Transforming growth factor beta 1 (TGF-ß1) in COVID-19 patients: relation to platelets and association with the disease outcome.

Transforming growth factor beta (TGF-ß) is a ubiquitously distributed cytokine known to contribute to the pathogenesis of numerous pathological processes. The aim of this study was to measure serum concentrations of TGF-ß1 in severely ill COVID-19 patients and to analyze its relationship with selected hematological and biochemical parameters and with the disease outcome. The study population included 53 COVID-19 patients with severe clinical expression of the disease and 15 control subjects. TGF-ß1 was determined in serum samples and supernatants from PHA-stimulated whole blood cultures using ELISA assay. Biochemical and hematological parameters were analyzed using standard accepted methods. Our results showed that serum levels of TGF-ß1 in COVID-19 patients and controls correlate with the platelet counts. Also, positive correlations of TGF-ß1 with white blood cell and lymphocyte counts, platelet-to-lymphocyte (PLR) ratio, and fibrinogen level were shown, while negative correlations of this cytokine with platelet distribution width (PDW), D-dimer and activated partial thromboplastin time (a-PTT) values in COVID-19 patients were observed. The lower serum values of TGF-ß1 were associated with the unfavorable outcome of COVID-19. In conclusion, TGF-ß1 levels were strongly associated with platelet counts and unfavorable disease outcome of severely ill COVID-19 patients.

DNA damage in peripheral blood lymphocytes of severely ill COVID-19 patients in relation to inflammatory markers and parameters of hemostasis.

Bearing in the mind that a variety of agents can contribute to genome instability, including viral infections, the aim of this study was to analyze DNA damage in hospitalized COVID-19 patients and its relationship with certain laboratory parameters. The potential impact of applied therapy and chest X-rays on DNA damage was also estimated. The study population included 24 severely COVID-19 patients and 15 healthy control subjects. The level of DNA damage was measured as genetic damage index (GDI) by comet assay. The standard laboratory methods and certified enzymatic reagents for the appropriate autoanalyzers were performed for the determination of the biochemical and hematological parameters. COVID-19 patients had significantly higher level of DNA damage compared with control subjects. The absolute number of neutrophil leukocytes was statistically higher, while the absolute number of lymphocytes was statistically lower in COVID-19 patients than in healthy controls. The analysis of the relationship between DNA damage and laboratory parameters indicated that GDI was positively correlated with interleukin 6 (IL-6) concentration and negatively with platelet count in COVID-19 patients. The level of DNA damage was slightly higher in female patients, in whom it was demonstrated a positive correlation of GDI with C-reactive protein (CRP) and procalcitonin. Likewise, there was a negative relationship of GDI and platelet count, and positive relationship of GDI and activated partial thromboplastin time (aPTT) in female population. The applied therapy (antibiotics, corticosteroid, anticoagulant, and antiviral therapy) as well as chest X rays has been shown to have genotoxic potential. The level of DNA damage significantly corresponds to the inflammatory markers and parameters of hemostasis in COVID-19 patients. In conclusion, inflammation, smoking habit, applied therapy, and chest X rays contribute to a higher level of DNA damage in COVID-19 patients.

Apoptosis and genome instability in children with autoimmune diseases.

As apoptosis and genome instability in children with autoimmune diseases (AIDs) are insufficiently investigated, we aimed to analyse them in peripheral blood lymphocytes (PBLs) of children and adolescents with Hashimoto's thyroiditis (HT), Graves' disease (GD) and type 1 diabetes mellitus (T1DM), including possible factors that could affect their occurrence. The study population included 24 patients and 19 healthy controls. Apoptotic cells were detected using an Annexin V-FITC/7-AAD kit. Genome instability was measured as micronuclei (MNs) frequency using the cytokinesis-block MN assay. In addition, comet assay was performed for determination of genome instability as genome damage index (GDI) in new subpopulation of patients with T1DM. The percentage of apoptotic PBLs in patients with AID was significantly lower than in control subjects. There was a positive correlation between thyroid-stimulating homone (TSH) concentration and the proportion of cells in late stage apoptosis in patients with autoimmune thyroid diseases (AITDs). The MN frequency in patients was significantly higher than in controls. Individuals with HT or T1DM had a significantly higher MN frequency than those with GD. Similarly, the value of GDI in patients with T1DM was significantly higher than in controls. The level of apoptosis was positively correlated with MN frequency as well as with GDI in patients with AID. In conclusion, children with AITD (HT and GD) and T1DM have a significantly lower level of apoptosis in PBLs and significantly higher MN frequency as GDI than healthy subjects. Apoptosis and the level of genome instability in these patients with AID are positively correlated.

Laboratory Puzzle of Oxidative Stress, Parameters of Hemostasis and Inflammation in Hospitalized Patients with COVID-19.

Bearing in mind that coronavirus disease (COVID-19) is associated with a wide range of laboratory abnormalities, the aim of this study was to examine the importance of determining the parameters of oxidative stress and antioxidant protection as well as markers of inflammation and hemostasis in hospitalized patients with COVID-19. The study population included 105 patients with severe COVID-19 and 65 healthy control subjects. The parameters of oxidative stress and the activity of enzymes of the antioxidant system were determined from the obtained samples using spectrophotometric methods. Standard laboratory methods were performed for the determination of the biochemical and hematological parameters. Patients with COVID-19 showed a significantly higher level of pro-oxidative parameters (hydrogen peroxide (H2O2) and the index of lipid peroxidation in the form of thiobarbituric acid-reactive substances (TBARSs)) and a significantly lower activity of the antioxidant system (catalase (CAT)). Patients with COVID-19 had significantly higher values of inflammation parameters (C-reactive protein (CRP), procalcitonin (PCT), ratio of the number of neutrophils to lymphocytes (NLR), and ratio of the number of platelets to lymphocytes (PLR)) and parameters of hemostasis (activated partial thromboplastin time (aPTT), prothrombin time (PT), D-dimer, fibrinogen) than the control healthy subjects. In addition, changes in hemostatic parameters correlated positively with inflammatory markers in the group of patients with COVID-19. The early determination of hemostasis parameters and the parameters of inflammation can help in the prediction of poor prognosis in COVID-19 patients.

Evaluation of quality of life in patients with schizophrenia: An inpatient social welfare institution-based cross-sectional study.

Schizophrenia is a chronic mental illness with a poor quality of life (QoL). The main aim of this study was to measure the QoL and factors that affect the QoL of patients with schizophrenia placed in a social welfare institution. This cross-sectional study included 287 patients with schizophrenia who were treated in a long-stay social care institution in which QoL was assessed using five different instruments: the World Health Organization Quality of Life scale, the EuroQoL Five-Dimension-Five-Level scale (including the visual analog scale), the Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form, and the Brief Psychiatric Rating Scale. To determine the impact of patients' characteristics on score values, multiple linear regression using backward elimination was employed. Due to non-normality in the distribution of the dependent variables, a Box-Cox power transformation was applied to each dependent variable prior to conducting multiple linear regression analysis. Results revealed that patients with schizophrenia have lower QoL. Our study revealed that age, level of education, type of accommodation, type of pavilion, age of onset of the disease, number of prescribed antipsychotics, number of psychiatric comorbidities, duration of therapy, and the number of daily doses of antipsychotics are dominant contributors to the QoL in patients with schizophrenia who were treated in social welfare institution.

Fractional Flow Reserve-Based Patient Risk Classification.

Cardiovascular diseases (CVDs) are a leading cause of death. If not treated in a timely manner, cardiovascular diseases can cause a plethora of major life complications that can include disability and a loss of the ability to work. Globally, acute myocardial infarction (AMI) is responsible for about 3 million deaths a year. The development of strategies for prevention, but also the early detection of cardiovascular risks, is of great importance. The fractional flow reserve (FFR) is a measurement used for an assessment of the severity of coronary artery stenosis. The goal of this research was to develop a technique that can be used for patient fractional flow reserve evaluation, as well as for the assessment of the risk of death via gathered demographic and clinical data. A classification ensemble model was built using the random forest machine learning algorithm for the purposes of risk prediction. Referent patient classes were identified by the observed fractional flow reserve value, where patients with an FFR higher than 0.8 were viewed as low risk, while those with an FFR lower than 0.8 were identified as high risk. The final classification ensemble achieved a 76.21% value of estimated prediction accuracy, thus achieving a mean prediction accuracy of 74.1%, 77.3%, 78.1% and 83.6% over the models tested with 5%, 10%, 15% and 20% of the test samples, respectively. Along with the machine learning approach, a numerical approach was implemented through a 3D reconstruction of the coronary arteries for the purposes of stenosis monitoring. Even with a small number of available data points, the proposed methodology achieved satisfying results. However, these results can be improved in the future through the introduction of additional data, which will, in turn, allow for the utilization of different machine learning algorithms.

UV irradiation induces apoptosis in the human endometrial stromal cell line (ThESC).

PURPOSE: The treatment options of endometrial hyperplasia consist of surgical, interventional and medical therapies including apoptosis-inducing agents. The purpose of the study was to evaluate the effects of ultraviolet (UV) radiation on the viability and the type of cell death on the human endometrial stromal cells (ThESC) line. METHODS: We investigated the effect of UV exposure on human endometrial stromal cell line (ThESC) on cell viability using MTT assay as well as changes in cell morphology using phase microscopy and acridine orange (AO)/ethidium bromide (EB) cell staining. RESULTS: UV treatment significantly decreased the percentage of the viable ThESC cells compared to the viability of untreated control cells using MTT assay (p<0.05). In addition, UV treatment of ThESC cells for 60 and 90 min induced high level of cell morphology disruption, followed with loss of both the cell shape and the presence of defragmented debris and stained with intense red color. CONCLUSIONS: The obtained results suggest the potential role of UV light application as additional treatment option of benign endometrium hyperplasia alone or in combination with other treatment modalities.

The association of circulating sclerostin level with markers of bone metabolism in patients with thyroid dysfunction.

BACKGROUND: The aim of this study was to compare serum sclerostin concentrations in patients with thyroid dysfunction with euthyroid control subjects and to assess the relationship between sclerostin and markers of bone metabolism (osteocalcin and beta-cross-laps). METHODS: The study included 30 patients with thyroid dysfunction (hypothyroidism, hyperthyroidism and subclinical hyperthyroidism) and ten euthyroid controls. Free thyroxine (FT4) was measured by radioimmunoassay, while thyroid stimulating hormone (TSH) concentration was determined immunoradiometrically. We used an ELISA kit to determine the sclerostin level. The electrochemiluminescence method was applied for measuring the bone markers. RESULTS: Sclerostin levels were significantly lower in hypothyroid patients (p=0.009) and significantly elevated in hyperthyroid patients (p=0.008) compared to control values. Hyperthyroid patients also had higher sclerostin than patients with subclinical hyperthyroidism (p=0.013). Sclerostin concentrations were negatively correlated with TSH levels (r=-0.746, p<0.001), but positively with FT4 (r=0.696, p < 0.001). Moreover, sclerostin was positively associated with osteocalcin (r=0.605, p=0.005) and beta-cross-laps levels (r=0.573, p=0.008) in all thyroid patients. CONCLUSIONS: Serum sclerostin is significantly affected in subjects with thyroid dysfunction. Both sclerostin and thyroid status affect bone homeostasis, which is reflected through the significant correlations with osteocalcin and beta-cross-laps.

Parameters of Calcium Metabolism Fluctuated during Initiation or Changing of Antipsychotic Drugs.

OBJECTIVE: Serum parameters of calcium homeostasis were measured based on previously published evidence linking osteoporotic fractures and/or bone/mineral loss with antipsychotics. METHODS: Prospective, four-week, time-series trial was conducted and study population consisted of patients of both genders, aged 35-85 years, admitted within the routine practice, with acute psychotic symptoms, to whom an antipsychotic drug was either introduced or substituted. Serial measurements of serum calcium, phosphorous, magnesium, 25(OH)D, parathyroid hormone, calcitonin, osteocalcin and C-telopeptide were made from patient venous blood samples. RESULTS: Calcium serum concentrations significantly decreased from baseline to the fourth week (2.42±0.12 vs. 2.33±0.16 mmol/L, p=0.022, n=25). The mean of all calcemia changes from the baseline was -2.6±5.7% (-24.1 to 7.7) with more decreases than increases (78 vs. 49, p=0.010) and more patents having negative sum of calcemia changes from baseline (n=28) than positive ones (n=10) (p=0.004). There were simultaneous falls of calcium and magnesium from baseline (63/15 vs. 23/26, p<0.001; OR=4.75, 95% CI 2.14-10.51), phosphorous (45/33 vs. 9/40, p<0.001; 6.06, 2.59-14.20) and 25(OH)D concentrations (57/21 vs. 13/35, p<0.001; 7.31, 3.25-16.42), respectively. Calcemia positively correlated with magnesemia, phosphatemia and 25(OH)D values. Parathyroid hormone and C-telopeptide showed only subtle oscillations of their absolute concentrations or changes from baseline; calcitonin and osteocalcin did not change. Adjustment of final calcemia trend (depletion/accumulation) for relevant risk factors, generally, did not change the results. CONCLUSION: In patients with psychotic disorders and several risks for bone metabolism disturbances antipsychotic treatment was associated with the decrease of calcemia and changes in levels of the associated ions.

Predictive parameters of survival in hemodialysis patients with restless leg syndrome.

Restless leg syndrome (RLS) affects the quality of life and survival in patients on hemodialysis (HD). The aim of this study was to determine the characteristics and survival parameters in patients on HD with RLS. This study was a non-randomized clinical study involving 204 patients on HD, of whom 71 were female and 133 were male. Symptoms of RLS were defined as positive responses to four questions comprising the criteria of RLS. We recorded the outcome of treatment, biochemical analyses, demographic, sexual, anthropometric and clinical characteristics in all study patients. Patients with RLS who completed the study had a significantly higher body mass index and lower intima-media thickness and flow through the arteriovenous fistula. Among patients with RLS who died, there were more smokers as well as higher incidences of cardiovascular disease and diabetes mellitus. Among patients with RLS who survived, there were a greater number of patients with preserved diuresis and receiving erythropoietin therapy. Patients who completed the study had significantly higher levels of hemoglobin, creatinine, serum iron and transferrin saturation. Diabetes mellitus (B = 1.802; P = 0.002) and low Kt/V (B = -5.218; P = 0.001) were major predictive parameters for survival.