Rare Neurological Diseases: an Overreview of Pathophysiology, Epidemiology, Clinical Features and Pharmacoeconomic Considerations in the Treating

Rare diseases (RD) are serious chronic diseases affecting small number of people compared to the general population. There are between 6000 and 8000 RDs, which affect about 400 million people worldwide. Drugs used for causal treatment of RDs are called orphan drugs. RDs bear great clinical and economic burden for patients, their families, healthcare systems and society overall. There are at least two reasons for the high cost of treatment of RDs. First, there is no causal therapy for majority of RDs, so exacerbations, complications, and hospitalizations in those patients are common. The second reason is high price of available orphan drugs, which are not cost-effective when traditional pharmacoeconomic evaluation is employed. The pharmacoeconomic aspect of the treatment of RDs is especially important in the field of neurology, since at least one fifth of all RDs is composed of neurological conditions. The aim of this paper was to provide a concise overview of the pathophysiological, epidemiological and clinical characteristics of some of the most important and common rare neurological diseases, with special reference to their impact on society and economy.

Swimming Attenuates Blood Pressure and Oxidative Stress in Hypertensive Rats

Hypertension presents one of the main risk factors for cardiovascular diseases which are the leading cause of morbidity and mortality worldwide. Structural and mechanical changes of the heart and blood vessels as well as overproduction of reactive oxygen species may occur due to the increased blood pressure. Therewith, the goal of our study was to estimate the effects and duration of swimming as a possible therapy approach on blood pressure and oxidative stress parameters in normotensive and hypertensive rats. The study was conducted on 60 male Wistar albino rats divided into two groups, normotensive and hypertensive rats. Each of these groups was divided into three subgroups according to the swimming protocol. The swimming training was kept constant (60 min/day, for five days a week) with two days of rest. After six or nine weeks of the swimming protocol, blood pressure and oxidative stress markers were measured. The control group rats were put in water for one minute a day, in order to avoid water-induced stress. Training significantly reduced systolic blood pressure in hypertensive rats, while diastolic pressure did not change in the group that swam six or nine weeks. The results showed that swimming increases the activity of all measured antioxidative parameters, while values of prooxidants varied depending on the training protocol. Our results confirmed that swimming, as an aerobic exercise, decreases blood pressure and has time-dependent positive system adaptations, especially on the antioxidant parameters.

Online Teaching and Learning in Biomedical Sciences: Students’ and Staff’ Attitudes and Experiences on the New Educational Environment Imposed by the COVID 19 Outbreak

The aim of this pilot study is a preliminary evaluation of previous models / modalities of online teaching at the Faculty of Medical Sciences in Serbia and to examine the attitudes of students and academic staff about education during the COVID-19 pandemic, as well as their previous experiences. The research was designed as an observational qualitative epidemiological study which was conducted on a population of students and academics staff at the Faculty of biomedical sciences, University of Kragujevac during the pandemic of SARS-CoV-2 infection in Serbia. The first phase is a pilot study which included 332 participants performed between December 2020 and January 2021. The pilot study questionnaire is formed for the purposes of the research and consists of 17 closed-ended questions with graduated answers. Students and academic staff completed the questionnaire through an online learning platform in all environments and from all electronic devices. The importance of this study is reflected in the fact that it provides detailed and valid data that can serve the purpose of improving the efficiency of online teaching at the faculties of medical sciences in Serbia In general, the results of our study indicate that in addition to great inexperience, both students and academic staff cope well during online education and the changed environment and learning conditions despite all the difficulties.

Correlation Between Ultrasound BI-RADS 4 Breast Lesions and Fine Needle Cytology Categories in a Sample of Iraqi Female Patients

Background: Breast cancer is the most common malignancy in female and the most registered cause of women’s mortality worldwide. BI-RADS 4 breast lesions are associated with an exceptionally high rate of benign breast pathology and breast cancer, so BI-RADS 4 is subdivided into 4A, 4B and 4C to standardize the risk estimation of breast lesions. The aim of the study: to evaluate the correlation between BI-RADS 4 subdivisions 4A, 4B & 4C and the categories of reporting FNA cytology results. Patients and Methods: A case series study was conducted in the Oncology Teaching Hospital in Baghdad from September 2018 to September 2019. Included patients had suspicious breast findings and given BI-RADS 4 (4A, 4B, or 4C) in the radiological report accordingly. Fine needle aspiration was performed under the ultrasound guide and the results were classified into five categories. The biopsy was performed for suspicious, malignant or equivocal FNA findings. Results: This study included 158 women with BIRADS 4 breast lesions with the mean age of (44.6 years); There was a highly significant association between BI-RADS 4 breast lesion and FNA results (p<0.001); 51.9% of BI-RADS IV-C had C5 FNA results. There was a highly significant association between BI-RADS 4 lesion and the final diagnosis (p<0.001); 41.2% of BI-RADS 4 B had a malignant breast lesion, while 37.3% of BIRADS 4 C had a malignant lesion. Conclusion: A clear relationship was observed between BI-RADS 4 subcategories and the fine needle aspiration cytology subgroups. BI-RADS 4-B is helpful in the discrimination between benign and malignant breast lesions; furthermore BI-RADS 4C has more acceptable validity in the diagnosis of breast malignancy. Therefore, BI-RADS subcategories are encouraged to be included and mentioned in the ultrasound report for more accurate estimation of the lesion nature.

The Impact of Nano-Crystal Hydroxyapatites on the Regeneration of Bone Defects

Calcium hydroxyapatite is a widely used material for replacing bone defects. However, the effectiveness of nano-crystalline calcium hydroxyapatite produced from eggshells in the replacement of bone defects has not been investigated yet. The study aimed to evaluate the effectiveness of using nano-crystalline calcium hydroxyapatite made from eggshell for the healing of bone defect of the femur in rats. Forty-eight (n=48) rats underwent a surgical procedure to simulate femoral defect. The animals were sub-divided into 4 groups (each with n=12) depending on the methods of bone defect replacement: I control group (CG) (without bone defect replacement); II intervention group (the bone defect was replaced by PRP (PRP); III intervention group (the bone defect was replaced by nano-crystalline hydroxyapatite obtained from eggshell) (HA) and IV interventional group (the bone defect was replaced by a combination of hydroxyapatite and PRP) (HA+PRP). The degree of effectiveness of studied methods was assessed using radiological (on the 14th day), histological (on the 61st day), and biomechanical analysis (on the 61st day). According to radiographic data, the CG group had the lowest level of bone regeneration after 14 days (4.2 ±1.7%). In the HA + PRP group, the level of bone regeneration was 22.1±7.1 %, which was higher in comparison with the rates of consolidation of bone defects in the HA group (20.7± 9.3) (p = 0.023). According to the histo-morphometry data, the rates of bone tissue regeneration in the PRP group (19.8 ±4.2%) were higher in comparison with the CG group (12.7 ± 7.3%), (p>0.05). In the HA+PRP group, bone regeneration rates (48.9±9.4 %) were significantly higher (p=0.001) than in the HA group (35.1±9.8%). According to the results of biomechanical assessment under the maximum stress (121.0722), the maximum bending deformation of the contralateral bone without defect was 0.028746, which was higher than the indicators of the HA+PRP group, where at the maximum stress (90.67979) the bending deformation was 0.024953 (p>0.05). Compared to CG, PRP, and HA, biomechanical bone strength was significantly higher in the HA + PRP group (p≤0.01). At the maximum stress (51.81391), the maximum bending strain in the CG group was 0.03869, which was lower than in the PRP group, where the maximum stress and bending strain were 59.45824 and 0.055171, respectively (p>0.05). However, the bone strength of the HA group was statistically significantly higher compared to the CG and PRP groups (p<0.01). The results demonstrated the effectiveness of the use of nanocrystalline calcium hydroxyapatite obtained from eggshell in the healing of a bone defect. The best results were observed in the group of the combined use of nano-crystalline calcium hydroxyapatite and PRP.

Comparative Evaluation of BGR-34 and Sitagliptin in Diabetic Subjects-Open Labelled Randomised Parallel Clinical Study

This article is mainly concerned with the simultaneous open model clinical study of the drug named sitagliptin, a potent hyperglycaemic drug against a novel entity of the natural origin BGR- 34 in diabetic subjects. This was a 3-month randomized, parallel, comparative study. One hundred subjects were planned to be included in the study. The patients were randomly divided into two groups and according to the appropriate sample size analysis, both groups consisted of 100 patients, following the inclusion and exclusion criteria. A total of 90 patients (both male and female) of the mean patient age 30-65 years with the type 2 diabetes were enrolled in the phase 4 of this study and then the data were analyzed on the basis of the different test which included HbA1c (glycated haemoglobin), RBS (random blood sugar), FBS (fasting blood sugar) and PPG (postprandial glucose) values. After completion of the data calibration, the results were analyzed and as a result 10-20% decreased values of HBA1C values accompanied with the RBS, FBS and PPG values were seen in the patients undergoing a 12-week course with BGR-34. Based on the results obtained in the present study, it can be concluded that BGR-34 is effective in reducing high blood sugar levels and this reflects that the BGR-34 therapy is more effective drug in the treatment of diabetes suggesting that it is better in efficacy, and reliability with little or no adverse effects.

Therapeutic Potential of „Derived-Multiple Allogeneic Proteins Paracrine Signaling-D-Mapps” in the Treatment of Dry Eye Disease

Dry eye disease (DED) is a chronic inflammatory disease of the lacrimal system and ocular surface. Considering the important role of inflammation in DED development, the main treatment strategy has shifted from hydration and lubrication of dry ocular surface to the immunomodulation and immunoregulationapproach that should address the main pathologic processes responsible for disease progression. Due to their capacity for production of immunosuppressive factors, mesenchymal stem cells (MSCs) and their secretome have been considered as potentially new agents in DED therapy. We recently developed an immunomodulatory ophthalmic solution “derived- Multiple Allogeneic Proteins Paracrine Signaling (d-MAPPS)” which activity is relied on immunosuppressive capacity of MSC-derived secretome. d-MAPPS contains MSC-derived exosomes, growth factors and immunosuppressive cytokines that are able to efficiently suppress generation of inflammatory phenotype in T cells and macrophages. Herewith, we demonstrated that d-MAPPS protected human corneal epithelial cells from chemical injury and efficiently alleviated ocular discomfort and pain in 131 DED patients during the 12-month follow-up, indicating d-MAPPS eye drops as potentially new remedy for the treatment of DED patients.

Mesenchymal Stem Cells Versus Covid-19. Can They Win the Battle?

Mesenchymal stem cells (MSCs) are multipotent stem cells with numerous features potentially useful in various pathologies. It has been shown that MSCs have regenerative potential due to modulation of immune system response, inflammation diminishing, trans differentiation into various types of cells, proangiogenetic and anti fibrotic influence. Besides all of these traits, MSCs posses anti viral capacity and have been further employed in clinical trails since last year. Here, we revised immunomodulatory, biological and antiviral traits of MSCs, but also pathogenesis of Covid-19 and it’s impact on immune system. Conspicuously, there is a growing number of studies examining effect of MSCs in patients suffering from Covid-19 pneumonia and ARDS. Since MSCs are in theory capable of healing lung injury and inflammation, here we discuss hypothesis, pros and cons of MSCs treatment in Covid-19 patients. Finally, we debate if MSCs based therapy can be promising tool for Covid-19 lung pathologies.

Role of IL-33/ST2 Axis in Chronic Inflammatory Neurological Disorderss

Interleukin-33 (IL-33) is a member of IL-1 family of cytokines, produced constitutively by fibroblasts, endothelial cells, and epithelial cells. IL-33 can be released passively from cells during tissue damage and cell necrosis, suggesting that it may act as an alarmin. Function of IL-33 is mediated by its interaction with ST2 molecule that is expressed on many immune cells: Th2 lymphocytes, NK, NKT and mast cells, monocytes, dendritic cells and granulocytes. IL-33/ST2 pathway plays, often dual, roles in different physiological and inflammatory processes, mediating both, pathological immune responses and tissue repair. Expression of IL-33 in the central nervous system (CNS) is significantly enhanced during various pathological processes, indicating its important role in the pathogenesis of neurological inflammatory and degenerative diseases. In this review the biological features, expression of IL-33 and its ligand ST2 in CNS, and the role of IL- 33/ST2 pathway in development of Alzheimer’s disease and multiple sclerosis are discussed.

The Corneal Changes in Diabetic Patients

Diabetes mellitus (DM) represents a systemic disorder which afects different organs. Ocular complications of the DM are the worldwide leading cause of blindness. The most common complications are diabetic retinopathy, diabetic cataract, neovascular glaucoma. Recently many investigations point out that DM can cause comlications at ocular surface as well. Condition such as decreased corneal sensitivity, dry eye or neurotrophic corneal ulceraction are the main clinical manifestations of the diabetic keratopathy (DK). Untreated, these conditions can lead to serious visual acuity decrease. Pathological processes, based on chronic inflammation, due to chronic hyperglycemia, are the main step in the process of DK development. Adequate treatment of the main disease - DM is an imperative in maintaining the healthy cornea without subjective sensations of diabetic patients.