The Role of DNA Repair (XPC, XPD, XPF, and XPG) Gene Polymorphisms in the Development of Myeloproliferative Neoplasms.

Background and Objectives: Several polymorphisms have been described in various DNA repair genes. Nucleotide excision DNA repair (NER) detects defects of DNA molecules and corrects them to restore genome integrity. We hypothesized that the XPC, XPD, XPF, and XPG gene polymorphisms influence the appearance of myeloproliferative neoplasms (MPNs). Materials and Methods: We investigated the XPC 1496C>T (rs2228000, XPC Ala499Val), XPC 2920A>C (rs228001, XPC Lys939Gln), XPD 2251A>C (rs13181, XPD Lys751Gln), XPF-673C>T (rs3136038), XPF 11985A>G (rs254942), and XPG 3507G>C (rs17655, XPG Asp1104His) polymorphisms by polymerase chain reaction-restriction fragment length polymorphism analysis in 393 MPN patients [153 with polycythemia vera (PV), 201 with essential thrombocythemia (ET), and 39 with primary myelofibrosis (PMF)] and 323 healthy controls. Results: Overall, we found that variant genotypes of XPD 2251A>C were associated with an increased risk of MPN (OR = 1.54, 95% CI = 1.15-2.08, p = 0.004), while XPF-673C>T and XPF 11985A>G were associated with a decreased risk of developing MPN (OR = 0.56, 95% CI = 0.42-0.76, p < 0.001; and OR = 0.26, 95% CI = 0.19-0.37, p < 0.001, respectively). Conclusions: In light of our findings, XPD 2251A>C polymorphism was associated with the risk of developing MPN and XPF-673C>T and XPF 11985A>G single nucleotide polymorphisms (SNPs) may have a protective role for MPN, while XPC 1496C>T, XPC 2920A>C, and XPG 3507G>C polymorphisms do not represent risk factors in MPN development.

The transition journey of EU vs. NON-EU countries for waste management.

This study aims to identify macroeconomic indicators that can be used as predictors of waste management on the European continent. The study was conducted taking in account the intensification of urbanizations, the increase of standard of leaving that fuels to consumerism phenomenon, and imposed challenges for waste management. The research focuses on the interval from 2010 to 2020 for 37 European countries grouped according to EU15/EU28/non-EU and EU/non-EU members. As macroeconomic indicators, human development index (HDI), GDP/capita. GNI/capita, general government expenditure with environment protection, people at risk of poverty or social exclusion, population by educational attainment level, sex, and age (%)-less than primary, primary and lower secondary education (levels 0-2) were used. A multilinear regression model with collinearity diagnosis was applied to find out the direction and intensity of the contribution of independent variables and to hierarchy the predictors of waste management.. For multiple comparison between and inside of each grouping of countries, statistical inference methods were used: one-way ANOVA with Bonferroni post hoc test multiple comparisons and independent samples Kruskal-Wallis test with Dunn's post hoc test. The main conclusions of the study are that EU15 countries have the highest average values for most indicators of waste management, comparative with EU28 and with non-EU countries, followed by a group of EU28 countries. For indicators of recycling rate of packaging waste by type of packaging-metallic and recycling rate of e-waste, the non-EU countries have the highest values of mean compared with the EU15 and EU28 groups of countries. This can be explained by the high level of development of the some non-euro area countries (Iceland, Norway, Switzerland, Liechtenstein) that have intense concerns about waste recycling and have the necessary financial strength to carry out complex environmental protection programs.

Dynamic Evaluation of Natural Killer Cells Subpopulations in COVID-19 Patients.

The aim of the study was to evaluate the dynamic changes of the total Natural Killer (NK) cells and different NK subpopulations according to their differentiated expression of CD16/CD56 in COVID-19 patients. Blood samples with EDTA were analyzed on day 1 (admission moment), day 5, and day 10 for the NK subtypes. At least 30,000 singlets were collected for each sample and white blood cells were gated in CD45/SSC and CD16/CD56 dot plots of fresh human blood. From the lymphocyte singlets, the NK cells subpopulations were analyzed based on the differentiated expression of surface markers and classified as follows: CD16-CD56+/++/CD16+CD56++/CD16+CD56+/CD16++CD56-. By examining the CD56 versus CD16 flow cytometry dot plots, we found four distinct NK sub-populations. These NK subtypes correspond to different NK phenotypes from secretory to cytolytic ones. There was no difference between total NK percentage of different disease forms. However, the total numbers decreased significantly both in survivors and non-survivors. Additionally, for the CD16-CD56+/++ phenotype, we observed different patterns, gradually decreasing in survivors and gradually increasing in those with fatal outcomes. Despite no difference in the proportion of the CD16-CD56++ NK cells in survivors vs. non-survivors, the main cytokine producers gradually decline during the study period in the survival group, underling the importance of adequate IFN production during the early stage of SARS-CoV-2 infection. Persistency in the circulation of CD56++ NK cells may have prognostic value in patients, with a fatal outcome. Total NK cells and the CD16+CD56+ NK subtypes exhibit significant decreasing trends across the moments for both survivors and non-survivors.

Demographic, hematologic, and endoscopic differences between predominant corporeal and antral atrophic gastritis: A STROBE-Compliant study.

ABSTRACT: The study aimed to assess demographic, clinical, and endoscopic parameters in patients with predominant corporeal atrophic gastritis (CAG) and enterochromaffin-like cell hyperplasia suggestive for autoimmune etiology in comparison with patients presenting Helicobacter pylori atrophic gastritis limited to the gastric antrum (AAG).Demographical, clinical, and pathological data of consecutive patients who underwent an upper digestive endoscopy for bleeding screening risk, symptoms, or anemia in a single endoscopy unit were retrieved. The final study group included 63 patients with CAG and enterochromaffin-like cell hyperplasia on histology and a control group of 142 patients with AAG.Female patients were predominant in the group with CAG versus AAG (69.8% vs 46.4%, P = .002). Microcytic anemia (P < .001), but not macrocytic anemia (P = .14) was associated with CAG, the mean corpuscular volume of erythrocyte (MCV) (82.5 vs 86.5 fl, P = .01), the mean value of serum iron (11.8 vs 14.3 µmol/L, P = .02), and hemoglobin level (11.0 vs 12.7 g/dL P < .01) being significantly lower in patients with CAG versus AAG. Upper digestive endoscopies with no visible mucosal lesions (P = .01) were also more frequent in the patients with CAG, but there were not differences regarding digestive symptoms between groups. The linear regression models revealed that the low hemoglobin (P < .001) and low MCV (P = .03) are the independent variables that can predict CAG on histology, but not the serum iron level (P = .77)Consecutive patients investigated on endoscopy with CAG in comparison with those having AAG are more frequent female, they have microcytic anemia, and no mucosal lesions on endoscopy. The decreased hemoglobin level and low MCV, rather than the serum iron level are predictors for CAG versus AAG on histology in endoscopic population.

Treatment With Cladribine Selects IFNγ+IL17+ T Cells in RRMS Patients - An In Vitro Study.

Background: Multiple sclerosis (MS) is an incurable autoimmune disease mediated by a heterogeneous T cell population (CD3+CD161+CXCR3-CCR6+IFNγ-IL17+, CD3+CXCR3+CCR6+IFNγ+IL17+, and CD3+CXCR3+IFNγ+IL17- phenotypes) that infiltrates the central nervous system, eliciting local inflammation, demyelination and neurodegeneration. Cladribine is a lymphocyte-depleting deoxyadenosine analogue recently introduced for MS therapy as a Disease Modifying Drug (DMD). Our aim was to establish a method for the early identification and prediction of cladribine responsiveness among MS patients. Methods: An experimental model was designed to study the cytotoxic and immunomodulatory effect of cladribine. T cell subsets of naïve relapsing-remitting MS (RRMS) patients were analyzed ex vivo and in vitro comparatively to healthy controls (HC). Surviving cells were stimulated with rh-interleukin-2 for up to 14days. Cell proliferation and immunophenotype changes were analyzed after maximal (phorbol myristate acetate/ionomycin/monensin) and physiological T-cell receptor (CD3/CD28) activation, using multiparametric flow cytometry and xMAP technology. Results: Ex vivo CD161+Th17 cells were increased in RRMS patients. Ex vivo to in vitro phenotype shifts included: decreased CD3+CCR6+ and CD3+CD161+ in all subjects and increased CD3+CXCR3+ in RRMS patients only; Th17.1 showed increased proliferation vs Th17 in all subjects; CD3+IL17+ and CD3+IFNγ+IL17+ continued to proliferate till day 14, CD3+IFNγ+ only till day 7. Regarding cladribine exposure: RRMS CD3+ cells were more resistant compared to HC; treated CD3+ cells proliferated continuously for up to 14 days, while untreated cells only up to 7 days; both HC/RRMS CD3+CXCR3+ populations increased from baseline till day 14; in RRMS patients vs HC, IL17 secretion from cladribine-treated cells increased significantly, in line with the observed proliferation of CD3+IL17+ and CD3+IFNγ+IL17+ cells; in both HC/RRMS, cladribine led to a significant increase in CD3+IFNγ+ cells at day 7 only, having no further effect at day14. IFNγ and IL17 secreted in culture media decreased significantly from ex vivo to in vitro. Conclusions: CD3+ subtypes showed different responsiveness due to selectivity of cladribine action, in most patients leading to in vitro survival/proliferation of lymphocyte subsets known as pathogenic in MS. This in vitro experimental model is a promising tool for the prediction of individual responsiveness of MS patients to cladribine and other DMDs.

Short-Term Impact of Iron Deficiency in Different Subsets of Patients with Precapillary Pulmonary Hypertension from an Eastern European Pulmonary Hypertension Referral Center.

BACKGROUND: Over the last few decades, interest in the role of iron status in pulmonary hypertension (PH) has grown considerably due to its potential impact on symptoms, exercise capacity (as assessed by the 6-minute walk distance [6MWD]), prognosis, and mortality. The aim of the present study was to identify iron deficiency (ID) prevalence in specific precapillary PH subgroups of Romanian patients and its short-term impact on 6MWD. PATIENTS AND METHODS: Complete datasets from 25 precapillary PH adults were examined and included in the analysis. Data were collected at baseline and after continuous follow-up of an average of 13.5 months. Enrolled patients were assigned to group 1 (pulmonary arterial hypertension) or subgroup 4.1 (chronic thromboembolic pulmonary hypertension), and individualized targeted therapy was prescribed. General characteristics, World Health Organization functional class, 6MWD, pulse oximetry, laboratory parameters, and echocardiographic and hemodynamic parameters were recorded. Ferritin values and transferrin saturation were used to assess ID. RESULTS: At baseline, 16 out of 25 patients were iron deficient. The univariate linear regression analysis did not show a statistically significant impact of ID on 6MWD (p=0.428). In multivariate regression analysis, possible predictors of 6MWD, including ID, were not statistically significant at baseline or after an average of 13.5 months follow-up (p=0.438, 0.361, respectively) and ID indicates a negative impact on 6MWD independent of applied corrections. CONCLUSION: The results of this study demonstrate that 1.4.1 subgroup PAH patients have an increased prevalence of ID compared with other etiologies. ID has a negative impact on the functional status (assessed by 6MWD), in specific groups and subgroups of patients with precapillary PH, albeit not independently nor significant to other known predictors such as age, gender, oxygen saturation, and hemoglobin value. These data can be integrated with global research and are consistent with phenotypes of patients diagnosed with PH of different etiologies.