Background

Since the outbreak of the COVID-19 pandemic, it has been obvious that virus infection poses a serious threat to human health on a global scale. Certain plants, particularly those rich in polyphenols, have been found to be effective antiviral agents. The effectiveness of Alchemilla viridiflora Rothm. (Rosaceae) methanol extract to prevent contact between virus spike (S)-glycoprotein and angiotensin-converting enzyme 2 (ACE2) and neuropilin-1 (NRP1) receptors was investigated. In vitro results revealed that the tested samples inhibited 50% of virus-receptor binding interactions in doses of 0.18 and 0.22 mg/mL for NRP1 and ACE2, respectively. Molecular docking studies revealed that the compounds from A. viridiflora ellagitannins class had a higher affinity for binding with S-glycoprotein whilst flavonoid compounds more significantly interacted with the NRP1 receptor. Quercetin 3-(6″-ferulylglucoside) and pentagalloylglucose were two compounds with the highest exhibited interfering potential for selected target receptors, with binding energies of −8.035 (S-glycoprotein) and −7.685 kcal/mol (NRP1), respectively. Furthermore, computational studies on other SARS-CoV-2 strains resulting from mutations in the original wild strain (V483A, N501Y-K417N-E484K, N501Y, N439K, L452R-T478K, K417N, G476S, F456L, E484K) revealed that virus internalization activity was maintained, but with different single compound contributions.

Aim To determine a prognostic value of cerebral blood flow parameters for the development of neurological sequelae in term neonates with hypoxic ischaemic encephalopathy (HIE). Methods We reviewed medical records of 47 term neonates with HIE who survived until the age of 12 months of life. According to the Sarnat and Sarnat clinical score, neonates were divided into 3 groups: mild HIE, moderate HIE and severe HIE. All included neonates had the colour Doppler brain sonography performed in the first 24 hours of life. The neurological assessment was done at the age of 12 months of life by using the Denver Developmental Screening Test (DDST). Logic regression analysis was performed using the colour doppler brain sonography parameters with the development of neurological impairment as the primary outcome. Results Out of 47 neonates, 19 (40.4%) were with mild, 17 (36.2%) with moderate and 11 (23.4%) with severe HIE. The values of cerebral blood flow parameters and resistance index (RI) significantly correlated with the neurological impairment at the age of 12 months of life (p<0.001). The limit value of RI indicating the poor neurodevelopmental outcome was 0.81, sensitivity 80%, specificity 85.3%, positive predictive value 52.2% and negative predictive value 95.2%. Conclusion The cerebral blood flow parameters measured with colour doppler brain sonography are good indicators of the severity of HIE and later neurodevelopmetal outcome.

For more than two years, coronavirus disease 19 (COVID-19) has represented a threat to global health and lifestyles. Computed tomography (CT) imaging provides useful information in patients with COVID-19 pneumonia. However, this diagnostic modality is based on exposure to ionizing radiation, which is associated with an increased risk of radiation-induced cancer. In this study, we evaluated the common dose descriptors, CTDIvol and DLP, for 1180 adult patients. This data was used to estimate the effective dose, and risk of exposure-induced death (REID). Awareness of the extensive use of CT as a diagnostic tool in the management of COVID-19 during the pandemic is vital for the evaluation of radiation exposure parameters, dose reduction methods development and radiation protection.

Nonlinear handheld detection of magnetic nanoparticles is used to assess the lymph node status of cancer patients. Joint sensitivity and resolving power of nonlinear handheld detection can be maximized by optimizing the frequency of the excitation field, which is strongly influenced by Brownian and Néel relaxation. The characteristic frequency of magnetic nanoparticles that defines sensitivity and resolving power is usually assessed by AC susceptometry. In this study, we used SPaQ data to predict handheld detection performance for magnetic nanoparticles with various particle sizes. SPaQ assesses dynamics by measuring the derivative of the magnetization originating from magnetic nanoparticles activated by an alternating excitation field. The ratio between the maximum signal difference and full-width-at-half-maximumis used to estimate the optimal excitation frequency. Thereupon, it was shown that a particle with a combination of Brownian and Néel relaxation is superior in nonlinear handheld detection compared to Brownian or Néel only particles. Moreover, the optimal excitation frequency is generally established at a slightly higher frequency compared to the characteristic frequency assessed by AC susceptometry. Consequently, this insight into the consequences of the dynamic behavior of magnetic nanoparticles under an alternating magnetic field enables the optimization of nonlinear handheld detection for specific clinical applications.

The expression pattern of the markers p19, Ki-67, MSX1, MSX2, PDL1, pRB, and CYCLINA2 was quantitatively and semiquantitatively analyzed in histologic sections of the developing and postnatal human eye at week 8, in retinoblastoma, and in various uveal melanomas post hoc studies by double immunofluorescence. The p19 immunoreactivity characterized retinal and/or choroidal cells in healthy and tumor tissues: expression was lower in the postnatal retina than in the developing retina and retinoblastoma, whereas it was high in epithelioid melanomas. Ki67 expression was high in the developing eye, retinoblastoma, and choroidal melanomas. MSX1 and MSX2 expression was similar in the developing eye and retinoblastoma, whereas it was absent in the postnatal eye. Their different expression was evident between epithelioid and myxoid melanomas. Similarly, PDL1 was absent in epithelioid melanomas, whereas it was highly expressed in developing and tumor tissues. Expression of pRB and CYCA2 was characteristic of developing and tumorous eye samples but not of the healthy postnatal eye. The observed expression differences of the analyzed markers correlate with the origin and stage of cell differentiation of the tissue samples. The fine balance of expression could play a role in both human eye development and ocular tumorigenesis. Therefore, understanding their relationship and interplay could open new avenues for potential therapeutic interventions and a better understanding of the mechanisms underlying the developmental plasticity of the eye and the development of neoplasms.

Reaction of diphenylmethanol (4) with n-butyllithium and subsequent treatment with selenium resulted in 12H-dibenzo[d,g][1,2,3]triselenocin-12-ol (5) comprising a novel heterocyclic ring system. The title compound 5 was analyzed by 1H-NMR, 13C-NMR and HPLC. Additionally, the structure of 5 was confirmed by single crystal X-ray diffraction.

Aim To evaluate the efficacy (rate of recanalization) of therapy with novel oral anticoagulants (NOAC; rivaroxaban, apixaban) compared to conventional treatment (low molecular weight heparin - LMWH and vitamin K antagonist) in the treatment of deep vein thrombosis (DVT) of the proximal segments of lower extremities. Methods The first group consisted of patients diagnosed with DVT and treated with NOAC (n = 100), while the second group consisted of patients diagnosed with DVT, who were treated by conventional treatment (low molecular weight heparin and vitamin K antagonists) (n = 100). In the first group, NOAC was included in the initial treatment. Patients in the second group were treated with LMWH for four days, and on the fifth day vitamin K antagonist was included in therapy, international ratio (INR) was titrated to therapeutic values (2.0-3.0), and then low molecular weight heparin was excluded from the therapy. Results There was a statistically significant difference in the estimated values of free lumen of the blood vessel between the examined groups after 30 days (p=0.0001), after 90 days (p=0.0001) and after 180 days (p=0.0001). After 180 days, the average free lumen values in the NOAC group were 85% (81-89%), which was significantly higher than the free lumen values in the second group, 73% (69-79%). Conclusion The use of NOAC represents more efficient treatment of DVT comparing to vitamin K antagonists.

Alpha-methylacyl-CoA racemase (AMACR/P504S) is a mitochondrial and peroxisomal enzyme involved in the branched-chain fatty acid and bile acid metabolism. AMACR is a useful diagnostic biomarker for prostate carcinomas and several other malignancies. Its expression in apocrine breast lesions had been previously reported, but its role in breast cancer progression has not been fully investigated. One hundred fifty breast samples (80 with invasive carcinomas) were studied. The expression of AMACR protein was analyzed using the immunohistochemical method (IHC). Lesions were considered positive if AMACR was detected in ≥10% of the cells at any intensity comprising a histologically defined normal epithelial structure or a pathologic lesion. In addition, AMACR mRNA relative expression was calculated from the whole-transcript RNA-Seq performed on >20,000 diverse tumor samples using a 20,000+ hybrid-capture NGS assay with the transcript capture panel based on the Agilent SureSelect Human All ExonV7. Expression of AMACR protein was restricted to epithelia. It was uncommon in the normal breast (7/81 samples, 9%). Increasing AMACR expression was observed with proliferative epithelial lesions (18% of usual ductal hyperplasias/adenosis, 70% of atypical lesions and 72% of DCIS/LCIS). Invasive ductal carcinomas NST and invasive lobular carcinomas expressed AMACR in 64% and 46%, respectively. The highest AMACR expression was observed in luminal B and HER2-positive breast carcinomas (86-100%). Triple-negative breast carcinomas exhibited AMACR in 50% of the cases. Apocrine lesions showed strong, nearly uniform overexpression of AMACR (100% of metaplasias, hyperplasias and in situ carcinomas and 88% of invasive apocrine carcinomas were positive). RNA-Seq analysis also confirmed AMACR expression in breast carcinomas, although its median value was substantially lower with a lower standard deviation than in prostate carcinomas. Over-expression of AMACR characterizes various proliferative, preinvasive and invasive breast lesions and is not specific to the apocrine morphology. It points to altered lipid metabolism (branched fatty acids) as one of the general characteristics of breast carcinogenesis, like several other malignancies. Its early detection may represent a potential target for cancer progression intervention.

Aim To determine the value of IFN (intzerferon)-α in the patients with systemic lupus erythematosus (SLE) and to correlate IFN-α with values of non-specific biochemical parameters of inflammation (C-reactive protein, leukocytes values, erythrocyte sedimentation rate, albumins and globulins). Methods Research included 55 patients with SLE diagnosis and a control group consisted of 25 healthy subjects (during period 2019-2020). IFN (Interferon)-α and non-specific biochemical parameters of inflammation were obtained using standard protocols. Results IFN-α values were independent of gender (p=0.95). The difference in serum IFN-α values in relation with the age in the SLE group was statistically significant (p=0.036). Only serum globulin was significantly higher (p=0.0023) in IFN-α positive compared to IFN-α negative SLE patients. A statistically significant correlation between the values of IFN-α and globulin was proved (r=0.315; p=0.019). No significant correlation was found between other non-specific biochemical parameters and IFN-α values. Conclusion Increased IFN-α values were observed in younger patients, and the correlation between IFN and globulin was proved.