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Aims: Long noncoding RNAs (lncRNAs) play key roles in the pathophysiology of DKD involving actions of microRNAs (miRNAs). The aims of the study were to establish the involvement of selected lncRNAs in the epigenetic mechanisms of podocyte damage and tubular injury in DKD of type 2 diabetes mellitus (DM) patients in relation to a particular miRNAs profile. Methods: A total of 136 patients with type 2 DM and 25 healthy subjects were assessed in a cross-sectional study concerning urinary albumin: creatinine ratio (UACR), eGFR, biomarkers of podocyte damage (synaptopodin, podocalyxin) and of proximal tubule (PT) dysfunction (Kidney injury molecule-1-KIM-1, N-acetyl-D-glucosaminidase-NAG), urinary lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), nuclear-enriched abundant transcript 1 (NEAT1), myocardial infarction-associated transcript (MIAT), taurine-upregulated gene 1 (TUG1), urinary miRNA21, 124, 93, 29a. Results: Multivariable regression analysis showed that urinary lncMALAT1 correlated directly with urinary synaptopodin, podocalyxin, KIM-1, NAG, miRNA21, 124, UACR, and negatively with eGFR, miRNA93, 29a (p

To describe the incidence and the characteristics of pregnancies complicated by hypertensive disorders of pregnancy (HDP) in one of the largest maternity hospitals in Romania.A retrospective cohort study including all deliveries at ≥24 weeks' gestation was performed.The incidence of preeclampsia was 1.2%, of gestational hypertension 2.2% and of chronic hypertension 0.4%. Pregnancies with HDP had higher rates of stillbirth, birthweight10Incidence of HDP in our population was relatively low, and was associated with early gestational age and adverse perinatal outcomes.

Background and Objectives: Hepatic diseases are an important public health problem. All patients with chronic hepatitis C virus (HCV) infection receive treatment, regardless of hepatic fibrosis severity. However, evaluation of hepatic fibrosis and steatosis is still useful in assessing evolution, prognosis and monitoring of hepatic disease, especially after treatment with direct-acting antivirals (DAAs). The aim of this study was to assess the link between patatin-like phospholipase domain-containing 3 (PNPLA3) polymorphism and the degree of hepatic steatosis and fibrosis in patients with chronic HCV infection, as well as changes in steatosis and fibrosis three monthsafter obtaining a sustained viral response (SVR). Materials and Methods:Ourstudy included 100 patients with chronic hepatitis C (CHC) infection and compensated cirrhosis who received DAA treatment and who were evaluated using Fibromax prior to and 3 months after SVR. The influence of PNPLA3 (CC, CG, GG) genotype among these patients on the degree of post-treatment regression of steatosis and fibrosis was assessed. Results: Regression was noticed in the degree of both hepatic steatosis and hepatic fibrosis post-DAA treatment (three months after SVR). Analysis of the correlation between PNPLA3 genotype and fibrosis indicated that the average level of fibrosis (F) before DAA treatment was higher in patients with the GG genotype than in patients with the CC or CG genotype. Three months after SVR, the average level of fibrosis decreased, however, it remained significantly increased in GG subjects compared to that in CC or CG patients. The degree of hepatic steatosis before treatment was not significantly different among patients with different PNPLA3 genotypes, and no significant correlations were observed three months after SVR. Conclusions: The genetic variants of PNPLA3 influence the evolution of hepatic fibrosis. The GG subtype plays an important role in the degree of hepatic fibrosis both before and after treatment (three months after SVR)and could be a prognostic marker for assessment of post-SVR evolution.

This paper presents the case of a 58-year-old heavy smoker female who came to our clinic with acute pain, as well as mastication and feeding difficulties. The macroscopic examination revealed oral erosive lesions and ulcerations. The polymorphic aspect of the lesions required the differential diagnosis of oral erythroplakia or carcinoma, which were excluded by biopsy. At the same time, we assessed the expression of S100 protein, Ki67 and the cluster of differentiation (CD) 4, CD8 (T-cell) and CD20 (B-cell) immune cell markers by immunohistochemical analysis. As a result, after the clinical and pathological assessment, the diagnosis of oral lichen planus was established, and a therapy plan was conducted. We observed a favorable clinical evolution after the administration of corticosteroids and immunomodulatory agents.

Objectives The purpose of this study was to evaluate the association between the follicle-stimulating hormone (FSH) receptor (c.-29G>A) and FSH beta chain (c.-280G>T) polymorphisms and endometriosis in Romanian women. Material and methods We performed the polymorphic analysis of the FSH receptor gene and FSH beta chain in 44 patients with endometriosis and 34 controls. Genomic DNA was obtained from peripheral blood and polymorphisms were investigated using restriction fragment length polymorphism analysis (RFLP). Results There were no significant differences in genotype frequencies of FSH receptor gene between endometriosis patients and controls. For the heterozygous type of the FSH receptor polymorphism (c.-29G>A) we did not find a significant difference in its frequency between patients with minimal/mild and moderate/severe endometriosis (p = 0.136). Also, the FSH beta chain (c.-280G> T) polymorphism frequency was not significantly associated with the severity of endometriosis (p = 0.966). Conclusions FSH receptor and FSH beta chain polymorphisms do not seem to influence the severity of endometriosis, but they could be correlated with female infertility (primary or secondary), therefore further studies are required to debate this topic.

Aim: The involvement of proinflammatory interleukins (IL) in diabetic kidney disease of Type 2 diabetes mellitus (DM) patients was studied in relation to a particular miRNA profile. Materials & methods: A total of 117 patients with Type 2 DM and 11 controls were enrolled in a case series study. Serum and urinary ILs and miRNAs were assessed. Results: IL-1α correlated with miRNA21, 124, estimated glomerular filtration rate (eGFR) and negatively with miRNA125a and 192; IL-8 with miRNA21, 124, eGFR and negatively with miRNA125a, 126 and 146a; IL-18 with miRNA21, 124 and negatively with miRNA146a, 192, eGFR. Conclusion: There is an association between specific serum and urinary ILs and serum and urinary miRNAs profiles in the inflammatory response in Type 2 DM patients with diabetic kidney disease.

Objective. Our research aims to assess a possible connection between tumour localization and histological subtypes of grade II meningiomas. Material and methods. 143 patients with grade II WHO meningiomas underwent surgical resection in "Prof. Dr. N. Oblu" Emergency Clinical Hospital Ia?i between 1990 and 2015. The collected data included: patient age, gender, tumour localization and histopathological diagnosis (atypical, clear cells and chordoid meningioma). Results. 135 (94.4%) of all 143 patients with grade II meningiomas were atypical meningiomas, 6 (4.2%) were cell clear meningiomas and only 2 (1.4%) were chordoid meningiomas. As concerns their distribution by gender, 79 (55.2%) were female and 64 (44.8%) were male. Grade II meningiomas were most commonly located at convexity 49.7% (n=71), followed by skull base in 30.8% (n=44) of the cases and parasagittal/falcine in 14.7% (n=21) of the patients. Conclusions. The most common localization of grade II meningiomas was convexity, followed by skull base, parasagittal/falcine and intraventricular areas. We have also noticed that convexity meningiomas are more frequent in women, unlike the other anatomical localizations in which the male-female ratio is almost equal. Therefore, further research is necessary to determine the role of embryological, anatomopathological and genetic factors in underlying the connection between meningioma grade and anatomical localization.

Clostridioides difficile (C. difficile) is a common cause of nosocomial diarrhea. The multi-modal infection control strategies designed to contain the COVID-19 pandemic have had an unintended positive effect on other hospital-acquired infections. The aim of the present study was to analyze the impact of the COVID-19 prevention measures on healthcare-associated C. difficile infections in a large regional acute care center. Electronic databases were reviewed from the start of the pandemic (March) up to November 2020. Average values from the same months from 2019 and 2018 were used as controls. Using the ICD-10 discharge coding, 65 C. difficile cases per 25,124 patients were identified in 2020 compared to 151/43,126 from the 2018 and 2019 averages (P=0.0484). The C. difficile cases were found to be decreased after the implementation of COVID-19 infection control strategies compared to previous years, despite an increase in antibiotic use. Subset analysis during lockdown showed a clear decrease but the difference was not statistically significant. For the months of recovery after lockdown, the number of cases was comparable to previous years.

Pallister–Killian syndrome (PKS) is a rare, sporadic disorder defined by a characteristic dysmorphic face, pigmentary skin anomalies, intellectual disability, hypotonia, and seizures caused by 12p tetrasomy due to an extra isochromosome 12p. We present three cases of PKS and two cases of trisomy 12p to illustrate and discuss features rarely cited in the literature, present certain particularities that not yet been cited, and analyze the differences between entities. Moreover, we present alternative methods of diagnosis that could be easily used in daily practice. Features not yet or rarely reported in PKS literature include marked excess of hair on the forehead and ears in the first months of life, a particular eye disorder (abnormal iris color with pointed pupil), connective tissue defects, repeated episodes of infection and autonomic dysfunction, endocrine malfunction as a possible cause of postnatal growth deficit, more complex sensory impairments, and mild early myoclonic jerks. After performing different combinations of tests, we conclude that MLPA (follow-up kit P230-B1) or array CGH using DNA extracted from a buccal swab is a reliable method of diagnosis in PKS and we recommend either one as a first intention diagnostic test. In cases without major defects associated (suspicion trisomy 12p), subtelomeric MLPA should be performed first.

Many developments were made in the area of endovascular treatment of intracranial aneurysms, but this procedure also requires a good assessment of vascular anatomy prior to intervention. Seventy-six cases with brain aneurysms were selected and 1:1 scale 3D printed models were created. We asked three interventional neurosurgeons with different degrees of experience (ten years, four years, and a fourth-year resident) to review the cases using CTA (computed tomography angiogram) with MPR (multiplanar reconstructions) and VRT (volume rendering technique) and make a decision: coil embolization or stent-assisted coil embolization. After we provided them with the 3D printed models, they were asked to review their treatment plan. Statistical analysis was performed and the endovascular approach changed in 11.84% of cases for ten-year experienced neurosurgeons, 13.15% for four years experienced neurosurgeon, and 21.05% for residents. The interobserver agreement was very good between the ten years experienced interventionist and four years experienced interventionist when they analyzed the data set that included the 3D printed model. The agreement was higher between all physicians after they examined the printed model. 3D patient-specific printed models may be useful in choosing between two different endovascular techniques and also help the residents to better understand the vascular anatomy and the overall procedure.

Background and Objectives: Heart failure with preserved ejection fraction (HFpEF) remains a worldwide management problem. Although there is a general effort for characterizing this population, few studies have assessed the predictive value of the echocardiographic E/e’ ratio in patients with acute HFpEF. The aim of the study was to identify groups with different prognosis in patients hospitalized with a first acute episode of HFpEF. Materials and Methods: The primary endpoint of the study was heart failure readmissions (HFR) at 6 months, while the secondary outcome was six-month mortality. We consecutively enrolled 91 patients hospitalized for the first time with acute HFpEF. We examined the E/e’ ratio as an independent predictor for HFR using univariate regression. Results: We identified and validated the E/e’ ratio as an independent predictor for HFR. An E/e’ ratio threshold value of 13.80 was calculated [(area under the receiver operating characteristic curve (AUROC) = 0.693, sensitivity = 78.60%, specificity = 55%, p &lt, 0.004)] and validated as an inflection point for an increased number of HFR. Thus, we divided the study cohort into two groups: group 1 with an E/e’ ratio &lt, 13.80 (n = 39) and group 2 with an E/e’ ratio &gt, 13.80 (n = 49). Compared to group 1, group 2 had an increased number of HFR (p = 0.003) and a shorter time to first HFR (p = 0.002). However, this parameter did not influence all-cause mortality within six months (p = 0.84). Conclusions: The dimensionless E/e’ ratio is a useful discriminator between patients with acute HFpEF. An E/e’ value over 13.80 represents a simple, yet effective instrument for assessing the HFR risk. However, all-cause mortality at six months is not influenced by the E/e’ ratio.

Background: The first admission for acute heart failure with preserved ejection fraction (HFpEF) drastically influences the short-term prognosis. Baseline characteristics may predict repeat hospitalization or death in these patients. Methods: A 103 patient-cohort, admitted for the first acute HFpEF episode, was monitored for six months. Baseline characteristics were recorded and their relation to the primary outcome of heart failure readmission (HFR) and secondary outcome of all-cause mortality was assessed. Results: We identified six independent determinants for HFR: estimated glomerular filtration rate (eGFR) (p = 0.07), hemoglobin (p = 0.04), left ventricle end-diastolic diameter (LVEDD) (p = 0.07), E/e’ ratio (p = 0.004), left ventricle outflow tract velocity-time integral (LVOT VTI) (p = 0.045), and diabetes mellitus (p = 0.06). Three of the variables were used to generate a risk score for HFR: LVEDD, E/e’, LVOT VTI -DEI Score = − 28.763 + 4.558 × log (LVEDD (mm)) + 1.961 × log (E/e’ ratio) + 1.759 × log (LVOT VTI (cm)). Our model predicts a relative amount of 20.50% of HFR during the first 6 months after the first acute hospitalization within the general population with HFpEF with a DEI Score over −0.747. Conclusions: We have identified three echocardiographic parameters (LVEDD, E/e’, and LVOT VTI) that predict HFR following an initial acute HFpEF hospitalization. The prognostic DEI score demonstrated good accuracy.

Association between phenotype and follicle-stimulating hormone (FSH) receptor and FSH beta chain genotype was evaluated in women with ovarian dysfunction. FSH receptor gene single nucleotide polymorphisms (SNPs) were analyzed by restricted fragment length polymorphism (RFLP) technique. Three groups were analyzed: two groups formed of poor responders (women with ovarian dysfunctions caused by endometriosis and patients who underwent ovarian stimulation protocols) and a third good responders group (normal-ovulatory women who gave birth to naturally conceived children). A higher average level of basal FSH values were found in mutants in the A919G/Ala307Thr/rs6165 or A2039G/Asn680Ser/rs6166 tests (7.16±1.09; P=0.659). Anti-mullerian hormone (AMH) below 1.2 ng/ml was associated with a higher frequency of mutations: 33.3% A919G/Ala307Thr and A2039G/Asn680Ser (P=0.137) and also in 66.6% FSH receptor less frequent polymorphism (c.-29G>A) rs 1394205 (P=0.522). The age, day 3 FSH, and AMH levels are widely used to investigate female infertility. However, we have not yet found the ideal biomarker to determine the best outcome and treatment plan for our patients. We cconsider that genetic markers will become the future in the personalization of controlled ovarian stimulation treatment in the upcoming period.

Background Familial hypercholesterolemia(FH) is one of the most frequent and important monogenic cholesterol pathologies. Traditional and non-traditional cardiovascular risk factors increase the prevalence of atherosclerotic cardiovascular disease(ASCVD) in this population. The aims of the study were: (a) to identify FH patients in the North-Eastern part of Romania and to analyze demographic, clinical and paraclinical data (b) to evaluate the risk of new cardiovascular events at follow-up in FH patients stratified by lipid-lowering agents. Methods This first prospective study in the North-Eastern part of Romania was carried out between October 2017 and October 2019; out of 980 patients with dyslipidemia evaluated with the Dutch Lipid Network(DLCN) and Simon Broome(SM) scores, 61 patients with DLCN score above 3 and possible/probable FH(SM score) were included. Results Nine hundred-eighty patients were examined and 61 (6.2%) were received the clinical diagnosis of FH. The mean age was 48.5±12.5 years, with more female patients than male patients (63.9% versus 36%). Hypertension was the main cardiovascular risk factor for both genders, followed by physical inactivity and obesity for the female group and active smoking for the male group. The measured DLCN score recorded: “possible” FH identified in 39.4%, “probable” FH in 45.9% and “definite” FH in 14.7%. The effective lipid-lowering drugs used were statin alone and statin in association with fenofibrate, which improved both the lipid profile values and the subclinical atherosclerosis markers (ankle-brachial index, carotid intima-media thickness and high-sensitivity C-reactive protein). New ASCVDs that emerged during the study were most commonly represented by coronary heart disease and stroke. At the same time, the new cardiovascular events were delayed in patients receiving the lipid-lowering drugs, without significant differences between them. Conclusions In patients with suspected FH, the lipid-lowering agents during the follow-up period delayed the new cardiovascular events, yet failed to reach the goals proposed by the guidelines.

There is a growing consensus that the antioxidant and anti-inflammatory properties of melatonin are of great importance in preserving the body functions and homeostasis, with great impact in the peripartum period and adult life. Melatonin promotes adaptation through allostasis and stands out as an endogenous, dietary, and therapeutic molecule with important health benefits. The anti-inflammatory and antioxidant effects of melatonin are intertwined and are exerted throughout pregnancy and later during development and aging. Melatonin supplementation during pregnancy can reduce ischemia-induced oxidative damage in the fetal brain, increase offspring survival in inflammatory states, and reduce blood pressure in the adult offspring. In adulthood, disturbances in melatonin production negatively impact the progression of cardiovascular risk factors and promote cardiovascular and neurodegenerative diseases. The most studied cardiovascular effects of melatonin are linked to hypertension and myocardial ischemia/reperfusion injury, while the most promising ones are linked to regaining control of metabolic syndrome components. In addition, there might be an emerging role for melatonin as an adjuvant in treating coronavirus disease 2019 (COVID 19). The present review summarizes and comments on important data regarding the roles exerted by melatonin in homeostasis and oxidative stress and inflammation related pathologies.

Background and Aims Interactions among multiple molecules and signalling pathways contribute to the pathogenesis and progression of diabetic kidney disease (DKD). Long noncoding RNAs (lncRNAs) play key roles in the pathophysiology of DKD involving actions of microRNAs (miRNAs). The aim of the study was to establish the involvement of selected lncRNAs in the epigenetic mechanisms of podocyte damage and tubular injury in DKD of type 2 diabetes mellitus (DM) patients. The molecular mechanisms of lncRNAs intervention were evaluated in relation to a particular miRNA profile. Method A total of 136 patients with type 2 DM and 25 healthy subjects were enrolled in a cross-sectional case series study and assessed concerning urinary albumin: creatinine ratio (UACR), eGFR, biomarkers of podocyte damage (synaptopodin, podocalyxin) and proximal tubule (PT) dysfunction (Kidney injury molecule-1-KIM-1, N-acetyl-D-glucosaminidase-NAG), urinary lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), nuclear-enriched abundant transcript 1 (NEAT1), myocardial infarction-associated transcript (MIAT), taurine-upregulated gene 1 (TUG1), and urinary miRNA21, 124, 93, 29a (quantified by a real-time PCR System). Results Multivariable regression analysis yielded models in which urinary lncRNA MALAT1 correlated directly with urinary synaptopodin, podocalyxin, KIM-1, NAG, miRNA21, 124, UACR, and negatively with eGFR, miRNA93 and 29a (p Conclusion In patients with type 2 DM lncRNAs exert distinct functions in different cell types, either deleterious or protective, at both glomerular and tubular level. LncRNAs may contribute to DKD through modulating miRNAs expression and activities. This observation holds true independently of albuminuria and DKD stage.

The presence of maternal Anti-Ro/Anti-La antibodies causes a passively acquired autoimmunity that may be associated with serious fetal complications. The classic example is the autoimmune-mediated congenital heart block (CHB) which is due in most cases to the transplacental passage of Anti-Ro/Anti-La antibodies. The exact mechanisms through which these pathologic events arise are linked to disturbances in calcium channels function, impairment of calcium homeostasis and ultimately apoptosis, inflammation and fibrosis. CHB still represents a challenging diagnosis and a source of debate regarding the best management. As the third-degree block is usually irreversible, the best strategy is risk awareness and prevention. Although CHB is a rare occurrence, it affects one in 20,000 live births, with a high overall mortality rate (up to 20%, with 70% of in utero deaths). There is also concern over the lifelong consequences, as most babies need a pacemaker. This review aims to offer, apart from the data needed for a better understanding of the issue at hand, a broader perspective of the specialists directly involved in managing this pathology: the rheumatologist, the maternal–fetal specialist and the cardiologist. To better illustrate the theoretical facts presented, we also include a representative clinical case.

Holt-Oram syndrome (HOS) is a rare monogenic disorder characterized by upper limb abnormalities, congenital heart defects and/or conduction abnormalities. It is determined by mutations of TBX5 gene and is inherited in an autosomal dominant manner. Penetrance is complete, but variable expressivity is present, which gives sometimes diagnostic difficulties. Our case is a young adult with a personal history of preaxial polydactyly operated in infancy, multiple cardiac malformations (atrial septal defect, bicuspid aortic valve, left ventricular non-compaction) and radiologic findings consistent with HOS. Family history is negative for HOS. In conclusion, we present a case of HOS diagnosed in the adult period to highlight the diagnostic problems for the proband and the family and the importance of an early diagnostic.

Blunt carotid artery injury is a relatively rare but potentially lethal injury that predominantly occurs in high-impact mechanisms such as motor-vehicle collision. Any simptoms or neurological deficits following a multiple trauma patient mandates a thorough evaluation and consideration of BCI. This is a case report on two young patients with neurologic simptoms developed after blunt trauma in the cervical region. Both patients had left internal carotid artery dissection diagnosed on a CT-angiography, followed by middle cerebral artery territory infarction. Although it can be a delayed onset with no signs of vascular demage, we believe that, by implementing a protocol with additional imaging for early detection, we can prevent a devastating outcome.

During gestation, the maternal body should increase its activity to fulfil the demands of the developing fetus as pregnancy progresses. Each maternal organ adapts in a unique manner and at a different time during pregnancy. In an organ or system that was already vulnerable before pregnancy, the burden of pregnancy can trigger overt clinical manifestations. After delivery, symptoms usually reside; however, in time, because of the age-related metabolic and pro-atherogenic changes, they reappear. Therefore, it is believed that pregnancy acts as a medical stress test for mothers. Pregnancy complications such as gestational hypertension, preeclampsia and gestational diabetes mellitus foreshadow cardiovascular disease and/or diabetes later in life. Affected women are encouraged to modify their lifestyle after birth by adjusting their diet and exercise habits. Blood pressure and plasmatic glucose level checking are recommended so that early therapeutic intervention can reduce long-term morbidity. Currently, the knowledge of the long-term consequences in women who have had pregnancy-related syndromes is still incomplete. A past obstetric history may, however, be useful in determining the risk of diseases later in life and allow timely intervention.

The aim of our study was to assess mRNA levels in visceral fat tissue and to correlate them with clinical-biological parameters in morbidly obese patients. 38 morbidly obese patients were selected and 8 cases of non obese subjects. The expression levels of adiponectin mRNA were determined through RT-PCR. Also we assessed biochemical parameters like seric glucose level, total cholesterol and triglicerides. The expression levels of adiponectin mRNA were correlated with demographic parameters (age, sex, BMI) and with clinical parameters (HTA, hypothyroidism and type 2 diabetes). This study showed significant correlations between adiponectin mRNA levels with obesity, age, triglicerids, total cholesterol and hypothyroidism. In conclusion, the expression level of adiponectin could be used as a molecular marker in the management of obesity.

Perinatal asphyxia (PA) is a burdening pathology with high short-term mortality and severe long-term consequences. Its incidence, reaching as high as 10 cases per 1000 live births in the less developed countries, prompts the need for better awareness and prevention of cases at risk, together with management by easily applicable protocols. PA acts first and foremost on the nervous tissue, but also on the heart, by hypoxia and subsequent ischemia-reperfusion injury. Myocardial development at birth is still incomplete and cannot adequately respond to this aggression. Cardiac dysfunction, including low ventricular output, bradycardia, and pulmonary hypertension, complicates the already compromised circulatory status of the newborn with PA. Multiorgan and especially cardiovascular failure seem to play a crucial role in the secondary phase of hypoxic-ischemic encephalopathy (HIE) and its high mortality rate. Hypothermia is an acceptable solution for HIE, but there is a fragile equilibrium between therapeutic gain and cardiovascular instability. A profound understanding of the underlying mechanisms of the nervous and cardiovascular systems and a close collaboration between the bench and bedside specialists in these domains is compulsory. More resources need to be directed toward the prevention of PA and the consecutive decrease of cardiovascular dysfunction. Not much can be done in case of an unexpected acute event that produces PA, where recognition and prompt delivery are the key factors for a positive clinical result. However, the situation is different for high-risk pregnancies or circumstances that make the fetus more vulnerable to asphyxia. Improving the outcome in these cases is possible through careful monitoring, identifying the high-risk pregnancies, and the implementation of novel prenatal strategies. Also, apart from adequately supporting the heart through the acute episode, there is a need for protocols for long-term cardiovascular follow-up. This will increase our recognition of any lasting myocardial damage and will enhance our perspective on the real impact of PA. The goal of this article is to review data on the cardiovascular consequences of PA, in the context of an immature cardiovascular system, discuss the potential contribution of cardiovascular impairment on short and long-term outcomes, and propose further directions of research in this field.

The term allergic angina, introduced for the first time by Nicholas Kounis in 1991, initially referred to the coexistence of acute coronary syndromes with allergy or hypersensitivity. At present, it is believed that Kounis syndrome is a particular case of systemic disease, with multiorgan arterial involvement generated during immediate hypersensitivity reactions. Myocardial bridging (MB), a condition that can induce coronary artery spasm, has long been regarded as a benign condition. Since both pathologies are associated with arterial spasm, Kounis syndrome and MB are considered to be confounding pathologies for acute coronary syndromes, and their association is quite a rare finding. To date, there are no precise data on the epidemiology, and the population affected by Kounis syndrome seems to be highly heterogeneous. Since this is a rare disease, even less is known about possible different phenotypes, including MB overlap. We report a case of type I variant Kounis syndrome associated with MB with no evidence of coronary artery disease, occurring as late presentation, following a severe systemic reaction (anaphylaxis) induced by a Hymenoptera sting. At present, only two other cases of type I and one case of type II Kounis syndrome occurring in patients with myocardial bridging have been described.

Purpose. Nontraditional cardiovascular risk factors as apolipoprotein A (ApoA), apolipoprotein B (ApoB), and the proprotein convertase subtilisin/kexin type 9 (PCSK9) increase the prevalence of cardiovascular mortality in chronic kidney disease (CKD) or in end-stage renal disease (ESRD) through quantitative alterations. This review is aimed at establishing the biomarker (ApoA, ApoB, and PCSK9) level variations in uremic patients, to identify the studies showing the association between these biomarkers and the development of cardiovascular events and to depict the therapeutic options to reduce cardiovascular risk in CKD and ESRD patients.Methods. We searched the electronic database of PubMed, Scopus, EBSCO, and Cochrane CENTRAL for studies evaluating apolipoproteins and PCSK9 in CKD and ESRD. Randomized controlled trials, observational studies (including case-control, prospective or retrospective cohort), and reviews/meta-analysis were included if reference was made to those keys and cardiovascular outcomes in CKD/ESRD.Results. 18 studies met inclusion criteria. Serum ApoA-I has been significantly associated with the development of new cardiovascular event and with cardiovascular mortality in ESRD patients. ApoA-IV level was independently associated with maximum carotid intima-media thickness (cIMT) and was a predictor for sudden cardiac death. The ApoB/ApoA-I ratio represents a strong predictor for coronary artery calcifications, cardiovascular mortality, and myocardial infarction in CKD/ESRD. Plasma levels of PCSK9 were not associated with cardiovascular events in CKD patients.Conclusions. Although the “dyslipidemic status” in CKD/ESRD is not clearly depicted, due to different research findings, ApoA-I, ApoA-IV, and ApoB/ApoA-I ratio could be predictors of cardiovascular risk. Serum PCSK9 levels were not associated with the cardiovascular events in patients with CKD/ESRD. Probably in the future, the treatment of dyslipidemia in CKD/ESRD will be aimed at discovering new effective therapies on the action of these biomarkers.

Introduction: Nowadays, obesity is a major worldwide health problem due to its serious consequences and toits increasing prevalence. Bariatric surgery has demonstrated a sustained weight loss and an efficient long-term control of the co-morbidities associated with obesity. The objective of our study was to compare cardiovascular risk factors before and after bariatric surgery. Material and Method: We have retrospectively studied 59 consecutive patients scheduled for bariatric surgery (gastric sleeve) in Ponderas Academic Hospital between January and March 2016, excluding the ones that didn't commit to respect the follow-up terms. The preoperative, 6 and 12 postoperative months blood tests and anthropometric measurements were comparatively analyzed. Results: BMI, waist circumference and total body weight decreased by 38%, 31%, and 41%; Glycemia, triglycerides and LDL cholesterol decreased by 16%, 37% and 9% respectively; HDL cholesterol increased by 18%. The decline was statistically significant for all variables (P 0.001) except for LDL cholesterol. The need for antihypertensive treatment was reduced by 60% and for lipid lowering treatment diminished by 21%. In diabetic patients glycated hemoglobin (HbA1c) decreased by 28% and the necessity for antidiabetic medical treatment dropped by 69%. Conclusions: Weight loss obtained by bariatric surgery in this study, improved the metabolic syndrome in all its components, obesity, hyperglycemia/type 2 diabetes, hypertension, and dyslipidemia, thus reducing the cardiovascular risk.

Background: The association of vascular remodeling in the kidney and the brain with a particular microRNAs (miRNA) profile is not well studied.Methods: Seventy-six patients with Type 2 diabetes and 11 healthy subjects were assessed concerning urine albumin: creatinine ratio (UACR), biomarkers of podocyte injury and of proximal tubule (PT) dysfunction. MiRNA were quantified in blood and urine by a real-time PCR System. Cerebrovascular ultrasound measurements were performed in the carotid and middle cerebral arteries.Results: MiRNA21 and miRNA124 correlated positively with nephrin, podocalyxin, synaptopodin, urinary N-acetyl-D-glucosaminidase (NAG), urinary kidney-injury molecule-1 (KIM-1), UACR, and negatively with eGFR; miRNA125a, 126, 146a, 192 correlated negatively with nephrin, podocalyxin, synaptopodin, urinary NAG, urinary KIM-1, UACR, and directly with eGFR. Plasma miRNA-21 and miRNA192 correlated directly with cerebral hemodynamics parameters of atherosclerosis and arteriosclerosis. MiRNA-124, 125a, 126, 146a showed negative correlations with the same parameters.Conclusions: In Type 2 diabetes patients there is an association of vascular remodeling in the brain and the kidney with a specific miRNAs pattern. Cerebrovascular changes occur even in normoalbuminuric patients, with 'high-to-normal' levels of podocyte injury and PT dysfunction biomarkers. These phenomena may be explained by the variability of miRNA expression within the two organs in early DKD.

Olfactory neuroblastoma, also known as esthesioneuroblastoma (ENB), is a rare malignant tumour of the basal layer of the olfactory epithelium, which originally develops unilaterally, accounting for 3-6% of all intranasal tumours. We present the case of a patient with a voluminous ethmoidal lesion that invaded the left basal frontal lobe and left orbit. The biopsy revealed a stage C KADISH, grade III neuroblastoma. The patient followed a multimodal treatment with chemotherapy and radiation therapy to which he responded partially, then returned after 11 months for sphincter disorder and bilateral sciatic type pain. An MRI showed metastasis of the filum terminale, the anatomopathological exam identifying also neuroblastoma. CT and MRI imaging are required for a correct assessment of the regional extension of olfactory neuroblastoma, response to oncological treatment but also for the detection of secondary lesions found in a small number of cases.

Wolf–Hirschhorn syndrome (WHS), a rare disorder determined by distal 4p deletion, is characterized by a pre and postnatal growth retardation, hypotonia, intellectual disability, epilepsy, craniofacial dysmorphism, and congenital fusion anomalies. The clinical aspects are dependent on the deletion’ size. Our aim was to identify rare specific characteristics in a cohort of seven cases with 4p deletion and to assess the utility of Multiplex ligation-dependent probe amplification (MLPA) (cheap and sensitive test)—combined kits—as a diagnostic test and selection tool for cases that require other investigations (chromosomal microarray analysis—CMA, karyotype). For all cases we conducted a clinical examination with the main features identified: facial dysmorphism, intellectual disability, postnatal development delay, cardiac defects and hypotonia. In some cases, we observed seizures, structural brain abnormalities, immunodeficiencies, and renal anomalies. Prenatal growth retardation was detected in a relatively small number of cases, but postnatal growth failure was a constant feature. In all cases, the clinical diagnosis was confirmed by genetic analyses: karyotype and/or MLPA. In conclusion, renal and brain defects, as well as immunodeficiency are rare manifestations and should be looked for. Although CMA is the standard test, in our experience, MLPA is also a reliable screening method as the identified cases were either confirmed by MLPA or selected for further investigations.

Even though the new thresholds for defining prediabetes have been around for more than ten years, there is still controversy surrounding the precise characterization of this intermediate glucose metabolism status. The risk of developing diabetes and macro and microvascular disease linked to prediabetes is well known. Still, the prediabetic population is far from being homogenous, and phenotyping it into less heterogeneous groups might prove useful for long-term risk assessment, follow-up, and primary prevention. Unfortunately, the current definition of prediabetes is quite rigid and disregards the underlying pathophysiologic mechanisms and their potential metabolic progression towards overt disease. In addition, prediabetes is commonly associated with a cluster of risk factors that worsen the prognosis. These risk factors all revolve around a common denominator: inflammation. This review focuses on identifying the population that needs to be screened for prediabetes and the already declared prediabetic patients who are at a higher risk of cardiovascular disease and require closer monitoring.

Fetal arrhythmias are mostly benign and transient. However, some of them are associated with structural defects or can cause heart failure, fetal hydrops, and can lead to intrauterine death. The analysis of fetal heart rhythm is based on ultrasound (M-mode and Doppler echocardiography). Irregular rhythm due to atrial ectopic beats is the most common type of fetal arrhythmia and is generally benign. Tachyarrhythmias are diagnosed when the fetal heart rate is persistently above 180 beats per minute (bpm). The most common fetal tachyarrhythmias are paroxysmal supraventricular tachycardia and atrial flutter. Most fetal tachycardias can be terminated or controlled by transplacental or direct administration of anti-arrhythmic drugs. Fetal bradycardia is diagnosed when the fetal heart rate is slower than 110 bpm. Persistent bradycardia outside labor or in the absence of placental pathology is mostly due to atrioventricular (AV) block. Approximately half of fetal heart blocks are in cases with structural heart defects, and AV block in cases with structurally normal heart is often caused by maternal anti-Ro/SSA antibodies. The efficacy of prenatal treatment for fetal AV block is limited. Our review aims to provide a practical guide for the diagnosis and management of common fetal arrythmias, from the joint perspective of the fetal medicine specialist and the cardiologist.

Background: Diabetic nephropathy is a severe complication of Type 2 diabetes. Tubular lesions may play an important role in its early stages. The aim of our study was to determine if atorvastatin protects the podocytes and the proximal tubule in patients with Type 2 diabetes. Methods: A total of 63 patients with Type 2 diabetes completed this 6-months prospective pilot study. They were randomized to continue rosuvastatin therapy (control group) or to be administered an equipotent dose of atorvastatin (intervention group), and were assessed regarding urinary podocytes, podocyte-associated molecules, and biomarkers of proximal tubule dysfunction. Results: The patients from the intervention group presented a significant reduction in podocyturia (from 7.0 to 4.0 cells/ml, p

Background: We have investigated the main genetic causes for non-syndromic hearing impairment (NSHI) in the hearing impairment individuals from the North-Eastern Romania and proposed a cost-effective diagnosis protocol. Methods: MLPA followed by Sanger Sequencing were used for all 291 patients included in this study. Results: MLPA revealed abnormal results in 141 cases (48.45%): 57 (40.5%) were c.35delG homozygous, 26 (18.44%) were c.35delG heterozygous, 14 (9.93%) were compound heterozygous and 16 (11.35%) had other types of variants. The entire coding region of GJB2 was sequenced and out of 150 patients with normal results at MLPA, 29.33% had abnormal results: variants in heterozygous state: c.71G&gt, A (28%), c.457G&gt, A (20%), c.269T&gt, C (12%), c.109G&gt, A (12%), c.100A&gt, T (12%), c.551G&gt, C (8%). Out of 26 patients with c.35delG in heterozygous state, 38.46% were in fact compound heterozygous. Conclusions: We identified two variants: c.109G&gt, A and c.100A&gt, T that have not been reported in any study from Romania. MLPA is an inexpensive, rapid and reliable technique that could be a cost-effective diagnosis method, useful for patients with hearing impairment. It can be adaptable for the mutation spectrum in every population and followed by Sanger sequencing can provide a genetic diagnosis for patients with different degrees of hearing impairment.

Retroperitoneal spontaneous hematoma is a serious condition, sometimes fatal. It occurs in association with anticoagulant therapy, unrelated to any trauma, surgery, invasive procedures or aortic aneurysm.A 68-year-old male patient is admitted for a non ST elevation myocardial infarction. He has a history of ischemic dilated cardiomyopathy with severe systolic dysfunction and atrial fibrillation. He is started on double antiplatelet therapy, anticoagulation, statin, beta blocker, ACE, and iv diuretic. Eight days later he suffers a syncope and the clinical examination reveals a large tender abdominal mass. The computed tomography examination shows a massive retroperitoneal hematoma. Although the antiplatelet and anticoagulant therapy is discontinued, the volume resuscitation (with crystalloids and packed red blood cells) is initiated and vasoconstrictor drugs are used, his condition continues to deteriorate. He is taken to the operation room for emergency laparotomy and the hematoma is evacuated. Although his clinical status improved and he remained hemodinamically stable, he suffers a cardiac arrest 27 days later and the resuscitation maneuvers are unsuccessful.

MicroRNAs (miRNAs) are short non-coding RNA species that are important post-transcriptional regulators of gene expression. The aim of the study was to establish a potential explanation of podocyte damage and proximal tubule (PT) dysfunction induced by deregulated miRNAs expression in the course of type 2 diabetes mellitus (DM). A total of 68 patients with type 2 DM and 11 healthy subjects were enrolled in a cross-sectional study and assessed concerning urinary albumin:creatinine ratio (UACR), urinary N-acetyl-β-D-glucosamininidase (NAG), urinary kidney injury molecule-1, urinary nephrin, podocalyxin, synaptopodin, estimated glomerular filtration rate (eGFR), urinary miRNA21, miRNA124, and miRNA192. In univariable regression analysis, miRNA21, miRNA124, and miRNA192 correlated with urinary nephrin, synaptopodin, podocalyxin, NAG, KIM-1, UACR, and eGFR. Multivariable regression analysis yielded models in which miRNA192 correlated with synaptopodin, uNAG, and eGFR (R2=0.902; P2=0.881; P2=0.882; P

Aim The study assessed mRNA expression of podocyte-associated molecules in urinary sediments of patients with type 2 diabetes mellitus (DM) in relation to urinary podocytes, biomarkers of podocyte injury and of proximal tubule (PT) dysfunction. Methods A total of 76 patients with type 2 DM and 20 healthy subjects were enrolled in a cross-sectional study, and assessed concerning urinary podocytes, urinary mRNA of podocyte-associated genes, urinary biomarkers of podocyte damage and of PT dysfunction. Results We found significant differences between urinary mRNA of podocyte-associated molecules in relation with albuminuria stage. In multivariable regression analysis, urinary mRNA of nephrin, podocin, alpha-actinin-4, CD2-associated protein, glomerular epithelial protein 1 (GLEPP1), ADAM 10, and NFκB correlated directly with urinary podocytes, albuminuria, urinary alpha1-microglobulin, urinary kidney-injury molecule-1, nephrinuria, urinary vascular endothelial growth factor, urinary advanced glycation end-products (AGE), and indirectly with eGFR (p

There is a stringent need to find means for risk stratification of coronary artery diseases (CAD) patients. We aimed at identifying alterations of plasma high-density lipoproteins (HDL) components and their validation as dysfunctional HDL that could discriminate between acute coronary syndrome (ACS) and stable angina (SA) patients. HDL2 and HDL3 were isolated from CAD patients’ plasma and healthy subjects. ApolipoproteinAI (apoAI), apoAII, apoCIII, malondialdehyde (MDA), myeloperoxidase (MPO), ceruloplasmin and paraoxonase1 (PON1) were assessed. The anti-inflammatory potential of HDL subfractions was tested by evaluating the secreted inflammatory molecules of tumor necrosis factor α-activated endothelial cells (EC) upon co-incubation with HDL2 or HDL3. We found in ACS versus SA patients: 40% increased MPO, MDA, apoCIII in HDL2 and HDL3, 35% augmented apoAII in HDL2, and in HDL3 increased ceruloplasmin, decreased apoAII (40%) and PON1 protein and activity (15% and 25%). Co-incubation of activated EC with HDL2 or HDL3 from CAD patients induced significantly increased levels of secreted inflammatory molecules, 15–20% more for ACS versus SA. In conclusion, the assessed panel of markers correlates with the reduced anti-inflammatory potential of HDL subfractions isolated from ACS and SA patients (mostly for HDL3 from ACS) and can discriminate between these two groups of CAD patients.

Aims To evaluate if there is a link between inflammation (expressed by inflammatory cytokines) and the early stage of diabetic kidney disease (DKD), as shown by markers of podocyte damage and proximal tubular (PT) dysfunction. Methods In this study were enrolled 117 type 2 DM patients (36-normoalbuminuria, 42-microalbuminuria, 39- macroalbuminuria), and 11 healthy subjects. Serum and urinary IL-1 alpha, IL-8, IL-18, urinary albumin:creatinine ratio (UACR), eGFR, biomarkers of podocyte damage (podocalyxin, synaptopodin, nephrin) and of PT dysfunction (KIM-1, NAG) were assessed. Results In multivariable regression urinary Il-1 alpha correlated positively with podocalyxin and NAG (p Conclusions Pro-inflammatory interleukins are associated with podocyte injury and PT dysfunction in early DKD. These could exert a key role in the pathogenesis of early DKD, before the development of albuminuria.

Dizabilitatea intelectuală (DI) este o afecțiune frecventă, cu consecințe majore pentru individ, familie și societate. Datorită heterogenității sale clinice și genetice, în aproximativ 50% din cazuri etiologia bolii nu poate fi stabilită. Scopul acestui studiu a fost evaluarea capacității de stabilire a diagnosticului etiologic la 369 pacienți cu DI sindromic și rezultat normal sau incert la cariotip folosind o combinație de kituri MLPA. Toţi pacienţii au fost investigaţi prin metoda MLPA, folosind fie kiturile SALSA MLPA P064 sau P096, dacă fenotipul a fost sugestiv pentru un sindrom cu microdeleţie (subgrupul A - 186 pacienți), fie kiturile subtelomerice P036 și P070, dacă fenotipul nu a fost sugestiv pentru un sindrom cu microdeleţie sau rezultatul la cariotipul standard a fost incert (subgrupul B - 183 pacienți). Rezultatele anormale detectate de aceste kituri au fost caracterizate folosind kiturile MLPA corespunzătoare de urmărire (Telomere Follow-up set, P029-A1, P250-B2, ME028-B1). În subgrupul A am identificat 25 de pacienți cu microdeleții (13,4%). Folosind kiturile de screening subtelomeric și de urmărire la subgrupul B am detectat rearanjări criptice în 7,5% din cazuri și am identificat originea materialului suplimentar observat la cariotipul standard la 10 din 11 pacienți. Sumarizând datele obţinute din cele două loturi, folosirea combinată a seturilor MLPA a dus la stabilirea diagnosticului la 10,6% (38/358) dintre pacienții cu cariotip normal. Folosirea seturilor MLPA de urmărire a permis atât confirmarea prezenţei anomaliei, cât şi determinarea dimensiunii ei, ceea ce a facilitat interpretarea semnificaţiei clinice a rearanjărilor. Pentru laboratoarele care nu au acces la tehnologiile bazate pe microarray, folosirea mai multor kituri MLPA reprezintă o strategie eficientă pentru stabilirea diagnosticului etiologic la pacienţii cu DI.

Aims Detection of podocytes in the urine of patients with type 2 diabetes may indicate severe injury to the podocytes. In the course of type 2 diabetes the proximal tubule is involved in urinary albumin processing. We studied the significance of podocyturia in relation with proximal tubule dysfunction in type 2 diabetes. Methods A total of 86 patients with type 2 diabetes (34-normoalbuminuria; 30-microalbuminuria; 22-macroalbuminuria) and 28 healthy subjects were enrolled in the study and assessed concerning urinary podocytes, podocyte-associated molecules, and biomarkers of proximal tubule dysfunction. Urinary podocytes were examined in cell cultures by utilizing monoclonal antibodies against podocalyxin and synaptopodin. Results Podocytes were detected in the urine of 10% of the healthy controls, 24% of the normoalbuminuric, 40% of the microalbuminuric, and 82% of the macroalbuminuric patients. In multivariate logistic regression analysis, urinary podocytes correlated with urinary albumin:creatinine ratio (p = 0.006), urinary nephrin/creat (p = 0.001), urinary vascular endothelial growth factor/creat (p = 0.001), urinary kidney injury molecule-1/creat (p = 0.003), cystatin C (p = 0.001), urinary advanced glycation end-products (p = 0.002), eGFR (p = 0.001). Conclusions In patients with type 2 diabetes podocyturia parallels proximal tubule dysfunction independently of albuminuria and renal function decline. Advanced glycation end-products may impact the podocytes and the proximal tubule.

Objectives With more children receiving cochlear implants during infancy, there is a need for validated assessments of pre-verbal and early verbal auditory skills. The LittlEARS® Auditory Questionnaire is presented here as the first module of the LittlEARS® test battery. The LittlEARS® Auditory Questionnaire was developed and piloted to assess the auditory behaviour of normal hearing children and hearing impaired children who receive a cochlear implant or hearing aid prior to 24 months of age. This paper presents results from two studies: one validating the LittlEARS® Auditory Questionnaire on children with normal hearing who are German speaking and a second validating the norm curves found after adaptation and administration of the questionnaire to children with normal hearing in 15 different languages. Methods Scores from a group of 218 German and Austrian children with normal hearing between 5 days and 24 months of age were used to create a norm curve. The questionnaire was adapted from the German original into English and then 15 other languages to date. Regression curves were found based on parental responses from 3309 normal hearing infants and toddlers. Curves for each language were compared to the original German validation curve. Results The results of the first study were a norm curve which reflects the age-dependence of auditory behaviour, reliability and homogeneity as a measure of auditory behaviour, and calculations of expected and critical values as a function of age. Results of the second study show that the regression curves found for all the adapted languages are essentially equal to the German norm curve, as no statistically significant differences were found. Conclusions The LittlEARS® Auditory Questionnaire is a valid, language-independent tool for assessing the early auditory behaviour of infants and toddlers with normal hearing. The results of this study suggest that the LittlEARS® Auditory Questionnaire could also be very useful for documenting children's progress with their current amplification, providing evidence of the need for implantation, or highlighting the need for follow-up in other developmental areas.

We aimed to determine the levels of microRNAs (miRNAs) in sera and HDL of acute coronary syndrome (ACS) compared to stable angina (SA) patients with/without hyperglycemia, and evaluate comparatively the functional effect of these sera on the processing machinery proteins (Drosha, DGCR8, Dicer) and miRNAs production in human macrophages. MiRNAs levels in sera and HDL from 35 SA and 72 ACS patients and 30 healthy subjects were measured by using microRNA TaqMan assays. MiR-223, miR-92a, miR-486, miR-122, miR-125a and miR-146a levels were higher in the hyperglycemic ACS compared to normoglycemic sera. MiR-223 and miR-486 prevailed in HDL2, while miR-92a predominated in HDL3, all three miRNAs discriminating between ACS and SA patients; their levels were increased in HDL from hyperglycemic ACS patients versus normoglycemic ones. The incubation of human macrophages with sera from ACS and SA patients showed that all patients’ sera induced an increase of Drosha, DGCR8 and Dicer expressions and of selected miRNAs levels compared to control sera, the effect being higher in the case of hyperglycemic versus normoglycemic ACS sera. The addition of glucose to SA and ACS sera increased Drosha, DGCR8 and Dicer expression and miRNAs levels in the exposed macrophages. In conclusion, hyperglycemia is associated with increased miR-223, miR-92a, miR-486 levels in HDL, which discriminate between ACS and SA patients. Exposure of human macrophages to ACS compared to SA sera determines the upregulation of Drosha, DGCR8 and Dicer expression and the increase of selected miRNAs production, the effect being augmented by an increased glucose concentration.

Diabetic atherosclerosis and microangiopathy parallel diabetic nephropathy. The aim of our study was to evaluate the pattern of endothelial dysfunction in two vascular territories, the kidney and the brain, both affected by diabetic vasculopathic complications. The endothelial variability was evaluated in relation to advanced glycation end-products modified peptides.Seventy patients with type 2 diabetes mellitus and 11 healthy subjects were assessed concerning urine albumin: creatinine ratio, plasma and urinary advanced glycation end-products, plasma asymmetric dimethyl-arginine, serum cystatin C, intima-media thickness in the common carotid arteries, the pulsatility index, the resistance index in the internal carotid arteries and the middle cerebral arteries, the cerebrovascular reactivity through the breath-holding test.The breath-holding index correlated with asymmetric dimethyl-arginine (R²=0.151; p0.001), plasma advanced glycation end-products (R²=0.173; p0.001), C-reactive protein (R²=0.587; p0.001), duration of diabetes mellitus (R²=0.146; p=0.001), cystatin C (R²=0.220; p0.001), estimated glomerular filtration rate (R²=0.237; p=0.001). Urine albumin: creatinine ratio correlated with urinary advanced glycation end-products (R²=0.257; p0.001), but not with asymmetric dimethyl-arginine (R²=0.029; p=0.147).In type 2 diabetic patients endothelial dysfunction in the cerebral vessels appears to be dissociated from glomerular endothelial dysfunction in early diabetic nephropathy. Advanced glycation end-products could impact both the cerebral vessels and the glomerular endothelium.

Background There is an ongoing debate as to whether early diabetic nephropathy in Type 2 diabetes mellitus may be attributed to the glomerulus or to the proximal tubule. Urinary excretion of nephrin and vascular endothelial growth factor may increase even in the normoalbuminuria stage. In the course of diabetic nephropathy, the proximal tubule may be involved in the uptake of urinary nephrin and vascular endothelial growth factor. Materials and Methods Two groups of consecutive Type 2 diabetes mellitus outpatients (38 normo-, 32 microalbuminuric) and 21 healthy subjects were enrolled in a cross-sectional study and evaluated concerning the relation of proximal tubule dysfunction with the podocyte biomarkers excretion, assessed by ELISA methods. The impact of advanced glycation end-products on this relation was also queried. Results Urinary alpha1-microglobulin and kidney injury molecule-1 correlated with urinary albumin:creatinine ratio (R2 = 0.269; p