University of Oradea

Rheumatoid arthritis (RA) is a multifactorial autoimmune disease of unknown etiology, primarily affecting the joints, then extra-articular manifestations can occur. Due to its complexity, which is based on an incompletely elucidated pathophysiological mechanism, good RA management requires a multidisciplinary approach. The clinical status of RA patients has improved in recent years due to medical advances in diagnosis and treatment, that have made it possible to reduce disease activity and prevent systemic complications. The most promising results were obtained by developing disease-modifying anti-rheumatic drugs (DMARDs), the class to which conventional synthetic, biologic, and targeted synthetic drugs belong. Furthermore, ongoing drug development has led to obtaining molecules with improved efficacy and safety profiles, but further research is needed until RA turns into a curable pathology. In the present work, we offer a comprehensive perspective on the management of RA, by centralizing the existing data provided by significant literature, emphasizing the importance of an early and accurate diagnosis associated with optimal personalized treatment in order to achieve better outcomes for RA patients. In addition, this study suggests future research perspectives in the treatment of RA that could lead to higher efficacy and safety profiles and lower financial costs.

The human gut possesses millions of microbes that define a complex microbial community. The gut microbiota has been characterized as a vital organ forming its multidirectional connecting axis with other organs. This gut microbiota axis is responsible for host-microbe interactions and works by communicating with the neural, endocrinal, humoral, immunological, and metabolic pathways. The human gut microorganisms (mostly non-pathogenic) have symbiotic host relationships and are usually associated with the host's immunity to defend against pathogenic invasion. The dysbiosis of the gut microbiota is therefore linked to various human diseases, such as anxiety, depression, hypertension, cardiovascular diseases, obesity, diabetes, inflammatory bowel disease, and cancer. The mechanism leading to the disease development has a crucial correlation with gut microbiota, metabolic products, and host immune response in humans. The understanding of mechanisms over gut microbiota exerts its positive or harmful impacts remains largely undefined. However, many recent clinical studies conducted worldwide are demonstrating the relation of specific microbial species and eubiosis in health and disease. A comprehensive understanding of gut microbiota interactions, its role in health and disease, and recent updates on the subject are the striking topics of the current review. We have also addressed the daunting challenges that must be brought under control to maintain health and treat diseases.

In the past few decades, polymeric nanocarriers have been recognized as promising tools and have gained attention from researchers for their potential to efficiently deliver bioactive compounds, including drugs, proteins, genes, nucleic acids, etc., in pharmaceutical and biomedical applications. Remarkably, these polymeric nanocarriers could be further modified as stimuli-responsive systems based on the mechanism of triggered release, i.e., response to a specific stimulus, either endogenous (pH, enzymes, temperature, redox values, hypoxia, glucose levels) or exogenous (light, magnetism, ultrasound, electrical pulses) for the effective biodistribution and controlled release of drugs or genes at specific sites. Various nanoparticles (NPs) have been functionalized and used as templates for imaging systems in the form of metallic NPs, dendrimers, polymeric NPs, quantum dots, and liposomes. The use of polymeric nanocarriers for imaging and to deliver active compounds has attracted considerable interest in various cancer therapy fields. So-called smart nanopolymer systems are built to respond to certain stimuli such as temperature, pH, light intensity and wavelength, and electrical, magnetic and ultrasonic fields. Many imaging techniques have been explored including optical imaging, magnetic resonance imaging (MRI), nuclear imaging, ultrasound, photoacoustic imaging (PAI), single photon emission computed tomography (SPECT), and positron emission tomography (PET). This review reports on the most recent developments in imaging methods by analyzing examples of smart nanopolymers that can be imaged using one or more imaging techniques. Unique features, including nontoxicity, water solubility, biocompatibility, and the presence of multiple functional groups, designate polymeric nanocues as attractive nanomedicine candidates. In this context, we summarize various classes of multifunctional, polymeric, nano-sized formulations such as liposomes, micelles, nanogels, and dendrimers.

Its increasing incidence has led stroke to be the second leading cause of death worldwide. Despite significant advances in recanalization strategies, patients are still at risk for ischemia/reperfusion injuries in this pathophysiology, in which neuroinflammation is significantly involved. Research has shown that in the acute phase, neuroinflammatory cascades lead to apoptosis, disruption of the blood-brain barrier, cerebral edema, and hemorrhagic transformation, while in later stages, these pathways support tissue repair and functional recovery. The present review discusses the various cell types and the mechanisms through which neuroinflammation contributes to parenchymal injury and tissue repair, as well as therapeutic attempts made in vitro, in animal experiments, and in clinical trials which target neuroinflammation, highlighting future therapeutic perspectives.

The aim of this survey paper is to offer a general view of the developments of fuzzy TOPSIS methods. We begin with a literature review an we explore different fuzzy models that have been applied to the decision making field. Finally, we present some applications of fuzzy TOPSIS.

The ever decreasing area of forests has lead to environmental and economical challenges and has brought with it a renewed interest in developing methodologies that quantify the extent of deforestation and reforestation. In this study we analyzed the deforested areas of the Apuseni Mountains, which has been under economic pressure in recent years and resulted in widespread deforestation as a means of income. Deforested surface dynamics modeling was based on images contained in the Global Forest Database, provided by the Department of Geographical Sciences at Maryland University between 2000 and 2014. The results of the image particle analysis and modelling were based on Total Area (ha), Count of patches and Average Size whereas deforested area distribution was based on the Local Connected Fractal Dimension, Fractal Fragmentation Index and Tug-of-War Lacunarity as indicators of forest fragmentation or heterogeneity. The major findings of the study indicated a reduction of the tree cover area by 3.8%, an increase in fragmentation of 17.7% and an increase in heterogeneity by 29%, while fractal connectivity decreased only by 0.1%. The fractal and particle analysis showed a clustering of forest loss areas with an average increase from 1.1 to 3.0 ha per loss site per year. In conclusion, the fractal and particle analysis provide a relevant methodological framework to further our understanding of the spatial effects of economic pressure on forestry.

The field of nanotechnology is concerned with the creation and application of materials having a nanoscale spatial dimensioning. Having a considerable surface area to volume ratio, nanoparticles have particularly unique properties. Several chemical and physical strategies have been used to prepare zinc oxide nanoparticles (ZnO-NPs). Still, biological methods using green or natural routes in various underlying substances (e.g., plant extracts, enzymes, and microorganisms) can be more environmentally friendly and cost-effective than chemical and/or physical methods in the long run. ZnO-NPs are now being studied as antibacterial agents in nanoscale and microscale formulations. The purpose of this study is to analyze the prevalent traditional method of generating ZnO-NPs, as well as its harmful side effects, and how it might be addressed utilizing an eco-friendly green approach. The study's primary focus is on the potential biomedical applications of green synthesized ZnO-NPs. Biocompatibility and biomedical qualities have been improved in green-synthesized ZnO-NPs over their traditionally produced counterparts, making them excellent antibacterial and cancer-fighting drugs. Additionally, these ZnO-NPs are beneficial when combined with the healing processes of wounds and biosensing components to trace small portions of biomarkers linked with various disorders. It has also been discovered that ZnO-NPs can distribute and sense drugs. Green-synthesized ZnO-NPs are compared to traditionally synthesized ones in this review, which shows that they have outstanding potential as a potent biological agent, as well as related hazardous properties.

The agricultural sector plays a key role in supplying quality food and makes the greatest contribution to growing economies and populations. Plant disease may cause significant losses in food production and eradicate diversity in species. Early diagnosis of plant diseases using accurate or automatic detection techniques can enhance the quality of food production and minimize economic losses. In recent years, deep learning has brought tremendous improvements in the recognition accuracy of image classification and object detection systems. Hence, in this paper, we utilized convolutional neural network (CNN)-based pre-trained models for efficient plant disease identification. We focused on fine tuning the hyperparameters of popular pre-trained models, such as DenseNet-121, ResNet-50, VGG-16, and Inception V4. The experiments were carried out using the popular PlantVillage dataset, which has 54,305 image samples of different plant disease species in 38 classes. The performance of the model was evaluated through classification accuracy, sensitivity, specificity, and F1 score. A comparative analysis was also performed with similar state-of-the-art studies. The experiments proved that DenseNet-121 achieved 99.81% higher classification accuracy, which was superior to state-of-the-art models.

Abstract This EAACI position paper aims at providing a state‐of‐the‐art overview on nonallergic rhinitis ( NAR ). A significant number of patients suffering from persistent rhinitis are defined as nonallergic noninfectious rhinitis ( NANIR ) patients, often denominated in short as having NAR . NAR is defined as a symptomatic inflammation of the nasal mucosa with the presence of a minimum of two nasal symptoms such as nasal obstruction, rhinorrhea, sneezing, and/or itchy nose, without clinical evidence of endonasal infection and without systemic signs of sensitization to inhalant allergens. Symptoms of NAR may have a wide range of severity and be either continuously present and/or induced by exposure to unspecific triggers, also called nasal hyperresponsiveness ( NHR ). NHR represents a clinical feature of both AR and NAR patients. NAR involves different subgroups: drug‐induced rhinitis, (nonallergic) occupational rhinitis, hormonal rhinitis (including pregnancy rhinitis), gustatory rhinitis, senile rhinitis, and idiopathic rhinitis ( IR ). NAR should be distinguished from those rhinitis patients with an allergic reaction confined to the nasal mucosa, also called “entopy” or local allergic rhinitis ( LAR ). We here provide an overview of the current consensus on phenotypes of NAR , recommendations for diagnosis, a treatment algorithm, and defining the unmet needs in this neglected area of research.

Despite not being utilized as considerably as other antidepressants in the therapy of depression, the monoamine oxidase inhibitors (MAOIs) proceed to hold a place in neurodegeneration and to have a somewhat broad spectrum in respect of the treatment of neurological and psychiatric conditions. Preclinical and clinical studies on MAOIs have been developing in recent times, especially on account of rousing discoveries manifesting that these drugs possess neuroprotective activities. The altered brain levels of monoamine neurotransmitters due to monoamine oxidase (MAO) are directly associated with various neuropsychiatric conditions like Alzheimer's disease (AD). Activated MAO induces the amyloid-beta (Aβ) deposition via abnormal cleavage of the amyloid precursor protein (APP). Additionally, activated MAO contributes to the generation of neurofibrillary tangles and cognitive impairment due to neuronal loss. No matter the attention of researchers on the participation of MAOIs in neuroprotection has been on monoamine oxidase-B (MAO-B) inhibitors, there is a developing frame of proof indicating that monoamine oxidase-A (MAO-A) inhibitors may also play a role in neuroprotection. The therapeutic potential of MAOIs alongside the complete understanding of the enzyme's physiology may lead to the future advancement of these drugs.

Monitoring human health for early detection of disease conditions or health disorders is of major clinical importance for maintaining a healthy life. Sensors are small devices employed for qualitative and quantitative determination of various analytes by monitoring their properties using a certain transduction method. A "real-time" biosensor includes a biological recognition receptor (such as an antibody, enzyme, nucleic acid or whole cell) and a transducer to convert the biological binding event to a detectable signal, which is read out indicating both the presence and concentration of the analyte molecule. A wide range of specific analytes with biomedical significance at ultralow concentration can be sensitively detected. In nano(bio)sensors, nanoparticles (NPs) are incorporated into the (bio)sensor design by attachment to the suitably modified platforms. For this purpose, metal nanoparticles have many advantageous properties making them useful in the transducer component of the (bio)sensors. Gold, silver and platinum NPs have been the most popular ones, each form of these metallic NPs exhibiting special surface and interface features, which significantly improve the biocompatibility and transduction of the (bio)sensor compared to the same process in the absence of these NPs. This comprehensive review is focused on the main types of NPs used for electrochemical (bio)sensors design, especially screen-printed electrodes, with their specific medical application due to their improved analytical performances and miniaturized form. Other advantages such as supporting real-time decision and rapid manipulation are pointed out. A special attention is paid to carbon-based nanomaterials (especially carbon nanotubes and graphene), used by themselves or decorated with metal nanoparticles, with excellent features such as high surface area, excellent conductivity, effective catalytic properties and biocompatibility, which confer to these hybrid nanocomposites a wide biomedical applicability.

Explosive blast has been extensively used as a tactical weapon in Operation Iraqi Freedom (OIF) and more recently in Operation Enduring Freedom(OEF). The polytraumatic nature of blast injuries is evidence of their effectiveness,and brain injury is a frequent and debilitating form of this trauma. In-theater clinical observations of brain-injured casualties have shown that edema, intracranial hemorrhage, and vasospasm are the most salient pathophysiological characteristics of blast injury to the brain. Unfortunately, little is known about exactly how an explosion produces these sequelae as well as others that are less well documented. Consequently, the principal objective of the current report is to present a swine model of explosive blast injury to the brain. This model was developed during Phase I of the DARPA (Defense Advanced Research Projects Agency) PREVENT (Preventing Violent Explosive Neurotrauma) blast research program. A second objective is to present data that illustrate the capabilities of this model to study the proximal biomechanical causes and the resulting pathophysiological, biochemical,neuropathological, and neurological consequences of explosive blast injury to the swine brain. In the concluding section of this article, the advantages and limitations of the model are considered, explosive and air-overpressure models are compared, and the physical properties of an explosion are identified that potentially contributed to the in-theater closed head injuries resulting from explosions of improvised explosive devices (IEDs).

The biological characteristics of the tumour are used to estimate prognosis and select appropriate systemic therapy for patients with (breast) cancer. The advent of molecular technology has incorporated new biomarkers along with immunohistochemical and serum biomarkers. Immunohistochemical markers are often used to guide treatment decisions, to classify breast cancer into subtypes that are biologically distinct and behave differently, and both as prognostic and predictive factors. Steroid hormone receptors, markers of tumour proliferation, and factors involved in angiogenesis and apoptosis are of scientific interest. In this review we will provide information on the immunohistochemical markers used in the management of breast cancer patients using available data from the literature. We consider the utility of established immunohistochemical markers, and discuss the challenges involved in integrating novel molecular markers into clinical practice.

The present paper reviews the most recent advances regarding the effects of chemical and organic fertilizers on soil microbial communities. Based on the results from the articles considered, some details are presented on how the use of various types of fertilizers affects the composition and activity of soil microbial communities. Soil microbes have different responses to fertilization based on differences in the total carbon (C), nitrogen (N) and phosphorus (P) contents in the soil, along with soil moisture and the presence of plant species. These articles show that the use of chemical fertilizers changes the abundance of microbial populations and stimulates their growth thanks to the nutrient supply added. Overall, however, the data revealed that chemical fertilizers have no significant influence on the richness and diversity of the bacteria and fungi. Instead, the abundance of individual bacterial or fungal species was sensitive to fertilization and was mainly attributed to the changes in the soil chemical properties induced by chemical or organic fertilization. Among the negative effects of chemical fertilization, the decrease in enzymatic activity has been highlighted by several papers, especially in soils that have received the largest amounts of fertilizers together with losses in organic matter.

Current advancements in nanotechnology and nanoscience have resulted in new nanomaterials, which may pose health and environmental risks. Furthermore, several researchers are working to optimize ecologically friendly procedures for creating metal and metal oxide nanoparticles. The primary goal is to decrease the adverse effects of synthetic processes, their accompanying chemicals, and the resulting complexes. Utilizing various biomaterials for nanoparticle preparation is a beneficial approach in green nanotechnology. Furthermore, using the biological qualities of nature through a variety of activities is an excellent way to achieve this goal. Algae, plants, bacteria, and fungus have been employed to make energy-efficient, low-cost, and nontoxic metallic nanoparticles in the last few decades. Despite the environmental advantages of using green chemistry-based biological synthesis over traditional methods as discussed in this article, there are some unresolved issues such as particle size and shape consistency, reproducibility of the synthesis process, and understanding of the mechanisms involved in producing metallic nanoparticles via biological entities. Consequently, there is a need for further research to analyze and comprehend the real biological synthesis-dependent processes. This is currently an untapped hot research topic that required more investment to properly leverage the green manufacturing of metallic nanoparticles through living entities. The review covers such green methods of synthesizing nanoparticles and their utilization in the scientific world.

Obesity is a chronic disease with high prevalence and associated comorbidities, making it a growing global concern. These comorbidities include type 2 diabetes, hypertension, ventilatory dysfunction, arthrosis, venous and lymphatic circulation diseases, depression, and others, which have a negative impact on health and increase morbidity and mortality. GLP-1 agonists, used to treat type 2 diabetes, have been shown to be effective in promoting weight loss in preclinical and clinical studies. This review summarizes numerous studies conducted on the main drugs in the GLP-1 agonists class, outlining the maximum achievable weight loss. Our aim is to emphasize the active role and main outcomes of GLP-1 agonists in promoting weight loss, as well as in improving hyperglycemia, insulin sensitivity, blood pressure, cardio-metabolic, and renal protection. We highlight the pleiotropic effects of these medications, along with their indications, contraindications, and precautions for both diabetic and non-diabetic patients, based on long-term follow-up studies.

The strategies involved in the development of therapeutics for neurodegenerative disorders are very complex and challenging due to the existence of the blood-brain barrier (BBB), a closely spaced network of blood vessels and endothelial cells that functions to prevent the entry of unwanted substances in the brain. The emergence and advancement of nanotechnology shows favourable prospects to overcome this phenomenon. Engineered nanoparticles conjugated with drug moieties and imaging agents that have dimensions between 1 and 100 nm could potentially be used to ensure enhanced efficacy, cellular uptake, specific transport, and delivery of specific molecules to the brain, owing to their modified physico-chemical features. The conjugates of nanoparticles and medicinal plants, or their components known as nano phytomedicine, have been gaining significance lately in the development of novel neuro-therapeutics owing to their natural abundance, promising targeted delivery to the brain, and lesser potential to show adverse effects. In the present review, the promising application, and recent trends of combined nanotechnology and phytomedicine for the treatment of neurological disorders (ND) as compared to conventional therapies, have been addressed. Nanotechnology-based efforts performed in bioinformatics for early diagnosis as well as futuristic precision medicine in ND have also been discussed in the context of computational approach.

In the last two decades, considerable interest has been shown in understanding the development of the gut microbiota and its internal and external effects on the intestine, as well as the risk factors for cardiovascular diseases (CVDs) such as metabolic syndrome. The intestinal microbiota plays a pivotal role in human health and disease. Recent studies revealed that the gut microbiota can affect the host body. CVDs are a leading cause of morbidity and mortality, and patients favor death over chronic kidney disease. For the function of gut microbiota in the host, molecules have to penetrate the intestinal epithelium or the surface cells of the host. Gut microbiota can utilize trimethylamine, N-oxide, short-chain fatty acids, and primary and secondary bile acid pathways. By affecting these living cells, the gut microbiota can cause heart failure, atherosclerosis, hypertension, myocardial fibrosis, myocardial infarction, and coronary artery disease. Previous studies of the gut microbiota and its relation to stroke pathogenesis and its consequences can provide new therapeutic prospects. This review highlights the interplay between the microbiota and its metabolites and addresses related interventions for the treatment of CVDs.

BACKGROUND: The EURObservational Research Programme-Atrial Fibrillation General Registry Pilot Phase (EORP-AF Pilot) provides systematic collection of contemporary data regarding the management and treatment of 3119 subjects with AF from 9 member European Society of Cardiology (ESC) countries. In this analysis, we report the development of symptoms, use of antithrombotic therapy and rate vs. rhythm strategies, as well as determinants of mortality and/or stroke/transient ischaemic attack (TIA)/peripheral embolism during 1-year follow-up in this contemporary European registry of AF patients. METHODS: The registry population comprised consecutive in- and out-patients with AF presenting to cardiologists in participating ESC countries. Consecutive patients with AF documented by ECG were enrolled. Follow-up was performed by the local investigator, initially at 1 year, as part of a long-term cohort study. RESULTS: At the follow-up, patients were frequently asymptomatic (76.8%), but symptoms are nevertheless common among paroxysmal and persistent AF patients, especially palpitations, fatigue, and shortness of breath. Oral anticoagulant (OAC) use remains high, ∼78% overall at follow-up, and of those on vitamin K antagonist (VKA), 84% remained on VKA during the follow-up, while of those on non-VKA oral anticoagulant (NOAC) at baseline, 86% remained on NOAC, and 11.8% had changed to a VKA and 1.1% to antiplatelet therapy. Digitalis was commonly used in paroxysmal AF patients. Of rhythm control interventions, electrical cardioversion was performed in 9.7%, pharmacological cardioversion in 5.1%, and catheter ablation in 4.4%. Despite good adherence to anticoagulation, 1-year mortality was high (5.7%), with most deaths were cardiovascular (70%). Hospital readmissions were common, especially for atrial tachyarrhythmias and heart failure. On multivariate analysis, independent baseline predictors for mortality and/or stroke/TIA/peripheral embolism were age, AF as primary presentation, previous TIA, chronic kidney disease, chronic heart failure, malignancy, and minor bleeding. Independent predictors of mortality were age, chronic kidney disease, AF as primary presentation, prior TIA, chronic obstructive pulmonary disease, malignancy, minor bleeding, and diuretic use. Statin use was predictive of lower mortality. CONCLUSION: In this 1-year follow-up analysis of the EORP-AF pilot general registry, we provide data on the first contemporary registry focused on management practices among European cardiologists, conducted since the publication of the new ESC guidelines. Overall OAC use remains high, although persistence with therapy may be problematic. Nonetheless, continued OAC use was more common than in prior reports. Despite the high prescription of OAC, 1-year mortality and morbidity remain high in AF patients, particularly from heart failure and hospitalizations.

BACKGROUND: Vadadustat is an oral hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor, a class of drugs that stabilize HIF and stimulate erythropoietin and red-cell production. METHODS: In two phase 3, randomized, open-label, active-controlled, noninferiority trials, we compared vadadustat with the erythropoiesis-stimulating agent (ESA) darbepoetin alfa in patients with non-dialysis-dependent chronic kidney disease (NDD-CKD) not previously treated with an ESA who had a hemoglobin concentration of less than 10 g per deciliter and in patients with ESA-treated NDD-CKD and a hemoglobin concentration of 8 to 11 g per deciliter (in the United States) or 9 to 12 g per deciliter (in other countries). The primary safety end point, assessed in a time-to-event analysis, was the first major adverse cardiovascular event (MACE; a composite of death from any cause, nonfatal myocardial infarction, or nonfatal stroke), pooled across the two trials. Secondary safety end points included expanded MACE (MACE plus hospitalization for either heart failure or a thromboembolic event). The primary and key secondary efficacy end points in each trial were the mean change in hemoglobin concentration from baseline during two evaluation periods: weeks 24 through 36 and weeks 40 through 52. RESULTS: A total of 1751 patients with ESA-untreated NDD-CKD and 1725 with ESA-treated NDD-CKD underwent randomization in the two trials. In the pooled analysis, in which 1739 patients received vadadustat and 1732 received darbepoetin alfa, the hazard ratio for MACE was 1.17 (95% confidence interval [CI], 1.01 to 1.36), which did not meet the prespecified noninferiority margin of 1.25. The mean between-group differences in the change in the hemoglobin concentration at weeks 24 through 36 were 0.05 g per deciliter (95% CI, -0.04 to 0.15) in the trial involving ESA-untreated patients and -0.01 g per deciliter (95% CI, -0.09 to 0.07) in the trial involving ESA-treated patients, which met the prespecified noninferiority margin of -0.75 g per deciliter. CONCLUSIONS: TECT ClinicalTrials.gov numbers, NCT02648347 and NCT02680574.).