This study unveils verapamil's compelling cytoprotective and proliferative effects on pancreatic β-cells amidst diabetic stressors, spotlighting its unforeseen role in augmenting cholecystokinin (CCK) expression. Through rigorous investigations employing MIN6 β-cells and zebrafish models under type 1 and type 2 diabetic conditions, we demonstrate verapamil's capacity to significantly boost β-cell proliferation, enhance glucose-stimulated insulin secretion, and fortify cellular resil-ience. A pivotal revelation of our research is verapamil's induction of CCK, a peptide hormone known for its role in nutrient digestion and insulin secretion, which signifies a novel pathway through which verapamil exerts its therapeutic effects. Furthermore, our mechanistic insights reveal that verapamil orchestrates a broad spectrum of gene and protein expressions pivotal for β-cell survival and adaptation to immune-metabolic challenges. In vivo validation in a zebrafish larvae model confirms verapamil's efficacy in fostering β-cell recovery post-metronidazole inflic-tion. Collectively, our findings advocate for verapamil's reevaluation as a multifaceted agent in diabetes therapy, highlighting its novel function in CCK upregulation alongside enhancing β-cell proliferation, glucose sensing, and oxidative respiration. This research enriches the therapeutic landscape, proposing verapamil not only as a cytoprotector but also as a promoter of β-cell re-generation, thereby offering fresh avenues for diabetes management strategies aimed at pre-serving and augmenting β-cell functionality.

Diabetes Mellitus (DM) is a chronic metabolic disease consisting of Type 1 or Type 2 diabetes. Although treatment of Type 1 diabetes primarily involves insulin therapy, inhibitors of sodium glucose co-transporters (SGLT’s) are a promising new therapeutic. Of particular interest are the two family members, SGLT1 and SGLT2 that collectively contribute to 100% of filtered glucose reabsorption within the kidneys. Consequently, sole SGLT2 inhibitors (SGLT2i) and dual SGLT1/2 inhibitors (SGLT1/2i) contribute to reducing blood glucose levels by reducing glucose reabsorption and promoting glucosuria and natriuresis. Research from our team on SGLT2i, showed that there is a compensatory mechanism whereby SGLT1 is upregulated. This therefore may warrant the combined use of SGLT1/2i. Our in vitro results demonstrated that whilst both the sole SGLT2i empagliflozin (EMPA) and dual SGLT1/2i sotagliflozin (SOTAG) significantly reduce glucose uptake within HK2 cells, the latter was more effective. In addition, our in vitro results indicate significantly more pronounced upregulation of SGLT1 protein with EMPA compared to SOTAG. Our in vivo mechanistic findings demonstrated that SGLT1/2i significantly increased renal SOD1 levels, whilst SGLT2i significantly elevated renal SOD2 levels. Therefore, our study highlighted that SGLT2i and SGLT1/2i differentially regulate protective anti-oxidant proteins in the kidney.

The pandemic of coronavirus disease (COVID-19), a disease caused by severe acute respiratory syndrome coronavirus 2 (SARSCoV-2), is causing substantial morbidity and mortality. Older age and presence of diabetes mellitus, hypertension and obesity significantly increases the risk for hospitalization and death in COVID-19 patients. In this Perspective, informed by the studies on SARS-CoV-2, Middle East respiratory syndrome (MERS-CoV), and the current literature on SARS-CoV-2, we discuss potential mechanisms by which diabetes modulates the host-viral interactions and host-immune responses. We hope to highlight gaps in knowledge that require further studies pertinent to COVID-19 in patients with diabetes mellitus, hypertension and obesity.

To assess the community health workers’ (CHWs) knowledge, attitude, and practices (KAP) in type-2 diabetes (T2D) and hypertension (HTN) management. We thus also sought to assess the potential health system barriers for incorporating CHWs in T2D and HTN management. Mixed-method study comprised (1) a survey among 153 active CHWs to assess their KAP of T2D and HTN, and (2) semi-structured interviews with key informants to understand challenges of the health system and proposed solutions in incorporating CHWs in T2D and HTN management. The majority of CHWs correctly answered general knowledge questions on NCDs, risk factors, and prevention; however, only one-quarter correctly answered questions on smoking, family history, or tobacco use as risk factors. Most respondents appeared to have positive attitudes and have been practicing some activities related to T2D and HTN. Both financial and non-financial resource constraints were cited as challenges of the health system; therefore, re-structuring the role definition of CHWs and task of responsibilities, and assessment the need and workload have been proposed as ways forwards to effectively incorporate CHWs in T2D and HTN care. CHWs in Cambodia have shown their potential in T2D and HTN management; however, a well-designed strategy including technical training, clearly defined roles and responsibilities, and strong supporting structure are important to maximize their potential in the health system.

Inflammation is implicated in the etiology of obesity-related diseases. Thromboxane-prostanoid receptor (TPR) is known to play a role in mediating an inflammatory response in a variety of cells. Gut-derived lipopolysaccharide (LPS), a TLR4 agonist, is elevated in obesity. Moreover, free fatty acids (FFAs) are important mediators of obesity-related inflammation. However, the role and mechanisms by which TPR regulates the inflammatory response in human immune cells remain unclear. We sought to determine the link between TPR and obesity and the role/mechanisms by which TPR alters LPS or stearic acid (SA)-induced inflammatory response in PBMCs. Cells were pre-treated with agents blocking TPR signaling, followed by treatment with LPS or stearic acid (SA). Our findings showed that TPR mRNA levels are higher in PBMCs from individuals with obesity. Blockade of TPR as well as ROCK which acts downstream of TPR, attenuated LPS and/or SA-induced pro-inflammatory response. On the other hand, TPR activation using its agonist enhanced the pro-inflammatory effects of LPS and/or SA. Of note, TPR agonist by itself elicits an inflammatory response which was attenuated by blocking TPR or ROCK. Our data suggest that TPR plays a key role in promoting an inflammatory response in human PBMCs and this effect is mediated via TLR4 and/or ROCK signaling.

Background: Diabetes mellitus (DM) and osteoporosis are two of the most widespread metabolic disease in the world. The aim of this study is to investigate the prevalence of DM among patients affected by osteoporosis and fragility fractures, and to search differences in clinical features. Methods: 713 patients belonging to CTO Bone Unit because of osteoporosis and fragility fractures were divided into two groups, according to the diagnosis of DM. The clinical and bone characteristics of patients were compared. Results: Prevalence of DM was 10.8%. When compared to patients without DM, the median age at the time of first fracture was similar (72 years ± 14 IQR vs 71 years ± 12 IQR); prevalence of combination of vertebral and hip fractures was higher (p=0.039), as well as prevalence of males, although not significantly (p=0.051). Bone mineral density (BMD) at all sites was higher in DM group; Trabecular Bone Score (TBS), instead, was significantly lower (p<0.001). Conclusions: Patients with fragility fractures and DM more frequently show combination of major fractures with higher BMD levels. In these patients, TBS could be a better indicator of bone health than BMD and therefore should be used as a diagnostic tool in clinical practice.

Background: Cardiovascular (CV) morbidity and mortality are many times higher in chronic kidney disease (CKD), as well as IgA nephropathy (IgAN), than in the general population. The occurrence of metabolic syndrome (MetS) and metabolic risk factors are independent risk factors for CV disease and renal progression. The study aimed to determine the prognostic role of metabolic profiles in a homogenous group of CKD patients. Methods: One hundred and forty-five IgA nephropathy patients (92 male, 53 female, age 54.7 ± 13 years) with CKD stage 1-4 were investigated and followed for a median of 190 months. The composite (CV and renal) endpoints included all-cause mortality and any CV event such as stroke, myocardial infarction, revascularization (CV), end-stage renal disease, and renal replacement therapy (renal). Results: Patients with MetS had significantly more endpoint events (16/27 patients vs. 15/98 patients, p = 0.001) compared to the nonMetS group. Of the secondary endpoints (CV or renal separately), the rate of the renal and CV endpoints was significantly higher in the MetS group (p = 0.001 and p = 0.029). The primary endpoint independent predictors of survival were dyslipidemia, eGFR, hemoglobin, urine albuminuria, and diabetes mellitus, as determined by Cox regression analysis. Independent predictors of secondary renal endpoint were dyslipidemia, hemoglobin, urine albumin, and eGFR. Predictors of secondary cardiovascular endpoints were gender, BMI, and diabetes. Kaplan-Meier curves showed significant differences in MetS and non-MetS when examined at the combined endpoints (CV and renal) or at each endpoint separately. The primary endpoint rate increased significantly with the increased number of MetS components (MetS comp. 0 vs. MetS comp. 2+, primary endpoints, p = 0.012). Conclusion: Our results showed that the metabolic profile has a prognostic role not only for renal endpoints but also for CV endpoints in IgAN. BMI, hyperuricemia, hypertension, and diabetes have a predictive value for the prognosis of IgA nephropathy.

Viscum album L., also known as “Mistletoe”, is a hemiparasitic plant native to the European continent that grows on various host trees. This plant contains a wide variety of active compounds that can be used for treat various diseases, such as diabetes, hypertension, as an anti- inflammatory and antioxidant. However, it is most indicated in human medicine for the adjuvant treatment of cancer patients. Both for its properties directed against neoplastic cells and for its antioxidant and anti-inflammatory properties. In Veterinary Medicine, I am very few studies are recorded for animals, although formulations are available for commercial use in oral and injectable form, mostly for homeopathic use. Many studies have been conducted on a large scale by groups of independent researchers and doctors in several countries, such as Switzerland, Germany and Brazil. Therefore, this review aimed to collect data on the use of Viscum album in Veterinary Medicine in order to encourage research in this sector not only in oncological diseases but in other directions in which Viscum can find use as an anti-pretensive and anti-diabetic agent. Introduction: Lectins, flavonoids, phenols such as phenylpropanoids, coumarins, sterols, lignans, terpenoids, phenylpropanoids, alkaloids, fatty acids and viscotoxins are among the main active ingredients present in the phytocomplexes of the Viscum album plant. In particular, Attention should be given to specific oligoproteins in consideration of their activity biological [1]. present in The foliage and fruits of V. album, as in other related species, contain low-weight proteins molecular type of thionin, called viscotoxins, as well as characteristic lectins, called viscolectins, both can contribute to its system defense and can be found in extracts and related products. These classes of Viscum microproteins have received considerable attention due to their contribution to effects cytotoxics and immunostimulants of mistletoe extracts used in medicine, as discussed later, including their mechanism of action [ 2–3] viscotoxins can increase the number of cells circulating naturalkillers and consequently improve the response host antitumor immunity [ 8]. Likewise, the a viscotoxin has an effective immunomodulatory impact on human and animal granulocytes [ 9, 10] and also acts on cellular apoptosis [11]. The cytotoxic action of viscotoxin is comparable to that of conventional chemotherapeutic agents [ 12].

Introduction/Aim: Central sensitivity to thyroid hormones refers to the sensitivity of the hypothalamic-pituitary-thyroid (HPT) axis to changes in circulating free thyroxine (fT4). The relationship between fT4 levels and iodine intake is complex. The aim of the present study was to assess central sensitivity to thyroid hormones in pregnancy against iodine intake. Materials & Methods: One thousand one hundred two blood and urine samples were collected from pregnant women (with a mean age+SD of 30.4+4.6 years) during singleton pregnancies; women with known/diagnosed thyroid disease were excluded. Specifically, TSH & fT4 and 24-hour urinary iodine excretion (UI) were measured in each trimester and at two months postpartum. The Thyroid Feedback Quantile-based Index (TFQI) was calculated to assess central sensitivity to thyroid hormones. For the statistical analysis of TFQI by time period, analysis of variance (ANOVA) was used, while Pearson's correlation was used to assess TFQI versus UI. Results: The mean TFQI index ranged from -0.06 (first trimester) to -0.07 (two months postpartum), while the corresponding UI was 141 and 172 μg/L, respectively. The TFQI-UI correlation was negative (Pearson r: -0.325, p: 0.04 and r: -0.399, p: 0.023), for UI values over 250 μg/L, in the first and the third trimester of pregnancy, respectively. Discussion: TFQI is a new index reflecting central sensitivity to thyroid hormones. Lower TFQI indicates higher sensitivity to thyroid hormones. In our sample TFQI was inversely related to iodine intake, in the first trimester of pregnancy (the critical period of organogenesis) and the third trimester (the critical period of fetal growth). Thus, the observed changes in TFQI may reflect different ways of central action of thyroid hormones, according to the phase of pregnancy. The negative association between maternal TFQI (indicative of central sensitivity to thyroid hormone) and urine iodine levels during the third trimester of pregnancy may reflect the combined influence of maternal and fetal thyroid function. Our results are intriguing and have the potential to enhance our comprehension of the changes in the HPT axis’ function via variations in central sensitivity to thyroid hormones and its interplay with nutritional iodine status during pregnancy.

Various symptoms have been reported to persist beyond acute phase of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which is referred as long coronavirus disease 19 (long COVID-19). Over 65 million individuals suffer from long COVID-19. However, the causes of long COVID-19 have been largely unknown. Since long COVID-19 symptoms are observed throughout the body, vascular endothelial dysfunction may be a strong candidate to induce long COVID-19. The angioten-sin-converting enzyme 2 (ACE2), the entry receptor of SARS-CoV-2, is ubiquitously expressed in endothelial cells. We previously found that the risk factors for athero-sclerotic cardiovascular disease (ASCVD) and the history of ASCVD can be the risk for severe COVID-19, suggesting a contribution of pre-existing endothelial dysfunction to severe COVID-19. Here, we show a significant association of endothelial dysfunction with development of long COVID-19 and show that biomarkers for endothelial dysfunction in patients with long COVID-19 are also crucial players in development of ASCVD. We consider the influence of long COVID-19 on development of chronic kidney disease (CKD) and ASCVD. Furthermore, we suggest the therapeutic interventions for long COVID-19 by considering endothelial dysfunction as the treatment tar-gets for long COVID-19. Such interventions may prevent pandemic of CKD and ASCVD in post COVID-19 era.

Lifestyle interventions can prevent type 2 diabetes (T2DM). However, some in-dividuals do not experience anticipated improvements despite weight loss. Bi-omarkers to identify such individuals at early stages are lacking. IGF-1 and IGFBP-1 were shown to predict T2DM onset in prediabetes. We assessed if these markers also predict the success of lifestyle interventions, thereby possibly guid-ing personalized strategies. We analyzed fasting serum levels of IGF-1, IGFBP-1 and IGFBP-2 in relation to changes in metabolic and anthropometric parameters, including intrahepatic li-pids (IHL) and visceral adipose tissue (VAT) volume measured by MRI, in 345 high-risk prediabetic participants (54% female; aged 36-80 years). Participants were enrolled in three randomized dietary intervention trials and assessed both at baseline and one year post-intervention. Statistical analyses were performed using IBM SPSS Statistics (version 28), significance set at p

Cardiac autonomic neuropathy (CAN) is a severe complication of diabetes mellitus (DM) strongly linked to a nearly five-fold higher risk of cardiovascular mortality. Patients with Type 2 Diabetes Mellitus (T2DM) are a significant cohort in which these assessments have particular relevance to the increased cardiovascular risk inherent in the condition. This study aimed to explore the subtle correlation between the Ewing test, Sudoscan-cardiovascular autonomic neuropathy score, and cardiovascular risk calculated using SCORE 2 Diabetes in individuals with T2DM. The cohort consisted of 211 patients diagnosed with T2DM with overweight or obesity without established ASCVD, aged between 40 to 69 years. The prevalence of CAN in our group was 67.2%. In the study group, according SCORE2-Diabetes, four patients (1.9%) were classified with moderate cardiovascular risk, thirty-five (16.6%) with high risk, and one hundred seventy-two (81.5%) with very high cardiovascular risk. On multiple linear regression, the SCORE2-Diabetes algorithm remained significantly associated with Sudoscan CAN-score and Sudoscan Nephro-score and Ewing test score. Testing for the diagnosis of CAN in very high-risk patients should be performed because approximately 70% of them associate CAN. Increased cardiovascular risk is associated with sudomotor damage and that Sudoscan is an effective and non-invasive measure of identifying such risk.

Background. During the COVID-19 pandemic, there was an increased number of the hospitalized COVID-19 positive patients suffering from type 2 diabetes mellitus (T2DM). The objective of this research was to explore factors associated with the length of hospitalization of patients with T2DM and mild form of COVID-19. Material and Methods. This retrospective cohort study involved all patients who tested positive for COVID-19 and were treated in the dedicated COVID department of the University Clinical Center (UCC) in Nis between September 10, 2021, and December 31, 2021. Upon admission, patients underwent blood tests for biochemical analysis, including blood count, kidney and liver function parameters (C-reactive protein-CRP, creatinine kinase, D-dimer), as well as glycemia and HbA1c assessments. Additionally, all patients underwent lung radiography. Univariate and multivariate regression analyses were employed to assess the impact of specific factors on the length of hospitalization among patients with T2DM. Results. Out of the total 549 COVID-19 positive patients treated, 124 (21.0%) had T2DM, while 470 (79.0%) did not have diabetes. Among patients with T2DM, men were significantly younger than women (60.6±16.8 vs. 64.2±15.3, p

Nanoparticles have been used as a novel drug delivery system. Drug-incorporated nanoparticles for local delivery might optimize the efficacy and minimize the side effects of drugs. The efficacy and safety of intratracheal administration of prostacyclin analog (beraprost)-incorporated nanoparticles and imatinib, a PDGF-receptor tyrosine kinase inhibitor, -incorporated nanoparticles in Sugen-hypoxia-normoxia or monocrotaline rat models of PAH and in human PAH-pulmonary arterial smooth muscle cells have been reported. The use of inhaled drug-incorporated nanoparticles might be a novel approach for treatment of PAH.

The prognosis of cancer patients has greatly improved in the last years, owing to the development of novel chemotherapeutic agents. However, this progress comes with an increasing occurrence of cardiovascular adverse reactions. A serious side effect is arterial hypertension, which is the most frequent comorbidity encountered in cancer patients, influencing the outcomes in cancer survivors. Even though secondary hypertension related to specific chemotherapeutic agents, such as vascular endothelial growth factor inhibitors, is usually mild and reversible, in rare instances it can be severe, leading to discontinuation of chemotherapy. In addition, hypertension per se has been studied as a potential risk factor for cancer development. The relationship is even more complex than previously thought, as concerning evidence recently highlighted the potential oncogenic effects of antihypertensive drugs, such as thiazide diuretics predisposing to skin cancer. As a result, under the light of the similar risk factors and overlapping pathophysiological mechanisms between hypertension and cancer, a promising concept of onco-hypertension has emerged, aiming to improve the understanding of the complicated interplay between these two pathologies and maintain a balance between the efficacy and risks of both antihypertensive drugs and chemotherapy agents.

Gestational diabetes mellitus (GDM) triggers alterations in the maternal gut microbiome. Alongside metabolic shifts, microbial products may impact clinical factors and influence pregnancy outcomes. Here, we performed two separate analyses to integrate the maternal microbiome-metabolomic differences from a subset of the “Choosing Healthy Options in Carbohydrate Energy” (CHOICE) study. Women diagnosed with GDM were randomized to a diet higher in complex carbohydrates (CHOICE, n=18, 60% complex carbohydrate/25% fat/15% protein) or a conventional GDM diet (CONV, n=16, 40% carbohydrate/45% fat/15% protein). All meals were provided, diets were eucaloric, and fiber content was similar. CHOICE diet was associated with increases in TMAO, lysophosphotidylcholines, indoxyl sulfate, and several triglyceride (TG) species, while CONV diet was associated with higher plasma hippuric acid, aspartic acid, betaine, glutamic acid, indole propionic acid, and indoleacetic acid, suggesting that differences in lipid metabolism and tryptophan utilization pathways are linked to specific maternal diets. We also identified two latent metabolic groups not associated with either diet treatment: one metabolome associated with higher fasting glucose, and the other associated with higher fasting TGs after 7 weeks on either diet. Our study underscores the importance of utilizing dietary approaches to optimize maternal-fetal health outcomes in GDM treatment.

ABSTRACTCaffeine is known to impair both growth and development in the model social amoeba Dictyostelium discoideum. However, little is known about the transcriptional regulation in response to caffeine treatment in Dictyostelium. In yeast cells, caffeine mimics the effect of rapamycin in inhibiting mTORC1 activity. Here, we investigated whether changes in growth and development of Dictyostelium in the presence of caffeine or rapamycin are mediated by mTORC1 and/or mTORC2. Results: Treatment of wild type cells with caffeine or rapamycin resulted in severely impaired growth and in the formation of small aggregates in comparison to untreated cells. rip3‾ cells (lacking a mTORC2 component) and lst8‾cells (lacking a component of both mTOR complexes) showed higher and slower growth rates, respectively, in comparison to parental AX3 cells. Parental AX3 and rip3‾ cells displayed similar sensitivity to rapamycin and caffeine, while lst8‾ cells were more sensitive to these compounds. When developed in the presence of caffeine or rapamycin, AX3 cells formed aggregates after a long delay. Caffeine did not alter the morphology of small rip3‾ mounds and lst8‾ cells continued to remain solitary. However, in the presence of 1µM rapamycin rip3‾cells failed to form mounds while AX3 cells streamed and formed aggregates. Complementation of lst8‾ cells with the wild type lst8 gene rescued the aggregation phenotype. cDNA microarray analysis to uncover the spectrum of differentially regulated genes in response to caffeine treatment revealed 104 and 193 differentially expressed genes at 3-and 6-hours of development, respectively, in comparison to control cells. After 6 hours of starvation in the presence of caffeine, 25 genes encoding ribosomal proteins and 4 encoding elongation factors were up regulated. Furthermore, we identified that upon caffeine treatment at the 3- and 6-hours’ time points, 12 (10 up and 2 down) and 21 (13 up and 8 down) genes, respectively, encoding proteins involved in early development. Conclusion: We conclude that caffeine and rapamycin have similar effects in decreasing the growth rate and in reducing the aggregate size of D. discoideum. Studies with lst8‾ and rip3‾ cells suggest that these compounds affect cell growth and aggregation by acting on both mTOR complexes, mTORC1 and mTORC2. Analysis of the differentially expressed genes after caffeine treatment suggests a key role of these genes in growth and aggregation.

Cardiovascular diseases, which are the leading cause of death in Croatia, are linked to the high prevalence of hypertension. Both are associated with high salt intake which was determined almost two decades ago when Croatian Action on Salt and Health (CRASH) was launched. The main objective of the present study was to evaluate salt, potassium, and iodine intake using 24-hour urine samples in a random sample of adult Croatian population, and to analyse trends in salt consumption after the CRASH has intensively started. Methods: In this national population-based EH-UH 2 study performed in 2018-2021 (participation rate 72 %) in which we analysed a single 24-hour urine sample, 1067 adult participants (mean age 57.12 (SD 13.9), men 35%) were included. Results: Mean salt and potassium intakes were 8.6 g/day (IQR 6.2-11.2) and 2.8 g/day (IQR 2.1-3.5), respectively, with sodium-to-potassium ratio of 2.6 (IQR 1.8-3.3). We detected a decrease of 17.6% (2 g/day less) in salt consumption compared to our previous salt-mapping study. However, only 13.7%, and 8.9 % met the WHO salt and potassium recommended target of 5 g/day, and 3.5 g/day, respectively. Salt intake was higher, and potassium ingestion was lower in rural vs. urban regions, and in continental vs. Mediterranean parts of Croatia. Moderate to severe iodine insufficiency was determined in only 3% adult participants. Conclusion: In the last fifteen years, salt consumption has been significantly reduced in Croatian adult population because of intensive and broad CRASH program led by the Croatian Society of Hypertension and the Croatian Hypertension League. However, salt intake is still too high, and potassium ingestion is too low. With expected more active engagement and help of the government, obtained results could be significantly improved. Salt reduction programs are most cost-effective methods of cardiovascular disease prevention and should be considered more seriously by the government and health policy makers.

The African continent has the highest prevalence of hypertension globally, with South Africa reporting the highest prevalence in Southern Africa. While the influence of genetic variability in the pathogenesis of hypertension is well described internationally, limited reports are available for African populations. This study aimed to assess the association of genetic variants and essential hypertension in a cohort of two ethnic South African population groups. Two hundred and seventy-seven hypertensive and one hundred and seventy-six normotensive individuals were genotyped for 79 variants. Genotyping was performed using the Illumina GoldenGate Assay and allele-specific polymerase chain reaction. The association of variants was assessed using the Fisher Exact test under the additive and allelic genetic models, while multivariate logistic regression was used to predict the development of hypertension. Five variants (CYP11B2 rs179998, AGT rs5051 and rs699, AGTR1 rs5186 and ACE rs4646994) were significantly associated with essential hypertension in the cohort under study. Furthermore, AGTR1 rs5186 and AGT rs699 were identified as risk factors for the development of hypertension in both ethnic groups. In two ethnic South African populations an association was observed between Renin-Angiotensin-Aldosterone System (RAAS) related genes and the development of hypertension.

(1) Background: Among the chronic complications of type 2 diabetes mellitus, cancer became the leading cause of death in several countries. Our objective was the determination of whether prevalent type 2 diabetes mellitus is associated with a higher incidence of cancer. (2) Methods: This study is a nationwide analysis performed in Hungary. Study population was divided into a group with type 2 diabetes mellitus and into a non-diabetic group. The primary outcome was the risk related to overall cancer incidence. A key secondary outcome was the overall incidence of cancer in distinct study years. Further outcomes were the annual percent changes. (3) Results: The odds ratio related to the overall incidence of cancer was 2.50 (95% confidence interval: 2.46-2.55, P<0.0001) in patients with diabetes as related to controls. The odds ratio was higher in males than in females. The highest risk was found in the 18-39-year-old subgroup. The annual cancer incidence rate declined in controls, but not in patients with diabetes. Several types of cancer showed a decreasing tendency in non-diabetic controls.; (4) Conclusions: type 2 diabetes is associated with a higher risk of cancer. High risk in young patients with type 2 diabetes suggests that these young individuals should be considered as a risk group.

(1) Background: Patients with type 2 diabetes mellitus (T2DM) are at higher risk of cancer but how these two diseases associate is still debated. The goal was the assessment of the overall incidence of cancer among patients with newly diagnosed T2DM in Hungary. Summarizing, incident T2DM is associated with a significantly higher overall risk of incident cancer, with a reverse correlation of age. Newly registered T2DM patients were suggested to be screened for cancer within 6 months. (2) Methods: A nationwide, retrospective, longitudinal study was performed using a Hungarian database. The incident T2DM and diabetes free Hungarian population were included in the study. The primary endpoints were the overall and site-specific incidence and annual percentage change of the incidence of cancer in both populations. (3) Results: The overall incidence of cancer in patients amounted to 29.4/1000 and 6.6/1000 with or without T2DM, respectively, and the OR (95%CI) of cancer of the T2DM group was 4.32 (4.14-4.53), p<0.0001. The risk of having cancer was age-dependent, having the highest odd in the age group 18-39. The incidence of cancer was declining in the non-diabetic but was unchanged in T2DM population. The average lag time of diagnosing a cancer after the detection of T2DM was 3.86 months.; (4) Conclusions: Iincident T2DM is associated with a significantly higher overall risk of incident cancer, with a reverse correlation of age. Newly registered T2DM patients were suggested to be screened for cancer within 6 months.

Maternal obesity and over/undernutrition can have a long-lasting impact on offspring health during critical periods in the first 1000 days of life. Children born to mothers with obesity have reduced immune responses to stimuli which increase susceptibility to infections. Recently, maternal western-style diets (WSD), high in fat and simple sugars, have been associated with skewing neonatal immune cell development, and recent evidence suggests that dysregulation of innate immunity in early life has long-term consequences on metabolic diseases and behavioral disorders in later life. Several factors contribute to abnormal innate immune tolerance or trained immunity, including changes in gut microbiota, metabolites, and epigenetic modifications. Critical knowledge gaps remain regarding the mechanisms whereby these factors impact fetal and postnatal immune cell development, especially in precursor stem cells in bone marrow and fetal liver. Components of the maternal microbiota that are transferred from mothers consuming a WSD to their offspring are understudied and identifying cause and effect on neonatal innate and adaptive immune development needs to be refined. Tools including single-cell RNA-sequencing, epigenetic analysis, and spatial location of specific immune cells in liver and bone marrow are critical for understanding immune system programming. Considering the vital role of immune function plays in offspring health, it will be important to understand how maternal diets can control developmental programming of innate and adaptive immunity.

Pulmonary hypertension (PH) is a serious condition linked to immune-system dysfunction. Myositis-specific/associated antibodies (MSA/MAA) play a role in idiopathic inflammatory myopathy (IIM) and interstitial lung disease (ILD), but their significance in PH remains unclear. We believe the presence of these antibodies, may be underestimated. This study analyzed adult PH patients without pre-existing IIM for MSA/MAA prevalence using a line-blot assay. We compared PH patients with and without ILD signs to a cohort clinically suspected of IIM/ILD (n=558). Our PH cohort (n=121) showed a significantly higher prevalence of overall weak positive MSA/MAAs and positive overlap syndrome-associated MAAs than the suspected IIM/ILD group (p

Background: Both hypertension and carotid atherosclerosis are independent risk factors for cardiovascular disease. Understanding their combined impact could enhance risk assessment and management strategies. Hypothesis: We hypothesized that the synergistic effects of hypertension and carotid plaques would increase the risk of both cardiovascular events and all-cause mortality. Methods: A follow-up study was conducted at the Preventive Cardiology department of Vilnius University Hospital Santaros klinikos between 2012 and 2021. The study recruited participants aged 40-60 who did not have overt CVD and were part of the Lithuanian High Cardiovascular Risk primary preventive program. The study collected demographic and clinical data, including an ultrasound assessment of carotid plaque. The participants were monitored for 4-10 years for CVD events and all-cause mortality. Results: Among 6,138 participants, 954 (16%) experienced cardiovascular disease (CVD) events. The presence of carotid plaque on both sides was significantly associated with CVD events, myocardial infarction, and all-cause mortality. However, the combination of hypertension and carotid plaque did not significantly increase the risk for CVD events, stroke, or all-cause mortality. Conclusion: The combination of hypertension and carotid plaque did not significantly increase the risk of CVD events or all-cause mortality. CV events depend on the spread of the atherosclerosis process in the carotid vessels.

Pulmonary hypertension (PH) is a progressive and potentially fatal complication of sickle cell disease (SCD) affecting 6-10% of adult SCD patients. Various mechanisms and theories have been evaluated to explain the pathophysiology of the disease. However, questions remain, particularly regarding the clinical heterogeneity of the disease in terms of symptoms, complications, and survival. Beyond the classical mechanisms that have been thoroughly investigated and include hemolysis, nitric oxide availability, endothelial disorders, thrombosis, and left heart failure, attention is focused nowadays on the potential role of the genes involved in such processes. Potential candidate genes are investigated through next-generation sequencing, with the TGF-β pathway being the initial target. This field of research may also provide novel targets for pharmacologic agents in the future as is already the case with idiopathic PH. The collection and processing of data and samples from multiple centers can yield safe results that will allow a better understanding of SCD-related PH as a part of the disease’s clinical spectrum. The following review attempts to capture the most recent findings of studies on gene polymorphisms that have been associated with PH in SCD patients.

Background: Despite advances in the treatment of hepatocellular carcinoma (HCC) over the last few decades, treatment opportunities for patients with HCC remain limited. HCC is the most common form of liver cancer, accounting for approximately 90% of all cases worldwide. Moreover, apart from the current pharmacological interventions, hepatic resection and liver transplantation are the mainstay curative approaches for patients with HCC. Methods: This systematic review included phase I, II, III, and IV clinical trials (CTs) and randomized controlled trials (RCTs) on current treatments for patients with HCC in an Asian population (2013–2023). A total of 427 articles were screened, and 184 non-duplicate publications were identified. After screening titles and abstracts, 96 publications were excluded, and another 28 were excluded after full-text screening. The remaining 60 eligible RCTs/CTs were finally included. Results: Sixty clinical trials fulfilled our inclusion criteria and screened 36 drugs as monotherapy or combination therapy for HCC. Most studies used sorafenib alone or in combination with any of the treatment regimens. Lenvatinib or atezolizumab with bevacizumab was used for HCC after initial sorafenib treatment. Eighteen studies compared the efficacy of sorafenib with that of other drugs, including lenvatinib, cabozantinib, tepotinib, tigatuzumab, linifanib, erlotinib, resminostat, brivanib, tislelizumab, selumetinib, and refametinib. Conclusion: This study provides comprehensive insights into effective treatment interventions for HCC in Asian populations. The overall assessment indicated that sorafenib alone or in combination with atezolizumab and bevacizumab has been the first treatment choice in the past decade to achieve better outcomes in patients with HCC in an Asian population

Recent interest in preventing the development of osteoporosis has focused on the regulation of redox homeostasis. However, the action of lycopene (LYC), a strong natural antioxidant com-pound, on osteoporotic bone loss remains largely unknown. Here, we show that the administra-tion of LYC to OVX rats reduces body weight gain, improves lipid metabolism and preserves bone quality. In addition, LYC treatment inhibits ROS overgeneration in serum and bone marrow in OVX rats, and in BMSCs upon H2O2 stimulation, leading to inhibiting adipogenesis and pro-moting osteogenesis during bone remodeling. Mechanically, LYC may improve bone quality via an increase in the expressions of FoxO1 and Runx2, and a decrease in the expressions of PPARγ and C/EBPα in OVX rats and BMSCs. Collectively, these findings suggest that LYC attenuates osteoporotic bone loss through promoting osteogenesis and inhibiting adipogenesis via regula-tion of the FoxO1/PPARγ pathway driven by oxidative stress, presenting a novel strategy for os-teoporosis management.

Diabetes mellitus is one of the most common endocrinopathies, estimated to affect about 5.4% of the world's population around 2025. It is thought that nearly a third of diabetic patients have some type of skin condition. Frequently, the cutaneous effects of this heterogeneous syndrome are ac-curately detected late in the progressive form of the disease. The main objective of the present study was to identify the main cellular characteristics of the cutaneous microenvironment in exper- imentally induced diabetes mellitus. Skin fragments were harvested from adult white Wistar rats of both sexes, with the weight of 200 g, 12 weeks after streptozotocin diabetes was induced. In parallel with histopathological diagnosis by using hematoxylin and eosine staining, samples were processed by transmission electron microscopy technique and examined with a Philips CM100 microscope. In the apparently macroscopically unchanged tegument, photon microscopy revealed both progres ive thinning of the epidermis in the early stages of diabetes and a significant process of fibrosis and collagen hyalinization in the dermis. In addition, in the early stages, the electron microscopic study provided ultrastructural details characteristic of a senescent phenotype with reduced cell proliferation. The morphological changes in the skin may be the first signs of disruption of carbohydrate metabolism and in the case of established diabetes may reflect its progression and the efficacy of therapy.

Hypertension is a frequent risk factor for cardiovascular diseases and the prevalence rate is continuously rising. Multiple pathophysiological mechanisms are responsible for hypertension, necessitating a combination of drugs from different classes for best management. Combination therapy is five times more effective in decreasing blood pressure compared to escalating the dose of a single agent. As per the ACCOMPLISH trial analysis, coupling a renin-angiotensin system inhibitor with a calcium channel blocker is more effective than the combination of a renin-angiotensin system inhibitor with diuretics in reducing major cardiovascular events, cardiovascular-related mortality, and the progression of chronic kidney disease. The renin-angiotensin system can be suppressed by inhibiting the angiotensin-converting enzyme or angiotensin type 1 receptor (AT1R), resulting, in decreased vascular smooth muscle contraction, heart performance, and reduced aldosterone synthesis. Calcium channel blockers work by inhibiting L-type calcium channels, reducing heart performance via negative inotropic, chronotropic, and bathmotropic effects, along with reducing vascular smooth muscle contraction. Diuretics exert their antihypertensive impact by changing body fluid volume and electrolytes. Initially, hypertension treatment commences with a single medication but often, different classes of two or more antihypertensive medications are necessary for achieving the target blood pressure goal. Sometimes, for Resistant hypertension four different classes of antihypertensive medications are necessary to reach the target blood pressure goal.

Maternal obesity and/or Western diet (WD) is associated with increased risk of metabolic dysfunction-associated steatotic liver disease (MASLD) in offspring, driven, in part, by dysregulation of the early life microbiome. Here, using a mouse model of WD-induced maternal obesity, we demonstrate that exposure to a disordered microbiome from WD-fed dams suppressed circulating levels of endogenous ligands of the aryl hydrocarbon receptor (AHR; indole, indole-3-acetate) and TMAO (a product of AHR-mediated transcription), as well as hepatic expression of Il10 (an AHR target), in offspring at 3 weeks of age. This signature was recapitulated by fecal microbial transfer from WD-fed pregnant dams to chow-fed germ-free (GF) lactating dams following parturition, and was associated with reduced abundance of Lactobacillus in GF offspring. Further, expression of Il10 was downregulated in liver myeloid cells and in LPS-stimulated bone marrow-derived macrophages (BMDM) in adult offspring, suggestive of a hypo-responsive, or tolerant, innate immune response. BMDMs from adult mice lacking AHR in macrophages exhibited a similar tolerogenic response, including diminished expression of Il10. Overall, our study shows that exposure to maternal WD alters microbial metabolites in the offspring that affect AHR signaling, potentially contributing to innate immune hypo-responsiveness and progression of MASLD, and highlights the impact of early life gut dysbiosis on offspring metabolism. Further investigations are warranted to elucidate the complex interplay between maternal diet, gut microbial function, and development of neonatal innate immune tolerance and potential therapeutic interventions targeting these pathways.

Pulmonary hypertension (PH) is a severe and chronic disease characterized by increased pulmonary vascular resistance and remodeling often precipitating right-sided heart dysfunction and death. Although the condition is progressive and incurable, current therapies for the disease focus on multiple different drugs and general supportive therapies to manage symptoms and prolong survival, ranging from medications more specific to pulmonary arterial hypertension (PAH) to exercise training. Moreover, there are multiple studies exploring novel experimental drugs and therapies including unique neurostimulation, to help better manage the disease. Here we provide a narrative review focusing on current PH treatments that target multiple underlying biochemical mechanisms, including but not limited to imbalances in vasoconstrictor-vasodilator and autonomic nervous system function, inflammation, and bone morphogenic protein (BMP) signaling. We also focus on the potential of novel therapies for managing PH, focusing on multiple types of neu-rostimulation including acupuncture. Lastly, we also touch upon the disease’s different subgroups, clinical presentations and prognosis, diagnostics, demographics, and cost.

Despite the effectiveness of insulin injections in managing hyperglycemia in Type 1 Diabetes, they fall short in addressing autoimmunity and regenerating damaged islets. This review aims to explore the potential of various treatment modalities for T1DM, including mesenchymal stem cells (MSCs), MSC-derived exosomes, gene therapy, islet allotransplantation, and pancreatic islet cell transplantation. Results: MSCs demonstrate efficacy in T1DM treatment through immunomodulation and tissue regeneration, although further research is warranted to optimize their therapeutic potential. Gene therapy presents a promising approach despite challenges such as donor shortage and immune rejection. Pancreatic islet cell transplantation emerges as a viable option, albeit with associated risks including graft rejection and the need for immunosuppression. Teplizumab, an FDA-approved humanized monoclonal antibody, revolutionizes the treatment landscape of Type 1 Diabetes by significantly delaying its onset, offering a paradigm shift since the discovery of insulin Conclusion: Ongoing studies and technological advancements in T1DM management offer a promising outlook for improved treatments and possibly even eradication on a global scale. MSCs, MSC-derived exosomes, gene therapy, and pancreatic islet transplantation hold considerable potential.

Haemolytic anaemia represents a risk factor for the development of pulmonary hypertension (PH), currently classified as World Health Organization group 5 PH and data regarding appropriate therapeutic strategy are limited. A total of 28 patients, 85.7% with thalassemia and 14,3% with sickle cell disease, with a diagnosis of PH confirmed by right heart catheterization, were included in the study. The patients were divided into three groups according to haemodynamics and overall diagnostic approach: 42,9% had precapillary PH (Pulmonary Arterial Hypertension -PAH group), 25% post-capillary PH and 32.1% Chronic Thromboembolic PH (CTEPH) (29% of b-thalassemia and 50% of SCD patients). The therapeutic approach in each group and its impact on the outcome and haemodynamics was recorded. PAH-specific drug therapy received 82.1% of patients and Balloon Pulmonary Angioplasty (BPA) was performed in 6 patients with CTEPH. There were statistically significant differences in baseline mPAP and PVR values between the CTEPH-haemolytic anaemia group and other groups. PAH-specific drug therapy resulted in haemodynamic improvement for PAH-group. Patients who underwent BPA improved Pulmonary Haemodynamics. Median survival time was 162 months and the survival rate was 1yr-100%, 2,3,4,5,6 years 96%, 9yrs 90% and 13yrs 78%. In patients with haemolytic anaemia, the wide spectrum of induced PH highlights the importance of a correct diagnosis. BPA in CTEPH patients and specific-PAH drug therapy for PAH patients represent potential therapeutic strategies, however the management should be offered in expert PH centers under patients’ individualized approach.

The high morbidity and mortality rate of the pulmonary arterial hypertension (PAH) is partially explained by the metabolic deregulation associated with the disease. The present study identified statistically significant increase of the glucose transporter solute carrier family 2 (Slc2a1), beta nerve growth factor (Ngf), and nuclear factor erythroid derived 2, like 2 (Nfe2l2) on three standard PAH rat models and their healthy counterpart. PAH was induced by subjecting the animals to hypoxia (HO group) or by injecting them with monocrotaline in either normal (CM) or hypoxic (HM) atmospheric conditions. The Western blot and double immunofluorescent experiments were complemented with the gene expression profiling of the animal lungs analyzed from the perspective of the Genomic Fabric Paradigm. We found substantial remodeling of the genomic fabrics of the citrate cycle, pyruvate metabolism, glycolysis/gluconeogenesis and fructose and manose pathways. According to the novel transcriptomic distance criterion, the most comprehensive measure of the transcriptomic alteration, glycolysis/gluconeogenesis was the most affected functional pathway in all three PAH models. PAH decoupled the coordinated expression of many metabolic genes and replaced Pmm2 with Pmm1 in the center of the fructose and mannose metabolism. Our data show that metabolic dysregulation is a major pathogenic factor of the PAH.

This article presents an estimation of the hypertension risk based on a dataset on 1007 individuals. The application of a Tobit Model shows that “Hypertension” is positively associated to “Age”, “BMI-Body Mass Index”, and “Heart Rate”. The data show that the element that has the greatest impact in determining inflation risk is “BMI-Body Mass Index”. An analysis was then carried out using the fuzzy c-Means algorithm optimized with the use of the Silhouette coefficient. The result shows that the optimal number of clusters is 9. A comparison was then made between eight different machine-learning algorithms for predicting the value of the Hypertension Risk. The best performing algorithm is the Gradient Boosted Trees Regression according to the analyzed dataset. The results show that there are 37 individuals who have a predicted hypertension value greater than 0.75, 35 individuals who have a predicted hypertension value between 0.5 and 0.75, while 227 individuals have a hypertension value between 0.0 and 0.5 units.

Background This study aimed to identify the prominent risk factors that may trigger danger signals of early onset of vascular deregulation in T1D. The risk factors we have identified may serve as dual-purpose biomarkers of rapid diagnosis that offer prospective tailor-made resolution therapeutics. Methods The healthy control (HC) was compared with individuals diagnosed with T1D for the risk factors of vascular deregulation in published research studies from year 2013 to 2023. The PubMed, Web of Science and Google Scholar databases were searched from 1/1/2013 to 1/9/2023. The risk of bias was assessed with the Cochrane (ROBINS-I ) tool, which is relevant to clinical subjects. A random effect model for continuous data was followed and analysed by RevMan 5.4 and GraphPad Prism software. Results 80 relevant case-control studies having 5293 HC and 7492 T1D patients were included. The age and sex-matched HC consisted of persons free of disease and not under any medication while clinical subjects of all age groups were included. 28 risk factors were grouped into six primary outcome models, all of which favoured the T1D synonymous with a high risk of CVD. Conclusions Our findings have strong implications for improving the quality of life and health economics related to vascular disease in T1D. HbA1c% is the most effective biomarker, followed by FBG, LDL-C, and AI% which the clinicians could evaluate using a simple blood test or non-invasive techniques. (Protocol registered at https://www.crd.york.ac.uk/prospero/ CRD42022384636).

Pulmonary arterial hypertension is a rare disease with high mortality despite recent therapeutic advances. The disease is caused by both genetic and environmental factors, and likely gene x environment interactions. While PAH can manifest across the lifespan, pediatric-onset disease is particularly challenging because it is frequently associated with a more severe clinical course and comorbidities including lung/heart developmental anomalies. In light of these differences, it is perhaps not surprising that emerging data from genetic studies of pediatric-onset PAH indicate that the genetic basis is different than that of adults. There is a greater genetic burden in children, with rare genetic factors contributing to at least 36% of pediatric-onset idiopathic PAH (IPAH) compared to ~11% of adult-onset IPAH. De novo variants are frequently associated with PAH in children, and contribute to at least 15% of all pediatric cases. The standard of medical care for pediatric PAH patients is based on extrapolations from adult data. However, the increased etiologic heterogeneity, poorer prognosis and increased genetic burden for pediatric-onset PAH calls for a dedicated pediatric research agenda to improve molecular diagnosis and clinical management. A genomics-first approach will improve the understanding of pediatric PAH and how it is related to other rare pediatric genetic disorders.

COVID-19 infection is extremely dangerous for persons with comorbidities such as kidney disease and diabetes. Although many people of all ages and socioeconomic backgrounds have suffered due to this pandemic, those with underlying medical conditions like kidney disease and diabetes are more vulnerable to becoming infected with COVID-19 related to weak immunity. However, the role of vaccination in the co-infection of COVID-19 with diabetics is not available in the literature. Therefore, we examine the unique challenges presented by the co-infection of COVID-19 in individuals with diabetes, focusing on its disease transmission dynamics. A mathematical modelling technique is to be employed in this work to analyse the dynamics of COVID-19 outbreaks with seven compartments, including vaccination with comorbidities such as diabetes. We also investigated analytically by displaying the solutions' existence, boundedness, positivity and sensitivity. After calculating the basic reproduction numbers, the stability analysis of model equilibrium points is also covered. If the reproduction numbers are less than unity, the disease-free equilibrium points of the model appear to be both locally and globally stable. The findings of this study are that as the vaccination rate rises, the incidence of COVID-19 and its co-infections with diabetes decreases. Effective disease treatment strategies may be based partly on the possible impact of vaccination on the co-infection of COVID-19 related to diabetic disease insights.

Introduction: A plethora of biological molecules regulate chondrogenesis in the epiphyseal growth plate. Disruptions of quantity and function of these molecules can manifest clinically as stature abnormalities of various etiologies. Traditionally, the growth hormone/insulin-like growth factor 1 (IGF1) axis represents the etiological center of final stature attainment. Of note, little is known about the molecular events that dominate the growth of the craniofacial complex and its correlation with somatic stature. Aim: Given the paucity of the relevant data, this review discusses available information regarding potential applications of lateral cephalometric radiography as a potential clinical indicator of genetic short stature in children. Materials and Methods: A literature search was conducted in the PubMed electronic database using the key words: cephalometric analysis and short stature; cephalometric analysis and achondroplasia; cephalometric analysis and hypochondroplasia; cephalometric analysis and skeletal abnormalities; cephalometr* and SHOX; cephalometr* and CNP; cephalometr* and ACAN; cephalometr* and CNVs; cephalometr* and IHH; cephalometr* and FGFR3; cephalometr* and Noonan syndrome; cephalometr* and “Turner syndrome”; cephalometr* and achondroplasia. Results: In individuals with genetic syndromes causing short stature, linear growth of the craniofacial complex is confined, following the pattern of somatic short stature regardless of its etiology. The angular cephalometric measurements differ from the average height normal individuals and are suggestive of a posterior placement of the jaws and a vertical growth pattern of the face. Conclusion: The greater part of the existing literature regarding cephalometric measurements in short statured children with genetic syndromes provides qualitative data. Furthermore, cephalometric data for individuals affected with specific rare genetic conditions causing short stature, should be the focus of future studies. These quantitative data are required to potentially establish cut-off values to refer for genetic testing based on craniofacial phenotypes.

Lipid-lowering therapy (LLT) is a cornerstone of atherosclerotic cardiovascular disease prevention. Although LLT might lead to different reductions in low-density lipoprotein cholesterol (LDL-C) levels in women and men, LLT diminishes cardiovascular risk equally effectively in both sexes. Despite similar LLT efficacy, the use of high-intensity statin, ezetimibe, and proprotein convertase subtilisin/kexin type 9 inhibitors is lower in women compared to men. Women achieve the guideline-recommended LDL-C levels less often than men. Greater cholesterol burden is particularly prominent in women with familial hypercholesterolemia. In clinical practice, women and men with dyslipidemia present with different cardiovascular risk profiles and disease manifestations. The concentrations of LDL-C, lipoprotein(a) and other blood lipids differ between women and men over a lifetime. Dissimilar levels of LLT’s target molecules partially result from sex-specific hormonal and genetic determinants of lipoprotein metabolism. Hence, to evaluate a potential need for sex-specific LLT, this comprehensive review (i) describes the impact of sex on lipoprotein metabolism and lipid profile, (ii) highlights sex differences in cardiovascular risk among patients with dyslipidemia, (iii) presents recent, up-to-date clinical trial and real-world data on LLT efficacy and safety in women, and (iv) discusses diverse medical needs of women and men with dyslipidemia and increased cardiovascular risk.

Type 2 diabetes mellitus (T2DM), a multifactorial and complicated metabolic disorder, is a growing public health problems. Numerous studies indicated that bioactive compounds from herbal medicine have beneficial effects on T2DM prevention and treatment, owing to their numerous biological properties. Curcumin, the major curcuminoid of turmeric, is one of the most studied bioactive components of herbal supplements, which has a variety of biological activities. Clinical trials and preclinical research have recently produced compelling data to demonstrate the crucial functions of curcumin against T2DM via several routes. Accordingly, this review systematically summarizes the antidiabetic activity of curcumin, along with various mechanisms. Results showed that effectiveness of curcumin on T2DM is due to it being anti-inflammatory, anti-oxidant, anti-hyperglycemic, anti-apoptotic, anti-hyperlipidemia and other activities. In light of these results, curcumin may be a promising prevention/treatment choice for T2DM.

Aims/Hypothesis): Type 1 diabetes is an immune-mediated disease with destruction of the pancreatic β-cells, a process that is conditioned by multiple genes and other factors. HLA counts as the major susceptibility gene. Significant variations in HLA genetic susceptibility to type 1 diabetes between Caucasians, African and Asian and other ethnic groups may have led to the variation in incidence of type 1 diabetes globally. Type 1 diabetes is characterized upon HLA identification. In this chapter we discuss global variations in genetic susceptibility of HLA with regard to type 1 diabetes globally with a particular attention to Arab population. Methods): Haplotype configuration of HLA class I A, B, C and Class II –DR/DQ/DP were studied in Caucasians, African and Asian and in Arab population to see if that is responsible for the exponential rise in the rate of type 1 diabetes. Results): Although Arabs have one of the highest global incidence and prevalence rates of type 1 diabetes, unfortunately, there is a dearth amount of information regarding HLA genetic susceptibility to type 1 diabetes in the Arab world. HLA haplotype configurations contribute to its risk value. However, out of an insufficient present study there are examples of misjudgment of HLA risk according to HLA alleles rather than haplotypes. Conclusion): To date HLA outlooks for the characterization of type 1 diabetes. There is an ethnicity difference in HLA characteristics which is responsible for variation in type 1 diabetes. Although Arab population have contributed heavily in the rise of burden of type 1 diabetes, however, there is significantly a dearth amount of studies on HLA in Arab population. Obviously, any future prediction, prevention or cure of the disease will be based on the HLA genetics. There is a dire need for a systematic screening of HLA for Arab population with type 1 diabetes, identification of Arab HLA-risk values and identify those who are prone to get the disease.

Genome-wide association studies (GWAS) have successfully revealed numerous susceptibility loci for obesity. PREDATORR study (2014) shows that in Romania, 34,6% of adults aged 20-79 y/o are overweight, 31,4% are obese with a high risk of cardiometabolic complications, a number that puts almost 67% of Romania's population in the abnormal weight group. Our study aims to investigate the current staus of genetic foundation in metabolic disease associated with obesity, applied to a pilot group of patients specifically examining the impact of known polymorphisms and their haplotype of six food intake-regulating genes: leptin (LEP), leptin receptor (LEP-R), serotonin receptor (5HTR2A), ghrelin (GHRL), neuropeptide Y (NPY) and fat-mass and obesity-associated (FTO) with the following polymorphisms: LEP A-2548G, LEPR A-223G, 5HTR2A G-1439A, GHRL G-72T, NPY T-29063C, FTO A-T and body mass index (BMI). A notable link between the LEP-2548 rs7799039 gene's AG genotype and the risk of obesity was observed, particularly pronounced in males aged 40-49, with an approximately sevenfold increased likelihood of obesity. The 5HTR2A rs6311 AA genotype was associated with a higher BMI, not statistically significant. The FTO rs9939609 gene's AA genotype emerged as a significant predictor of obesity risk. Besides these significant findings, no substantial associations were observed with the LEPR, 5HTR2A, GHRL and NPY genes. Haplotype association analysis showed a suggestive indication of GRGMLA (rs7799039, rs1137101, rs6311, rs696217, rs16139, rs9939609 sequence) haplotype with susceptibility effect towards obesity predisposition. Linkage disequilibrium (LD) analysis showed statistically significant associations between LEP and LEPR gene (p = 1e-04), LEP and GHRL gene (p = 0.0047), GHRL and FTO gene (p=0.03). The outcomes of this study, to our knowledge, one of the very few on the Romanian population, aimed to be a starting point for further research on the targeted interventional strategies to reduce cardiometabolic risks.

Background: Diabetes mellitus (DM) and periodontitis are two chronic diseases that are interconnected. The coexistence of these conditions leads to increased severity of periodontitis and challenges in controlling blood glucose levels in diabetic patients. Objectives: The aim of this study was to evaluate both the influence of periodontal disease and its treatment in patients with DM in terms of a reduction in glycosylated hemoglobin levels at 3 and 6 months after treatment. Methods: A sequential, nonprobabilistic, controlled, prospective and longitudinal case−control study was carried out at the University Dental Clinic of the Morales Meseguer Hospital in Murcia, Spain. Thirty diabetic patients were divided into two groups: patients with periodontitis (test group) and patients without periodontitis (control group). The periodontal and endocrine-metabolic variables were measured at baseline and at 3 and 6 months after periodontal treatment for both groups. Results: Statistically significant differences were found at 3 and 6 months after periodontal treatment with respect to HbA1c levels in the group of periodontal patients. However, these differences were not observed in the control group. Conclusion: The presence of periodontal disease increased HbA1c levels in patients with DM. Nonsurgical periodontal treatment significantly decreased the degree of periodontal inflammation and the HbA1c level at 3 and 6 months after treatment.

Aim: We estimated the correlation between serum bilirubin concentrations and insulin resistance in advanced maternal age without diabetes mellitus. Method: The cross-sectional study involved consecutive 50 women of advanced maternal age without diabetes mellitus, and insulin resistance (IR) was diagnosed according to the homeostatic model assessment insulin resistant (HOMA-IR) formula and the cut-off point was set to more than 2.5. Serum bilirubin and HOMA-IR were compared between the IR (+) and IR (-) groups. Results: We found that serum bilirubin levels in the IR subjects were significantly decreased compared to those without IR (p = 0.0252). Serum bilirubin concentrations were negatively correlated with the weight and the fasting insulin concentrations in all subjects (r=−0.282, p=0.047, r=-0.424, p=0.002). Additionally, serum bilirubin had a negatively correlation with HOMA-IR (r = -0.410, p = 0.003) in all subjects. The multiple linear regression analysis found that serum total bilirubin levels were independently correlated with HOMA-IR (beta = -0.392, p= 0.015) in these subjects. Conclusions: The study demonstrated that serum bilirubin concentrations had negatively correlation with insulin resistance in advanced pregnant women without diabetes mellitus, and decreased serum bilirubin may forebode increased gestational diabetes mellitus risk in our study population.

Gestational Diabetes Mellitus (GDM) is related with adverse outcomes for both the mother and the offspring. Immune and senescence play a crucial role in GDM progression. This study aims to explore the diagnostic significance of immune-related senescence (IRS) genes in GDM. We used weighted gene co-expression network analysis (WGCNA) and single sample gene set enrichment analysis (ssGSEA) to compute the immune score and aging score in control and GDM samples. Machine learning identified core IRS genes. Then we performed unsupervised cluster analysis in GDM patients to explore immune infiltration. Finally, we validated the core genes in clinical samples. We used the intersection of MEblack module from WGCNA and differentially expressed genes (DEGs) to obtain the potential genes. Next, a univariate logistic regression model including 23 potential genes were constructed, and these genes were filtered by least absolute shrinkage and selection operator (LASSO) algorithm. There were 5 potential genes (COX17, RRAS2, RRAGC, CECR1, and TACC2), which defined as biomarkers, remained eventually, and the efficacy of these biomarkers was evaluated by nomogram. Finally, the results from both qRT-PCR and western blot analyses demonstrated CECR1 was down-regulated, while TACC2 was up-regulated in GDM placental tissue. Our study identified CECR1 and TACC2 as diagnostic biomarkers for GDM associating with immune and senescence, providing a new perspective on GDM progression.

The burden of hypertension remains unacceptably high globally, particularly in low- and middle-income countries (LMICs). Workplace offer enormous potential as an idea setting for early detection and treatment of hypertension among the working class. Analysis of such a Workplace Screening Programme can reveal information about its potential impact. Machine learning techniques such as k-Means Clustering are untapped tools for such analyses. We set out to deploy this tool for the analysis of our university annual medical screening of workforce for hypertension. An anonymized dataset containing the demography and blood pressure measurements values obtained from staffs of different departments/units in an academic institution was obtained. The total number of samples or data points are 1, 723 in which the input dataset contains six features, including year category (2018, 2019, 2021,2022), Department/Unit (academic and non-academic), gender (male and female), while the target output is the blood pressure status (low, normal and high) respectively. Analysis of the dataset was carried out using machine learning techniques. In this retrospective analysis, it was observed that the mean age for this working class is 42 years old. Similarly, it was discovered that hypertension was prevalent among members of staff above the age of 40 irrespective of their gender or professional category (academic or non-academic). The analysis also revealed that there was a steady decline in the prevalence of hypertension from 2018 to 2022. From the research, it is evident that the adoption of machine learning techniques for periodic analyses of workplace health status screening initiative (especially for hypertension) is effective, feasible, and sustainable to diagnose and control hypertension among the working class.

Coronary artery disease (CAD) and hypertension significantly contribute to cardiovascular morbidity and mortality. MicroRNAs (miRNAs) have recently emerged as promising biomarkers and therapeutic targets for these conditions. This systematic review conducts a thorough analysis of the literature, with a specific focus on investigating miRNA expression patterns in patients with CAD and hypertension. The review encompasses an unspecified number of eligible studies that employed a variety of patient demographics and research methodologies, resulting in diverse miRNA expression profiles. This review highlights the complex involvement of miRNAs in CAD and hypertension and the potential for advances in diagnostic and therapeutic strategies. Future research endeavours are imperative to validate these findings and elucidate the precise roles of miRNAs in disease progression, offering promising avenues for innovative diagnostic tools and targeted interventions.

Hypertension is a common and growing medical problem that leads to enormous cardiovascular and kidney disease worldwide. While many drugs exist to treat hypertension, there is large individual variation in how a given individual responds to different agents, which contributes to dismal rates of hypertension control. While demographic factors predict which drugs may work better in certain individuals, a great degree of this variation has a genetic basis. In recent years, genome wide association studies have begun to identify specific gene variants that predict drug response to particular agents. This review identifies the major genetic variants influencing antihypertensive response that have emerged from this growing body of work. For novel genetic variants without a previously known biologic basis in blood pressure, it is crucial to validate initial findings in subsequent studies. This information may eventually lead to a more personalized approach to hypertension management that will improve blood pressure control and patient outcomes. The integration of this large amount of data and its real world application will be highly challenging, but strategies to accomplish this are discussed.

Polycystic ovary syndrome (PCOS) is a common condition in reproductive-age women. Women with PCOS are at higher risk of pregnancy complications including gestational diabetes (GDM). The prevalence of PCOS and GDM varies according to the diagnostic criteria used. The mechanism for the occurrence of GDM in women with PCOS is still unclear. Materials & Methods- A systematic search of the electronic database was done using keywords like PCOS, and GDM to include studies between April 2008 and March 2023 where uniform diagnostic criteria were used. Studies were excluded with high-risk of bias after the assessment of bias, and meta-analysis was done with relative risks and confidence intervals. Results & Discussion-Out of 1896 search results, 95 were selected for full-text. The quality of the studies was scrutinized and a total of 28 studies were included as they fulfilled the inclusion criteria. The incidence of GDM in women with PCOS was found to be 10.55 % (2.9- 54.9%) from pooled data involving 1,280,245. The prevalence of PCOS in women diagnosed with GDM was found from pooled data of 36,351 women in retrospective studies to be 2.47% (1.5- 50.1%). Selection predominantly included cohort studies, most commonly from China. The meta-analysis reported the risk of GDM is higher in women with PCOS than in those without PCOS (HR: 1.59, 95% CI: 1.27–1.91, p < 0.001). Family history of diabetes, ethnicity, pre-pregnancy BMI, insulin resistance, gestational weight gain, use of assisted reproductive techniques, and multifetal gestation were the risk factors for GDM in women with PCOS. Conclusion- The prevalence of GDM in patients with PCOS is high, but the causality is complex. The newer predictive models are promising in clarifying the causative relationships, yet use various parameters at different cut-offs. There is a need for the development of universally acceptable parameters for the early prediction of GDM in women with PCOS.

Gestational diabetes mellitus (GDM) pathophysiology comprises clinical and genetic factors. In fact, GDM has been associated with several single nucleotide polymorphisms (SNPs). This study aimed to build a prediction model of GDM combining clinical and genetic risk factors. A total of 1588 pregnant women from the San Carlos Cohort participated in the present study, 1069 (67.3%) Caucasian (CAU) and 519 (32.7%) Latin American (LAT), 255 (16.1%) with GDM. The incidence of GDM was similar in both groups (16.1% CAU and 16.0% LAT). Genotyping was performed by IPLEX Mass ARRAY PCR selecting 110 SNPs based on literature references. The SNPs showing the strongest likelihood of GDM development were the rs10830963, rs7651090 and rs1371614 in CAU and rs1387153 and the rs9368222 in LAT. Clinical variables including age, pre-pregnancy body mass index and fasting plasma glucose (FPG) at 12 gestational weeks predicted the risk of GDM (AUC 0.648, 95%CI 0.601-0.695 in CAU; AUC 0.688, 95%CI 0.628-9.748 in LAT) and adding the SNPs modestly improved prediction (AUC 0.722, 95%CI 0.680-0.764 in CAU; AUC 0.769, 95%CI 0.711-0.826 in LAT). In conclusion, adding genetic variants enhanced the prediction model of GDM risk in CAU and LAT pregnant women. An RCT is underway to demonstrate its usefulness

Postprandial plasma glucose between 4 and 7.9 hours is associated with the diagnosis of diabetes, diabetes mortality, and cardiovascular mortality. However, it is unknown whether 2-hour plasma glucose during the oral glucose tolerance test conducted in this postprandial period (4–7.9 hours), termed as 2-h PGOGTT@4–7.9h, can accurately classify diabetes diagnosis and predict mortality risks. This study aimed to address these questions using 2,347 adult participants. Diabetes was defined as HbA1c ≥6.5%, and the ability of 2-h PGOGTT@4–7.9h to classify diabetes was analyzed using receiver operating characteristic curves. Cox proportional hazards models were employed to estimate mortality hazard ratios (HRs) and 95% confidence intervals (CIs). The results showed that 2-h PGOGTT@4–7.9h could classify diabetes with 92% accuracy. Participants were followed up for a mean of 21.4 years. A 1-natural-log higher 2-h PGOGTT@4–7.9h was associated with an increased risk of mortality from diabetes (adjusted HR, 21.1; 95% CI, 9.2–48.0) and cardiovascular disease (adjusted HR, 1.47; 95% CI, 1.13–1.91). Simulation analysis indicated that future studies may require at least 100 participants to investigate 2-h PGOGTT@4–7.9h for diabetes diagnosis. In conclusion, 2-h PGOGTT@4–7.9h may be useful for diabetes classification and prediction of mortality risk.

One of the most prevalent illnesses, diabetes does not directly result in patient mortality. But, it increases the risk of death. Any disease that may be predicted in its early stages can lessen its fatal effects while also enhancing the quality of the healthcare system. For the early-stage prediction of diabetes or such types of non-communicable diseases, we need the proper set of influential features. This research has developed a machine learning-based disease prediction model to identify the influential features for diabetes prediction and give a near-perfect classification accuracy. This model includes Min-Max normalization for data normalization, Isolation Forest (iForest) for outlier removal, Synthetic Minority Oversampling Technique (SMOTE) for oversampling, Random Forest based Recursive Feature Elimination (RFE-RF) test, Chi-Square test, and Minimum Redundancy Maximum Relevancy (mRMR) test based feature selection methods for identifying the influential features, and Support Vector Machine (SVM), K Nearest Neighbor (KNN), and Naive Bayes (NB) for the classification. The results clarify that the proposed model outperforms the previous models and studies. The SVM has attained an accuracy of 99.58% in classification using the five features chosen from the Chi-Square test. Lastly, SHAP, an explainable AI model, has been used to assess the classifier model’s performance. These selected features and the classifier model can be used for early-stage diabetes prediction.

Background: The adoption of self-care behaviors among patients with arterial hypertension (AH) plays an important role in the management of their health condition. However, a lack of scales assessing self-care is observed. We aimed to develop and validate the Hippocratic hypertension self-care scale. Methods: From a pool of questions derived from a literature review, 18 items were included in the scale and reviewed by a committee of experts. Participants indicate the frequency at which they follow the self-behavior prescribed in each statement on a five-point Likert scale. Data were collected between April 2019 and December 2019. Re-sults: 202 consecutive adult patients with AH were enrolled in the study. The internal consistency of the scale was found to be 0.807, using Cronbach’s alpha coefficient. An exploratory factor analysis identified two do-mains that accounted for 92.94% of the variance of the scale items; however, each sub-scale could not be used as an independent scale. Finally, the test- retest of the scale showed a significant strong correlation (r=0.0095, p<0.001). Conclusion: Our data indicate that the scale is a reliable and valid tool for assessing self-behaviors in patients with AH. Health professionals can use it in their clinical practice to improve the management of patients’ health condition.

The oxidative stress is one of the main cause for cardiovascular diseases (like Hypertension) also one of the results of these diseases. This study involved 56 subjects matched ages and sex divided into two groups; 28 hypertensive subject and 28 healthy subject as control group. The following analysis was done: 4-Hydroxy-2-nonenal(4HNE) and albumin. The results show that there is a significant increase in (4HNE) between patients group and control group. The increase in 4HNE which is a product of lipid peroxidation is attributed to destruction in body cell caused by due to the increase in stress events. It has been concluded that is important nappy on ideal weight, because obesity considered main factors for heart disease and hardening of the arteries. The aim of this study was to investigate the relationship between of some oxidative stress markers and cardiovascular diseases.

The fetal splenic artery pulsatility index (PI) is a parameter that reflects fetal well-being and has been used as a predictor of adverse pregnancy outcomes. The aim of this study was to investigate the predictive value of splenic artery PI in GDM class A1 cases for NICU admission. In this prospective case controlled study, only sixty single pregnancy cases diagnosed with gestational diabetes mellitus class A1 were evaluated. Fetal splenic artery Doppler parameters Peak systolic velocity (PSV), Pulsatility index (PI), Resistivity index (RI) and End diastolic velocity (EDV) were measured in all cases. The rate of re-quirement of need of neanoatal intensive care unit was noted. In cases with need fetal intensive care, fetal splenic PI index was found to be statistically significantly lower than in healthy cases without it (0.94 ± 0.29 vs. 1.70 ± 0.53, respectively, p

The Roma population constitutes the largest ethnic minority in Europe, however, data regarding the prevalence of non- communicable diseases are still scarce in the medical literature. The aim of this study was to assess the clinical and metabolic particularities of a Roma population with diabetes, in comparison with a group of Romanian Caucasians. We conducted an observational, transversal study and evaluated 808 adult patients with diabetes mellitus, from a tertiary hospital providing diabetes care, aged between 18 and 89 years old, of whom the majority were men (52.84%). Most of them had type 2 diabetes mellitus (T2DM), reaching 95.1% the Caucasian group and 87.8% among the Roma patients. 81.1% of the Caucasian patients had hypertension, approximately 15% higher than the Roma group, while more than half of the patients in both groups had obesity. There were no differences concerning myocardial infarction, however, the number of patients with history of stroke was 2.1 times higher in the Roma group compared to Caucasians. Chronic kidney disease was present in 22.1% of the Roma patients, 33.25% had retinopathy, and 72.7% presented polyneuropathy. The prevalence of cardiovascular risk factors, cardiovascular disease and microvascular complications among the study Roma population are quite significant, underscoring the importance of ethnic disparities in approaching healthcare management strategies.

Intermittent religious fasting increases a risk of hypo- and hyperglycemia in individuals with diabetes, but its impact in those without diabetes is poorly investigated. The study aim was to examine the effects of religious Bahá'í fasting (BF) on glycemic control and variability and compare these effects with time-restricted eating (TRE). In a three-arm randomized controlled trial, 16 subjects without diabetes were assigned to a BF, 16:8 TRE or control group. Continuous glucose monitoring and food intake documentation was conducted before and during the 19 days of intervention, and 24-hour mean glucose, glycemic variability indices, and glucotypes were assessed. BF and TRE groups, but not the control group, markedly reduced the daily eating window while maintaining macronutrient composition. Only the BF group decreased caloric intake (-677.8 ± 357.6 kcal, p=0.013), body weight (-1.92 ± 0.95 kg, p=0.011) and BMI (-0.65 ± 0.28 kg, p=0.006). Higher maximum glucose values were observed during BF in the within-group (+1.41 ± 1.04, p=0.039) and between-group comparison (BF vs. Control: p= 0.010 and TRE vs. BF: p= 0.022). However, there were no alterations of 24-hour mean glucose, intra- and inter-day glycemic variability indices, or glucotypes in any group. Proportions of time above and below range (70-180mg/dl) and HbA1c values remained unchanged. BF and TRE do not exhibit negative effects on glycemic control and variability in subjects without diabetes.

Objective: Lower extremity ischemia-reperfusion injury (IRI) may occur with trauma-related vascular injury and various vascular diseases, during the use of a tourniquet, temporary clamping of the aorta in aortic surgery, and acute or bilateral acute femoral artery occlusion. Mitochondrial dysfunction and increased basal oxidative stress in diabetes may cause an increase in the effects of increased reactive oxygen species (ROS) and mitochondrial dysfunction due to IRI. It is of great importance to examine therapeutic approaches that can minimize the effects of IRI, especially for patient groups under chronic oxidative stress. Cerium oxide (CeO2) nanoparticles mimic the antioxidant enzymes and act as a catalyst that scavenges ROS. In this study, it was aimed to investigate whether CeO2 has protective effects on skeletal muscles in lower extremity IRI in mice with streptozocin-induced diabetes. Methods: A total of 38 Swiss albino mice were divided into six groups as follows: control group (group C, n=6), diabetes group (group D, n=8), diabetes-CeO2 (group DCO, n=8), diabetes-ischemia/reperfusion (group DIR, n=8), and diabetes-ischemia/reperfusion-CeO2 (group DIRCO, n=8). DCO and DIRCO groups were given doses of CeO2 0.5mg/kg intraperitoneally 30 minutes before the IR procedure. A 120-minute ischemia-120-minute reperfusion period with 100% O2 was performed. At the end of the reperfusion period, muscle tissues were removed for histopathological and biochemical examinations. Results: Total antioxidant status (TAS) levels were found to be significantly lower in group DIR compared with group D (p=0.047 and p=0.022, respectively). In group DIRCO and total oxidant status (TOS) levels were found to be significantly higher than in group DIR (p

Postprandial glucose levels between 4 and 7.9 hours (PPG4–7.9h) correlate with mortality from various diseases including hypertension, diabetes, cardiovascular disease, and cancer. This study aimed to assess if predicted PPG4–7.9h could diagnose diabetes. Two groups of participants were involved: Group 1 (4420 participants) had actual PPG4–7.9h, while Group 2 (8422 participants) lacked this measure but had all the diabetes diagnostic measures. Group 1 underwent multiple linear regression to predict PPG4–7.9h using 30 predictors, achieving accuracy within 11.1 mg/dL in 80% of the participants. Group 2 had PPG4–7.9h predicted using this model. Receiver operating characteristic curve analysis showed that predicted PPG4–7.9h could diagnose diabetes with an accuracy of 87.3% in Group 2, with a sensitivity of 75.1% and specificity of 84.1% at the optimal cutoff of 102.5 mg/dL. Simulation on 10,000 random samples from Group 2 revealed that 175 participants may be needed to investigate PPG4–7.9h as a diabetes diagnostic marker with a power of at least 80%. In conclusion, predicted PPG4–7.9h appears to be a promising diagnostic indicator for diabetes. Future studies seeking to ascertain its definitive diagnostic value might require a minimum sample size of 175 participants.

The incidence of diabetes mellitus (DM) continues to rise worldwide and one of the most serious microvascular complications is diabetic kidney disease (DKD), which is the leading cause of end-stage renal disease. Current bi-omarkers such as urinary albumin excretion rate have limitation for early detection of DKD. In our study we used ultra-high-performance liquid chromatography coupled with electrospray ionization-quadrupole-time of flight-mass spectrometry (UHPLC-QTOF-ESI+-MS) techniques to quantify previously analyzed metabolites, such as tryptophan, kynurenic acid, taurine, l-acetylcarnitine, glycine, and tiglylglycine. We performed the targeted analy-sis of metabolites from urine and serum samples, collected from 110 subjects. Of these, 90 patients with type 2 DM (T2DM) were divided according to the urinary albumin/creatinine ratio (UACR) into normoalbuminuria 300 mg/g groups, respectively, while 20 subjects were rep-resented by healthy controls. Through various validation methods, we identified several metabolites as potential biomarkers, such as kynurenic acid, glycine, and l-tryptophan in serum and l-acetylcarnitine, tiglylglycine, and tau-rine in urine.

Abstract Incretin mimetics, also known as glucagon-like peptide-1 (GLP-1) receptor agonists, are a class of medications used to treat type 2 diabetes by mimicking the actions of incretin hormones in the body. These hormones are responsible for promoting insulin release from the pancreas in response to nutrient intake, as well as decreasing glucagon secretion, slowing gastric emptying, and promoting satiety. By imitating these actions, incretin mimetics help to regulate blood sugar levels in individuals with diabetes and glucose intolerance. One of the key benefits of incretin mimetics is its ability to lower blood sugar levels without causing hypoglycemia. This is especially important for individuals with diabetes who may experience dangerous drops in blood sugar levels when using other medications. Additionally, incretin mimetics have been shown to promote weight loss in some individuals, making them a valuable option for those struggling with obesity in addition to diabetes. Incretin mimetics are administered by injection, once or twice daily, depending on the specific medication. They are often combined with other diabetes medications, such as metformin or insulin, for optimal blood sugar control. These medications are generally well-tolerated, with common side effects including nausea, vomiting, and diarrhea, which usually diminish over time as the body adjusts to the medication. Studies have shown that incretin mimetics can help improve cardiovascular outcomes in individuals with diabetes, including reducing the risk of heart attacks and strokes. This is particularly significant given the increased risk of cardiovascular disease in individuals with diabetes. Incretin mimetics also have been shown to preserve pancreatic beta-cell function, which is responsible for producing insulin. This can help slow the progression of diabetes and reduce the need for higher insulin doses over time. Despite their many benefits, incretin mimetics are not without limitations. They can be expensive compared to other diabetes medications, which may make them less accessible for some individuals. Additionally, there have been concerns about the potential risk of pancreatitis and pancreatic cancer associated with the use of these medications. However, more research is needed to fully understand these risks. It is important for healthcare providers to carefully assess each individual's unique needs and medical history when considering the use of incretin mimetics. They may not be appropriate for everyone, particularly those with a history of pancreatitis or pancreatic cancer. Patients should also be educated about these medications' proper administration and potential side effects to ensure their safety and efficacy. Overall, incretin mimetics have emerged as an important therapeutic option for individuals with type 2 diabetes, offering a unique mechanism of action that can help improve blood sugar control, promote weight loss, and reduce cardiovascular risk. With ongoing research and development in this field, incretin mimetics continue to show promise as valuable tools in managing diabetes and its associated complications and comorbidities.

The right heart catheterisation constitutes the gold standard for pulmonary hypertension (PH) diagnosis. However, echocardiography remains a reliable, non-invasive, inexpensive, convenient, and easily reproducible modality not only for the preliminary screening of PH but also for PH prognosis. The aim of this review is to describe a cluster of echocardiographic parameters for the detection and prognosis of PH and analyse the challenges of echocardiography implementation in patients with suspected or established PH. The most important echocardiographic index is the calculation of pulmonary arterial systolic pressure (PASP) through the tricuspid regurgitation (TR). It has shown high correlation with invasive measurement of pulmonary pressure, but several drawbacks have questioned its accuracy. Besides this, the right ventricular outflow track acceleration time (RVOT-AT) has been proposed for PH diagnosis. A plethora of echocardiographic indices: right atrial area, pericardial effusion, the tricuspid annular plane systolic excursion (TAPSE), the TAPSE/PASP ratio, tricuspid annular systolic velocity (s′) and recently, can reflect the severity and prognosis of PH. Recent advances in echocardiography with 3-dimensional right ventricular (RV) ejection fraction, RV free wall strain and right atrial strain may further assist the prognostication of PH.

Coronary microvascular dysfunction (CMD) is a clinical entity linked with various risk factors that significantly affect cardiac morbidity and mortality. Hypertension, one of the most important, causes both functional and structural alterations in the microvasculature, promoting the occurrence and progression of microvascular angina. Endothelial dysfunction and capillary rarefaction play the most significant role in the development of CMD among patients with hypertension. CMD is also related to several hypertension-related morphological and functional changes in the myocardium in the subclinical and early clinical stages, including left ventricular hypertrophy, interstitial myocardial fibrosis, and diastolic dysfunction. This indicates the fact that CMD, especially if associated with hypertension, is a subclinical marker of end-organ damage and heart failure, particularly the one with preserved ejection fraction. This is why it is important to search for microvascular angina in every patient with hypertension and chest pain not associated with obstructive coronary artery disease. Several highly sensitive and specific non-invasive and invasive diagnostic modalities have been developed to evaluate the presence and severity of CMD, but also to investigate additional complications that can affect further prognosis, especially among those with hypertensive heart disease. Although various pharmacological and interventional treatments demonstrated certain clinical effects, integrated diagnostic and therapeutic algorithms are necessary to reduce the burden of this emerging condition.

There is high prevalence of hypertension and is rapidly increasing around the world, despite the intervention programme implemented, this study aimed at estimating the prevalence rate, test of association between hypertension and risk factors and model hypertension rate. Data used was obtained from the health record of Federal Medical Centre, Keffi from January 2016 – January 2019. Ordinal logistic regression model was used; Model Fitting Information, Goodness-of-Fit, Pseudo R-Square and Test of Parallel Lines are fitted to the data sets to test the accuracy and correctness of the model. The results indicated that the overall prevalence of hypertension rate is high at 36.4%, among the adult population, body mass index and gender are statistically significant, and Age is not significant in the study. Individuals that are overweight are more likely to be hypertensive compare to other weights. At age 40 – 49 years which have the highest rate of 26.5% and the odd ratio is 0.75 compared to others. One year increase in age 30 – 39, the cumulative odd of being hypertensive is 0.91 while other independent variables are held constant. The odd ratio of female being hypertensive is 0.85, therefore the females are more likely to be hypertensive with 54.4% compared to the males at 45.6% . There is no presence of multicolinearity among the variables and Logit models were formulated to calculate probabilities of the various possible outcomes.

Correlations among estrus cycle, pyometra, and canine diabetes mellitus (CDM) have been described since the late 1950s, and substantial progress in understanding mechanisms beyond was achieved nowadays. Progesterone-related diabetes mellitus (PRDM) in dogs is known for its particular potential for diabetes remission. Thus, a deep understanding of the physiopathological aspects involved is crucial to postulate treatment guidelines to improve the PRDM remission rate, as well as to inform preventive measures. This narrative review aims to provide relevant detailed information on 1) canine estrus cycle and its impact on CDM etiology and management, 2) the role of pyometra as a further cause of insulin resistance, and 3) useful individual therapeutic and preventive strategies. Pharmacological annulment of progesterone effects, as well as inflammatory and progesterone-related conditions resolution in association with adequate exogenous insulin therapy, and residual beta cell function, are key aspects to achieve remission, or at least to improve diabetic clinical control. In this way, spaying should be considered mandatory in most PRDM cases. Preventive measures against CDM can include spaying recommendations; however, individual-based recommendations should be considered since castration may be associated with some long-term health issues.

Hypertension is a global public health challenge, with a high prevalence across various regions and significant implications for cardiovascular risk. This article reviews the effectiveness of herbal medicine as a potential therapeutic approach for hypertension, offering an alternative or complementary solution to conventional pharmacological treatments. It highlights several natural agents that have demonstrated efficacy in lowering systolic blood pressure (SBP) in clinical and meta-analytical studies. The methodology involved a systematic review of articles that discuss herbal therapeutics for hypertension, focusing on their efficacy compared to placebo and standard treatments. The findings suggest that certain nutraceuticals, such as garlic, hawthorn, and CoQ10, can significantly reduce SBP, presenting a viable option for managing hypertension. This review underscores the need for further research to validate these findings and optimize herbal treatment strategies, potentially expanding the use of these natural products in clinical practice. The article aims to increase awareness among medical professionals and patients about the benefits and applications of herbal medicines in treating hypertension.

Pulmonary arterial hypertension (PAH) is a pathophysiological condition characterized by pulmonary vascular remodeling and elevated vascular resistance, which may ultimately result in cardiovascular failure and sudden cardiac death. In recent years, the occurrence of pregnancy complicated by pulmonary arterial hypertension has witnessed a notable increase, whereas the incidence of postpartum pulmonary arterial hypertension is comparatively rare. This study presents a case involving a 39-year-old female who exhibited severe pulmonary arterial hypertension, finally diagnosed as idiopathic pulmonary arterial hypertension, within 2 days postpartum. The diagnosis was made following a thorough clinical examination. This case report emphasizes the significance of promptly initiating targeted therapy as an initial step in effectively managing patients and the criticality of conducting a thorough assessment of multidisciplinary collaboration in postpartum management. Furthermore, the report has the potential to enhance awareness and education regarding the future management of similarly intricate conditions.

Background: Indonesia is an archipelago with various cultured, will bee affects all aspects of people's lives, including beliefs related to health behavior and health care. One problem that needs serious attention is the elderly group because the elderly are a vulnerable group who have a high risk of experiencing health problems, such as anemia with hypertension, so they need good care management. The research objective was to determine self-management intervention for hypertensive elderly. Methods: This research is a literature review with five databases (Scopus, CINAHL, ScienceDirect, PubMed, Proquest), the study design used is an experimental, descriptive, cross-sectional, and review systematic, in March 2021. Guidelines for using JBI to measure quality and listing check out Prisma in this review guide. A feasibility study based on title, abstract, full text, and research methodology. The data analysis used narrative analysis based on the research findings. Results: Twelve articles met the predefined review inclusion criteria. The study found eight interventions for self-management in elderly hypertension, namely: 1) Knowledge of hypertension, 2) Regulation of physical activity, 3) Limitation of alcohol and cigarette consumption, 4) Sleep rest and stress management, 5) Diet and body weight management, 6) Blood pressure control, 7) Family and social support, 8) Adherence to therapy regimens. Conclusion: The conclusion of the study results obtained eight elderly self-management interventions, this done properly will affect compliance in optimizing the health of the elderly.

Endothelial autocrine signaling is essential to maintain vascular hemostasis. There is limited in-formation about the role of endothelial autocrine signaling in regulating severe pulmonary vas-cular remodeling during the onset of pulmonary arterial hypertension (PAH). In this study, we employed the first severe PAH mouse model, Egln1Tie2Cre (Tie2Cre-mediated disruption of Egln1) mice, to identify the novel autocrine signaling mediating the pulmonary vascular endothelial cells (PVECs) hyperproliferation and the pathogenesis of PAH. PVECs isolated from Egln1Tie2Cre lung expressed upregulation of many growth factors or angiocrine factors such as CXCL12, and exhib-ited hyperproliferative phenotype in coincident with upregulation of proliferation specific tran-scriptional factor FoxM1. Treatment of CXCL12 on PVECs increased FoxM1 expression, which was blocked by CXCL12 receptor CXCR4 antagonist AMD3100 in culture human PVECs. Endo-thelial specific deletion of Cxcl12 (Egln1/Cxcl12Tie2 Cre) or AMD3100 treatment in Egln1Tie2Cre mice downregulated FoxM1 expression in vivo. We then generated and characterized a novel mouse model with endothelial specific FoxM1 deletion in Egln1Tie2Cre mice (Egln1/Foxm1Tie2Cre), and found that endothelial FoxM1 deletion reduced pulmonary vascular remodeling and right ventricular systolic pressure. Together, our study identified a novel mechanism of endothelial autocrine sig-naling in regulating PVECs hyperproliferation and pulmonary vascular remodeling in PAH.

Background and Objectives: In this current state, Type 2 Diabetes Mellitus (T2DM) is more prevalent in the population, and metformin is used as a first-line medication for treating it. There was up surge in the utilization of alternative therapies in the management of diabetes. Especially in diabetes, Herbal medicines are considered safe and reliable by majority of the population. Aim: The purpose of this research is aimed to estimate the safety and efficacy of Polyherbal Metabolite Compounds (PHMC) capsules in adults with T2DM. Materials and Methods: In this study, 60 T2DM patients aged 18-60 years were randomly assigned to Groups A (30) receiving Metformin 500 mg twice a day after food and Group B (30) receiving PHMC capsule 500 mg twice a day after food in a prospective, randomized and open-label clinical study. The in-silico simulation study was performed to selected plants major compounds on target protein Insulin-like Growth Factor-1 (1K3A). Result: The PHMC is found to be safe and effective in the management of T2DM. The FBS, PPBS and HbA1c were significantly lowered (p

This is a single center retrospective study to assess safety and tolerability of continuous inhaled iloprost use as rescue therapy for refractory pulmonary hypertension (PH) in critically ill neonates and infants. Retrospective chart review was performed on 58 infants and data was collected at baseline, 1, 6, 12, 24, 48, and 72 hours of iloprost initiation. Primary outcomes were change in heart rate (HR), fraction of inspired oxygen (FiO2), mean airway pressures (MAP), blood pressure (BP) and oxygenation index (OI). Secondary outcomes were need for extracorporeal membrane oxygenation (ECMO) and death. 51 patients treated for > 6 hours were analyzed in 2 age groups, neonate (≤28 days: n=32) and infant (29-365 days: n=19). FiO2 (p

Diabetes mellitus (DM) poses a significant challenge to global health, with its prevalence projected to rise dramatically by 2045. This narrative review explores the bidirectional relationship between periodontitis (PD) and type 1 diabetes mellitus (T1DM), focusing on cellular and molecular mechanisms derived by the interplay between oral microbiota and the host immune response. A comprehensive search of literature published between 2008 and 2023 was conducted to elucidate the association between these two diseases. Preclinical and clinical evidence suggests a bidirectional relationship, with individuals with T1DM exhibiting heightened susceptibility to periodontitis, and vice versa. The review includes recent findings from human clinical studies, revealing variations in oral microbiota composition in T1DM patients, including increases in certain pathogenic species such as Porphyromonas gingivalis, Prevotella intermedia, and Aggregatibacter actinomycetemcomitans, along with shifts in microbial diversity and abundance. Molecular mechanisms underlying this association involve oxidative stress and dysregulated host immune responses, mediated by inflammatory cytokines such as IL-6, IL-8, and MMPs. Furthermore, disruptions in bone turnover markers, such as RANKL and OPG, contribute to periodontal complications in T1DM patients. While preventive measures to manage periodontal complications in T1DM patients may improve overall health outcomes, further research is needed to understand the intricate interactions between oral microbiota, host response, periodontal disease, and systemic health in this population.

The association between normal-range triglycerides and diabetes mortality remains unclear. This cohort study aimed to elucidate this relationship by examining 19,010 US adult participants with fasting serum triglycerides below 150 mg/dL. Cox proportional hazards models were employed to estimate mortality hazard ratios (HRs) and 95% confidence intervals (CIs). Participants were followed up for a mean of 15.3 years, during which 342 diabetes deaths were recorded. A 1-natural-log-unit increase in triglycerides was associated with a 57% higher risk of diabetes mortality (adjusted HR, 1.57; 95% CI, 1.04–2.38). Comparable results were obtained when triglycerides were analyzed in quartiles. Receiver operating characteristic curve analysis identified an optimal triglyceride cutoff of 94.5 mg/dL for diabetes mortality; individuals with triglyceride levels above this threshold faced a greater risk of diabetes mortality (adjusted HR, 1.43; 95% CI, 1.12–1.83). Further investigation revealed a positive association between normal triglyceride levels and all-cause mortality, though no association was observed between normal triglycerides and mortality from hypertension or cardiovascular disease. In conclusion, elevated triglycerides within the normal range were associated with an increased risk of diabetes mortality. Individuals with triglyceride levels of 95 mg/dL or higher may require vigilant monitoring for diabetes and its associated complications.

Purpose is to o review the pathogenic mechanism for ocular hypertension and glaucoma development after pars plana vitrectomy. Both acute and chronic causes are considered and special attention is paid to the theories and clinical evidence on the risk of developing Open Angle Glaucoma (OAG) after Pars Plana Vitrectomy (PPV). Most existing scientific literature on the issue agree on the role of ascorbate as an oxygen scavenger within the vitreous chamber. Oxygen tension in the vitreous and anterior chamber is maximum inn proximity of the retinal surface and endothelium, respectively and steeply decreases toward the lens; on both sides, and trabeculate. Vitreous removal and, to a lesser extent, liquefaction, greatly reduces oxygen tension gradient in vitreous chamber while cataract extraction has similar effects on anterior chamber oxygen gradients. Oxygen derivatives originated from the cornea and retina are actively reduced by the vitreous gel and/or the crystalline lens. Vitreous removal and cataract extraction reduce drastically this function. Most reported clinical series confirm this hypothesis although protocol difference and follow-up length greatly impact the reliability of results.

Elevated circulating triglyceride levels have been linked to an increased risk of diabetes, although the precise mechanisms remain unclear. This study aimed to investigate whether low-density lipoprotein (LDL) cholesterol, homeostatic model assessment (HOMA) for insulin resistance, and C-reactive protein served as mediators in this association across a sample of 18,435 US adults. Mediation analysis was conducted using the PROCESS Version 4.3 Macro for SPSS. Simple medi-ation analysis revealed that all three potential mediators played a role in mediating the associa-tion. However, in the parallel mediation analysis, where all three mediators were simultaneously included, HOMA for insulin resistance remained a significant mediator (indirect effect coefficient, 0.47; 95% confidence interval [CI], 0.43—0.52; p < 0.05) after adjusting for all tested confounding factors. Conversely, LDL cholesterol (indirect effect coefficient, -0.13; 95% CI, -0.31—0.05; p > 0.05) and C-reactive protein (indirect effect coefficient, 0.01; 95% CI, -0.003—0.02; p > 0.05) ceased to be significant mediators. HOMA for insulin resistance accounted for 49% of the association between triglycerides and diabetes. In conclusion, HOMA for insulin resistance was the dominant mediator underlying the association between triglycerides and diabetes. Therefore, reducing triglyceride levels may hold promise for improving insulin sensitivity in diabetic patients.

Pulmonary Hypertension (PH) is a terminal disease characterized by severe pulmonary vascular remodeling. Unfortunately, targeted therapy to prevent disease progression is limited. Here, the vascular cell populations that contribute to the molecular and morphological changes of PH in conjunction with current animal models for studying vascular remodeling in PH will be examined. The status quo of epigenetic targeting for treating vascular remodeling in different PH subtypes will be dissected, while parallel epigenetic threads between pulmonary hypertension and pathogenic cancer provide insight into future therapeutic PH opportunities.

Abstract: Arterial hypertension is the main preventable risk factor for premature death and stroke worldwide and anxiety is a real public health problem. Stress is the common denominator for both cases. In the last 3 years, the aggressive exposure of the population to negative emotions (fear of disease in a pandemic, fear of war, financial instability) was the trigger factor. The psycho-neuro-endocrine mechanisms include the hypothalamic-pituitary-adrenal axis and induce sympathetic-parasympathetic imbalance, hypercortisolemia, endothelial dysfunction, oxidative stress, inflammation, cytokine growth, and atherosclerosis. The individual’s vulnerability to stress depends on many factors, but the key role in the perception of stress belongs to immunogenic personality traits. Among them, self-efficacy is a protective factor against stress. Our research aimed to evaluate the connections between psycho-emotional factors and hypertension, using psychometric tests, to identify vulnerability to stress, perceived stress level, anxiety, self-efficacy, and psychobehavioral type, for 215 patients, 104 hypertensive and 111 non-hypertensive patients. The results of the study confirmed that there is a statistically significant difference, which requires psychological screening measures to identify patients vulnerable to stress, as well as medical education courses for doctors in the field of psychology.

WHO estimates that around 600 million people suffer from high blood pressure which causes high costs for health systems and influences the economy of these countries. In this study, we investigate the sociodemographic characteristics and risk factors related to hypertension among individuals from Huambo, Angola. This cross-sectional study was conducted with 158 participants consulted in the Cardiology services at Hospital Geral do Huambo, between January and July 2023. A total of 67.1% of the studied patients were hypertensive. The mean age of the hypertensive (55.8±11.3) patients was higher than non-hypertensive (53.1±13.4) patients, although no significance was observed (p=0.199). Patients aged between 30 and 40 (OR=1.19, P=0493), male (OR=1.17, P=660), employees (OR=9.94, P=0935), patients consuming alcohol (OR=1.11, P=0.864), and practising physical activity (OR=1.12, P=0.742) presented a high chance of developing hypertension, while those living in urbanized areas (OR=0.78, P=0.59) and with a low educational level (OR=0.43, P=0.194), had a low chance to develop hypertension. There was no statistical significance between demographic or behavioural characteristics with hypertension (P>0.05). Regarding clinical characteristics, body mass index was statistically related to hypertension (p=0.011). Our findings show that hypertension is a major health problem for the young population of Huambo. There is an urgent need to create strategies to improve the prevention, diagnosis, and treatment of hypertension, not only in Huambo but throughout the country. Further studies to understand determinants related to hypertension should be carried out among the young population in Angola.

Pregnancy-induced hypertension and preeclampsia are associated with significant maternal and fetal mortality. A better understanding of those diseases, delineation of molecular pathomechanism, and efficient treatment development are some of the most urgent tasks in obstetrics and gynecology. Recent findings indicate a crucial role of inflammation in the development of hypertension and preeclampsia. Although the mechanism is very complex and needs further explanation, it appears that high levels of cholesterol, urate, and glucose activates NLRP3 inflammasome, which produces IL-1β, IL-18 and gasdermin D. Production of these proinflammatory chemokines is a beginning of local and general inflammation, what results in sympathetic outflow, angiotensin II production, proteinuria, hemolysis, liver damage, immunothrombosis, and coagulopathy. NLRP3 inflammasome is a critical complex in the mediation of inflammatory response, which makes it crucial for the development of pregnancy-induced hypertension and preeclampsia, as well as its complications, such as placental abruption and HELLP syndrome. Herein presented the article delineate molecular mechanisms of those processes, indicating directions of future advance.

Background: Hypertension is a cardiovascular syndrome with the highest morbidity and mortality worldwide. Hypertension caused by various stress factors is called stress-induced hypertension (SIH). The rostral ventrolateral medulla (RVLM) "neuroinflammatory-sympathetic overactivation" is involved in SIH formation. Melatonin has anti-inflammatory, anti-oxidant and blood pressure lowering effects. The present study is to explore the antihypertensive effects and mechanism of central melatonin which based on microglia derived neuroinflammation. Methods: Stress-induced hypertension (SIH) was induced by electric foot-shock stressors with noise interventions in rats. Melatonin (0.01，0.1，1 mmol/L) was administered to RVLM and then blood pressure (BP) and serum norepinephrine (NE) were monitored to reflect sympathetic vasomotor activity in SIH rats. Excitatory neurotransmitter (Glutamate) and inhibitory neurotransmitter [γ-aminobutyric acid (GABA)] were measured using ELISA kits. Markers of microglia M1 polarization (CD86) and pro-inflammatory cytokines (PICs (IL-1β, TNF-α)) expression in the RVLM were measured by RT-qPCR. Results: (1) Stress-induced increase in blood pressure and serum NE concentration; RVLM microinjection melatonin attenuated the elevation of blood pressure and increase of plasma NE in SIH rats in a dose-dependent manner. (2) The expression of CD86, PICs (IL-1β, TNF-α) and c-fos were increased in SIH rats; RVLM injection melatonin attenuated RVLM neuroinflammation and its effect is concentration-dependent. (3). Stress-induced increase in glutamate concentration in RVLM; RVLM injection melatonin reduced glutamate level and increased GABA level in SIH rats in a concentration-dependent manner. Conclusion: RVLM injection of melatonin inhibits M1 polarization and has anti-hypertensive effects. Melatonin reduces M1 polarization in microglia might be a novel target and a new strategy for anti-stress induced-hypertension.

Arterial hypertension is a common condition worldwide and an important risk factor for cardio- and cerebrovascular events, renal diseases as well as microvascular eye diseases. Established hypertension leads to chronic vasoconstriction of small arteries as well as to decreased lumen diameter and thickening of the arterial media or wall with a consequent increased media-to-lumen ratio (MLR) or wall-to-lumen ratio (WLR). This process, defined as vascular remodeling, was first demonstrated in small resistance arteries isolated from subcutaneous biopsies and measured by micromyography, and this is still considered the gold-standard method for the assessment of structural alteration in small resistance arteries; however microvascular remodeling seems to represent a generalized phenomenon. An increased MLR may impair organ flow reserve, being relevant in the maintenance and, probably, also in the progressive worsening of hypertensive disease, as well as in the development of hypertension-mediated organ damage/cardiovascular events, possessing, therefore, a prognostic relevance. New, non-invasive techniques, such as Scanning Laser Doppler Flowmetry or Adaptive Optics, are presently under development, focusing mainly on the evaluation of WLR in retinal arterioles; recently, also retinal microvascular WLR was demonstrated to have a prognostic impact in term of cardio- and cerebrovascular events. A rarefaction of capillary network has also been reported in hypertension which may contribute to flow reduction and impairment in oxygen delivery to different tissues. These microvascular alterations seem to represent an early step in hypertension-mediated organ damage since they might concur to microvascular angina, stroke, and renal dysfunction. In addition, they could be a marker useful in monitoring the beneficial effect of antihypertensive treatment. Also conductance arteries may be affected by a remodeling process in hypertension, and a cross-talk may exist between structural changes in the small and large arteries. The review will address the possible relations between structural microvascular alterations and hypertension-mediated organ damage and their potential improvement with antihypertensive treatment.

Pulmonary hypertension (PH) is a serious disorder with high morbidity and mortality rate. We analyzed the right ventricular systolic pressure (RVSP), right ventricular hypertrophy (RVH), lung histology and transcriptomes of six weeks old male rats with PH induced by: 1) hypoxia (HO), 2) administration of monocrotaline (CM) or 3) administration of monocrotaline and exposure to hypoxia (HM). The results in PH rats were compared to those in control rats (CO). After four weeks exposure, increased RVSP and RVH, pulmonary arterial wall thickening, and alteration of the lung transcriptome were observed in all PH groups. The HM group exhibited the largest alterations and also neointimal lesions and obliteration of lumen in small arteries. We found that the PH increased the expression of caveolin1, matrix metallopeptidase 2 and numerous inflammatory and cell proliferation genes. The cell-cycle, vascular smooth muscle contraction and the oxidative phosphorylation pathways, as well as their interplay were largely perturbed. Our results also suggest that the up-regulated Rhoa (ras homolog family member A) mediates its action through expression coordination with several ATPases. The upregulation of antioxidant genes and the extensive mitochondrial damage observed especially in HM group, indicate metabolic shift towards aerobic glycolysis.

Background: Diabetes is among the most prevalent diseases worldwide, of all the affected individuals a significant proportion of the population remains undiagnosed because of a lack of specific symptoms early in this disorder and inadequate diagnostics. Diabetes and its associated sequela, i.e., comorbidity are associated with microvascular and macrovascular complications. As diabetes is characterized by an altered metabolism of key metabolites and regulatory pathways. Metabolic phenotyping can provide us with a better understanding of the unique set of regulatory perturbations that predispose to diabetes and its associated comorbidities. Methodology: The present study utilizes the analytical platform NMR spectroscopy coupled with Random Forest statistical analysis to identify the discriminatory metabolites of diabetes (DB) and diabetes-related comorbidity (DC) along with the healthy control (HC) subjects. A combined and pairwise analysis was performed, between the serum samples of HC (n=50), and DB (n=38), and DC (n=35) individuals to identify the discriminatory metabolites responsible for class separation. The perturbed metabolites were further rigorously validated using t-test, AUROC analysis to examine the statistical significance of the identified metabolites. Results: The DB and DC patients were well discriminated from HC. However, 15 metabolites were found to be significantly perturbed in DC patients compared to DB, the identified panel of metabolites are TCA cycle (succinate, citrate), methylamine metabolism (trimethylamine, methylamine, betaine), -intermediates; energy metabolites (glucose, lactate, pyruvate); and amino acids (valine, arginine, glutamate, methionine, proline and threonine). The metabolites were further used to identify the perturbed metabolic pathway and correlation of metabolites in DC patients. Conclusion: The 1H NMR metabolomics may prove a promising technique to differentiate and predict diabetes and its comorbidities on their onset or progression by determining the altered levels of the metabolites in serum.

In the whole world, including Mexico, the rising prevalence of diabetes poses significant challenges to healthcare systems, with a notable impact on hospital admissions even being an ambulatory care sensitive condition, that means, hospital admissions are avoidable. Traditional healthcare methodologies have been instrumental in managing diabetes and preventing complications, yet they often face limitations such as merging, cleansing, and outlier analysis of health data to identify and address diseases effectively. This paper aims to address this gap by conducting a comprehensive comparison of the methodologies used in healthcare and data science for this purpose. This work uses hospital diabetes discharge records from 2010 to 2023, a total of 36,665,793 records, which belong to medical units of the Ministry of Health of Mexico. In this work, we seek to provide the arguments why as a data scientist it is mandatory to learn the field of knowledge of the problem and its implications if this is not done, and therefore to disclose insights that can help in policy decisions and reduce the burden of avoidable hospitalizations. The approach is mainly based on the standardization or adjust rates by sex and age groups. This study provides the foundations for a new way of data scientist must deal with health data.

The increased prevalence of obesity worldwide has been implicated for the alarming rise of the incidence of gestational diabetes and preeclampsia as well, both considered as threatening conditions for both mother and fetus. We studied gene polymorphisms of the proinflammatory cytokine Interleukin 6 (IL-6) and the gene expression levels of VEGF and VEGF-receptor all known to be involved in pregnancy complications aiming to identify possible predisposing risk factors in pregnancies with obesity. G allele of IL-6 was found to correspond with an increased risk for gestational diabetes and preeclampsia occurrence. Furthermore, in obese pregnant mothers with either gestational diabetes or pre-existing type 2 diabetes and to those developed preeclampsia it was confirmed that gene expression levels of VEGF were reduced while they were increased for VEGF receptor. We conclude that the genetic profile of the obese pregnant woman shares a common background with that of a pre-existing type 2 diabetes mellitus and therefore predisposes to complications in pregnancy.

Background: Annual influenza epidemics are a serious public health problem, causing particularly severe morbidity and mortality in high-risk groups. The study aimed to understand Poles' attitudes and beliefs towards influenza vaccinations in the flu season of 2022–2023, analyze preferences and unmet needs regarding influenza vaccinations, and examine the perception and acceptance of the influenza vaccine among individuals at risk of flu complications. Methods: A cross-sectional survey-based study was carried out on a sample of 1446 respondents. The Google Forms questionnaire was created and disseminated electronically using social media and e-mail. The pre-test was performed at the beginning of the project. Results: The majority of respondents (71%) could identify "high-risk groups" recommended for influenza vaccination. Furthermore, it was observed that individuals aged 21 to 59 demonstrated a higher level of knowledge in this regard compared to those below 20 and above 65 years old, and individuals with higher and medium education levels were much better at identifying risk groups for influenza virus infection. The majority of respondents (52.01%) reported receiving influenza vaccination at some point in the past, with 32.12% receiving it in the 2022–2023 flu season and 41.09% in the 2021–2022 season. The majority of respondents declaring acceptance of the vaccine for the 2022-2023 season were in the high-risk group. Only 17.28% of respondents declared receiving both influenza and SARS-CoV-2 vaccines in the 2022-2023 season, with the vast majority being respondents from the "high-risk group" (p

Background: To assess the prevalence of Hypertension (HTN) in Burning Mouth Syndrome (BMS) patients and to investigate its relationship with sociodemographic factors, pain and the psychological profile. Methods: A case-control study was conducted by enrolling 242 BMS patients and 242 controls matched for age and gender. Sociodemographic and clinical characteristics were recorded, and all the participants completed the numeric rating scale (NRS), the short-form of the McGill pain questionnaire (SF-MPQ), the Hamilton rating scale for anxiety and depression (HAM-A, HAM-D), the Pittsburgh sleep quality index (PSQI) and the Epworth sleepiness scale (ESS). Results: The BMS patients presented a statistically significant higher prevalence of HTN compared to the controls (55% versus 33.5%; p-value: &lt;.001**) and higher median scores of the NRS, SF-MPQ, HAM-A, HAM-D, PSQI and ESS (p &lt; .001**). Multivariate regression analysis in the BMS patients indicated positive correlations between HTN and age, systemic diseases, drug consumption and anxiety (p-value: &lt;.001**) and these predictors were responsible for 11.3% of the HTN variance in the BMS patients, when considered together. Conclusions: The prevalence of HTN was significantly higher in the BMS patients, since ageing, the presence of comorbidities, drug consumption and anxiety were potential predictors. Further studies are needed to better investigate the relationship between BMS and HTN.

: Intermittent fasting has drawn significant interest in the clinical research community due to its potential to address metabolic complications such as obesity and type 2 diabetes mellitus. Various intermittent fasting regimens include alternate-day fasting (24 hours of fasting followed by 24 hours of eating), time-restricted fasting (fasting for 14 hours and eating within a 10-hour window), and the 5:2 diet (fasting for two days and eating normally for the other five days). Intermittent fasting is associated with a reduced risk of type 2 diabetes mellitus-related complications and can slow their progression. The increasing global prevalence of type 2 diabetes mellitus highlights the importance of early management. Since prediabetes is a precursor to type 2 diabetes mellitus, understanding its progression is essential. However, the long-term effects of intermittent fasting on prediabetes are not yet well understood. Therefore, this review aims to comprehensively compile existing knowledge on the therapeutic effects of intermittent fasting in managing type 2 diabetes mellitus and prediabetes.

A recent report from the American Heart Association in 2018 shows that over 103 million American adults have hypertension. The angiotensin-converting enzyme (ACE) (EC 3.4.15.1) is a dipeptidyl carboxylase that, when inhibited, can reduce blood pressure through the renin-angiotensin system. ACE inhibitors are used as a first-line medication to be prescribed to treat hypertension, chronic kidney disease, heart failure among others. It has been suggested that ACE inhibitors can reduce the symptoms in mouse models. Despite the benefits of ACE inhibitors, previous studies also have suggested that alterations in the ACE gene are risk factors for Alzheimer’s disease (AD) and other neurological diseases. In mice, overexpression of ACE in the brain reduces symptoms of the AD-model systems. Thus, we find opposing effects of ACE on health. To clarify the effects, we dissect the functions of ACE as follows: (1) angiotensin-converting enzyme that hydrolyzes angiotensin I to make angiotensin II in the renin-angiotensin system; (2) amyloid-degrading enzyme that can hydrolyze beta-amyloid and reduce amyloid toxicity. The efficacy of the ACE inhibitors is well established in humans, while the knowledge specific to AD remains to be open for further research. We provide an overview of ACE and inhibitors that link a wide variety of age-related comorbidities from hypertension to Alzheimer’s disease to aging. ACE also serves as an example of the middle-life crisis theory that assumes deleterious events during the midlife, leading to age-related later events.

Background: Essential hypertension is a major public health associated with increase pressure on the vascular walls and red blood cells (RBCs). In the present work, osmotic fragility (OF) of RBCs was reexamined in the means of its correlation with two risk factor; iron status and lipid profile. Experimental: OF, iron status parameters, and lipid profile components were measured in 60 patients and compared with the results of 30 controls. Results: The results showed a significant increase in all iron indices of hypertensive patients in comparing with healthy control group except TIBC, UIBC, and transferrin concentrations, which decrease in these patients in comparing with control group. Serum TGs, total cholesterol, VLDLc, and LDLc were increased while there is no significant in serum HDLc in patients to comparing with control group. There is no significant change in OF between patients and controls where p=0.173. The iron status parameters and lipid profile components were dependent on sex and smoking state. Hemoglobin and PCV were correlated significantly with total cholesterol and LDLc. Transferrin saturation showed a positive correlation with cholesterol, LDLc, and TGs, but negatively correlated with HDL_c. No significant correlation between all the measured parameters and OF in HT patients. There is a significant correlation between serum ferritin and systolic BP and between Hb and systolic BP. Conclusion: No significant effect on the OF in HT patients. HT patients have elevated level of iron parameters in comparing with controls. OD has no correlation with iron status parameters or with lipid profile components.

Obesity is a risk factor for the development of gestational diabetes mellitus (GDM). However, the most optimal type of nutritional intervention to prevent GDM in high-risk women is not clearly defined. This study investigates if nutritional treatment based on the Mediterranean diet (MedDiet) before 12th gestational week (GW) in women at high risk due to a body mass index (BMI)≥25kg/m2, reduces the rate of GDM and metabolic syndrome (MetS) at 3 years postpartum. We performed a post-hoc analysis of the San Carlos Gestational Prevention Study. A total of 735 women with BMI≥25kg/m2 were evaluated between 2015-2018, 246 in standard diet control group (CG) and 489 in MedDiet intervention group (IG). The rate of GDM was significantly lower in IG compared to CG (25.1%vs31.7%;p=0.037). Postnatal follow-up was completed by 141 women in CG (57%) and 312 women in IG (64%). At 3 years postpartum, we observed a reduction (relative risk 95% confidence interval) in the rates of impaired fasting glucose (IFG) (0.51 (0.28-0.92);p=0.019), obesity (0.51 (0.28-0.92),p=0.041), waist circumference (WC)≥89.5cm (0.54 (0.31-0.94);p=0.022) and MetS (0.56 (0.33-0.94);p=0.003). MedDiet reduces the rate of GDM and postpartum MetS in women with BMI)≥25kg/m2, suggesting that its implementation should be routinely recommended from the first GWs.

Cardiovascular morbidities are the main cause of mortality in pituitary disorders accruing either from hormonal excess or deficiency. Cushing disease is associated with various cardiovascular abnormalities;visceral obesity, insulin resistance, atherosclerosis, arterial hypertension, dyslipidaemia and hypercoagulability, structural and functional changes in heart, which do not seem to reverse completely even after remission. Acromegaly is related with insulin resistance, but also with structural and functional heart changes which consist acromegalic cardiomyopathy. Patients with prolactinomas demonstrate an aggravation of metabolic parameters, obesity, dysregulation of glucose and lipid metabolism and endothelial dysfunction. On the other hand, hypopituitarism and conventional hormonal replacement which is far from ideal contribute to an unhealthy metabolic status which leads to atherosclerosis and premature mortality. This review aims to update literature on cardiovascular risk and relevant morbidities in pituitary disorders.

Type 2 diabetes mellitus (T2DM) accounts for one-sixth of deaths, globally, whereas cancer is the second leading cause of death in the U.S. T2DM is a known risk factor for many cancers. This review examines the link of Reactive oxygen Species (ROS)-altered metabolic and signaling pathways in T2DM to cancer. These reprogrammed metabolic and signaling pathways are activated that contribute to diabetic complications, impact redox balance (Oxidative Stress), and have differential roles in early and late stages of cancer. If the respiratory chain is highly reduced (as under hyperglycemic conditions) or if reduced cofactors accumulate, ROS are greatly elevated. ROS may cause mutations in mitochondrial DNA (mtDNA) that result in further ROS elevation. Amplification of ROS results in activation of PKC, an overarching signaling pathway that activates MAPK with subsequent regulation of several factors that result in pathophysiological manifestations of T2DM and cancer. Upregulation of PKC leads to deregulation of NF-kß that regulates the PKB/P13/Akt pathway that orchestrates cell survival, growth, proliferation, and glucose metabolism manifested in cancer. It also affects Insulin Receptor Substrate (IRS-1), decreasing insulin stimulated glucose transport and glucose uptake, disrupting subsequent cell signaling pathways contributing to the development of T2DM. Dyslipidemia is a hallmark of T2DM and cancer. ROS-induced lipid peroxidation leads to systemic inflammation, producing inflammatory prostaglandins, cytokines and chemokines that result in tumor proliferation, rapid tumor growth, and modulation of immunity. The dual role of ROS in early and late stages of cancer make antioxidant therapy precarious and may be responsible for controversial results. A system that delivers an antioxidant directly to mitochondria may be useful in inhibiting formation of ROS early during the pre-diabetic stage whereas antioxidant therapy must be halted in later stages to retard metastasis.

Diabetes self-management education helps to improve health outcomes, quality of life and to reduce expenses for diabetic patients. This systematic review aimed to examine the effectiveness of diabetes self-management education used for newly diagnosed patients with type 2 diabetes (T2DM). A review of studies that have researched the use and the impact of health education in newly diabetic patients with T2DM was implemented. A literature search was conducted using the electronic database of Pub MED, Walters Kluwer, Cochrane Library, Elsevier, JSTORE between January 2017 – November 2022. The data on participants and intervention characteristics were extracted by two reviewers independently. We found 789 studies and after selection of PRISMA flow chart we selected 19 studies, including 2512 newly diagnosed adult T2DM. Biomedical results presented the pooled effect of HbA1c -0.64%, FBG -0.32. The evaluation of emotional and social results and behavioral effects has been evaluated respectively in 10 and 9 studies. The education and support of recently diabetic patients help to improve biomedical, psychosocial, and behavioral results. This intervention must be ongoing to maintain healthy behaviors

The current echocardiography reference values are derived primarily from populations in North America and Europe. It becomes necessary to study ethnically different groups of the population, which often have different living conditions, food habits and lifestyle. The aim of the study was to compare echocardiography indicators in urbanized patients with arterial hypertension of the Shor and non-indigenous ethnic groups living in the Gornaya Shoria region. The study included patients with arterial hypertension: 58 Shors (20 men and 38 women) and 50 non-indigenous residents (15 men and 35 women) of Gornaya Shoria. All underwent an echocardiographic study with an assessment of the left heart parameters. We assessed the left ventricular hypertrophy (LVH) severity, LV geometry and diastolic function in the ethnic and sex groups. Shor with hypertension no showed a significant difference in left ventricular dimensions compared to Caucasian. Severe abnormal LVH was associated in the Shors with glucose levels (OR 3.24, 95%CI 1.56-6.7, p=0,001), and in Caucasians with systolic (p=0.021) and diastolic (p=0.011) blood pressure, and heart rate (p=0.033). The Shor men were more likely to have normal LV diastolic function (p=0.029) and LV concentric remodeling (p=0.023), and less often to have normal LV geometry (p=0.015) compared to non-indigenous men. Thus, this study can be useful in assessing the impact of the development of arterial hypertension, as well as the impact of changing the lifestyle of the Shors when moving to the city from rural areas on ethnic differences in echocardiography.

Background: As part of the Heart Healthy Lenoir Project, we developed a practice level intervention to improve blood pressure control. The goal of this study was: i) determine if single nucleotide polymorphisms (SNPs) that associate with blood pressure variation, identified in large case-control studies, are applicable to blood pressure control in subjects from a rural population; ii) measure the association of these SNPs with subjects’ responsiveness to the hypertension intervention; and iii) identify other SNPs that may help understand patient-specific responses to an intervention. Methods and Results: We used a combination of candidate SNPs and genome-wide analyses to test associations with either baseline systolic blood pressure (SBP) or change in systolic blood pressure one year after the intervention in two genetically defined ancestral groups: African Americans (AA) or Caucasian Americans (CAU). Of the 48 candidate SNPs, 13 SNPs associated with baseline SBP in our study; however, one candidate SNP, rs592582, also associated with a change in SBP after one year. Using our study data, we identified 4 and 15 additional loci that associated with a change in SBP in the AA and CAU groups, respectively. Our analysis of gene-age interactions identified genotypes associated with SBP improvement within different age groups of our populations. Moreover, our integrative analysis identified AQP4-AS1 and PADI2 as genes whose expression levels may contribute to the pleiotropy of complex traits involved in cardiovascular health and blood pressure regulation in response to an intervention targeting hypertension. Conclusions: Identification of SNPs associated with the success of a hypertension treatment intervention suggests that genetic factors in combination with age may contribute to an individual’s success in lowering SBP. If these findings prove to be applicable to other populations, the use of this genetic variation in making patient-specific interventions may help providers with making decisions to improve patient outcomes. Further investigation is required to determine the role of this genetic variance with respect to the management of hypertension such that more precise treatment recommendations may be made in the future as part of personalized medicine.

A previous report showed that the urine output of HPLBII-P in patients with diabetes mellitus and SARS-Cov-2 infection was increased as a sign of glomerular dysfunction. . The aim of this report was to investigate the relation of urine output of HPLBII-P to diabetes mellitus in two large community-based elderly populations i.e. the ULSAM and PIVUS cohorts. Methods HPLBII-P was measured by ELISA in the urine of a community-based cohort of 839 men (ULSAM) collected at 77 years of age and in urine of a community-based cohort of 75-year-old men, n=387, and women, n=401 (PIVUS). KIM-1, NGAL and Albumin were measured in urine and Cathepsin S and Cystatin C in serum. Results HPLBII-P was significantly raised among males with diabetes in the ULSAM (p

The following article presents an analysis of the determinants of diabetes using a dataset containing the surveys of 2000 patients from the Frankfurt Hospital in Germany. The data were analyzed using the following models, namely: Tobit, Probit, Logit, Multinomial Logit, OLS, WLS with heteroskedasticity. The results show that the presence of diabetes is positively associated with "Pregnancies", "Glucose", "BMI", "Diabetes Pedigree Function", "Age" and negatively associated with "Blood Pressure". A cluster analysis is realized using the fuzzy c-Means algorithm optimized with the Elbow method and three clusters were found. Finally a confrontation among eight different machine learning algorithms is realized to select the best performing algorithm to predict the probability of patients to develop diabetes.

This article investigates the effectiveness of feature extraction and selection techniques for enhancing the performance of classifiers accuracy in Type II Diabetes Mellitus (DM) detection using microarray gene data. To address the inherent high dimensionality of the data by employing three Feature Extraction (FE) methods are used namely, Short-Time Fourier Transform (STFT), Ridge Regression (RR), and Pearson Correlation Coefficient (PCC). To further refine the data, meta-heuristic algorithms like Bald Eagle Search Optimization (BESO) and Red Deer Optimization (RDO) are utilized for feature selection. The performance of seven classification techniques such as Non-Linear Regression - NLR, Linear Regression - LR, Gaussian Mixture Model - GMM, Expectation Maximization - EM, Logistic Regression - LoR, Softmax Discriminant Classifier - SDC, and Support Vector Machine with Radial Basis Function kernel - SVM-RBF are evaluated with and without feature selection. The analysis reveals that the combination of PCC with SVM-RBF achieved a promising accuracy of 92.85% even without feature selection. Notably, employing BESO with PCC and SVM-RBF maintained this high accuracy. However, the highest overall accuracy of 97.14% was achieved when RDO was used for feature selection alongside PCC and SVM-RBF. These findings highlight the potential of feature extraction and selection techniques, particularly RDO with PCC, in improving the accuracy of DM detection using microarray gene data.