Therapeutical Approach to Arterial Hypertension - Current State of the Art.

Arterial hypertension (AH) is recognized as the most common illness within the group of cardiovascular diseases and the most massive chronic non-infectious disease in the world. The number of hypertensive patients worldwide has reached 1.28 billion, contributing to an increase in cardiovascular diseases and premature death globally. The high prevalence of hypertension emphasizes the importance of effectively treating this condition. Elevated blood pressure often leads to lethal complications (heart failure, stroke, renal disorders, etc.) if left untreated. Considering an increase in AH prevalence in the future, a successful therapeutical approach to this disease and its complications is essential. The goal of AH treatment is to maintain normotensive blood pressure through various approaches, including lifestyle changes, a well-balanced diet, increased physical activity, psychoeducation, and, when necessary, pharmacotherapy. The evolving pharmacotherapeutic landscape reflects the progress made in our understanding of hypertension and emphasizes the need for continuous innovation to meet the challenges posed by this prevalent global health concern. The journey toward more effective and tailored treatments for hypertension is ongoing, and the introduction of new medications plays a pivotal role in shaping the future of antihypertensive pharmacotherapy.

Anti-seizure Medications: Challenges and Opportunities.

Epilepsy is a chronic neurological condition characterized by unprovoked, recurrent seizures. There are several types of epilepsy, and the cause of the condition can vary. Some cases of epilepsy have a genetic component, while others may be caused by brain injuries, infections, or other underlying conditions. Treatment for epilepsy typically involves anti-seizure medications (ASMs), although different approaches, such as surgery or a special diet, may be considered in specific cases. The treatment aims to effectively manage and potentially eliminate seizures while minimizing any accompanying side effects. Many different ASMs are available, and the choice of medication depends on several factors, including the type of seizures, the patient's age, general health, and potential drug interactions. For the treatment of epilepsy, there have been significant advancements in recent decades, which have led to the approval of many different ASMs. Newer ASMs offer a broader range of mechanisms of action, improved tolerability profiles, and reduced drug interactions compared to older drugs. This review aims to discuss the pharmacological characteristics, clinical applications, effectiveness, and safety of ASMs, with a particular emphasis on various age groups, especially children. Moreover, this review seeks to provide a comprehensive understanding of ASM therapy for epilepsy management, assisting physicians in selecting suitable ASMs for their patients.

Ethical considerations on artificial intelligence in dentistry: A framework and checklist.

OBJECTIVE: Artificial Intelligence (AI) refers to the ability of machines to perform cognitive and intellectual human tasks. In dentistry, AI offers the potential to enhance diagnostic accuracy, improve patient outcomes and streamline workflows. The present study provides a framework and a checklist to evaluate AI applications in dentistry from this perspective. METHODS: Lending from existing guidance documents, an initial draft of the checklist and an explanatory paper were derived and discussed among the groups members. RESULTS: The checklist was consented to in an anonymous voting process by 29 Topic Group Dental Diagnostics and Digital Dentistry, ITU/WHO Focus Group AI on Health's members. Overall, 11 principles were identified (diversity, transparency, wellness, privacy protection, solidarity, equity, prudence, law and governance, sustainable development, accountability, and responsibility, respect of autonomy, decision-making). CONCLUSIONS: Providers, patients, researchers, industry, and other stakeholders should consider these principles when developing, implementing, or receiving AI applications in dentistry. CLINICAL SIGNIFICANCE: While AI has become increasingly commonplace in dentistry, there are ethical concerns around its usage, and users (providers, patients, and other stakeholders), as well as the industry should consider these when developing, implementing, or receiving AI applications based on comprehensive framework to address the associated ethical challenges.

Responsible Use of Artificial Intelligence in Dentistry: Survey on Dentists' and Final-Year Undergraduates' Perspectives.

The introduction of artificial intelligence (AI)-based dental applications into clinical practice could play a significant role in improving diagnostic accuracy and reforming dental care, but its implementation relies on the readiness of dentists, as well as the health system, to adopt it in everyday practice. A cross-sectional anonymous online survey was conducted among experienced dentists and final-year undergraduate students from the School of Dental Medicine at the University of Belgrade (n = 281) in order to investigate their current perspectives and readiness to accept AI into practice. Responders (n = 193) in the present survey, especially final-year undergraduates (n = 76), showed a lack of knowledge about AI (only 7.9% of them were familiar with AI use) and were skeptical (only 34% of them believed that AI should be used), and the underlying reasons, as shown by logistic regression analyses, were a lack of knowledge about the AI technology associated with a fear of being replaced by AI, as well as a lack of regulatory policy. Female dentists perceived ethical issues more significantly than men regarding AI implementation in the practice. The present results encourage an ethical debate on education/training and regulatory policies for AI as a prerequisite for regular AI use in dental practice.

Importance of decisional capacity tools in obtaining informed consent in clinical settings.

Informed consent represents a specific protocol for obtaining consent from a fully informed human subject to take part in clinical research. Still, informed consent is not only required for clinical trials but it also represents a critical precondition before enrolment in standard everyday medical procedures. Relevant fundamental criteria for obtaining informed consent must be followed, and that is that patient must have the decisional capacity to reach autonomous decision. The patient must be adequately informed and not coerced. Evaluating decisional capacity is crucial to providing the required level of care. The decision of which decisional capacity tool to use can be challenging because of various dissimilarities among the instruments. In this paper, four widely documented instruments have been evaluated, namely, the MacArthur Competence Assessment Tool for Treatment (MacCAT-T), the Hopkins Competency Assessment Test (HCAT), the Structured Interview for Competency/Incompetency Assessment Testing, Ranking Inventory (SICIATRI), and the Capacity Assessment Tool (CAT). Some of them include a fully structured interview; semi-structured forms characterise others. Most of them are adaptable for different scenarios, and yet, some are tailored for specific treatment decisions. Some evaluate all four components of decisional capacity, while others do not. Although a broad range of capacity assessment tools is available, it has been shown that they notably improve the accuracy of capacity evaluations. Given that many pathological conditions could result in impaired decisional capacity, physicians must be able to correctly and consistently assess the capacity for which education and previous experience are pivotal.

Acute Peripheral Facial Nerve Palsy in Children and Adolescents: Clinical Aspects and Treatment Modalities.

BACKGROUND: Peripheral facial nerve palsy is a relatively frequent, rather idiopathic, and isolated nonprogressive disorder with a tendency toward spontaneous recovery in children. It is primarily characterized by unilateral paresis or paralysis of the mimic musculature affecting verbal communication, social interactions, and quality of life. OBJECTIVE: This study aimed to evaluate the clinical aspects and efficacy of different therapeutic modalities in the population of children and adolescents with acute peripheral facial nerve palsy, the quality and recovery rate in comparison to different therapy modalities and etiological factors as well as to determine parameters of recovery according to the age of patients. METHODS: The retrospective study included children and adolescents (n=129) with an acute onset of peripheral facial nerve palsy, diagnosed and treated in the Clinic of Neurology and Psychiatry for Children and Youth in Belgrade (2000-2018). The mean age of the patients was 11.53 years (SD±4.41). Gender distribution: 56.6% female and 43.4% male patients. RESULTS: There were 118 (91.5%) patients with partial and 11 (8.5%) patients with complete paralysis. Left-sided palsy occurred in 67 (51.9%) patients, right-sided in 58 (45.0%), while there were 4 (3.1%) bilateral paralyses. The most common etiological factor was idiopathic (Bell's palsy) - 74 (57.4%) patients followed by middle ear infections - 16 (12.4%). Regardless of etiology, age, and therapy protocols, there was a significant recovery in most of the patients (p<0.001), without significant differences in recovery rate. Comparison of inpatient and outpatient populations showed significant differences regarding the number of relapses, severity of clinical presentation, and recovery rate in relation to etiology. CONCLUSION: Bell's palsy is shown to be the most common cause of peripheral facial nerve palsy in children and adolescents, regardless of gender. It is followed by mid-ear infections, respiratory infections, and exposure to cold. Most children and adolescents recovered in three weeks after initial presentation, regardless of etiology, age, and therapy.

Potentially Inappropriate Medications in Belgrade, Serbia Nursing Home Residents: A Comparison of Two Approaches.

There is currently limited information on the comparative effectiveness of the European Union(7)-potentially inappropriate medication (EU(7)-PIM) list and the Beers criteria for screening PIMs, of which PIMs are a significant concern, in the geriatric population of nursing home residents. This study aims to determine and compare the rates of PIMs detected with the Beers criteria (five sections of which the first is a list of inappropriate medications in older adults) and the EU(7)-PIM list (based on the first section of the Beers criteria). The study, conducted in Gerontology Center Belgrade (n = 427), is retrospective and observational. The EU(7)-PIM list detected 876 PIMs, while the first section of the Beers criteria detected 782 PIMs (1,803 with all five sections). The majority of PIMs belong to psychotropic drugs (benzodiazepines being the most common). The EU(7)-PIM list detected significantly more PIMs than the first section of the Beers criteria (2.03 ± 1.63 vs. 1.83 ± 1.27; p = .0005). The number of detected PIMs with both criteria correlates with age, the number of chronic illnesses, the number of medication prescribed, and the comorbidity status. Ultimately, the EU(7)-PIM list detected more PIMs compared to the first section of the Beers criterion.

GheOP3 S tool and START/STOPP criteria version 2 for screening of potentially inappropriate medications and omissions in nursing home residents.

RATIONALE, AIMS, AND OBJECTIVE: There is limited information about the comparative effectiveness of the START/STOPP (Screening Tool of Older Person's Prescriptions/Screening Tool to Alert doctors to Right Treatment) criteria and the Ghent Older People's Prescriptions community Pharmacy Screening tool (GheOP3 S tool) for the screening of potentially inappropriate prescribing (PIP) in the geriatric population. Considering this, the aim of this study was to compare the ability of the START/STOPP criteria and GheOP3 S tool to identify the PIP and potential prescribing omissions (PPOs) among elderly patients visiting their primary care physician. METHODS: This is a retrospective observational study where a total of 422 subjects were included. The Charlson Co-morbidity Index (CCI) and the Medicines Co-morbidity Index (MCI) for older people were used to determine the co-morbidity status. The user's diagnosis and medications prescribed were analysed with the START/STOPP criteria and GheOP3 S tool. The Wilcoxon signed rank test was used to compare these criteria. The statistical relationship between the occurrence of PIP and users' age, the number of medication prescribed, the number of diagnoses, CCI, and MCI was determined with one-tailed bivariate correlation. RESULTS: The START/STOPP criteria detected 843 PIPs and 1067 PPOs, while the GheOP3 S tool detected 936 PIPs and 202 PPOs. The GheOP3 S tool detected significantly more PIPs than did the STOPP criteria (P = 0.003). A significantly higher number of PPOs were detected with the START criterion (P < 0.0001). The results obtained with the START/STOPP criteria positively correlated with mentioned variables. Oppositely, there is a negative correlation between the results obtained with the GheOP3 S tool and age. Still, the positive correlation could be found with the rest of the variables. CONCLUSION: The results of this study indicate that both tested tools demonstrated efficiency to detect PIPs and PPOs. The GheOP3 S tool detected significantly more PIPs than did the STOPP criteria. On the other hand, the START criteria performed much better for the screening of PPOs.

Pioglitazone attenuates kidney injury in an experimental model of gentamicin-induced nephrotoxicity in rats.

Gentamicin, belonging to the aminoglycosides, possesses the greatest nephrotoxic effect of all other antibiotics from this group. On the other hand, pioglitazone, which represents peroxisome proliferator-activated receptor γ (PPARγ) agonist recently showed antiinflamatory, antioxidative effects, amelioration of endothelial dysfunction etc. Therefore, the goal of our study was to investigate the effects of pioglitazone on kidney injury in an experimental model of gentamicin-induced nephrotoxicity in rats. These effects were observed by following values of biochemical (serum urea and creatinine) parametars, total histological kidney score, urine level of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) as well as parametars of oxidative stress (malondialdehyde, superoxide dismutase, catalase, total oxidant status, total antioxidant status, oxidative stress index and advanced oxidation protein products). It seems that pioglitazone protects the injured rat kidney in a U-shaped manner. Medium dose of pioglitazone (1 mg/kg, i.p.) was protective regarding biochemical (serum urea and creatinine), total histological score and the values of kidney injury molecule-1 (KIM-1) (P < 0.05 vs. control group, i.e. rats injected with gentamicin only). This finding could be of great importance for the wider use of aminoglycosides, with therapy that would reduce the occurrence of serious adverse effects, such as nephrotoxicity and acute renal failure.

The enhancement of serotonin-induced contraction of rat femoral artery is mediated by angiotensin II release from intact endothelium.

We have performed an in vitro study on isolated intact or denuded femoral artery (FA) of healthy, diabetic, and/or rats submitted to the FA occlusion. The aim was to determine the contribution of endothelium and endothelial dysfunction (ED) on serotonin-induced action in FA. Further, the contribution of angiotensin II and cyclooxygenase products of arachidonic acid was investigated. A marker of ED, vWF was measured in animal serum. Serotonin induced contraction-dependent contraction of isolated FA, which was increased in preparations with endothelium. Pathological conditions such as endothelial denudation, nicotine-induced ED, diabetes or occlusion of FA reduced serotonin-induced contraction. Comparable reduction of serotonin-induced contraction was achieved after inhibition of AT1 receptors with losartan in isolated FA with intact endothelium. Our results demonstrate that angiotensin II contributes to the enhancement of serotonin-induced contraction of femoral arteries with intact endothelium. This increase is attenuated by endothelium removal, nicotine treatment, vascular occlusion, and/or hyperglycemia.

Calcium Channel Blockers in Restoration of Endothelial Function: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Clinical evaluation of the Endothelial Function (EF) is becoming an essential step in the quality assessment of cardiovascular risk prevention and rational pharmacotherapy of cardiovascular disorders. The existing pieces of evidence suggested that Calcium Channel Blockers (CCB) can induce positive effects on impaired EF. OBJECTIVE: To evaluate the effects of CCB on EF, we performed a meta-analysis of available data from randomized and placebo-controlled or other treatment-controlled clinical studies encompassing effects of CCB on EF, as measured by Flow-Mediated Dilation (FMD) of the brachial artery. METHODS: The relevant clinical studies were searched by systematic exploration of the appropriate databases until November 30, 2017. A random-effect model was conducted. The primary outcome was the percentage change in FMD between the baseline and the final levels in response to investigated drugs. RESULTS: Fifteen randomized clinical studies with 33 arms were identified. CCB improved FMD more pronounced than thiazide diuretics - TD (3 studies, 157 participants, WMD=2.08%, 95% CI=0.35-3.80%; P=0.02). Oppositely, ACE Inhibitors (ACEI) and Angiotensin Receptor Blockers (ARB) notably improved FMD if compared to CCB (CCB vs. ACEI: 5 studies, 533 participants, WMD = -1.62%, 95% CI = -2.74% to -0.50%; P=0.005; and CCB vs. ARB: 9 studies, 669 participants, WMD = -1.52%, 95% CI = -2.22% to -0.81%; P=0.0001). CCB effects on EF were similar to those evoked by beta blockers or placebo. CONCLUSION: CCB improved EF to a more prominent extent only if paralleled to TD, while inversely; ACEI and ARB were more effective in augmenting FMD.

"Dangerous duo": Chronic nicotine exposure intensifies diabetes mellitus-related deterioration in bone microstructure - An experimental study in rats.

AIMS: Bony complications of diabetes mellitus (DM) are still insufficiently understood. Our aims were to analyze the individual and combined effects of chronic hyperglycemia and nicotine exposure on the femoral trabecular and cortical microarchitecture on a rat experimental model. MAIN METHODS: The micro-computed tomography based bone microstructural evaluation was performed on male Wistar rats divided into four groups: control (n = 7), experimentally-induced DM (n = 8), chronically exposed to nicotine (n = 9) and the DM group exposed chronically to nicotine (n = 9). KEY FINDINGS: Chronic hyperglycemia caused mild trabecular deterioration; yet, the combination of hyperglycemia and nicotine exposure showed more deleterious effects on the trabecular bone. Namely, the DM + nicotine group had significantly lower bone volume fraction, fewer and more rod-like shaped trabeculae, along with higher trabecular separation and lower connectivity than the control group (p < 0.05). Nicotine alone did not show any significant deterioration compared to the control group. DM and DM + nicotine groups had lower cortical porosity than control and nicotine groups (p < 0.05). Cortical thickness did not show any significant intergroup differences, whereas bone perimeter and the mean polar moment of inertia were reduced in DM + nicotine group. SIGNIFICANCE: Mild effects of chronic hyperglycemia on bone structure were accentuated by the chronic nicotine exposure, although nicotine alone did not cause any significant bone changes. That suggests a synergistic effect of hyperglycemia and nicotine on bone deterioration and increased propensity to fracture. Indeed, better understanding of risk factors driving bone structural deterioration is a precondition to limit the complications associated with DM.

The role of artichoke leaf tincture (Cynara scolymus) in the suppression of DNA damage and atherosclerosis in rats fed an atherogenic diet.

CONTEXT: Polyphenols and flavonoids in artichoke leaf tincture (ALT) protect cells against oxidative damage. OBJECTIVES: We examined ALT effects on deoxyribonucleic acid (DNA) damage and lipid profiles in rat plasma and gene expression in rat aorta [haemeoxygenase-1 (HO1), haemeoxygenase-2 (HO2), NADPH oxidase 4 (NOX-4), monocyte chemoattractant protein-1 (MCP-1) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2)]. MATERIALS AND METHODS: Eighteen male Wistar albino rats were divided into three groups (n = 6/group): The control group (CG) was fed with standard pellet chow for 11 weeks; the AD group was fed for a similar period of time with pellet chow supplemented with 2% cholesterol, 3% sunflower oil and 1% sodium cholate. The ADA group was fed with pellet chow (for 1 week), the atherogenic diet (see above) for the following 4 weeks and then with ALT (0.1 mL/kg body weight) and atherogenic diet for 6 weeks. According to HPLC analysis, the isolated main compounds in ALT were chlorogenic acid, caffeic acid, isoquercitrin and rutin. RESULTS: Normalized HO-1 [0.11 (0.04-0.24)] and MCP-1 [0.29 (0.21-0.47)] mRNA levels and DNA scores [12.50 (4.50-36.50)] were significantly lower in the ADA group than in the AD group [0.84 (0.35-2.51)], p = 0.021 for HO-1 [0.85 (0.61-3.45)], p = 0.047 for MCP-1 and [176.5 (66.50-221.25)], p = 0.020 for DNA scores. HO-1 mRNA was lower in the ADA group than in the CG group [0.30 (0.21-0.71), p = 0.049]. CONCLUSIONS: Supplementation with ALT limited the effects of the atherogenic diet through reduced MCP-1 expression, thereby preventing oxidative damage.

Toxicity evaluation of two polyoxotungstates with anti-acetylcholinesterase activity.

A toxicity evaluation of two Keggin-type heteropolytungstates, K7[Ti2PW10O40]·6H2O and K6H[SiV3W9O40]·3H2O, with different inhibitory potencies toward acetylcholinesterase activity (IC50 values of 1.04×10-6 and 4.80×10-4mol/L, respectively) was performed. Wistar albino rats were orally treated with single doses (5 and 50mg/kg) of both investigated compounds. The biochemical parameters of renal (serum urea and creatinine) and liver function (direct and total bilirubin, alanine transaminase, and aspartate aminotransferase) were determined after 24h and 14days. A histopathological analysis of liver tissue was carried out 14days after the polyoxotungstate administration. Both applied doses of the investigated compounds did not induce statistically significant alterations of the renal function markers. However, the polyoxotungstate treatment caused an increase in the activities of serum alanine transaminase and aspartate aminotransferase in a time- and concentration-dependent manner, although statistically significant changes in bilirubin concentrations were not observed. Furthermore, the detected hepatotoxic effect was confirmed by histhopathological analysis that suggested some reversible liver tissue damage two weeks after the treatment, especially in the case of K6H[SiV3W9O40]·3H2O. Accordingly, the toxicity of these two polyoxotungstates with anti-acetylcholinesterase effect cannot be considered as a severe one, but their potential clinical application would require a more complex toxicological study.

Clarification of serotonin-induced effects in peripheral artery disease observed through the femoral artery response in models of diabetes and vascular occlusion: The role of calcium ions.

Recent findings have demonstrated that serotonin is an important participant in the development and progression of peripheral artery diseases. Taking this into consideration, the goals of this study were to investigate the effects of serotonin on isolated Wistar rat femoral arteries in both healthy and diabetic animals, with and without artery occlusion, with a particular focus on determining the role of calcium in this process. Contraction experiments with serotonin on intact and denuded femoral artery rings, in the presence or absence of nifedipine and ouabain (both separately, or in combination), as well as Ca2+ -free Krebs-Ringer bicarbonate solution were performed. The serotonin-induced results were concentration dependent, but only in healthy animals. The endothelium-dependent contraction of the femoral artery was assessed. In healthy animals, the endothelium-reliant part of contraction was dependent on the extracellular calcium, while the smooth muscle-related part was instead dependent on the intracellular calcium. In diabetic animals, both nifedipine and ouabain influenced serotonin-induced vascular effects by blocking intracellular calcium pathways. However, this was diminished after the simultaneous administration of both blockers.

A meta-analysis of randomized and placebo-controlled clinical trials suggests that coenzyme Q10 at low dose improves glucose and HbA1c levels.

The influence of coenzyme Q10 (CoQ10) on blood glucose (BGL) and HbA1c (HL) levels has been previously investigated; however, the results are inconsistent. Therefore, the purpose of this meta-analysis was to determine if CoQ10 could affect BGL and HL levels based on the existing evidence. PubMed, Cochrane Library, Web of Science, Embase, and Scopus databases were searched for randomized clinical trials from September 1, 1956, to March 01, 2016. To calculate pooled overall effects, a random effect model was used. Because of the presence of heterogeneity, the subgroup analysis and the meta-regression were performed. In total, 18 studies (19 study arms) were included in our investigation focusing on the effects of CoQ10 on BGL (17 arms) and HL (12 arms) changes. CoQ10 significantly reduced BGL, whereas it was ineffective in the reduction of the HL. Because of the significant heterogeneity, in the arms involving BGL, we found that lower doses of CoQ10 (<200 mg/d) and a shorter duration of study created a positive effect on BGL. Also, it appeared that CoQ10 could reduce BGL in patients with a glucose level >6 mmol/L as well as in certain ethnic groups. However, because the meta-regression failed to support the subgroup analysis, the result related to the ethnic group should be used only to generate a hypothesis, which is planned in the future. In conclusion, CoQ10 can reduce BGL, particularly when used in lower doses (< 200 mg/d) and when administration was not longer than 12 weeks, in patients both with and without high BGL.

Angiotensin receptor blockers & endothelial dysfunction: Possible correlation & therapeutic implications.

The endothelium is one of the most important constituents of vascular homeostasis, which is achieved through continual and balanced production of different relaxing and contractile factors. When there is a pathological disturbance in release of these products, endothelial dysfunction (ED) will probably occur. ED is considered to be the initial step in the development of atherosclerosis. This pathological activation and inadequate functioning of endothelial cells was shown to be to some extent a reversible process, which all together resulted in increased interest in investigation of different beneficial treatment options. To this point, the pharmacological approach, including for example, the use of angiotensin-converting enzyme inhibitors or statins, was clearly shown to be effective in the improvement of ED. One of many critical issues underlying ED represents instability in the balance between nitric oxide and angiotensin II (Ang II) production. Considering that Ang II was confirmed to be important for the development of ED, the aim of this review article was to summarize the findings of up to date clinical studies associated with therapeutic application of angiotensin receptor blockers and improvement in ED. In addition, it was of interest to review the pleiotropic actions of angiotensin receptor blockers linked to the improvement of ED. The prospective, randomized, double-blind, placebo or active-controlled clinical trials were identified and selected for the final evaluation.

Endothelial Dysfunction in Renal Failure: Current Update.

Endothelial dysfunction is principally characterized by impaired endothelium- dependent transduction mechanisms related to vascular relaxation, as an outcome of decreased release of endothelium-derived relaxing factors, mainly nitric oxide, as well as augmented oxidative stress, increased inflammation and predominance of vascular action produced by endothelium-derived contracting factors. Current data strongly suggest that pathological development of different types of kidney impairment with further progression to renal failure includes notable vascular changes associated with endothelial dysfunction. In accordance, this scientific field represents an advancing area of investigation, involving different biomarkers of endothelial dysfunction linked to renal impairment, as well as clinical findings with new information that can provide a more comprehensive understanding of the role of endothelial dysfunction in kidney disease. With regards to quoted facts, the aim of this article was to review the latest data related to endothelial dysfunction and renal failure by selection of relevant articles released from 2010 to 2015.