The interaction of the SARS-CoV-2 spike (S) glycoprotein receptor-binding domain with the host-cell ACE2 receptor is a well-known step in virus infection. Neuropilin-1 (NRP-1) is another host factor involved in virus internalization. The interaction between S-glycoprotein and NRP-1 has been identified as a potential COVID-19 treatment target. Herein, the effectiveness of folic acid and leucovorin in preventing contact between S-glycoprotein and NRP-1 receptors was investigated using in silico studies and then confirmed in vitro. The results of a molecular docking study showed that leucovorin and folic acid had lower binding energies than EG01377, a well-known NRP-1 inhibitor, and lopinavir. Two hydrogen bonds with Asp 320 and Asn 300 residues stabilized the leucovorin, while interactions with Gly 318, Thr 349, and Tyr 353 residues stabilized the folic acid. The molecular dynamic simulation revealed that the folic acid and leucovorin created very stable complexes with the NRP-1. The in vitro studies showed that the leucovorin was the most active inhibitor of the S1-glycoprotein/NRP-1 complex formation, with an IC75 value of 185.95 µg/mL. The results of this study suggest that folic acid and leucovorin could be considered as potential inhibitors of the S-glycoprotein/NRP-1 complex and, thus, could prevent the SARS-CoV-2 virus’ entry into host cells.

Agricultural practices in Bosnia and Hercegovina demand different improvements, including smart management of land and water resources. A new H2020 project started in 2021 in this regard. The objective of this publication is to spread knowledge about SMARTWATER project by describing different achievements in two years of implementation (2021-2022), to invite target groups to participate in the action and to promote smart agricultural practices. Presented results indicate that the implementation is at a satisfactory level. Project consortium will continue with efforts, including twinning, networking, research, dissemination and increasing competency and fund rising skills.

Primary cardiac tumors, which are uncommon types of tumors, can be presented with a variety of clinical signs and symptoms, depending on their location. We present a case of a 57-year-old female patient with a severe right-sided heart failure. Examination using 2-dimensional transthoracic and 3-dimensional transoesophageal echocardiography detected a large, oval, tumor-like formation within the right atrium, which compromised the blood flow from the superior and inferior vena cava. It appeared to have an irregular echo-free space in its central part, probably due to necrosis. Thoracic multislice computed tomography revealed a heterogeneous, expansive, tumor-like mass in the right atrium, with signs of bleeding in its center. Although there were no signs of metastatic dissemination, it could not be excluded that the tumor-like mass originated outside of the heart. The patient underwent surgical resection of the tumor. The surgery was accompanied with bleeding complications that developed due to the central necrosis with local infiltration. During the postoperative period, severe systemic inflammatory response syndrome developed and the patient died. Pathologists diagnosed undifferentiated pleomorphic cardiac sarcoma for which the prognosis is usually poor. The median survival of patients with this type of diagnosis is less than 1 year, even with surgical resection and further adjuvant therapy.

Background: Coronavirus disease 2019 (COVID-19) can cause a wide clinical spectrum, ranging from asymptomatic to severe disease with a high mortality rate. In view of the current pandemic and the increasing influx of patients into healthcare facilities, there is a need to identify simple and reliable tools for stratifying patients. Objective: Study aimed to analyze whether hemogram-derived ratios (HDRs) can be used to identify patients with a risk of developing a severe clinical form and admission to hospital. Methods: This cross-sectional and observational study included 500 patients with a confirmed diagnosis of COVID-19. Data on clinical features and laboratory parameters were collected from medical records and 13 HDRs were calculated and analyzed. Descriptive and inferential statistics were included in the analysis. Results: Of the 500 patients, 43.8% had a severe form of the disease. Lymphocytopenia, monocytopenia, higher C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were found in severe patients (p < 0.05). Significantly higher neutrophil-to-lymphocyte ratio (NLR), derived NLR (dNLR), neutrophil-to-platelet ratio (NPR), neutrophil-to-lymphocyte-to-platelet ratio (NLPR) and CRP-to-lymphocyte ratio (CRP/Ly) values were found in severe patients (p < 0.001). In addition, they have statistically significant prognostic potential (p < 0.001). The area under the curve (AUC) for CRP/Ly, dNLR, NLPR, NLR, and NPR were 0.693, 0.619, 0.619, 0.616, and 0.603, respectively. The sensitivity and specificity were 65.7% and 65.6% for CRP/Ly, 51.6% and 70.8 for dNLR, 61.6% and 57.3% for NLPR, 40.6% and 80.4% for NLR, and 48.8% and 69.1% for NPR. Conclusion: The results of the study suggest that NLR, dNLR, CRP/Ly, NPR, and NLPR can be considered as potentially useful markers for stratifying patients with a severe form of the disease. HDRs derived from routine blood tests results should be included in common laboratory practice since they are readily available, easy to calculate, and inexpensive.

Background: Cognitive dysfunctions are often presented as a symptom in multiple sclerosis which is associated with both structural and functional imapirments of neuronal networks in the brain. Objective: The aim of the study was to evaluate the influence of dysability, duration and type of disesase on cognitive functions in multiple sclerosis patients. Methods: This study included 60 MS patients treated at the Department of Neurology, Clinical Center University of Sarajevo. Inclusion criteria were clinically definite diagnosis of multiple sclerosis, 18 years of age or older and were able to give written informed consent. Cognitive function was evaluated by the Montreal Cognitive Assessment (MoCa) screening test. Mann-Whitney and Kruskal-Wallis test were used for comparisons between clinical characteristics and MoCa test scores. Results: Out of 63.33% of patients had EDSS <=4.5. Disease lasted longer than 10 years in 30% of patients. 80% had relapsing-remitting MS and 20% had secondary progressive MS. 84,2 % of patients with EDSS ≤ 4.5 had cognitive dysfunction. Higher disability (rho=0,306, p<0,05), progressive type of disease (rho=0,377, p< 0,01) and longer disease duration (rho=0,282, p<0,05) were associated with worse overall cognitive functions. Level of disability showed statistical significant correlation with the executive functions and language domains of cognition (p<0.01). Longer disease duration was significant correlated with executive functions (p<0,01) and language domains (p<0,01), while progressive type of disease was signifacant correlated only with executive functions domain (p<0,01). MoCa score variables did not show a statistically significant difference in relation to the number of relapses per year and the use of imunoterapy. Statistically significant negative correlation was obtained between executive functions domain and level of disability, disease duration and progressive type of disease, while language domain significantly correlated only with disability level and progressive type of disease. Conclusion: High percentage of MS patients has cognitive impairment. Patients with higher disability were presented with lower cognitive abilities, especially in executive functions and language domains. Higher frequency of cognitive impairment were presented in progessive forms of disaese and longer disease duration with strong influence on executive functions domains of cognition.

For many years, researchers have been making efforts to find a manufacturing technique, as well as a drug delivery system, that will allow for oral delivery of biopharmaceuticals to their target site of action without impairing their biological activity. Due to the positive in vivo outcomes of this formulation strategy, self-emulsifying drug delivery systems (SEDDSs) have been intensively studied in the last few years as a way of overcoming the different challenges associated with the oral delivery of macromolecules. The purpose of the present study was to examine the possibility of developing solid SEDDSs as potential carriers for the oral delivery of lysozyme (LYS) using the Quality by Design (QbD) concept. LYS was successfully ion paired with anionic surfactant, sodium dodecyl sulphate (SDS), and this complex was incorporated into a previously developed and optimized liquid SEDDS formulation comprising medium-chain triglycerides, polysorbate 80, and PEG 400. The final formulation of a liquid SEDDS carrying the LYS:SDS complex showed satisfactory in vitro characteristics as well as self-emulsifying properties (droplet size: 13.02 nm, PDI: 0.245, and zeta potential: −4.85 mV). The obtained nanoemulsions were robust to dilution in the different media and highly stable after 7 days, with a minor increase in droplet size (13.84 nm) and constant negative zeta potential (−0.49 mV). An optimized liquid SEDDS loaded with the LYS:SDS complex was further solidified into powders by adsorption onto a chosen solid carrier, followed by direct compression into self-emulsifying tablets. Solid SEDDS formulations also exhibited acceptable in vitro characteristics, while LYS preserved its therapeutic activity in all phases of the development process. On the basis of the results gathered, loading the hydrophobic ion pairs of therapeutic proteins and peptides to solid SEDDS may serve as a potential method for delivering biopharmaceuticals orally.

High-risk human papillomaviruses (HPVs) are considered risk factors in the origin of several human malignancies, such as breast, cervical, head and neck, as well as colorectal cancers. However, there are no data reported on the HPV status in colorectal cancer in the State of Qatar. Therefore, we herein examined the presence of high-risk HPVs (16, 18, 31, 33, 35, 45, 51, 52, and 59), using polymerase chain reaction (PCR) in a cohort of 100 Qatari colorectal cancer patients, and their association with tumor phenotype. We found that high-risk HPV types 16, 18, 31, 35, 45, 51, 52, and 59 were present in 4, 36, 14, 5, 14, 6, 41, and 17% of our samples, respectively. Overall, 69 (69%) of the 100 samples were HPV positive; among these, 34/100 (34%) were positive for single HPV subtypes, while 35/100 (35%) of the samples were positive for two or more HPV subtypes. No significant association was noted between the presence of HPV and tumor grade, stage, or location. However, the presence of coinfection of HPV subtypes strongly correlated with advanced stage (stage 3 and 4) colorectal cancer, indicating that the copresence of more than one HPV subtype can significantly worsen the prognosis of colorectal cancer. The results from this study imply that coinfection with high-risk HPV subtypes is associated with the development of colorectal cancer in the Qatari population.

Abstract Objectiv: Anatomic characterization of the nutrient artery of upper extremity long bones differs among the several textbooks on human anatomy. To elucidate the anatomical features of the nutrient foramen (NF) through which the nutrient arteries pass, we examined the morphology and topography of the NF on the diaphysis of the long bones of the upper extremities. Methods: A total of 150 (50 humeri, 50 radii, 50 ulnae) macerated and degreased adults, long bones of the upper extremities, unknown age, and gender were used as material in this study. The following parameters were determined for each bone: total number of NF, foramina index (FI), total bone length, position of the NF based on the FI value and the surface of the shaft/body of the bones, and obliquity of the nutritional canal (NC). Results: The largest number of NF was found on the middle third of the anteromedial side of the humerus diaphysis, with NC directed distally, that is, towards the elbow. Radius and ulna had predominantly one NF, on middle third of anterior surface, with NC directed proximally. Conclusion: This study provides additional and important information on the location and number of NF in the long bones of the upper and lower extremities in the Bosnian and Herzegovinian population.