Insights into Innate Immune Response Against SARS-CoV-2 Infection

The innate immune system is mandatory for the activation of antiviral host defense and eradication of the infection. In this regard, dendritic cells, natural killer cells, macrophages, neutrophils representing the cellular component, and cytokines, interferons, complement or Toll-Like Receptors, representing the mediators of unspecific response act together for both activation of the adaptive immune response and viral clearance. Of great importance is the proper functioning of the innate immune response from the very beginning. For instance, in the early stages of viral infection, the defective interferon response leads to uncontrolled viral replication and pathogen evasion, while hypersecretion during the later stages of infection generates hyperinflammation. This cascade activation of systemic inflammation culminates with cytokine storm syndrome and hypercoagulability state, due to a close interconnection between them. Thus an unbalanced reaction, either under- or over- stimulation of the innate immune system will lead to an uncoordinated response and unfavorable disease outcomes. Since both cellular and humoral factors are involved in the time-course of the innate immune response, in this review we aimed to address their gradual involvement in the antiviral response with emphasis on key steps in SARS-CoV-2 infection.

The Expression of miR-155-5p and Local Matrix Gla Protein in Meningiomas

Meningiomas are classified by the World Health Organization (WHO) in three grades, based on morphological features. Independent of this grading, the presence of calcification in meningiomas influences their growth rate. The messenger RNA of matrix Gla protein (MGP), an extra-hepatic protein with different conformations involved in the homeostasis of ectopic calcification has been found in meningiomas and was shown to be regulated in breast cancer by miR-155-5p, a specific micro RNA. Therefore, we investigated the expression of miR-155-5p and its relationship with local MGP conformations in different grade meningiomas. According to the WHO classification, our 41 samples of meningiomas were stratified in groups WHO I and WHO II. Using real time polymerase chain reaction, we observed a higher miR-155-5p expression in group WHO I versus group WHO II [with a fold change (FC) of 3.83, p=0.027)]. Moreover, the expression of miR-155-5p was higher in calcified tumors compared to non-calcified tumors in all samples (FC=3.01, p=0.047) and in group WHO I (FC=3.65, p=0.048). Utilizing immunohistochemistry, we determined the concurrent presence of all MGP conformations in calcified meningiomas. This study was the first to establish higher miR-155-5p expression in grade WHO I and calcified meningiomas, which could improve molecular classification and targeted therapy and also the presence of all MGP conformations in calcified meningiomas, confirming the existence of an anti-calcification mechanism in meningiomas..

Lupus anticoagulant in children – a confounding factor in diagnosis and targeted therapy

Introduction: Lupus anticoagulant (LAC) belongs to a heterogeneous group of antibodies directed against negatively charged phospholipid-binding proteins, inhibiting phospholipid-dependent reactions. We assessed the frequency, etiological background, clinical and biological expression as well as the appropriate management and outcome of LAC in a pediatric population. Patients and methods: We included 19 pediatric patients diagnosed with a positive LAC test during a period of 1 year. LAC detection was carried out according to the ISTH/SCC guidelines 2012. Coagulometric assays were performed in order to check for coagulation factor activities. The presence of specific inhibitors has been tested by the Bethesda assay. Results: LAC was positive in 0.4% of the patients monitored for increased activated partial thromboplastin time (aPTT) during the study period of 1 year. In contrast to the asymptomatic clinical image presented by the majority of our patients, the biological picture was dominated by an elevated aPTT (79 %), the aPTT ratio correlating significantly with the strength of LAC. In 58 % of the patients LAC became negative within 12 weeks, in another 4 (21%) patients within 20 weeks, whereas in 4 (21%) patients LAC remained positive throughout the follow-up. Conclusion: Albeit usually innocent in asymptomatic patients, LAC needs to be seriously taken into consideration from the diagnostic point of view in order to avoid dangerous therapeutic attitudes..

Essentials in the diagnosis of postoperative myocardial lesions similar to or unrelated to rejection in heart transplant

Background, objectives: Histological diagnosis of control biopsies in patients with heart transplant represents a significant step of monitoring, with a great influence on adjusting immunosuppressive treatment. Histological lesions are usually related to ischemia and reperfusion, with varying degrees of intensity. This study aimed to highlight the most important aspects of the histological diagnosis and differential diagnosis of postoperative myocardial lesions associated or unrelated to rejection in heart transplant. Materials and Methods: This retrospective study involved 53 patients who received cardiac transplant between 2000 and 2017. Patients were monitored by lesion quantification of endomyocardial biopsies, with diagnoses established based on biopsy material in the early, medium and late post-transplant periods. Hematoxylin eosin, Masson’s trichrome, and Van Gieson stains were used; immunohistochemical determinations used CD4, CD20, CD45, CD68, HLA-DR, VEGF and CD31. Results: Ischemia and reperfusion lesions were diagnosed on all biopsies in the first 6 weeks post-transplant. Nine cases of the Quilty effect were identified, and in 12 cases, the biopsies were performed on the same spot as previous biopsies. A significant number of transplanted patients presented cytomegalovirus that was difficult to diagnose on endomyocardial biopsies. Conclusions: The detailed study of ischemia and reperfusion lesions, as well as of changes un-related to rejection becomes a major objective in the short, medium and late post-transplant period. Overdiagnosis of rejection induces changes of the immunosuppressive therapeutic protocol, with alarming repercussions on cytomegalovirus reactivation, and risks of potentiating inflammation, myocyte destruction and the recurrence of disorders related to both inducing and aggravating heart failure.

The effects of microwave radiation generated by mobile phones on the tear film

Electromagnetic radiation (ER) emitted by mobile phones and other modern devices has potentially harmful effects on ocular tissue. Their effects on the eye surface and tear film are little known so far. The aim of this paper was to investigate the effects of ER emitted by the phone mobile on the tear film. For this study, we selected a total of 50 subjects, young, healthy, without chronic treatment, who are not contact lens wearers and who have no history of ophthalmic surgery. Schirmer I test, tear pH and tear ferning test (TFT) were performed on all subjects before (“-pre”) being exposed to ER emitted by the mobile phone and after (“-post”) exposure for 5 minutes, the pH and TFT of the tears were performed. Following the analysis of the obtained results, we found that there are significant changes in tear quality and increased tear pH, which over time can lead to tear film instability, damage to the eye surface and the appearance of dry eye syndrome.

Correction factor between two calcitonin assays: DiaSorin LiaisonXL and Cobas E601

Introduction: Calcitonin measurement is important for the diagnosis and monitoring of medullary thyroid carcinoma. Unfortunately, in clinical practice, different detection systems assays are used in the follow-up of the patients, which can be misleading. Objective: To identify the correction factor for calcitonin measurement on two different immunoanalysers: DiaSorin-LiaisonXL (immunochemiluminescence) and CobasE601 (electro-immunochemiluminescence). Methods: We selected 89 registered CT samples (28-from men; 61-from women), that were analysed on CobasE601 with reported values between 0.5 pg/ml and 2812 pg/ml (128.5±513.98). These CT samples were selected randomly to cover as wide a range of values as possible, and represented either basal CT (n=38) or selected from CT stimulation tests (n=51). Samples were evaluated subsequently on DiaSorin-LiaisonXL. All patients gave their informed consent. Results: Between the two assays a segmented linear correlation was noted. We identified the following general linear regression equation: 1.108x+19.337 (p<0.05). The bias increased at high calcitonin values. Therefore, for a better accuracy we analysed the regression equation segmentally. A statistic difference (p<0.05) was noted for CT values ranged between 350-2600 pg/ml (n=31) on DiaSorin-LiaisonXL, for which the linear regression equation for CobasE601 becomes 1.009x+169.796. Conclusions: Calcitonin correction factors are highly important in the dynamic follow up of a patient suffering from medullary thyroid carcinoma when different detection systems assays are used to determine calcitonin. We identified the correction factors for calcitonin determination between two different frequently used chemiluminescence immunoanalysers: DiaSorin-LiaisonXL and CobasE601. However, it is strongly advisable to use the same analyser in order to establish biochemical evolution of calcitonin.

Deity, love, punishment, rage, and mythonyms from head to toes. A brief history of some medical terms

Although it is undoubtful that today’s Medical English is rooted in Greek and Latin, it is particularly interesting that figures from Greek mythology are the roots of words to describe conditions, body parts, feelings, substances, etc. While there are numerous medical terms that are derived from the names of Greek mythological figures, this paper will only investigate words ranging from A to H and will try to justify the relationship between the concepts and the choice of terminology.

Genetic Diagnostic Approaches in Familial Hypercholesterolemia Evaluation

Familial hypercholesterolemia (FH) manifested as atherosclerosis is a major cause of coronary heart disease. Different scoring systems based on clinical and paraclinical data are currently used, but the FH diagnosis should be made only in the presence of the causative genetic defect. In the present study, 12 symptomatic (previously diagnosed with atherosclerosis) and asymptomatic family members were investigated. Serum lipids were measured using commercial reagents. A genetic investigation was performed by Sanger sequencing using commercial reagents and custom primers, while copy number variations and a selected set of 40 point mutations were evaluated using in vitro diagnostic medical devices. For the investigated patients, serum lipids were within the reference range, due to the fact that the subjects were following lipid-lowering therapy, and smoking was the only identifiable additional risk factor. Four benign exon variants and three intron variants situated within the low-density lipoprotein cholesterol receptor gene were identified by Sanger sequencing. No copy number variations and none of the 40 investigated point mutations were determined. Although independently considered benign, the combined effect of the identified genetic conditions could be pathogenic under the influence of additional risk factors. Even in the presence of a diagnosis made using clinical scores, the molecular diagnosis is often challenging, attesting to the complexity of FH genetic etiology.

Predictors associated with increased troponin in acute decompensated and chronic heart failure patients

Background: Myocardial injury (INJ) expressed by elevated high-sensitivity troponin (hs-Tn) is common in heart failure (HF), due to cardiovascular and non-cardiac conditions. The mechanisms of INJ in acute decompensated HF (ADHF) versus chronic HF (CHF) are still debated. This study’s purpose was to evaluate the determinants of elevated hs-TnT in ADHF and CHF. Methods: We retrospectively analyzed consecutive HF patients with hs-TnT measured on admission, hospitalized in a tertiary-care hospital. Rehospitalizations, acute coronary syndromes, embolisms, infections, autoimmunity and malignancy were excluded. Cut-off point for hs-TnT was 14 ng/L. Results: Our study included 488 HF patients, 56.55% with ADHF. Mean age was 72.52±10.09 years. 53.89% were females. 67.75% ADHF and 45.75% CHF patients had elevated hs-TnT. Median hs-TnT was higher in ADHF versus CHF (21.05[IQR 12.74-33.81] vs 13.20[IQR 7.93-23.25], p<0.0001). In multivariable analysis in ADHF and CHF, log10NT-proBNP (HR=5.30, 95%CI 2.71–10.38, p<0.001, respectively HR=5.49, 95%CI 1.71–17.57, p=0.004) and eGFR (HR=0.72, 95%CI 0.62–0.85, p<0.001, respectively HR=0.71, 95%CI 0.55–0.93, p=0.014) were independent predictors for increased hs-TnT. Independent factors associated with elevated hs-TnT in ADHF were male sex (HR=2.52, 95%CI 1.31-4.87, p=0.006) and chronic pulmonary obstructive disease (COPD) (HR=10.57, 95%CI 1.26-88.40, p=0.029), while in CHF were age (HR=2.68, 95%CI 1.42-5.07, p=0.002) and previous stroke (HR=5.35, 95%CI 0.98-29.20, p=0.053). Conclusion: HF severity, expressed by NT-proBNP levels, and kidney disease progression, expressed by eGFR, were independent predictors associated with increased hs-TnT in both ADHF and CHF. Specific independent predictors were also indentified in ADHF (male sex, COPD) and CHF (age, history of stroke).

The possibility of clinical use for the oxidative stress marker in correlation with blood flow parameters in pregnancy-induced hypertension

Introduction: In pregnancy-induced hypertension (PIH) there is a disorder in placental blood flow which causes intrauterine fetal hypoxia, and oxidative stress has a significant role in this condition. The aims of this research were to analyze the relation of thiobarbituric acid reactive substance (TBARS), as a marker of oxidative stress and absent end-diastolic flow (AEDF), as well as the relation of TBARS and cerebroplacental ratio (CPR). Methods: The research included 200 pregnant women in the gestation period from 28th to 40th, 100 were in a control group and 100 were with PIH. The CPR and TBARS were analyzed in all examined pregnant women. The CPR was calculated by dividing the Doppler indices of the middle cerebral artery by the umbilical artery. Results: Mean value of TBARS in the group with the PIH who had AEDF was in the interval of high values - 43.22 μmol/l. The result shows that through the application of Spearman’s coefficient, the correlation results in a statistically significant correlation between CPR and TBARS values: ρ = - 0.249, p = 0.0001. Conclusion: PIH has a very high level of oxidative stress, especially in pregnant women with absent end-diastolic flow in the umbilical artery and pathologic CPR. The Spearman’s test results in statistical significance and negative correlation, which means that in higher TBARS values, values of CPR are lower and vice versa, which indicates a possibility of clinical application of TBARS.