation end products association with diabetic retinopathy severity

Aims/Purpose: Advanced glycation end products (AGEs) are proteins or lipids that become glycated as a result to exposure to sugars and diabetes (DM) can accelerate its usually slow accumulation. Higher levels of AGEs are associated with microvascular complications as diabetic retinopathy (DR). AGEs can be measured in human skin using ultra‐violet light to excite autofluorescence. The purpose of this study was to determine the association between AGEs levels and DR severity.Methods: A total of 152 patients were enrolled. DR severity was determined by an ophthalmologist. AGEs concentrations were measured with non‐invasive AGE Reader device.Results: 69 men and 83 women with type 1 (50.7%) and type 2 (49.3%) diabetes were included in the analysis. Age median was 51.85 (min.18, max. 85) years with duration of diabetes 15.99 ± 11.18 years. Mean HbA1C was 8.34 ± 1.99%. 43.7% had no signs of DR, 40.4% had non‐proliferative DR (NPDR), 15.9% – proliferative DR (PDR). Age and HbA1C did not differ between different severity DR groups (p = 0.081 and p = 0.196). AGEs concentration increases with age (r = 0.498, p < 0.001) and duration of diabetes (r = 0.308, p < 0.001). Mean concentration of AGEs were higher in type 2 DM group (p = 0.015). The concentration of AGEs did not differ between DR groups (p = 0.473), thought in type 1 DM subgroup mean concentration of AGEs was higher in PDR patients compared to no DR patients (1.89 vs. 2.43, p = 0.006), whereas no significant difference was found between type 2 DM patients in different DR groups (p = 0.343). There was no significant correlation between HbA1C and AGEs concentration (p = 0246) in all DM patients, but in type 1 DM, AGEs concentration significantly increases with higher HbA1C values (r = 0.309, p = 0.007), but not significantly in type 2 DM (p = 0.282).Conclusions: The levels of AGEs might have association with the severity of DR in type 1 diabetes, but not type 2. More investigations regarding the association of AGEs and DR severity should be performed.

The Predictive Value of PKC and ET-1 Levels in Cerebrospinal Fluid for Vasospasm and Prognosis in Patients with Aneurysmal Subarachnoid Hemorrhage.

To analyze the predictive value of protein kinase C (PKC) and endothelin-1 (ET-1) in cerebrospinal fluid for vasospasm and prognosis in patients with aneurysmal subarachnoid hemorrhage (ASH). One hundred and forty-eight ASH patients hospitalized in our hospital during February 2019 to February 2022 were optioned as observation subjects. These subjects were graded into good prognosis group (mRS score 0-2, n = 102) and poor prognosis group (mRS score 3-6, n = 46) according to the Rankin Revised Scale Score (mRS) after 6 months of follow-up. Cerebrospinal fluid was collected from patients to detect the content of ET-1 and PKC. The prognostic factors were analyzed using multifactorial logistic regression. The predictive value was assessed using receiver operating characteristic (ROC) curve. The patients with poor prognosis had a higher age level and a higher proportion of ≥2 aneurysms, aneurysm diameter ≥6 mm, cerebral vasospasm, and Hunt-Hess grade ≥III than those with good prognosis (P < 0.05). The patients with poor prognosis had higher content of PKC and ET-1 than those with good prognosis (P < 0.05). Age, aneurysm diameter ≥6 mm, cerebral vasospasm, Hunt-Hess classification ≥grade III, PKC and ET-1 were all risk factors related to the prognosis of ASH (P < 0.05). The area under the curve (AUC) of PKC and ET-1 for diagnosing poor prognosis of ASH was 0.803 and 0.720, respectively. The AUC of the combined detection was 0.873 (P < 0.05). Patients with cerebrovascular spasm had higher content of PKC and ET-1 than those without (P < 0.05). The AUC of PKC and ET-1 for diagnosing cerebral vasospasm in ASH was 0.891 and 0.816, respectively, which was 0.932 for combined detection (P < 0.05). The combination of PKC and ET-1 in cerebrospinal fluid had certain value in predicting the poor prognosis of patients with ASH.

Association between Mediterranean Diet and Advanced Glycation End Products in University Students: A Cross-Sectional Study.

The aim of this study was to evaluate the association between the Mediterranean diet (MD) and the accumulation of advanced glycation end products (AGEs) measured by skin autofluorescence. This cross-sectional study included 1016 healthy students from the University of Split, Croatia. Participants completed a self-administered questionnaire. Adherence to the MD was assessed using the Mediterranean Diet Serving Score (MDSS), and tissue AGEs accumulation was measured using the AGE Reader mu (DiagnOptics). Multivariate linear regression was used in the analysis. Students' age and female gender were associated with higher levels of AGEs, which was likewise found for greater coffee intake, adequate olive oil consumption, smoking, and lower levels of physical activity. Higher consummation of vegetables and eating breakfast regularly were associated with lower AGEs levels. The overall MD adherence was not associated with AGEs, possibly due to very low overall compliance to the MD principles among students (8.3% in women and 3.8% in men). Health perception was positively associated with the MD and nonsmoking and negatively with the perceived stress level, while AGEs did not show significant association with self-rated students' health. These results indicate that various lifestyle habits are associated with AGEs accumulation even in young and generally healthy people. Hence, health promotion and preventive measures are necessary from an early age.

Association of Advanced Glycation End Products with Cognitive Function: HealthyDance Study.

The current research on advanced glycosylation end products (AGEs) and cognitive function is limited. We aimed to investigate the relationship between multiple plasma AGEs and cognitive function and mild cognitive impairment (MCI). Baseline data from The Lifestyle and Healthy Aging of Chinese Square Dancer Study was used in this cross-sectional study. Ultra-high-performance liquid chromatography tandem mass spectrometry was used to determine plasma levels of carboxymethyl lysine (CML), carboxyethyl lysine (CEL), and methyl imidazolinone (MG-H1). Four cognitive tests were used to obtain the four cognitive domain scores and the composite z scores. The Petersen criteria were used to diagnose MCI. The data were analyzed by multivariable linear and logistic regression models. This study included 1,018 participants (median age 61.0 years, 87.3% female). After multivariate adjustment, the βs of the highest quartile of CML and CEL compared to the lowest quartile were -0.28 (-0.38, -0.17) and -0.13 (-0.23, -0.03), respectively, for the composite z score. For the four cognitive domains, CML was negatively correlated with memory, attention, and executive function, and CEL was negatively associated with memory and language function. In addition, higher CML was associated with a higher odds of MCI. MG-H1 was not associated with cognitive function. High plasma AGE levels were correlated with poorer cognitive function, particularly CML and CEL, higher levels of CML were also associated with higher odds of MCI. To clarify the effects of different AGEs on cognitive function and the underlying mechanisms, further longitudinal and experimental studies are needed.

Differential metal and metalloid contents in fresh and cooked Charu mussels (Mytella charruana) from a southeastern Brazilian estuary and associated human health risks

Sepetiba Bay, a key estuarine ecosystem in southeastern Brazil, faces significant metal inputs, with a differential pollution gradient from the bay's entrance to inner areas, raising environmental and public health concerns. This study assessed metal levels in fresh and cooked samples of highly consumed Charu mussels (Mytella charruana) from three bay areas, one near the bay entrance (P1), with higher water renewal rates, one in the northern bay area (P2) and one the eastern bay (P3), presenting lower water renewal rates. Variations in metal and metalloid concentrations across sites were observed, with P3 exhibiting higher levels in fresh mussels for most elements, except for As, which was higher at P2 (0.35 ± 0.45 mg kg−1). Cooked samples demonstrated similar trends for Cu (1.30 ± 0.39 mg kg−1), Ni (0.28 ± 0.20 mg kg−1), and V (0.75 ± 0.28 mg/kg−1), indicating that cooking in contaminanted estuary water does not significantly reduce contamination. Significant differences were detected for Ni, Cd (0.014 ± 0.008 mg kg−1), Zn (14.28 ± 2.50 mg kg−1), and V at P1, which were significantly higher than at P3. Significant Fe (246 ± 68 mg kg−1), Al (109 ± 33 mg kg−1), and Mn increases were observed from P1 to P3. Mussels sampled from P3, near an abandoned military area and urban center, exhibited high Fe and Al levels, attributed to both natural processes and industrial activities. Metal concentrations in Charu mussels often exceeded regulatory limits set by Brazilian, North American, and European agencies. Calculated Se molar ratios indicate that while Se can mitigate Hg toxicity, high Hg levels in Sepetiba Bay's Charu mussels still pose significant health risks. Similarly, high levels of Ag, Cd, and Pb suggest ineffective Se protection. However, Se appears effective against As toxicity. The Health Benefit Value of Selenium (HBVSe) indicate Se's overall protective benefits against Hg toxicity. Higher HBVSe values in cooked mussels at P1 and P2 suggest that cooking increases Se bioavailability. However, raw mussels at P3 had higher HBVSe values than cooked ones, highlighting the need for site-specific assessments. Calculated Hazard Indices indicate general high health risks from mussel consumption, and As levels in Charu mussels indicate high carcinogenic risks. These findings emphasize the need for comprehensive Charu mussel monitoring and environmental management efforts at Sepetiba Bay.

A preliminary probabilistic nomogram model for predicting renal arteriolar damage in IgA nephropathy from clinical parameters.

IgA nephropathy (IgAN) is a significant contributor to chronic kidney disease (CKD). Renal arteriolar damage is associated with IgAN prognosis. However, simple tools for predicting arteriolar damage of IgAN remain limited. We aim to develop and validate a nomogram model for predicting renal arteriolar damage in IgAN patients. We retrospectively analyzed 547 cases of biopsy-proven IgAN patients. Least absolute shrinkage and selection operator (LASSO) regression and logistic regression were applied to screen for factors associated with renal arteriolar damage in patients with IgAN. A nomogram was developed to evaluate the renal arteriolar damage in patients with IgAN. The performance of the proposed nomogram was evaluated based on a calibration plot, ROC curve (AUC) and Harrell's concordance index (C-index). In this study, patients in the arteriolar damage group had higher levels of age, mean arterial pressure (MAP), serum creatinine, serum urea nitrogen, serum uric acid, triglycerides, proteinuria, tubular atrophy/interstitial fibrosis (T1-2) and decreased eGFR than those without arteriolar damage. Predictors contained in the prediction nomogram included age, MAP, eGFR and serum uric acid. Then, a nomogram model for predicting renal arteriolar damage was established combining the above indicators. Our model achieved well-fitted calibration curves and the C-indices of this model were 0.722 (95%CI 0.670-0.774) and 0.784 (95%CI 0.716-0.852) in the development and validation groups, respectively. With excellent predictive abilities, the nomogram may be a simple and reliable tool to predict the risk of renal arteriolar damage in patients with IgAN.

Are There Differences in Skin Autofluorescence-Measured Advanced Glycation End-Product Levels between Chronic Kidney Disease and Kidney Transplant Recipients?

The aim of this cross-sectional study was to evaluate the differences in the levels of advanced glycation end products (AGE) between patients with chronic kidney disease (CKD) and kidney transplant recipients (KTRs) and to investigate the risk factors for the AGE levels in each group of these patients. There were 217 participants total, of which 99 (45.6%) were KTRs and 118 (54.4%) had CKD. Data on the levels of AGE, body mass composition, anthropometric parameters, central and peripheral blood pressure, and clinical and laboratory parameters were gathered for each study participant. The AGE values of the CKD and KTRs groups did not differ from one another. In both groups, a lower estimated glomerular filtration rate, male sex, and older age were positive predictors for increased AGE values. Furthermore, higher levels of AGE were linked to lower central systolic blood pressure (cSBP) in the CKD group, whilst, in the KTRs group, higher levels of AGE were linked to a shorter time since kidney transplantation (KTx), more years of dialysis prior to KTx, lower levels of trunk visceral fat, the presence of arterial hypertension, and the absence of prescriptions for the antihypertensive medications urapidil and angiotensin II receptor blockers. Further studies are needed to better understand the above associations. Consequently, a personalised multidisciplinary approach to assess the cardiovascular as well as dietary and lifestyle risk factors to reduce the AGE levels in both KTRs and CKD patients may be implemented.

Accumulation of Intracellular Protein Advanced Glycation End Products Alters Cellular Homeostasis for Protein Clearance in Pancreatic Ductal Epithelial Cells.

Protein advanced glycation end products (AGEs) can be formed via nonenzymatic glycation and accumulated intracellularly to disrupt cellular homeostasis for protein clearance. Here, we investigated the formation particulars of intracellular protein AGEs and sought to elucidate the molecular events implicated in the impact of cellular clearance systems. The formation and accumulation of intracellular protein AGEs increased protein aggregation and protease resistance, potentially overwhelming the ubiquitin-proteasome system (UPS). At high levels of protein AGEs, the abundance of many E3 ligases decreased and the overall ubiquitination level was reduced, all of which indicated decreased UPS activity. On the other hand, autophagy activity was stimulated, as evidenced by the upregulation of autophagy marker LC3II and important proteins in autophagosome and autolysosome formation, as well as downregulation of mTOR. Understanding the functional impacts of intracellular protein AGEs on the UPS and autophagy could pave the way for the future development of pharmaceutical agents targeting AGE-related diseases.

Association of whole blood copper, zinc, calcium, magnesium, and iron with non-alcoholic fatty liver disease in overweight and obese children.

Non-alcoholic fatty liver disease (NAFLD) is a common metabolic disorder in overweight and obese children, and its etiology and pathogenesis remain unclear, lacking effective preventive and therapeutic measures. This study aims to explore the association between whole blood copper, zinc, calcium, magnesium and iron levels and NAFLD in overweight and obese children aged 6 to 17 years, providing a scientific basis for the prevention and intervention of early NAFLD in overweight and obese children. A cross-sectional study design was used to collect relevant data from overweight and obese children who visited the Hunan Children's Hospital from January 2019 to December 2021 through questionnaire surveys. Fasting blood samples were collected from the subjects, and various indicators such as blood glucose, blood lipid, and mineral elements were detected. All children were divided into an overweight group (n=400) and a NAFLD group (n=202). The NAFLD group was divided into 2 subgroups according to the ALT level: A non-alcoholic fatty liver (NAFL) group and a non-alcoholic steatohepatitis (NASH) group. Logistic regression analysis was used to analyze the association between minerals (copper, zinc, calcium, magnesium, and iron) and NAFLD, NAFL and NASH. A total of 602 subjects were included, of whom 73.6% were male, with a median age of 10 (9, 11) years, and a body mass index (BMI) of 24.9 (22.7, 27.4) kg/m2. The intergroup comparison results showed that compared with the overweight group, the NAFLD group had higher levels of age, BMI, diastolic blood pressure (DBP), systolic blood pressure (SBP), triglyceride (TG), low density lipoprotein (LDL), alanine transaminase (ALT) and aspartate aminotransferase (AST), and lower level of high density lipoprotein (HDL). The NAFL group had higher levels of age, BMI, DBP, SBP, ALT, and AST, and lower levels of HDL compared with the overweight group. The levels of age, BMI, DBP, SBP, TG, LDL, ALT, and AST of NASH were higher than those in the overweight group, while the level of HDL was lower than that in overweight group (all P<0.017). After adjusting for a variety of confounders, the OR of NAFLD for the highest quantile of iron was 1.79 (95% CI 1.07 to 3.00) compared to the lowest quantile, and no significant association was observed between copper, zinc, calcium, and magnesium, and NAFLD. The subgroup analysis of NAFLD showed that the OR for the highest quantile of iron in children with NAFL was 2.21 (95% CI 1.26 to 3.88), while no significant association was observed between iron level and NASH. In addition, no significant associations were observed between copper, zinc, calcium, and magnesium levels and NAFL or NASH. High iron level increases the risk of NAFLD (more likely NAFL) in overweight and obese children, while copper, zinc, calcium, magnesium, and other elements are not associated with the risk of NAFLD in overweight and obese children.

Carbonyl stress in menopausal women with insomnia

To assess the level of advanced oxidation protein products (AOPP) and advanced glycation end products (AGEs) in menopausal women with insomnia. One hundred and thirty-six menopausal women were examined. After collecting medical history, general clinical examination, examination by a gynecologist and identifying the presence and nature of sleep disorders, the subjects were divided into 4 groups: 1 - control/perimenopause (n=21); 2 - insomnia/perimenopause (n=34); 3 - control/postmenopause (n=31); 4 - insomnia/postmenopause (n=50). The content of AOPP and the level of AGEs were determined using enzyme immunoassay. A high percentage of menopausal women with insomnia have carbonyl stress values above the confidence interval (AGEs - 49.2% of women, AOPP - 55.2%). The insomnia in perimenopause is associated with high levels of AGEs (4533.10 [3834.09; 5098] ng/ml, p=0.039) and AOPP (28.92 [22.27; 40] nmol/L, p=0.002) as compared to controls (3685.87 [3376.11; 4318] ng/ml and 19.8 [16.85; 23.97] nmol/L, respectively). There are no significant differences in the studied parameters in postmenopause with insomnia. Insomnia in perimenopause is a provoking factor for the development of free radical pathology and is associated with the formation of carbonyl stress, and in postmenopause it does not make significant changes in metabolic pathways involving carbonyl compounds.

AN INTEGRATED MACHINE LEARNING FRAMEWORK FOR ACCURATE CARDIOVASCULAR DISEASE PREDICTION

This paper introduces an advanced real-time system designed to predict cardiovascular diseases with integrated machine learning. Cardiovascular diseases, with the highest global mortality rate, have become increasingly prevalent, straining healthcare systems worldwide. These diseases, driven by factors such as high blood pressure, stress, age, gender, and cholesterol levels, have prompted numerous early diagnosis approaches, but their accuracy requires refinement due to the critical nature of cardiovascular diseases. This paper presents the DLCDD (Deep Learning based Cardiovascular Disease Diagnosis) framework, specifically addressing data-related challenges such as missing values and imbalances. The mean replacement technique is employed for handling missing values, while the Synthetic Minority Over-sampling Technique (SMOTE) is utilized to address imbalances in the dataset. In essence, DLCDD represents a significant advance in precise cardiovascular disease prediction, uniting deep learning with cutting-edge data processing and feature selection methods, addressing critical diagnostic challenges.

47 Mind-Wandering in Older Adults: Implications for Fluid Cognition and Perceived Psychological Quality of Life

Objective:Mind-wandering is defined as a spontaneous shift of attention away from the external environment to inner thoughts. With mind-wandering being a ubiquitous phenomenon, there has been increasing interest in examining the role these spontaneous, and often unintentional, thought processes may have for metrics of cognitive and psychological health. However, much of this literature is mired with inconsistencies, potentially stemming from the use of variegated experimental methods and quantification of mind-wandering through different metrics. For example, mind-wandering has been investigated through endorsement of self-report probes embedded in tasks of sustained attention, with participants asking to endorse whether they were engaging in task-unrelated thoughts or task-related, but evaluative thoughts about the task (task-related interference). Other studies have instead focused on behavioral metrics of task performance, like omission and commission errors, the variability in response time (RTCV), and speeding or slowing prior to errors to quantify mind-wandering. In this study, employing a large sample of older adults, and implementing the novel technique of partial least squares regression, we examined the combined and simultaneous effect of different mind-wandering metrics in explaining variance in fluid cognition and psychological health in older adults.Participants and Methods:One hundred and fifty older adults with normal cognition or mild cognitive impairment were administered a Go/No-Go Task (GNG) with embedded mind-wandering probes, the Conners CPT-3, the NIH Toolbox-Cognition Battery, and the WHO Quality of Life Assessment Brief Version at baseline in a clinical trial examining the impact of two mind-body interventions on aging. Based on previous research, the following variables were considered behavioral measures of mind-wandering: quantity of omission and commission errors, RTCV, pre-error speeding, and post-error slowing. Percentage of self-reported task-related interference (i.e. evaluating current performance) and task-unrelated thoughts were included as self-report measures of mind-wandering. These mind-wandering measures, along with demographic variables (age, sex, and education), were regressed using Partial Least Squares Regression to determine the impact of mind-wandering measures on fluid cognition (NIHT-CB) and perceived psychological well-being (WHOQOL-BBREF). Validation tests were completed to assess model fit.Results:A single latent factor explained 26% of the variance in fluid cognition (p=0.0001). Higher levels of age, errors of omission on both tasks, and task-related interference were all associated with worse fluid cognition, whereas task-unrelated thoughts were associated with better fluid cognition.A two-factor latent model explained 12% of the variance in perceived psychological well-being (p=0.0004). Age and task-unrelated thoughts were positively associated with psychological well-being. In contrast, errors of omission on both tasks, response time variability on the CPT, and task-related interference were negatively associated with perceived psychological well-being.Conclusions:Mind-wandering is associated with fluid cognition and perceived psychological well-being in older adults. Select behavioral measures were better than self-report measures at linking mind-wandering to fluid cognition and perceived psychological well-being. Interestingly task-unrelated thoughts, but not task-related interference, was positively associated with fluid cognition, supporting the cognitive resource-based account of mind-wandering. The result of our study provides novel insights into differential relationships between various metrics of mind-wandering and cognitive and psychological health.

Oxidative Stress in Health and Disease.

Oxidative stress, resulting from the excessive intracellular accumulation of reactive oxygen species (ROS), reactive nitrogen species (RNS), and other free radical species, contributes to the onset and progression of various diseases, including diabetes, obesity, diabetic nephropathy, diabetic neuropathy, and neurological diseases, such as Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and Parkinson's disease (PD). Oxidative stress is also implicated in cardiovascular disease and cancer. Exacerbated oxidative stress leads to the accelerated formation of advanced glycation end products (AGEs), a complex mixture of crosslinked proteins and protein modifications. Relatively high levels of AGEs are generated in diabetes, obesity, AD, and other I neurological diseases. AGEs such as Ne-carboxymethyllysine (CML) serve as markers for disease progression. AGEs, through interaction with receptors for advanced glycation end products (RAGE), initiate a cascade of deleterious signaling events to form inflammatory cytokines, and thereby further exacerbate oxidative stress in a vicious cycle. AGE inhibitors, AGE breakers, and RAGE inhibitors are therefore potential therapeutic agents for multiple diseases, including diabetes and AD. The complexity of the AGEs and the lack of well-established mechanisms for AGE formation are largely responsible for the lack of effective therapeutics targeting oxidative stress and AGE-related diseases. This review addresses the role of oxidative stress in the pathogenesis of AGE-related chronic diseases, including diabetes and neurological disorders, and recent progress in the development of therapeutics based on antioxidants, AGE breakers and RAGE inhibitors. Furthermore, this review outlines therapeutic strategies based on single-atom nanozymes that attenuate oxidative stress through the sequestering of reactive oxygen species (ROS) and reactive nitrogen species (RNS).

Diyet ileri glikasyon son ürünleri (AGE) ve kadın infertilitesi

Advanced glycation end products (AGEs) are molecules formed by non-enzymatic reactions between reducing sugars and proteins, nucleic acids, or lipids. Advanced glycation end products may be formed endogenously under normal metabolic conditions or metabolic conditions such as diabetes and hyperglycemia, or exogenously during processing of foods at high temperatures and low humidity, including roasting, grilling, and frying. The accumulation of AGEs has a significant role in the development of disorders associated with infertility. Infertility is an increasingly common health problem in recent years. Dietary habits and nutrient intake are among the many factors affecting infertility in women. Receptor AGEs (RAGE) and AGEs have been observed in theca and granulosa cells of the ovaries. High levels of AGEs affect fertility through ovarian dysfunction, follicular growth, oocyte number, fertilization rate, embryo development, adverse effects on pregnancy rate, insulin resistance, apoptosis, endothelial dysfunction, increased inflammation, and reactive oxygen species (ROS). This review aims to investigate the pathophysiology of AGEs and their receptors, as well as their possible implications for female reproductive health.

Pubertal exposure to dietary advanced glycation end products disrupts ductal morphogenesis and induces atypical hyperplasia in the mammary gland

BackgroundAdvanced glycation end products (AGEs) are reactive metabolites intrinsically linked with modern dietary patterns. Processed foods, and those high in sugar, protein and fat, often contain high levels of AGEs. Increased AGE levels are associated with increased breast cancer risk, however their significance has been largely overlooked due to a lack of direct cause-and-effect relationship.MethodsTo address this knowledge gap, FVB/n mice were fed regular, low AGE, and high AGE diets from 3 weeks of age and mammary glands harvested during puberty (7 weeks) or adulthood (12 weeks and 7 months) to determine the effects upon mammary gland development. At endpoint mammary glands were harvested and assessed histologically (n ≥ 4). Immunohistochemistry and immunofluorescence were used to assess cellular proliferation and stromal fibroblast and macrophage recruitment. The Kruskal–Wallis test were used to compare continuous outcomes among groups. Mammary epithelial cell migration and invasion in response to AGE-mediated fibroblast activation was determined in two-compartment co-culture models. In vitro experiments were performed in triplicate. The nonparametric Wilcoxon rank sum test was used to compare differences between groups.ResultsHistological analysis revealed the high AGE diet delayed ductal elongation, increased primary branching, as well as increased terminal end bud number and size. The high AGE diet also led to increased recruitment and proliferation of stromal cells to abnormal structures that persisted into adulthood. Atypical hyperplasia was observed in the high AGE fed mice. Ex vivo fibroblasts from mice fed dietary-AGEs retain an activated phenotype and promoted epithelial migration and invasion of non-transformed immortalized and tumor-derived mammary epithelial cells. Mechanistically, we found that the receptor for AGE (RAGE) is required for AGE-mediated increases in epithelial cell migration and invasion.ConclusionsWe observed a disruption in mammary gland development when mice were fed a diet high in AGEs. Further, both epithelial and stromal cell populations were impacted by the high AGE diet in the mammary gland. Educational, interventional, and pharmacological strategies to reduce AGEs associated with diet may be viewed as novel disease preventive and/or therapeutic initiatives during puberty.

Clinical significance of adanced glycation end products and inflammation products in the development of vascular calcification and cardiovascular complications in chronic kidney disease

Background. Vascular calcification underlies cardiovascular complications, which remain the leading cause of high mortality in chronic kidney disease (CKD). Uremic toxins, including the advanced glycation end products, play a significant role in the formation of this process.The Aim of the study is to clarify the role of the advanced glycation end products (AGEs) and inflammationproducts in the processes of vascular calcification at different stages of CKD.Patients and Methods. 105 patients aged 18 to 66 years at different stages of CKD C1-C5D were examined, 75 of which were caused by diabetic nephropathy (DN), 30 by other nosological forms. Serum concentrations of AGEs, IL6, TNF-α, troponin I, parathyroid hormone (PTH) were determined by enzyme immunoassay (ELISA). To study the AGEs concentration, the serum was separated by centrifugation (in Eppendorf tubes). The samples were stored at – 70 °C. The left ventricular myocardial mass index (LVMI) was determined. Left ventricular hypertrophy (LVH) was diagnosed with LVH&gt;115 g/m2 for men and &gt;95 g/m2 for women. The peak systolic velocity of blood flow in the aortic arch (Vps) was studied by duplex scanning using the Doppler effect.Results. A significant increase in serum phosphorus concentration (p &lt; 0.05) and PTH (p&lt; 0.01) was revealed as the glomerular filtration rate decreased. An increase in the concentration of AGEs, IL6 and TNF-α was found at all stages of CKD, most pronounced at the later stages – C4-C5D ((p&lt; 0.01, p&lt; 0.05, p&lt;0.05, respectively). Pronounced changes in LVMI and Vps were associated with high levels of AGEs, IL6 and TNF-α. CONCLUSION. An increase in the level of glycation end products and inflammatory factors directly and reliably correlated with the severity of uremia and the severity of morphofunctional changes in the heart and aorta, which confirms their significant role in the development of cardiovascular complications in CKD. Keywords: advanced glycation end products, inflammation, vascular calcification, chronic kidney disease&gt;˂0.05, respectively). Pronounced changes in LVMI and Vps were associated with high levels of AGEs, IL6 and TNF-α.Conclusion. An increase in the level of glycation end products and inflammatory factors directly and reliably correlated with the severity of uremia and the severity of morphofunctional changes in the heart and aorta, which confirms their significant role in the development of cardiovascular complications in CKD.

Factors Influencing the Attitudes of Local Community towards Protected Areas, Case Study on Ambatara Protected Area Forest Conservation, Northwest Ethiopia

Protected areas (PAs) are crucial for natural resources and biodiversity conservation. However, they also hurt local communities by limiting access to farmland, forest product resources, and imposing fees. In some cases, local communities may view PAs as a risk to their livelihood or appreciate benefits of having PAs at other times. Hence, improving the positive attitudes of the local community toward PAs is important for the success of PAs preservation. This paper examined factors influencing the attitudes of the local community towards protected areas, a Case Study on Ambatara Protected Area (APA) forest Conservation, Northwest Ethiopia. Data was collected through household surveys. Econometric model were used for further analysis. The result identified influential factors and revealed that higher levels of age, education, family size, farmland size, livestock size, benefits, and awareness were all significantly associated with a more positive attitude of the local community towards PAs but having severe problems with a negative attitude. These were the key factors influencing the attitudes of the local community and should be a consideration when designing conservation initiatives and policy decisions. In general, most respondents had a positive attitude(supportive) towards PA and believed the conservation of APA is essential for them. However, they had some concerns about the management and lack of access to appropriate resources; this needs to be addressed to ensure their long-term sustainability. This study concludes that understanding the attitudes of local communities toward protected areas is essential to provide a successful conservation strategy and tangible benefits to local communities and PAs. These will help to ensure and preserve PAs for generations to come.

Predictors of disease severity and outcomes in pediatric patients with croup and COVID-19 in the pediatric emergency department

BackgroundCroup caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging disease, and data on the risk factors associated with disease severity are still limited.The Westley croup score (WS) is widely used to assess croup severity. The current study aimed to analyze biomarkers associated with the WS and clinical outcomes in patients with croup and coronavirus disease 2019 in the pediatric emergency department (PED). Population and methodPatients diagnosed with croup caused by SARS-CoV-2 were admitted at two PEDs. Clinical data including age, WS, length of hospital stay, initial laboratory data, and treatment were analyzed. Clinical parameters were evaluated via multivariate logistic regression analysis. The best cutoff values for predicting croup severity and outcomes were identified using the receiver operating characteristic curve. ResultIn total, 250 patients were assessed. Moreover, 128 (51.2%) patients were discharged from the PED, and 122 (48.8%) were admitted to the hospital. Mild, moderate, and severe croup accounted for 63.6% (n = 159), 32% (n = 80), and 4.4% (n = 11) of all cases, respectively. A high mean age (years), neutrophil count (%), neutrophil-to-lymphocyte ratio (NLR), ALT (U/L), procalcitonin (ng/mL), and hemoglobin (g/dL) level, and length of hospital stay (days), and a low lymphocyte count (%) and blood pH were associated with croup severity and need for intensive care. Based on the multivariate logistic regression model, the NLR remained independent factors associated with croup severity and prognosis. Further, NLR was significantly correlated with WS. The area under the receiver operating characteristic curve of NLR for predicting a WS of ≥3 was 0.895 (0.842–0.948, p < 0.001), and that for predicting ICU admission was 0.795 (0.711–0.879, p < 0.001). The best cutoff values for a WS of ≥3 and ICU admission were 1.65 and 2.06, respectively. ConclusionNLR is correlated with WS and is a reliable, easy-to-use, and cheap biomarker for the early screening and prognosis of croup severity in the PED. A higher NLR may indicate severe croup and the need for further treatment. And the WS score remains reliable for estimating the severity of croup caused by SARS-CoV-2 and the risk of intensive care.

INCREASED LEVELS OF ADVANCED GLYCATION END PRODUCTS ARE ASSOCIATED WITH HIGHER AORTIC STIFFNESS IN YOUNGER INDIVIDUALS OF THE GENERAL POPULATION

Objective: Advanced Glycation End products (AGEs) is an established risk marker in diabetic vascular disease, and associated with the degree of diabetes complications, renal failure, and atherosclerosis in older individuals. The relationship between aortic stiffness and AGEs has not been thoroughly examined in the younger population. We aimed to evaluate the association between AGEs and aortic stiffness in the general population of young and mid-aged adults with few comorbidities. Design and method: We cross-sectionally analysed 2518 participants from a prospective population-based cohort (mean age 41.8±14.5 years, 52.2% women). Advanced glycation end-products were measured as skin autofluorescence with AGE-Reader™, which is a well-validated, non-invasive method. Aortic stiffness was assessed by carotid-femoral pulse wave velocity (cf-PWV) and augmentation index adjusted for resting heart rate (Aix) at the arteria radialis using SphygmoCor®. Linear regression stratified by age equal to or below 50 years (n = 1689) and 51 years and above (n = 829) was used to analyse associations between AGEs, and PWV and Aix in a univariate model and multivariable model adjusted for sex, body mass index, systolic blood pressure, heart rate, fasting glucose, estimated glomerular filtration rate, low-density-lipoprotein, and current smoking. Results: Mean cf-PWV and Aix across quartiles of AGEs in both age groups are shown in Figure 1. We found that one unit increase in skin autofluorescence was significantly associated with direct aortic stiffness (cf-PWV) after adjustment in younger individuals below or equal to 50 years old (unstandardized beta-coefficient (B) cf-PWV 0.59 m/s, p&lt;0.001), however not in older individuals (B 0.14m/s, p = 0.32). Higher levels of AGEs were significantly associated with indirect aortic stiffness as assessed by mean Aix in both younger individuals (B 8.27, p&lt;0.001) and older individuals (B 3.98, p&lt;0.001). Conclusions: Our findings show that higher levels of advanced glycation end products are positively associated with increased direct and indirect arterial stiffness in younger individuals with few comorbidities, independent of cardiometabolic risk factors. Future studies are warranted to elucidate the effect of reduced AGE dietary consumption and AGE-inhibition on aortic stiffness.

Correlation of systemic immune-inflammation index and moderate/major depression in patients with depressive disorders: a large sample cross-sectional study.

To evaluate the clinical value of systemic immune-inflammation index (SII) based on peripheral blood neutrophil, lymphocyte, and platelet count in evaluating the subtype and severity of depression in patients with depressive disorder. This retrospective cohort study was conducted in the Third People's Hospital of Fuyang City from January 1, 2020 to December 31, 2022. The data included sociodemographic information at admission, clinical data, discharge diagnosis and inflammatory markers. Patients were divided into low SII group and high SII group according to the optimal threshold of SII determined by receiver operating characteristic curve (ROC curve). Binary logistic regression was used to analyze the correlation between moderate/major depression and SII level. Compared to the low SII group, the high SII group had a higher age level (χ2 = 7.663, p = 0.006), more smokers (χ2 = 9.458, p = 0.002), more moderate/major depression patients (χ2 = 45.645, p < 0.001), and a higher proportion of patients with accompanying somatic symptoms (χ2 = 14.867, p < 0.001). In the final logistic regression model, after controlling for confounding factors, SII at admission was significantly associated with moderate/major depression [β =1.285, p < 0.001; odds ratio (95% confidence intervals) = 3.614 (2.693-4.850)]. Patients with high SII scores were 3.614 times more likely to have moderate/severe depression than those with low SII scores. We propose a cut-off value of SII =540.78 (sensitivity = 36.4% and specificity = 80.3%) according to the maximum Youden index. Our research indicates that SII may be a useful, repeatable, convenient, and affordable index to identify moderate/major depression in depressive disorder.