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The ubiquitin-proteasome system (UPS) is responsible for up to 90% of intracellular protein degradation. Alterations in UPS are extensively involved in the development and advancement of malignant pathologies. Thus, the components of the UPS can become potential targets for cancer therapeutics. KPC1 is an E3 ubiquitin ligase component of the UPS that regulates key pathways and processes in cancer. KPC1 sustains the ubiquitination of cytoplasmic p27, determining its elimination and transition between cell-cycle phases. KPC1 also regulates NF-κB signaling by inducing ubiquitination of p105 to allow subsequent proteasomal processing to the functional form p50. It has been shown that the KPC1-p50 duo is reduced or absent in multiple malignancies and that therapeutic reinforcement of the functional axis can exhibit significant tumor suppressor activity. Here, we highlight the potential role of KPC1 as a tumor suppressor by fully describing its crucial role in p27 signaling and the canonical NF-κB pathway.

Psoriasis is a chronic autoimmune disease affecting over 2% of the worldwide population. From an anatomopathological point of view, psoriasis is characterized by immune cells infiltration, epidermal hyperproliferation, and abnormal keratinocyte differentiation. Understanding the pathogenesis of psoriasis will allow clinicians to manage this complex disease. Under these conditions, the application of effective treatments requires a thorough knowledge of all the pathogenetic mechanisms that lead to psoriasis. Numerous immunopathological pathways play crucial roles in the development of new therapies, such as biological therapies, which have been a breakthrough in psoriasis's treatment. Pharmacogenetics is an essential factor in the patient's response to treatment. One important pathway targeted by modern treatments is the interleukin (IL)-23∕T-helper (Th)17 axis. Like IL-17 inhibitors, IL-23 blockers are a very effective therapy for this autoimmune disease. It is considered that micro-ribonucleic acids (microRNAs) are the starting point for any autoimmune disease. Studying certain microRNA (miR) involved in the inflammatory pathway in psoriasis can find direct targets to future treatments that can even be more specific than actual biological therapies. As such, miR-210 has proven to be up-regulated in psoriasis, also leading to the up-regulation of the Th1∕Th17 axis. On the other hand, miR-187 was found to be down-regulated, influencing the outcome of psoriasis by increasing the proliferation of IL-6 stimulated keratinocytes and consecutively generating epidermal thickening. In this review, we are aiming to do an up-to-date briefing of psoriasis histopathology and pharmacogenetic factors that are considered for the accurate evaluation of treatment response.

Vaccines represent an important preventive strategy in paediatric populations, but the rate of vaccination has been constantly declining in the last decade. Concerns about vaccines’ safety represent one of the main causes of vaccine hesitancy among parents. The aim of this study was the analysis of the immediate adverse reactions induced by vaccines included in the national program of immunization for the first year of life. Method: Eighty-one children born between 1st of January 2018 and 31st of March 2019 were included. The vaccination refusal rate, and incidence and severity of adverse effects induced by three mandatory vaccines (Hexavalent, Prevenar 13 and MMR) were analyzed. The level of parents’ education and the sources of information that were consulted in order to understand the adverse effects were also analyzed. Results and conclusions: The rate of adverse events was lower than 30% of the total number of doses, and most of them were mild. The incidence and severity of vaccine-induced adverse effects were correlated with prematurity. The vaccine hesitancy rate was lower than the national one, possibly due to a high level of education and good information provided by doctors that might have led to parents’ concerns regarding vaccination being answered.

The restoration and maintenance of sinus rhythm is a desirable strategy for many patients with atrial fibrillation (AF) since it has been associated with improvement in symptoms and a better quality of life. Sinus rhythm can be achieved by pharmacological or electrical cardioversion or after catheter ablation of AF. Despite high rates of successful cardioversion, AF recurrence remains a major challenge. Anti-arrhythmic drug therapy currently plays a significant role in maintaining sinus rhythm after cardioversion. Amiodarone is the most commonly prescribed anti-arrhythmic drug for patients with AF. This is due to its particular electrophysiological properties and superior anti-arrhythmic effects in comparison with other anti-arrhythmic drugs. Understanding the cardiac electrophysiology and arrhythmogenesis mechanisms may result in identification of new targets for anti-arrhythmic therapy. The aim of this article was to review amiodarone’s clinical pharmacology and evaluate evidence supporting amiodarone for treatment and prevention of AF recurrence after cardioversion.

Viral B and C hepatitis are a major current health issue, both diseases having a chronic damaging effect on the liver and its functions. Chronic liver disease can lead to even more severe and life-threatening conditions, such as liver cirrhosis and hepatocellular carcinoma. Recent years have uncovered an important interplay between the liver and the gut microbiome: the gut-liver axis. Hepatitis B and C infections often cause alterations in the gut microbiota by lowering the levels of 'protective' gut microorganisms and, by doing so, hinder the microbiota ability to boost the immune response. Treatments aimed at restoring the gut microbiota balance may provide a valuable addition to current practice therapies and may help limit the chronic changes observed in the liver of hepatitis B and C patients. This review aims to summarize the current knowledge on the anato-functional axis between the gut and liver and to highlight the influence that hepatitis B and C viruses have on the microbiota balance, as well as the influence of treatments aimed at restoring the gut microbiota on infected livers and disease progression.

Gut microbiota, the total microorganisms in our gastrointestinal tract, might have an implication in multiple sclerosis (MS), a demyelinating neurological disease. Our study included 50 MS patients and 21 healthy controls (HC). Twenty patients received a disease modifying therapy (DMT), interferon beta1a or teriflunomide, 19 DMT combined with homeopathy and 11 patients accepted only homeopathy. We collected in total 142 gut samples, two for each individual: at the study enrolment and eight weeks after treatment. We compared MS patients’ microbiome with HC, we analysed its evolution in time and the effect of interferon beta1a, teriflunomide and homeopathy. There was no difference in alpha diversity, only two beta diversity results related to homeopathy. Compared to HC, untreated MS patients had a decrease of Actinobacteria, Bifidobacterium, Faecalibacterium prauznitzii and increased Prevotella stercorea, while treated patients presented lowered Ruminococcus and Clostridium. Compared to the initial sample, treated MS patients had a decrease of Lachnospiraceae and Ruminococcus and an increased Enterococcus faecalis. Eubacterium oxidoreducens was reduced after homeopathic treatment. The study revealed that MS patients may present dysbiosis. Treatment with interferon beta1a, teriflunomide or homeopathy implied several taxonomic changes. DMTs and homeopathy might influence the gut microbiota.

We investigated the in vivo effect of curcumin nanoparticles (nC) in addition to diclofenac sodium on local edema and oxidative stress parameters in carrageenan-induced paw edema on rats. Seven groups were investigated: control group (C), the acute inflammation (AI) group, an AI group treated with Diclofenac (AID, 5 mg/kg b.w. Diclofenac sodium), two AI groups treated with cC (conventional Curcumin)—AIC200 and AIcC200D (D = Diclofenac, 200 represent the concentration of active substance expressed in mg/kg b.w.), and two AI groups with nC (Curcumin nanoparticles)—AIC200 and AIcC200D. Serum and tissue oxidative stress was assessed by measuring five parameters. Curcumin nanoparticles alone and in combination with D better reduced the paw edema than D alone (p < 0.027). The rats treated with D and nC (AIcC200D) had the highest inhibition percentage on edema, reaching the maximum level of inhibition (81%) after 24 h. Conventional curcumin and nC presented antioxidant effects in acute inflammation, with significantly better results obtained for nC. The pro-oxidant markers were reduced up to 0.3 by the cC and up to 0.4 times by the nC and both solutions increased the antioxidant markers up to 0.3 times. The nC enhanced the antioxidative efficacy of D, as this combination reduced the pro-oxidant markers up to 1.3 times. Curcumin nanoparticles could represent a therapeutic option in association with classical nonsteroidal anti-inflammatory medication in acute inflammation, as they might offer a reduction of drug dose and possible limitation of their associated side effects.

Coronavirus disease 2019 (COVID-19), caused by a severe acute respiratory syndrome coronavirus 2 infection, has raised serious concerns worldwide over the past 3 years. The severity and clinical course of COVID-19 depends on many factors (

Flavonoids, stilbenes, lignans, and phenolic acids, classes of polyphenols found in grape pomace (GP), were investigated as an important alternative source for active substances that could be used in the management of oxidative stress and inflammation. The benefic antioxidant and anti-inflammatory actions of GP are presented in the literature, but they are derived from a large variety of experimental in vitro and in vivo settings. In these in vitro works, the decrease in reactive oxygen species, malondialdehyde, and thiobarbituric acid reactive substances levels and the increase in glutathione levels show the antioxidant effects. The inhibition of nuclear factor kappa B and prostaglandin E2 inflammatory pathways and the decrease of some inflammatory markers such as interleukin-8 (IL-8) demonstrate the anti-inflammatory actions of GP polyphenols. The in vivo studies further confirmed the antioxidant (increase in catalase, superoxide dismutase and glutathione peroxidase levels and a stimulation of endothelial nitric oxide synthase -eNOS gene expression) and anti-inflammatory (inhibition of IL-1𝛼, IL-1β, IL-6, interferon-𝛾, TNF-α and C-reactive protein release) activities. Grape pomace as a whole extract, but also different individual polyphenols that are contained in GP can modulate the endogenous pathway responsible in reducing oxidative stress and chronic inflammation. The present review analyzed the effects of GP in oxidative stress and inflammation, suggesting that it could become a valuable therapeutic candidate capable to reduce the aforementioned pathological processes. Grape pomace extract could become an adjuvant treatment in the attempt to reduce the side effects of the classical anti-inflammatory medication like non-steroidal anti-inflammatory drugs (NSAIDs).

Grape pomace (GP) represents a very reliable source of polyphenols because it could be found globally as a remnant of the wine industry. During the winemaking process, two types of GP are generated: red GP and white GP, according to the produced wine, red or white. Grape pomace represents a viable source of polyphenols, mainly flavanols, procyanidins anthocyanins, and resveratrol which possess antioxidant and anti-inflammatory activities. Multiple differences were observed between red and white GP in terms of their antioxidant and anti-inflammatory activity in both in vitro and in vivo studies. Although most studies are focused on the antioxidant and anti-inflammatory effect of red grape pomace, there are still many variables that need to be taken into consideration, as well as extensive study of the white GP. It was observed that in both in vitro and in vivo studies, the GP polyphenols have a direct antioxidant activity by acting as a free radical scavenger or donating a hydrogen atom. It also possesses an indirect antioxidant and anti-inflammatory activity by reducing mitochondrial reactive oxygen species (ROS) generation, malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), interleukin-1-beta (IL-1β), interleukin-6 (IL-6), nuclear factor kappa-light-chain-enhancer of activated B cells (NF- κβ), and inhibitor of nuclear factor kappa-B kinase subunit beta (Iκκβ) levels or nitrate oxide-4 (NOX4) expression and by increasing the levels of antioxidants enzymes like superoxide dismutase (SOD), catalase (CAT) glutathione reductase (GRx) and glutathione peroxidase(GPx). Besides these activities, many beneficial effects in ischemic heart diseases were also observed, such as the maintenance of the ventricular function as close as possible to normal, and the prevention of infarcted area extension. In this context, this review intends to present the actual knowledge of grape pomace’s potential antioxidant and anti-inflammatory activity in ischemic heart disease, knowledge gathered from existing in vitro and in vivo studies focused on this.

Crisis situations, which cause disturbances in the daily routine of the individual can contribute to the development of mental problems. On the 26th of February, 2020, the first confirmed case of COVID-19 was reported in Romania. On the 16th of March, the President of Romania declared The State of Emergency. The following day, by Order of the Ministry of the Internal Affairs medical students starting with the 4th year of study were to be recruited, on a voluntary basis, to support activities in the Emergency Rooms, if needed. Numerous medical students volunteered. The medical students were exposed to online learning and the possibility of being recruited as volunteers in COVID-19 units. In April 2020, we created and distributed an online survey via www.psysafe.org, which collected data on demographics, personal status of infection, and general mental health, including medication and substance use, sleeping problems in the previous week, perceived stress in the previous month, and burnout in the previous two months. We translated and adapted 2 questionnaires to assess the COVID-19 related anxiety and fear. The participants were Romanian medical students. Data was statistically analysed with SPSS 20. Out of 550 surveys filled, we analysed 545 valid surveys. The mean age of the respondents was 21.66 (±2.55) years, with 81.7% female (445) and 18.3% male (100). 91.6% of the respondents declared that they were never diagnosed with a psychiatric disorder. Coffee was used on a daily basis by 53.8% of the students, with tobacco coming in second in 19.4%. Female students perceived a higher level of stress and showed a higher level of burnout. Female students scored higher for the anxiety and fear related to Covid-19. Medical students with mental health history scored higher on perceived stress, burnout, anxiety and fear related to COVID-19. Perceived stress indicated a level of moderate stress regardless of the mental history status. For all students, the burnout value indicated that some attention was needed, as they might had been candidates to burnout. Moreover, students diagnosed with a psychiatric disorder during the pandemic showed signs that they were on the road to burnout, with changes needed to be done at the time. There were statistically significant positive correlation, of various degrees between perceived stress, burnout, anxiety and fear related to COVID-19, with the strongest one observed for the perceived stress and burnout, in Romanian medical students.

Alexandra Dadarlat-Pop,1 Dana Pop,1,2 Lucia Procopciuc,3 Adela Sitar-Taut,4 Dumitru Zdrenghea,1,2 Gyorgy Bodizs,2 Raluca Tomoaia,1 Diana Gurzau,1 Florina Fringu,1 Silvana Susca-Hojda,1 Anca D Buzoianu5 1Department of Cardiology, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania; 2Department of Cardiology, Clinical Rehabilitation Hospital, Cluj-Napoca, 400347, Romania; 3Department of Medical Biochemistry, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania; 4 4th Medical Clinic, Department of Internal Medicine, “Iuliu HaÅ£ieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania; 5Department of Pharmacology, Toxicology and Clinical Pharmacology, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, RomaniaCorrespondence: Dana PopDepartment of Cardiology, Clinical Rehabilitation Hospital, 46-50 Viilor Street, Cluj-Napoca, 400347, RomaniaTel +40 744 159 933Fax +40 364 818 027Email pop67dana@gmail.comBackground and Aims: Leptin, one of the best-known adipocytes, together with the renin-angiotensin-aldosterone system and galectin-3 are important players in inflammation, arterial hypertension and heart failure pathophysiology. Moreover, uninucleotide A1166C polymorphism is associated with hypertension and poor prognosis in heart failure. The aim of the study was to investigate a possible relationship between leptin serum values, specific heart failure biomarkers and the presence of AT1 receptor A1166C polymorphism in overweight and obese heart failure patients.Methods: The study included 88 consecutive overweight and obese patients admitted for decompensated heart failure. NT-proBNP, MR-proANP, galectin-3 and leptin levels were determined on the arrival day. Genotyping of the A1166C allele – AT1 receptor gene was performed in all patients in order to find variants.Results: We found a strong positive correlation (r = 0.347, p = 0.001) between leptin serum concentrations and BMI. Leptin levels were not correlated with heart failure biomarkers (NT-proBNP, MR-proANP and galectin-3). All homozygote CC variants were hypertensive, but we registered no significant difference in genetic AC and AA variants distribution between hypertensive and normotensive. Leptin was not significantly modified by the presence of potentially pathogenic A1166C–AT 1 receptor genotypes (AC + CC). But, galectin-3 was found in higher concentrations in patients with heterozygous and homozygous A1166C mutations.Conclusion: Overweight and obese patients with heart failure display high leptin serum levels. Leptin does not offer incremental prognostic value in heart failure overweight and obese patients. But, galectin-3 was found in higher concentrations in patients with heterozygous and homozygous A1166C mutations, suggesting a worse prognosis probably due to more advanced cardiac fibrosis.Keywords: leptin, galectin-3, heart failure, obesity, arterial hypertension, AT1 receptor mutation

This prospective meta-analysis summarizes results from the CAPTAIN trial series, evaluating the effects of Cerebrolysin for moderate-severe traumatic brain injury, as an add-on to usual care. The study included two phase IIIb/IV prospective, randomized, double-blind, placebo-controlled clinical trials. Eligible patients with a Glasgow Coma Score (GCS) between 6 and 12 received study medication (50 mL of Cerebrolysin or physiological saline solution per day for ten days, followed by two additional treatment cycles with 10 mL per day for 10 days) in addition to usual care. The meta-analysis comprises the primary ensembles of efficacy criteria for 90, 30, and 10 days after TBI with a priori ordered hypotheses based on multivariate, directional tests. A total 185 patients underwent meta-analysis (mean admission GCS = 10.3, mean age = 45.3, and mean Baseline Prognostic Risk Score = 2.8). The primary endpoint, a multidimensional ensemble of functional and neuropsychological outcome scales indicated a “small-to-medium” sized effect in favor of Cerebrolysin, statistically significant at Day 30 and at Day 90 (Day 30: MWcombined = 0.60, 95%CI 0.52 to 0.66, p = 0.0156; SMD = 0.31; OR = 1.69; Day 90: MWcombined = 0.60, 95%CI 0.52 to 0.68, p = 0.0146; SMD = 0.34, OR = 1.77). Treatment groups showed comparable safety and tolerability profiles. The meta-analysis of the CAPTAIN trials confirms the safety and efficacy of Cerebrolysin after moderate-severe TBI, opening a new horizon for neurorecovery in this field. Integration of Cerebrolysin into existing guidelines should be considered after careful review of internationally applicable criteria.

Usually, the first responses against new communicable diseases are quarantines and travel bans. As of March, the 16th, 2020 until May, the 14th, 2020 The State of Emergency was declared on all the territory of Romania. People had to comply with "stay-at-home orders" while some regions were under total lockdown. In late April 2020, we created and distributed an online survey, via www.psysafe.org. We addressed ethical issues towards both the individual and populational levels measures designed to prevent and reduce COVID-19, as well as assessed the attitudes towards hypothetical public health sanctions infringed on people who do not follow the regulations. In total, 3.122 respondents took part in the survey. The majority consider that physical distancing, self-isolation, quarantine, and nation/region-wide lockdown imposed to prevent and reduce COVID-19 are both necessary and morally justified. The participants do not agree with a hypothetical sanction of not offering medical treatment but would agree with a hypothetical sanction of having to pay for the medical treatment. In the end, we examined the justice of quarantine and isolation from an ethical point of view.

The ubiquitin-proteasome system is the crucial homeostatic mechanism responsible for the degradation and turnover of proteins. As such, alterations at this level are often associated with oncogenic processes, either through accumulation of undegraded pathway effectors or, conversely, excessive degradation of tumor-suppressing factors. Therefore, investigation of the ubiquitin- proteasome system has gained much attraction in recent years, especially in the context of hematological malignancies, giving rise to efficient therapeutics such as bortezomib for multiple myeloma. Current investigations are now focused on manipulating protein degradation via fine-tuning of the ubiquitination process through inhibition of deubiquitinating enzymes or development of PROTAC systems for stimulation of ubiquitination and protein degradation. On the other hand, the efficiency of Thalidomide derivates in myelodysplastic syndromes (MDS), such as Lenalidomide, acted as the starting point for the development of targeted leukemia-associated protein degradation molecules. These novel molecules display high efficiency in overcoming the limitations of current therapeutic regimens, such as refractory diseases. Therefore, in this manuscript we will address the therapeutic opportunities and strategies based on the ubiquitin-proteasome system, ranging from the modulation of deubiquitinating enzymes and, conversely, describing the potential of modern targeted protein degrading molecules and their progress into clinical implementation.

A few months after the onset of the 2019 coronavirus disease pandemic (COVID-19), it has been suggested that the use of certain nonsteroidal anti-inflammatory drugs may increase the severity and mortality of the disease, therefore it should be avoided in those who become ill. The hypothesis was based on previous preclinical and clinical studies that analyzed the role of cyclooxygenase in inflammatory processes in viral infections. Based on the existing data analyzed, there is no evidence of a worsening of the disease in patients previously treated with ibuprofen.

Background and purpose In Romania, robust data about the prevalence of obesity and heart failure are lacking, especially in the elderly; therefore, this study aims to analyze the profile of overweight and obese patients aged >65 years admitted to a Romanian hospital for worsening heart failure, and also their risk in the presence of comorbidities. Patients and methods This cross-sectional study was conducted in 126 consecutive elderly patients with overweight and obesity admitted to a Romanian hospital for worsening heart failure. They were divided into three groups: with reduced ( 65 years) to 30 (extensive comorbidity). Results NT-proBNP values are negatively correlated with BMI only in patients with HFpEF. Creatinine clearance (p=0.0166), the presence of atrial fibrillation (p=0.0095) and NYHA functional class were independent predictors of increased NT-proBNP values. CCI score is negatively correlated with NT-proBNP values in patients with HFmrEF (r= -0.448, p=0.009) and HFpEF (r= -0.273, p=0.043). The CCI risk was not significantly different between the three groups. Conclusion Elderly heart failure patients with overweight or obesity have particular characteristics in terms of NT-proBNP values and presence of comorbidities. In the studied population, NT-proBNP levels were strongly influenced by renal function, NYHA functional class, the presence of atrial fibrillation and left ventricular ejection fraction.

Chronic heart failure and obesity are two conditions which despite all the advances made in the recent years, still represent two of the leading causes of morbidity and mortality worldwide. Moreover, a well-known fact is that the risk of sudden cardiac death, mostly related to malignant arrhythmias is higher in apparently healthy obese individuals in comparison with lean subjects. On the other hand, obese heart failure patients bring unique challenges in the diagnosis of heart failure, having a better prognosis than their normal or underweight counterparts. Taking into account the above-mentioned existing data, there are questions regarding whether cardiac arrhythmias such as atrial fibrillation or ventricular arrhythmias in this population have certain evolutive particularities. This paper describes various mechanisms of cardiac arrhythmias found in obese heart failure patients, such as myocardial architectural changes, neurohormonal and paracrine modifications.

There are limited neuroprotective strategies for various central nervous system conditions in which fast and sustained management is essential. Neuroprotection-based therapeutics have become an intensively researched topic in the neuroscience field, with multiple novel promising agents, from natural products to mesenchymal stem cells, homing peptides, and nanoparticles-mediated agents, all aiming to significantly provide neuroprotection in experimental and clinical studies. Dexmedetomidine (DEX), an α2 agonist commonly used as an anesthetic adjuvant for sedation and as an opioid-sparing medication, stands out in this context due to its well-established neuroprotective effects. Emerging evidence from preclinical and clinical studies suggested that DEX could be used to protect against cerebral ischemia, traumatic brain injury (TBI), spinal cord injury, neurodegenerative diseases, and postoperative cognitive disorders. MicroRNAs (miRNAs) regulate gene expression at a post-transcriptional level, inhibiting the translation of mRNA into functional proteins. In vivo and in vitro studies deciphered brain-related miRNAs and dysregulated miRNA profiles after several brain disorders, including TBI, ischemic stroke, Alzheimer’s disease, and multiple sclerosis, providing emerging new perspectives in neuroprotective therapy by modulating these miRNAs. Experimental studies revealed that some of the neuroprotective effects of DEX are mediated by various miRNAs, counteracting multiple mechanisms in several disease models, such as lipopolysaccharides induced neuroinflammation, β-amyloid induced dysfunction, brain ischemic-reperfusion injury, and anesthesia-induced neurotoxicity models. This review aims to outline the neuroprotective mechanisms of DEX in brain disorders by modulating miRNAs. We address the neuroprotective effects of DEX by targeting miRNAs in modulating ischemic brain injury, ameliorating the neurotoxicity of anesthetics, reducing postoperative cognitive dysfunction, and improving the effects of neurodegenerative diseases.

Objectives: This study focuses on the assessment of attitudes and practices regarding research among undergraduate medical students from Cluj-Napoca, Romania. Material and Methods: A cross-sectional study was performed thorough anonymous questionnaires (May–June 2018) among 510 third- and fifth-year students of Iuliu Hatieganu University of Medicine and Pharmacy from Cluj-Napoca, Romania. Results: More than 60% of the third- and fifth-year students declared that they were interested and willing to perform research during medical studies, while more than two-thirds were interested in doing so after graduation. In total, 6% of third-year students and 31% of fifth-year students declared that they had prepared a scientific presentation for a medical congress at least once. Around 9% of the third-year students contributed to the writing of a scientific article and participated in research projects. Among fifth-year students, one-quarter were involved in writing scientific papers, and 21% participated in research projects. Conclusions: To the best of our knowledge, this study assesses, for the first time in Romania, the perspectives and behaviors of medical undergraduate students with regard to involvement in research activities. The results show that Romanian medical students value opportunities for conducting research, which encourages institutional initiatives that support their involvement in curricular and extracurricular research activities.

The present study aims to compare the oxidative stress biomarkers, pro-inflammatory cytokines, and histological changes induced by three cardiovascular risk factors, namely, hypertension, dyslipidemia, and type 1 diabetes mellitus. Hypertension was induced with 40 mg/kg body weight (b.w.) of N omega-nitro-L-arginine-methyl (L-NAME) administered orally. Dyslipidemia was induced by the administration of a diet with a high cholesterol (2%) content. Diabetes mellitus was induced by intraperitoneal administration of a single dose of streptozocin (65 mg/kg). Malondialdehyde (MDA) and total oxidative status (TOS) are increased by all three cardiovascular risk factors (up to 207%). The indirect assessment of NO synthesis (NOx) is observed to be reduced after L-NAME administration (43%), and dyslipidemia induction (16%), while type 1 diabetes mellitus is associated with the highest levels of NOx (increased 112%). Hypertension, dyslipidemia, and type 1 diabetes reduced the total antioxidative capacity (TAC) and total thiol (SH) levels (up to 57%). The values of evaluated pro-inflammatory cytokines, tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β), assessed from the ascending aorta were elevated by all three cardiovascular risk factors, with the highest levels induced by type 1 diabetes mellitus (up to 259%). The histopathological examination of the ascending and descending aorta revealed reversible pro-atherogenic changes consisting of the accumulation of lipid droplets in the subendothelial connective tissue on rats with hypertension and dyslipidemia. Irreversible pro-atherogenic changes consisting of a reduction of the specific elasticity of the arteries were observed in rats with type 1 diabetes mellitus. Type 1 diabetes mellitus demonstrates an alteration of the oxidative stress parameters, the elevation of tissue levels of the pro-inflammatory cytokines and causing irreversible pro-atherogenic changes on the aortic wall.

Sensorineural hearing loss is a prevailing health issue worldwide which usually occurs due to sensory inner ear cell destruction. These cells, once damaged, do not regenerate in mammals resulting in permanent hearing loss. Effective treatment of inner ear diseases is strongly correlated with efficient drug delivery to the inner ear. Researchers have made important efforts to deliver drugs locally to the inner ear in a safe and controllable manner. Different strategies and drug delivery systems were used to mitigate the resistance exerted by the multiple anatomical barriers found in the inner ear. Nanoparticles represent an option for sustained drug delivery to the inner ear. Nanocarrier-based systems can diffuse through the round and oval window membrane allowing for direct delivery into the inner ear components. Certain types of enhanced nanoparticles can focus on specific parts of the inner ear, providing targeted delivery which might represent the future therapy for sensorineural hearing loss. In this article, we will present the latest advances in the treatment of hearing loss based on nanoparticles.

Aim: The present study analyzed clinical and biological factors that might predict achievement of tolerance in patients with IgE-mediated cow milk allergy (CMA). Method: Seventy patients with IgE-mediated CMA (44.24 ± 24.16 months) were included in the study. The patients were evaluated clinically through skin prick test and sIgE to whole milk, casein, beta-lactoglobulin and alpha-lactalbumin. An eviction diet of 6 months was established, followed by oral food challenge test (OFC) and oral immunotherapy (OIT) with baked milk for 6 months. The tolerance was assessed after 2 years follow up. Results: Thirty percent of patients presented anaphylaxis of different degrees of severity as first manifestation of CMA. Sixty-two patients followed OIT or an accelerated reintroduction of milk. Ten patients (14.28%) did not obtain tolerance to milk within 2 years. A larger wheal in SPT and higher sIgE to milk, casein and betalactoglobulin were noted in patients with positive OFC. A basal level of

Our study aimed to evaluate the analgesic and antioxidant effects of ginger (Zingiber officinale) root capsule extract (GRCE) in addition to diclofenac (D) sodium treatment in carrageenan-induced acute inflammation (AI). Seven groups of eight Wistar-Bratislava white rats were included in the study. One group was the control (C), and AI was induced in the other six groups. The following treatments were applied: saline solution for C and AI groups, D for the AID group, GRCE for two groups and GRCE and D for another two groups. The GRCE was administered by gavage in two doses (100 mg/Kg b.w. or 200 mg/kg b.w.), while D was administered intraperitoneally in a dose of 5 mg/kg b.w. The association of GRCE with this low dose of diclofenac reduced pain threshold and improved mobility with the best results for the dose of 200 mg/kg b.w. Moreover, this combination reduced, better than D alone, the serum levels of the evaluated pro-oxidant parameters (malondialdehyde, the indirect assessment of NO synthesis, total oxidative status and oxidative stress index) up to 78%, especially oxidative stress index (p < 0.0001). GRCE alone slightly improved the antioxidant parameters (total antioxidant capacity and total thiols), but when associated with, D the results were better, especially for total thiols as their plasma levels increased up to 50% (p < 0.0010), with the best results obtained for the 200 mg/kg b.w. dose of GRCE. In conclusion, ginger root capsules associated with diclofenac might offer additional antioxidant and analgesic effects in a dose-dependent manner in acute inflammation.

Atherosclerotic cardiovascular disease is the most common cause of morbidity and mortality worldwide. Diabetes mellitus increases cardiovascular risk. Heart failure and atrial fibrillation are associated comorbidities that share the main cardiovascular risk factors. The use of incretin-based therapies promoted the idea that activation of alternative signaling pathways is effective in reducing the risk of atherosclerosis and heart failure. Gut-derived molecules, gut hormones, and gut microbiota metabolites showed both positive and detrimental effects in cardiometabolic disorders. Although inflammation plays a key role in cardiometabolic disorders, additional intracellular signaling pathways are involved and could explain the observed effects. Revealing the involved molecular mechanisms could provide novel therapeutic strategies and a better understanding of the relationship between the gut, metabolic syndrome, and cardiovascular diseases.

Grape pomace and grape seeds, by-products of the wine industry, and grapevine cane resulting from grapevine pruning are cheap matrices containing important amounts of polyphenols. While there is a continuous need of introducing new ways of these by-products valorization, we propose their use as a source of bioactive polyphenols for complementary therapy in ischemic heart diseases. As oxidative stress plays an important role in these diseases, by their antioxidant/pro-oxidant properties, these compounds, mainly flavan-3-ols, procyanidins, and resveratrol may counteract the damage of the oxidative stress. For instance, to some extent, the grape seed extract, considered as an antioxidant nutritive supplement, may have pro-oxidant activity as well, depending on dose, duration of administration, and other dietary components.In vitrostudies confirm that the antioxidant activity of this extract might be mediated by pro-oxidanto-quinones and oxidation products of the polyphenols from grape and winery byproducts, indicating that quinones, as oxidation products, are involved in the modulation of the antioxidant/pro-oxidant balance at the cellular level in the case of catechin-type compounds, in the absence or presence of oxidative stress inducers.In vivo, studies indicate that a grape pomace-rich diet results in a significant increase of the total antioxidant status in the plasma, liver, spleen, and kidneys. Also, the administration of grape pomace shows antioxidant activity with positive effects on health. In this context, the present review aims to present the most recent research focused on the antioxidant/pro-oxidant actions of the bioactive polyphenols from grapevine and wine byproducts, in conditions of ischemic heart diseases as assessedin vitroorin vivo.

Atrial fibrillation (AF) is associated with oxidative stress and inflammation. Paraoxonase-1 (PON1), circulates in blood bound to high-density lipoproteins and reduces systemic oxidative stress. The aim of this study was to evaluate PON1 serum concentration and PON1 arylesterase activity (AREase) in patients with AF. We studied a group of 67 patients with symptomatic paroxysmal or persistent AF admitted for cardioversion and a control group of 59 patients without AF. Clinical parameters, lipid profile, PON1 concentration and AREase were evaluated. A significant difference in serum PON1 concentration and in AREase was found among the two groups. In a multivariate linear regression model, the presence of AF was associated with low PON1 concentration (P = .022). The body mass index was also independently associated with PON1 values (P .001). Only the high-density lipoproteins-cholesterol level was independently associated with AREase (P = .002). PON1 serum concentrations and AREase were diminished in patients with AF, and the presence of AF was independently associated with low PON1 values.

Atrial fibrillation (AF) recurrence after radiofrequency catheter ablation (RFCA) remains a challenging issue. This study aims to explore the left atrial appendage function by transesophageal echocardiography (TEE) and assess its value in predicting AF recurrence following RFCA in paroxysmal AF patients. Eighty-one patients with paroxysmal AF that underwent RFCA were recruited. TEE was performed before ablation with the assessment of left atrial appendage emptying flow velocity (LAAeV). AF recurrence occurred in 24 patients (29.6%) within 12 months after RFCA. The left atrium diameter (LAD) and left atrium volume index (LAVI) were both significantly higher in the recurrence group compared to the non-recurrence group, while the LAAeV was significantly lower in the recurrence group. LAD, LAVi and LAAeV were univariately significant risk factors for AF recurrence after ablation. Based on receiver operating curve (ROC), LAAeV < 40.5 cm/s, LAVi > 40.5 mL and LAD > 41 mm were identified as cut-off values for predicting AF recurrence. In multivariate regression analysis LAAeV < 40.5 cm/s (HR 8.194, 95% CI 2.980–22.530, p < 0.001) was identified as the only statistically significant independent predictor of AF recurrence, as the statistical significance threshold was not achieved for LAVI > 40.5 mL and LAD > 41 mm (p = 0.319; p = 0.507, respectively). A low LAAeV was the only important independent predictor of AF recurrence within 1 year after first RFCA.

Obesity and Overweight have the highest rate of incidence and prevalence in the past 3 decades, as global pathologies. The purpose of this study was to evaluate cardiovascular, classic and modern risk factors in overweight and obese patients by studying lipid metabolism (total cholesterol, HDL-cholesterol, non-HDL-cholesterol, LDL-cholesterol, serum triglycerides), glucose metabolism, insulin resistance and insulin sensitivity, the prevalence of hypertension (HBP) and the prevalence of metabolic syndrome (MS). This analytical study was performed on 111 subjects divided as follows: Group I consisting of 27 normal weight subjects - NW; Group II consisting of 84 overweight and obese subjects - OW + O: 36 overweight patients - OW; 33 patients with grade I obesity - O-I; 13 patients with grade II obesity - O-II; 2 patients with grade III obesity - O-III. The overweight and obese, although unknown with heart disease, have significant metabolic changes, such as atherogenic dyslipidemia, dysglycemia, high insulin resistance and low insulin sensitivity, metabolic syndrome, these being the first steps towards endothelial dysfunction and early atherosclerosis.

Introduction: Osteoporosis has a strong genetic contribution, and several genes have been shown to influence bone mineral density. Variants in the human genome are considered important causes of differences in drug responses observed in clinical practice. In terms of bone mineral density, about 26–53% of patients do not respond to amino-bisphosphonate therapies, of which alendronate is the most widely used. Material and method: The current study is prospective, observational, analytical, longitudinal and cohort type. It included 25 postmenopausal women treated with alendronate for 1 year. Bone mineral density at lumbar spine and proximal femur was measured and bone turnover markers (C-terminal telopeptide of type I collagen and procollagen 1N-terminal propeptide) were evaluated at 0 and 12 months of treatment. Six single nucleotide polymorphisms in osteoporosis-candidate genes were genotyped (FDPS rs2297480, LRP5 rs3736228, SOST rs1234612, VKORC1 rs9934438, GGPS1 rs10925503 and RANKL rs2277439). Treatment response was evaluated by percentage changes in bone mineral density and bone turnover markers. Results: The heterozygous CT of FDPS rs2297480 showed lower increases in BMD values in the lumbar spine region and the homozygous CC of the GGPS1 rs10925503 showed lower increases in terms of BMD at the total hip region. No association was found for LRP5 rs3736228, SOST rs1234612, VKORC1 rs9934438 and RANKL rs2277439. Conclusions: Romanian postmenopausal women with osteoporosis carrying the CT genotype of FDPS rs2297480 or the CC genotype of GGPS1 rs10925503 could have an unsatisfactory response to alendronate treatment. Key words: osteoporosis; genetic polymorphism; alendronate; bone mineral density; bone turnover markers

Asthma is defined by The Initiative for Asthma (GINA 2018) as a heterogeneous disease, which include chronic airway inflammation and a history of respiratory symptoms. In the last decades asthma had a rise in prevalence, becoming one of the most frequent diagnosed diseases in the world. The main goals of asthma management are to achieve good symptom control, minimize the risks of exacerbations, decrease rescue medication intake, improve the quality of life by decreasing respiratory system inflammation and ameliorating the patient’s lung function. Beside effective medications, asthma continues to impair quality of life for most patients. Due to the difficulty of controlling symptoms and exacerbations, the need of developing complementary options of treatment is increasing in order to achieve an optimum control and a lower risk of acute episodes or fatal events. Pulmonary rehabilitation is suggested for asthma patients when adequate medical therapy poorly control the symptoms and mental, physical or social consequences of illness persist during the daily life. The following non-drug therapy components are included in the rehabilitation program: physical training, comprehensive smoking cessation program, comprehensive patient education, respiratory physiotherapy, psychosocial support and comprehensive nutritional counseling. These complementary therapies have been proven to improve muscle strength, exercise capacity and symptomatology. Also, it has been associated to fewer exacerbations and a lower use of rescue medication, leading to a better quality of life. Key words: asthma, quality of life, symptomatology, rehabilitation, physiotherapy

Heart failure continues to be a major worldwide medical issue, associated with high morbidity and mortality. The need for ideal biomarkers to aid the diagnosis and prognosis in certain situations, such as obesity or atrial fibrillation is still ongoing. Obese patients are commonly hyperleptinemic. The aim of the study is to assess the role of several biomarkers in overweight and obese patients diagnosed with heart failure, depending on the presence or absence of atrial fibrillation and also their relationship with leptin. The study included 88 overweight and obese patients, with a body mass index (BMI) ≥25 kg/m2, admitted for worsening heart failure. Of these, 52.2% had atrial fibrillation. Dosage of NT-proBNP was performed using the chemiluminescence method. MR-proANP, galectin-3 and leptin were dosed using the ELISA method. A value of P [0.05 was defined as statistically significant. The values of natriuretic peptides NT-proBNP and MR-proANP were significantly increased. Only NT-proBNP was significantly influenced by renal function. No statistically significant correlation was found between heart failure-specific biomarkers and leptin secretion. There were no significant differences in the biomarkers levels between the 2 groups of patients. No statistically significant correlation was found between heart failure-specific biomarkers and leptin secretion. Obese patients with heart failure had significantly increased values of all the studied parameters, but the presence of atrial fibrillation did not influence their levels. High leptin levels were not directly correlated with the levels of heart failure-specific biomarkers.

In those countries where education and smoking prevention campaigns are carried out at school level, there has been a decline in the prevalence of smoking among pupils. Nicotine addiction represents a sum of pharmacological, electrophysiological and molecular genetic mechanisms and behavior patterns. The study was conducted from December 2016, to July 2017 and it consisted in an online survey posted on a website. The participants accessed the survey through an e mail link. The study population consisted of 1144 teachers (from primary school, gymnasium and college). The declared percentage of daily smokers was 14%, below the European average, while 20.5% were declared ex-smokers, 11.2% were occasional smokers and 54.4% never smoked. The theme of smoking was approached by 79.2% of teachers during conducting classes and 81.6% of them advised smokers to stop smoking. Teachers can influence the pupils� behavior by personal example and by teaching, inside and outside the school, thus preventing nicotine addiction. Decreasing the prevalence of smoking among teachers will inevitably lead in the future to a decrease of adolescent smokers� incidence. Our study was a pilot project that can draw important directions in educational and preventive campaigns in schools.

The ability of Berberis vulgaris bark extract (BVE) to improve the lipid profile was evaluated in an experimental model of dyslipidemia, along with its effects on liver and kidney functions. Fifty rats divided into five groups of ten animals each were fed with normal or lard-based diet and orally treated with 0.9% saline solution, atorvastatin (2.5 mg/kg per body weight) or extract of BVE (300 and 500 mg/kg/day) for eight weeks. Lipid profile, liver and renal functions were assessed in normal and diet-induced hypercholesterolemic rats. The results were compared between the groups treated with Berberis extract and the group without treatment, respectively that one treated with the standard drug (atorvastatin). Administration of BVE or atorvastatin significantly decreases the elevated serum lipid profile (p [0.05). The extract also protects against dyslipidemia-induced non-alcoholic fatty liver disease (NAFLD). The activities of the plant extract are dose dependent and it compares favorably with the standard drug atorvastatin. Variations in aspartate aminotransferase (AST), alanine aminotransferase (ALT), and urea level measurements were neither different between the two determinations nor between groups, but creatinine values decreased in rats in the BVE or atorvastatin-treated groups. The findings of the current study have suggested that BVE intake suppresses the accumulation of hepatic lipids and lipid parameters and reduce the risk of NAFLD. So, BVE can be useful in hypercholesterolemia.

The overlap syndrome (OS) is defined as a synergic relation between obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD). Patients with overlap syndrome present the clinical features of each disorder to a greater or a lesser extend depending on the predominant disease. We assessed the main differences between patients with OS and patients with OSA and we highlight the importance of nocturnal hypoxemia on clinical status and management of the patients with overlap syndrome, in order to simplify OSA screening tests in patients with COPD. The study population included 62 selected patients divided in two groups: the first group � subjects diagnosed with OS and the second group - subjects with OSA, without the diagnostic of COPD. The majority of the patients were male, with a mean age of 55�9.84 years in the OSA group and 65.5�10.32 years in the OS group. The nocturnal hypoxemia was more important in the OS grup, with 276.83 minutes spent at a SpO2 below 90% versus 132.98 minutes in the OSA group. The mean AHI was 57.7�29.244 events/hour of sleep in the OS group and 50.7�26.01 events/hour of sleep in the OSA group. At the diagnosis, the mean daytime SpO2 was 90.9�3.59% in the OS group and 95.9�1.57 % in the OSA group. There were statistically significant differences between the two groups concerning age, AHI, Epworth Slepiness Scale, nocturnal desaturation, medium and minimum SpO2 during sleep, daytime SpO2 at the diagnosis and at 1-year follow-up, the presence of cardiovascular comorbidities such as pulmonary hypertension and heart failure. Our study showed that patients with COPD have OSA predictors that differ from those usually recognise in the general population. In OS patients, the most important parameter is the nocturnal hypoxemia. So, it is very useful that the clinicians be trained to include in the management of selected obese COPD patients, comprehensive sleep history, sleep hygiene and OSA screening because, in clinical practice, OSA is quite often underdiagnosed in these patients.