bluuebunny/crossref_metadata_2025_split huggingface dataset:
EFFECTIVENESS OF TREATMENT OF COMBINED PATHOLOGY OF DIABETES MELLITUS AND MULTIDRUG-RESISTANCE TUBERCULOSIS
Authors: Semianiv Ihor , Todoriko Liliia , Semianiv Marianna , Sukholitky Yuriy 
Published: June 2023

Objective:
The objective of the study is a comprehensive retrospective assessment of the prevalence, features, course of treatment of diabetes mellitus and multidrug-resistant tuberculosis.

Design and method:
Our study is based on an analysis of statistical data obtained from a retrospective study of 762 case histories and cases of MDR-TB in the register of tuberculosis patients in different regions of Ukraine for 2016-2020.

Results:
Depending on the type of TB case in our patients, we found that in both groups of the study the recurrence of TB prevailed – 49 cases (55.7%) against TB 39 cases (44.3%) of people in the main group; 363 cases (53.9%) against 311 (46.1%) in the control group (p <0.05).
The rate of successful treatment in gr.2 is probably higher than in gr. 1 (64.7% vs. 61.4%; (p <0.05)). However, a more significant probable difference is characterized by the treatment rate, which in the main group is 27.3% versus 40.3% in the control group (almost 2 times; p <0.05). The rate of ineffective treatment, which in patients with comorbidity was 27.3% (almost every third patient) against 17.6% in group 2 is also important for scientists and practitioners.

Conclusions:
There is a clear tendency to increase the combined pathology and chemoresistance in the structure of the incidence of tuberculosis, the proportion of recurrences of tuberculosis in the presence of diabetes mellitus. The pulmonary tuberculosis developed significantly more often in middle-aged patients with type 2 diabetes mellitus with moderate and severe states, the subcompensated form, with a complicated course.
MYOCARDIAL REDUCTION OF SYMPATHETIC ACTIVITY IS INVOLVED IN THE ANTIFIBROTIC AND ANTIHYPERTROPHIC EFFECTS OF SGLT2 INHIBITION IN ANGIOTENSIN II-DEPENDENT HYPERTENSION
Authors: Castoldi Giovanna , Carletti Raffaella , Ippolito Silvia , Colzani Massimiliano , Perseghin Gianluca , Zerbini Gianpaolo , Zatti Giovanni , Gioia Cira Di 
Published: June 2023

Objective:
The beneficial myocardial effects of SGLT2 inhibitors, a new class of antidiabetic drugs, have been described not only in diabetic patients, but also in heart diseases not associated with diabetes. The positive effects of these drugs go beyond glycemic control and involve multiple mechanisms.
In the present study we investigate whether the cardioprotective effects of empagliflozin, a SGLT2 inhibitor, may be dependent on myocardial sympathetic activity in experimental model of angiotensin II-dependent hypertension.

Design and method:
Experiments were performed in Sprague Dawley rats (n = 26) followed for 4 weeks and divided in the following groups: a) Angiotensin II-treated group (Ang II, 200 ng/kg/min, osmotic minipumps s.c, n = 7); b) Ang II +Empagliflozin-treated group (Empa, 10 mg/kg/day, per os, n = 6); c) control group (physiological saline s.c., n = 7); d) Control+Empagliflozin-treated group (n = 6). Systolic blood pressure was measured by tail cuff method. At the end of the experimental period myocardial interstitial fibrosis (Sirius Red staining) and myocardial hypertrophy were measured by histomorphometric analysis. Myocardial tyrosine hydroxylase expression, used as marker of sympathetic activity, was measured by immunohistochemistry.

Results:
Ang II caused a significant increase of blood pressure (p<0.0001), myocardial interstitial fibrosis (p<0.01), hypertrophy (p<0.01), and tyrosine hydroxylase expression (p<0.01) as compared to control groups. Empagliflozin treatment did not modify blood glucose in the different groups of rats. Empagliflozin administration did not modify the increase in blood pressure in Ang II treated rats, but prevented the development of myocardial fibrosis, hypertrophy, and tyrosine hydroxylase over-expression.

Conclusions:
These data demonstrate that in Ang II dependent hypertension Empagliflozin administration prevented the onset of myocardial fibrosis and hypertrophy through the reduction of local sympathetic activity. This effect is independent on the modulation of blood pressure and blood glucose levels.
EFFECT OF LOW DOSE ALLOPURINOL ON GLYCEMIC CONTROL AND GLYCEMIC VARIABILITY IN PATIENTS WITH TYPE 2 DIABETES MELLITUS: A CROSS-SECTIONAL STUDY
Authors: Manal Mohammed Alem 
Published: June 2023

Objective:
Type 2 diabetes mellitus (DM), gout, and asymptomatic hyperuricemia are inter-connected pathologies. Glycemic control (GC), involving a range of treatments is central to the management of DM, whereas allopurinol continues to be the most widely recommended urate lowering agent. Allopurinol has been shown to possess anti-oxidant properties: this study explores the potential effect of allopurinol on glucose homeostasis.

Design and method:
This is an observational study with a cross-sectional design performed on patients with type 2 diabetes mellitus (DM), recruited from centers in Saudi Arabia. Patients were divided into two groups; allopurinol users; (for gout or asymptomatic hyperuricemia) and a matching disease control group. Patient demographics, co-morbid conditions, biochemical tests, and pharmacological treatments were extracted from electronic records to investigate the effect of allopurinol therapy on Glycemic control (GC), as assessed by glycated haemoglobin (HbA1cas primary endpoint), and on parameters of glycaemic variability (GV) (secondary endpoints).

Results:
A total of 194 patients with type 2 DM were recruited (97 in both groups). The two groups were matched for age, sex, and duration of DM:mean age: 59.4 years, 73% males, and 122 months in the allopurinol group vs 59.6 years, 73% males, and 113 months in the control group. Antidiabetic medications were matched between the two groups. In the allopurinol group, it was prescribed with a daily dose of 100 mg, for 77% of the patients, with median duration of 39.5 months. HbA1c values were; 6.90% (6.20, 7.80) in the allopurinol group vs 7.30% (6.60, 8.40) in the control group (P = 0.010). Parameters of GV were calculated from 3 consecutive fasting blood sugar (FBS) readings: variability independent of the mean (VIM) was 0.140 in the allopurinol group vs 0.987 in the control group (P<0.001).

Conclusions:
Concomitant low-dose allopurinol therapy in patients with type 2 DM was associated with modest but significant improvements in GC and GV.
SCREENING RATES FOR PRIMARY ALDOSTERONISM ARE UNSATISFACTORY EVEN IN HYPERTENSION EXCELLENCE CENTERS. A CALL FOR COMPULSORY SCREENING FOR ALL HYPERTENSIVE PATIENTS
Authors: Leiba Adi , Seged-German Hadassah , Rappoport Vladimir , Sofer Shelly , Leiba Ronit , Katzir Zeev , Hausmann Michael , Korman Avital Angel 
Published: June 2023

Objective:
The Endocrine Society guidelines recommend screening for primary aldosteronism (PA) in high risk hypertensive patients. These include patients with sustained blood pressure (BP) above 150/100 mmHg, patients with resistant hypertension (HTN), hypertensive patients with spontaneous or diuretic-induced hypokalemia, adrenal incidentaloma, sleep apnea, family history of early onset HTN or cerebrovascular accident at a young age and all hypertensive first-degree relatives of patients with PA.
Even though guidelines are clear and screening is simple, compliance rates among clinicians are extremely low ranging between 0.1% to 2.7%. This results in underdiagnosis of early disease, leading to an enormous extra-burden of advanced chronic kidney disease, heart failure, atrial fibrillation, and stroke.
We aimed to examine the screening rate, according to the abovementioned guidelines, at our recently recognized Hypertension Excellence Center in Assuta Ashdod University Hospital.

Design and method:
A retrospective cohort study. We analyzed all hypertensive patients, eligible for screening between 01/18 and 12/20.
We calculated screening rates and in univariate and multivariate regression analyses, looked at parameters that influence screening.

Results:
Of 661 patients over 18 years of age with HTN, 218 patients (33%) met the Endocrine Society guidelines for PA screening. However only 46 of them (21.1%), were referred for screening. A multivariate regression analysis, demonstrated that advanced age and male gender were associated with lower rates of screening referral. Odds ratio for age was 0.945 for every year (95% CI 0.915-0.975).

Conclusions:
A 21% screening rate in a Hypertension Excellence Center, although higher than prior published studies, suggests that many cases of PA are likely missed, more often in elderly population in whom adrenal micro as well as macronodular-hyperplasia is extremely common and can be the cause of secondary HTN.
We therefore advocate for PA screening at least once of all hypertensive patients, preferably before the patient is started on multiple anti-hypertensive medications. This should be done regardless of patients’ age and gender, as the absolute risk for cardiovascular events in both hypertensive and PA patients increases with rising age, and treatment with mineralocorticoid receptor antagonists can be lifesaving.
AUTOREACTIVE T CELLS TO ANGIOTENSIN II TYPE 1 RECEPTOR IN SALT-DEPENDENT HYPERTENSION DUE TO PRIMARY ALDOSTERONISM
Authors: Scarpa Riccardo , Piazza Maria , Caroccia Brasilina , Carraro Samuela , Torresan Francesca , Iacobone Maurizio , Vianello Fabrizio , Cinetto Francesco , Agostini Carlo , Seccia Teresa Maria , Rossi Gian Paolo 
Published: June 2023

Objective:
Compelling evidence suggested a role of acquired immunity in hypertension and hypertension-mediated organ damage (HMOD), but its pathogenic role is still unknown. Primary Aldosteronism (PA), the paradigm of salt-dependent hypertension, is characterised by a more prominent HMOD than primary hypertension and by high titer of autoantibodies against the angiotensin type-1 receptor (AT1R). As T cells are broadly recognised as HMOD-mediators we investigated: 1) the presence of AT1R-autoreactive T cells in PA; 2) aldosterone rapid and chronic effect on AT1R-autoreactive T lymphocytes; 3) the presence and functional role of aldosterone receptors on T lymphocytes.
Design and Methods: The presence of AT1R-autoreactive T cells in 11 PA patients was investigated by flow cytometry after stimulation with pool of peptides spanning the full length of AT1R. The expression of mineralocorticoid receptor (MR) and G Protein-Coupled Estrogen Receptor (GPER) on T cells was tested by measuring mRNA copy number and immunoblotting from healthy donors and PA patients. PBMCs from PA patients were exposed to aldosterone 10-10 M with or without MR antagonist (canrenone) and GPER agonist (G1) and antagonist (G36). We evaluated the effect of aldosterone on CD8+ T cells by measuring IFN? release with flow cytometry.

Results:
PA patients were found to have CD8+ AT1R-autoreactive T cells after activation of PBMC with AT1R peptides. MR and GPER were detected both at mRNA and protein level in CD4+ and CD8+ T cells with the following rank of expression GR>MR>>GPER. Aldosterone significantly increased IFN? release in CD8+ T-cell both under chronic and acute stimulation. Chronic exposure to aldosterone increased IFN-? production by CD8+ T cells by acting via the MR, as it was prevented (p<0.004) by canrenone, while the rapid aldosterone action was MR and GPER mediated, as it was reduced by canrenone (p<0.003), but also by G36 (p<0.02), and mimicked by G1.
Conclusion: These results showed the presence of AT1R-autoreactive T cells in patients with PA and demonstrates that, upon of MR and GPER receptor stimulation with aldosterone, AT1-R specific CD8+ T cells undergo profound changes that mediated a strong cytotoxic response towards AT1-R-expressing organs.
TRANSCRIPTOMIC ANALYSIS OF URINARY EXTRACELLULAR VESICLES IN HYPERTENSIVE PATIENTS WITH PRIMARY ALDOSTERONISM
Authors: Mango Gabriele , Castagna Annalisa , Veneri Mariangela , Ambrosani Francesca , Begali Francesca , Spillere Carlotta , Pattini Patrizia , Santis Domenica De , Brazzarola Paolo , Friso Simonetta , Olivieri Oliviero , Pizzolo Francesca 
Published: June 2023

Objective:
To perform transcriptomic analysis of RNA samples extracted from urinary extracellular vesicles (uEVs) of patients with primary aldosteronism (PA), subtype aldosterone-producing adenoma (APA), before and after adrenalectomy, and patients with essential hypertension (EH). Then, to compare the differentially expressed genes (DEGs) for evaluating gene expression differences between PA and EH, and PA before and after adrenalectomy.

Design and method:
Urinary extracellular vesicles were isolated using a commercially available precipitating reagent and differential centrifugations. RNA libraries were prepared according to the TruSeq Stranded Total RNA protocol and sequenced by NextSeq System (Illumina).

Results:
Gene set enrichment analysis on DEGs in 5 patients with PA compared to 8 EH subjects revealed several significantly overrepresented classes of transcripts, including ion binding, sodium ion transmembrane transport and collagen-containing extracellular matrix. Among the more interesting genes, we found some associated to the activity of voltage-dependent ion channels (CACNA2D1, CACNA2D4, CACNG2, SCN3A, SCN5A, SCN9A, SCN11A). Moreover, in order to identify potentially aldosterone-regulated genes, we focused on DEGs in common between the comparisons APA pre-surgery vs EH and APA pre surgery vs APA post-surgery. We found, among DEGs shared across these two groups, some transcripts involved in the regulation of extracellular matrix remodeling and Phosphoinositide 3-kinases pathway (CST3, EPHB2, ITGA5, PIK3R2).

Conclusions:
This study contributes to a more precise characterization of the molecular mechanisms underlying PA. To our knowledge, this is the first transcriptomic study on uEVs from patients with PA and EH, confirming evidence found in other studies on different tissues (biological fluids and adrenal tissue). Our results suggest that the mRNA content of these vesicles may reflect the pathophysiological processes occurring in the urinary tract and especially in the kidney.
RISK OF ENDOTHELIAL DYSFUNCTION AND CAROTID ARTERIES INTIMA MEDIA THICKNESS DEPENDING ON GUANINE NUCLEOTIDE-BINDING PROTEIN BETA-3 AND ENDOTHELIAL NITRIC OXIDE SYNTHASE GENES’ PO
Authors: Sydorchuk Andrii , Voroniuk Ksenia , Sydorchuk Larysa , Dzhuriak Valentina , Sydorchuk Ruslan , Gutnitska Adelina , Iftoda Oksana 
Published: June 2023

Objective:
Endothelial dysfunction (ED) is an initial step to vascular insufficiency, atherosclerosis. The study is aimed to clarify the risk of ED and carotid arteries (CA) intima media thickness (IMT) changes depending on guanine-nucleotide-binding-protein-beta-3 (GNB3, rs5443) and endothelial-nitric-oxide-synthase (NOS3, rs2070744) genes’ polymorphisms in essential arterial hypertension (EAH).

Design and method:
One-hundred EAH patients with target-organ damage, moderate/high/very high cardiovascular risk were involved in the case-control study: 79.0% females, 21.0% males, mean age 59.87±8.02; disease duration 6-25 years. Control - 48 practically healthy persons . GNB3 (rs5443) and NOS3 (rs2070744) genes’ polymorphisms examined in Real-Time-PCR. Soluble-Vascular-Cell-Adhesion-Molecule (sVCAM-1), total NO-metabolites (NO2-/NO3-), transcriptional activity of NOS3 gene, Endothelium-Dependent-Flow-Mediated-Dilation of the Brachial Artery (FMD BA) and carotid IMT were studied.

Results:
Severe EAH course (SBP/DBP>160>100 mmHg) is associated with the structural changes of the CA (IMT>0.9 mm) increasing the likelihood more than 3.5 times [OR 95%CI:1.28-10.23; p = 0.012], atherosclerotic plaques on the CA – 4 and 3.5 times as much [OR 95%CI:1.18-13.59; p = 0.018 and 1.23-10.71; p = 0.014], and decreased NOS3 gene transcriptional activity by the mRNA level (<0.5 U) – threefold [OR 95%CI: 1.0-9.66; p = 0.042]). Moderate/severe ED enhance the risk of severe EAH 3-5.5 times [OR 95%CI:1.13-9.34; p = 0.025 and 1.96-14.45; p<0.001]. C-allele of NOS3 (rs2070744) gene elevates the risk of atherosclerotic lesion in CA 3.5 times [OR 95%CI:1.24-11.20; p = 0.019 and 1.22-10.18; p = 0.018], ED – by decrease of total NO metabolites (<25 μmol/l) and sVCAM-1 growth (>1050 ng/ml) almost 12 and 4 times [OR 95%CI: 1.23-112.7; p = 0.023 and 1.24-11.20; p = 0.019]. C-allele of NOS3 gene heighten the probability of low NOS3 gene expression by mRNA level (<0.5 U) 69 times [OR95%CI:17,72-520,0; p<0,001]. Minor T-allele (rs5443) increases the risk of CA changes by IMT (>0,9 mm) threefold [OR 95%CI:1.09-7.74; p = 0.027], CA atherosclerotic plaques – almost 10 and 5 times [OR 95%CI:2.55-38.0; p<0.001 and 1.61-13.27; p = 0.003]. T-allele of GNB3 gene enhances the probability of high sVCAM-1 (>1050 ng/ml) threefold [OR 95%CI:1.06-9.59; p = 0.032].

Conclusions:
C-allele of NOS3 (rs2070744) gene contributes more to ED risk elevation. T-allele of GNB3 (rs5443) gene increases the risk of the carotid arteries structural changes.
VASCULAR REMODELING AND FIBROSIS INDEXES IN NAFLD SUBJECTS
Authors: Rosson Marco , Grillo Andrea , Barbato Vincenzo , Pierro Giuliano Di , Rovina Matteo , Zorat Francesca , Comar Consuelo , Fabris Bruno , Puato Massimo 
Published: June 2023

Objective:
Non-alcoholic fatty liver disease (NAFLD) is a growing public health problem and is related to an increased burden of cardiovascular disease.
Aim of the study: to assess the relation between non-invasive scoring systems for liver fibrosis (Fibrosis-4 Index and NAFLD Fibrosis Score) and structural and functional vascular properties in NAFLD patients.

Design and method:
The study enrolled 30 consecutive patients (mean age 64±13, BMI 29.3±6.1 kg/m2, male 60%) who underwent hepatological evaluation in our department. Atherosclerotic burden was evaluated by B-mode ultrasound in each carotid artery segment (common, bulb, internal), bilaterally, and expressed as mean of carotid intima-media thickness (mean-IMT) and mean of maximum IMT (M-MAX), right common carotid artery distensibility and stiffness (CardioVascular Suite 4, Quipu, Italy). Aortic stiffness was measured by applanation tonometry (PulsePen DiaTecne, Italy) and was expressed as carotid-femoral pulse wave velocity (PWV).

Results:
In our cohort vascular properties were: carotid mean-IMT 0.83±0.15 mm, M-MAX 0.98±0.17 mm, carotid distensibility 18.8±8.3 10-3/kPa, and carotid compliance CC 0.88±0.40 mm2/kPa. We found a significant correlation between NAFLD Fibrosis Score and PWV (mean PWV = 10.9±2.9m/s; Fibrosis Score = -0.97±1.80; R = 0.422, p = 0.020), which remained significant after adjustment for mean arterial blood pressure and sex (p = 0.017). No correlation was found between carotid ultrasound parameters and fibrosis scores.

Conclusions:
In NAFLD patients, our preliminary observation shows a correlation between a liver fibrosis score and PWV, an established marker of aortic stiffness, while no correlation was observed with carotid atherosclerosis markers. This vascular remodeling phenotype needs to be confirmed in a larger population.
ENDOTHELIAL FUNCTION, AS ASSESSED BY FLOW MEDIATED DILATION AND ASYMMETRIC DIMETHYLARGININE IS IMPAIRED IN NEWLY DIAGNOSED TYPE 2 DIABETES MELLITUS
Authors: Nikolaidou Barbara , Anyfanti Panagiota , Lazaridis Antonios , Gavriilaki Eleni , Dolgyras Panagiotis , Mastrogiannis Konstantinos , Kavelidou Maryanthe , Triantafyllou Areti , Doumas Michalis , Gkaliagkousi Eugenia 
Published: June 2023

Objective:
Endothelial dysfunction precedes the onset of clinically detectable atherosclerosis diabetes mellitus in type 2 (T2DM) and contributes significantly to the development of vascular complications and mortality. The aim of the present study was to investigate the endothelial function in patients with a recent diagnosis of T2DM.

Design and method:
We studied patients with newly diagnosed T2DM (<6 months from diagnosis) that did not receive antidiabetic treatment (except for metformin) and otherwise healthy individuals matched for age and blood pressure (BP). We recorded somatometric, BP (office and 24-hour) and hematological (lipids, renal function, fasting glucose, HBA1c) data. We also calculate the 10-year atherosclerotic cardiovascular risk (ASCVD risk score). We determined endothelial dysfunction with 2 methods: Asymmetric Dimethylarginine (ADMA) by ELISA (enzyme-linked immunosorbent assay) and the gold standard non-invasive method Flow Mediated Dilation (FMD).

Results:
Ninety subjects were studied, 33 patients with T2DM and 57 controls. Twenty T2DM patients were enrolled within 1 month from diagnosis, while the rest 13 had been diagnosed 3.69±2.14 months before. Similarly, 16 (48.48%) had received metformin for a median of 3 (interquartile range 18) weeks. T2DM showed significantly impaired FMD [4.68 (4.58)% versus 7.85 (7)%, (p = 0.012)] and higher ADMA [0.926±0.569 μmol/l versus 0.468 (0.27) μmol/l, (p = 0.032)], compared to controls. There was also an independent association of T2DM and FMD (Beta = -0.278, p = 0.012). Results were similar in the sub-group analysis of patients without hypertension. In this cohort, FMD lower than 7.5% was able to predict T2DM diagnosis with 87.5% sensitivity and 70.8% specificity.

Conclusions:
Patients with a very recent diagnosis of T2DM show impaired endothelial function as demonstrated by FMD and ADMA findings. This assessment highlights the early severe, damaging effect of hyperglycemia on the endothelium, emphasizing the need for early detection and management.
HIGH SERUM TRIMETHYLAMINE N-OXIDE LEVEL IS ASSOCIATED WITH ENDOTHELIAL DYSFUNCTION IN PATIENTS WITH HYPERTENSION
Authors: Hsiao Chien-Hao , Yang Chiu-Fen , Wang Ji-Hung , Hsu Bang-Gee 
Published: June 2023

Objective:
Trimethylamine N-oxide (TMAO) is a metabolite derived from gut microbial metabolism and dietary intake and plays important roles in cardiovascular disease pathogenesis. Endothelial dysfunction is associated with risk factors of cardiovascular disease in patients with hypertension. The present study aimed to determine the correlation between serum TMAO and endothelial function, measured by vascular reactivity index (VRI) in patients with hypertension.

Design and method:
The present study collected fasting blood samples from 110 patients with hypertension. Serum TMAO levels were determination of by high-performance liquid chromatography–mass spectrometry. The endothelial function and VRI values were measured using digital thermal monitoring test, and VRI values of >2.0, 1.0–1.9 and <1.0 indicated good, intermediate and poor vascular reactivity, respectively.

Results:
Ten hypertensive patients (9.1%) were categorized as poor vascular reactivity (VRI < 1.0), 57 hypertensive patients (51.8%) were categorized as intermediate vascular reactivity (1.0 < VRI < 2.0), and 43 hypertensive patients had good vascular reactivity. Older age (P = 0.010), higher levels of serum total cholesterol (TCH, P = 0.007), low-density lipoprotein cholesterol (LDL-C, P = 0.009), and TMAO levels (P < 0.001) were associated with poor vascular reactivity. Furthermore, after multivariable forward stepwise linear regression analysis noted that logarithmically transformed serum level of TMAO (log-TMAO, adjusted R2 change = 0.274, P < 0.001) was significantly and independently associated with VRI values in hypertensive patients. Compared with good vascular reactivity index, patients with vascular reactivity dysfunction (intermediate vascular reactivity and poor vascular reactivity; odds ratio (OR) = 1.100; 95% confidence interval (CI) = 1.047–1.155; P < 0.001) or poor vascular reactivity (OR = 1.580, 95% CI = 1.002–2.492, P = 0.049) also noted TMAO was positively associated with poor vascular reactivity after multivariate logistic regression analysis.

Conclusions:
Serum TMAO levels were negatively associated with VRI and associated with endothelial dysfunction in patients with hypertension.