Circulating E-Selectin Levels in Chronic Hepatitis C Patients with Normal or Elevated Transaminase Before and After Alpha-Interferon Treatment

E-selectin, an adhesion molecule of the selectin family, is involved in leukocyte adhesion to the endothelium and in the cellular immunological reactions. Expression of this molecule, in fact, is physiologically absent, but it becomes evident on sinusoidal lining cells during inflammatory liver disease. The aim of this study was to evaluate the behavior of E-selectin in chronic hepatitis C (CH-C) patients with persistently normal transaminase in comparison to patients with CH-C and elevated transaminase, and its changes during alpha-interferon therapy. Immunohistochemical localization of E-selectin was also performed on liver tissue specimens of both groups. Fifty-eight subjects were divided into 3 groups: group A included 18 patients with CH-C and persistently normal transaminase; group B 20 patients with CH-C and persistently elevated transaminase levels and group C included 20 healthy subjects, representing the control group. The first two groups were treated with r-IFN at a dose of 6 MU 3 times a week for 3 months and followed-up with 3 MU 3 times a week for another 3 months. Serum baseline values of E-selectin in groups A and B were significantly higher than those in group C (P < 0.04), but there was no difference between groups A and B. Furthermore, there was a trend toward higher E-selectin values as histological severity increased (r = 0.69; P < 0.0001). Post-treatment E-selectin serum values showed a moderate decrease in both groups, but only among responder patients; while E-selectin levels were unchanged in non responders. Immunohistochemical localization showed no staining for E-selectin in normal liver specimens, while there was a quite similar staining for E-selectin in the two groups of patients. In conclusion, this study shows that serum E-selectin levels in patients with CH-C and persistently normal transaminase are higher than in controls and they are associated with severity of liver disease. Liver of these patients express E-selectin molecules, suggesting an activation of the immune system almost identical to that of patients with CH-C and elevated transaminase. In both groups only responder patients showed a moderate decrease below baseline serum values.     

Association between intra-operative cardiac arrest and country Human Development Index status: a systematic review with meta-regression analysis and meta-analysis of observational studies*

Intra-operative cardiac arrests differ from most in-hospital cardiac arrests because they reflect not only the patient's condition but also the quality of surgery and anaesthesia care provided. We assessed the relationship between intra-operative cardiac arrest rates and country Human Development Index (HDI), and the changes occurring in these rates over time. We searched PubMed, EMBASE, Scopus, LILACS, Web of Science, CINAHL and SciELO from inception to 29 January 2020. For the global population, rates of intra-operative cardiac arrest and baseline ASA physical status were extracted. Intra-operative cardiac arrest rates were analysed by time, country HDI status and ASA physical status using meta-regression analysis. Proportional meta-analysis was performed to compare intra-operative cardiac arrest rates and ASA physical status in low- vs. high-HDI countries and in two time periods. Eighty-two studies from 25 countries with more than 29 million anaesthetic procedures were included. Intra-operative cardiac arrest rates were inversely correlated with country HDI (p = 0.0001); they decreased over time only in high-HDI countries (p = 0.040) and increased with increasing ASA physical status (p < 0.0001). Baseline ASA physical status did not change in high-HDI countries (p = 0.106), while it decreased over time in low-HDI countries (p = 0.040). In high-HDI countries, intra-operative cardiac arrest rates (per 10,000 anaesthetic procedures) decreased from 9.59 (95%CI 6.59–13.16) pre-1990 to 5.17 (95%CI 4.42–5.97) in 1990–2020 (p = 0.013). During the same time periods, no improvement was observed in the intra-operative cardiac arrest rates in low-HDI countries (p = 0.498). Odds ratios of intra-operative cardiac arrest rates in ASA 3–5 patients were 8.48 (95%CI 1.67–42.99) times higher in low-HDI countries than in high-HDI countries (p = 0.0098). Intra-operative cardiac arrest rates are related to country-HDI and decreased over time only in high-HDI countries. The widening gap in these rates between low- and high-HDI countries needs to be addressed globally.     

Activator of G protein signaling 3 null mice: I. Unexpected alterations in metabolic and cardiovascular function

Activator of G protein signaling (AGS)-3 plays functional roles in cell division, synaptic plasticity, addictive behavior, and neuronal development. As part of a broad effort to define the extent of functional diversity of AGS3-regulated-events in vivo, we generated AGS3 null mice. Surprisingly, AGS3 null adult mice exhibited unexpected alterations in cardiovascular and metabolic functions without any obvious changes in motor skills, basic behavioral traits, and brain morphology. AGS3 null mice exhibited a lean phenotype, reduced fat mass, and increased nocturnal energy expenditure. AGS3 null mice also exhibited altered blood pressure control mechanisms. These studies expand the functional repertoire for AGS3 and other G protein regulatory proteins providing unexpected mechanisms by which G protein systems may be targeted to influence obesity and cardiovascular function.     

Comparison of Cytomegalovirus (CMV) Enzyme-Linked Immunosorbent Spot and CMV Quantiferon Gamma Interferon-Releasing Assays in Assessing Risk of CMV Infection in Kidney Transplant Recipients

Assessing cytomegalovirus (CMV)-specific cell-mediated immunity (CMI) represents an appealing strategy for identifying transplant recipients at risk of infection. In this study, we compared two gamma interferon-releasing assays (IGRAs), Quantiferon-CMV and CMV enzyme-linked immunosorbent spot (ELISPOT), to determine the ability of each test to predict protective CMV-specific T-cell responses. Two hundred twenty-one Quantiferon-CMV and ELISPOT tests were conducted on 120 adult kidney transplant recipients (KTRs), including 100 CMV-seropositive transplant recipients (R⁺) and 20 CMV-seronegative transplant recipients of a CMV-positive donor (D⁺/R⁻). As a control cohort, 39 healthy adult subjects (including 33 CMV-seropositive and 6 CMV-seronegative subjects) were enrolled. CMV IgG serology was used as a reference for both tests. In the CMV-seropositive individuals, the ELISPOT and Quantiferon-CMV assays provided 46% concordance with the serology, 12% discordance, 18% disagreement between ELISPOT or Quantiferon-CMV and the serology, and 24% gray areas when one or both tests resulted in weak positives. None of the CMV-seronegative subjects showed detectable responses in the ELISPOT or the Quantiferon-CMV test. In transplant recipients, both the ELISPOT and Quantiferon-CMV assays positively correlated with each other and negatively correlated with CMV DNAemia in a significant way (P < 0.05). During the antiviral prophylaxis, all 20 D⁺/R⁻ KTRs we examined displayed undetectable Quantiferon-CMV and ELISPOT results, and there was no evidence of CMV seroconversion. The receiving operator curve (ROC) statistical analysis revealed similar specificities and sensitivities in predicting detectable viremia (areas under the curve [AUC], 0.66 and 0.62 for Quantiferon-CMV and ELISPOT, respectively). ELISPOT and Quantiferon-CMV values of >150 spots/200,000 peripheral blood mononuclear cells (PBMCs) and >1 to 6 IU gamma interferon (IFN-γ) were associated with protection from CMV infection (odds ratios [OR], 5 and 8.75, respectively). In transplant recipients, the two tests displayed similar abilities for predicting CMV infection. Both the ELISPOT and Quantiferon-CMV assays require several ameliorations to avoid false-negative results.     

Patient attitude and habits regarding removable denture home hygiene and correlation with prosthesis cleanliness: A cross-sectional study of elderly Italians

Statement of problemWith the aging population, an increasing number of patients will require removable dental prostheses. Despite the recent public efforts to improve oral healthcare, knowledge of hygiene procedures for removable dental prostheses is sparse.PurposeThe purpose of this cross-sectional study was to determine, through questionnaires, the level of awareness and education of home hygiene procedures among elderly Italian individuals wearing removable dental prostheses and to correlate self-reported hygiene habits and prosthesis cleanliness, as determined by a clinical examination.Material and methodsA cross-sectional study was performed by questionnaires administered by a dental hygienist to patients attending the dental clinics (prosthodontic and periodontology clinical units) at San Paolo Hospital of Milan from January 2014 to October 2015 and who volunteered to participate. The questionnaire included demographic data and oral hygiene habits. Each participant received an intraoral and prosthesis examination performed by the same dental hygienist. The cleanliness of the removable dental prosthesis was classified according to a 3-point scoring system. Categorical variables were expressed as a percentage of study participants and compared by using the χ² test, while, for the statistical correlations between continuous and categorical variables, the point-biserial correlation calculator was used (α=.05).ResultsQuestionnaires were collected from 161 study participants: 92 women (mean ±standard deviation age: 76 ±7.59 years; range: 65-93 years) and 69 men (mean ±standard deviation age: 74 ±6.31 years; range: 65-86 years). A total of 239 prostheses were considered. A significant correlation was found between older participants, older removable dental prostheses, and reduced prosthesis cleanliness, correlating age ranges of participants as well as of removable dental prostheses with the degrees of prosthesis cleanliness (P=.001 and P=.004, respectively). Half the study participants (n=81; 50.3%) reported prosthesis removal during the night, while the others reported sleeping with the prosthesis in place. Some study participants (n=32; 19.9%) reported that they had never received instructions about how to clean the prosthesis. Mechanical brushing with toothbrush and toothpaste was the most common cleaning method (n=47; 29.2%), while the recommended combined cleaning method based on both mechanical brushing and immersion in dental cleanser was applied by 34 (21.1%) study participants. A similar number (n=25; 15.5%) reported at least 1 episode of denture-related stomatitis.ConclusionsIn the analyzed cohort, patient attitude and habits toward home procedures for denture hygiene resulted in poor prosthesis cleanliness. Most individuals used a toothbrush and toothpaste to clean their device, although combining mechanical and chemical cleaning is typically reported to be the optimal method.     

UDP‐glucose enhances outward K+ currents necessary for cell differentiation and stimulates cell migration by activating the GPR17 receptor in oligodendrocyte precursors

In the developing and mature central nervous system, NG2 expressing cells comprise a population of cycling oligodendrocyte progenitor cells (OPCs) that differentiate into mature, myelinating oligodendrocytes (OLGs). OPCs are also characterized by high motility and respond to injury by migrating into the lesioned area to support remyelination. K⁺ currents in OPCs are developmentally regulated during differentiation. However, the mechanisms regulating these currents at different stages of oligodendrocyte lineage are poorly understood. Here we show that, in cultured primary OPCs, the purinergic G‐protein coupled receptor GPR17, that has recently emerged as a key player in oligodendrogliogenesis, crucially regulates K⁺ currents. Specifically, receptor stimulation by its agonist UDP‐glucose enhances delayed rectifier K⁺ currents without affecting transient K⁺ conductances. This effect was observed in a subpopulation of OPCs and immature pre‐OLGs whereas it was absent in mature OLGs, in line with GPR17 expression, that peaks at intermediate phases of oligodendrocyte differentiation and is thereafter downregulated to allow terminal maturation. The effect of UDP‐glucose on K⁺ currents is concentration‐dependent, blocked by the GPR17 antagonists MRS2179 and cangrelor, and sensitive to the K⁺ channel blocker tetraethyl‐ammonium, which also inhibits oligodendrocyte maturation. We propose that stimulation of K⁺ currents is responsible for GPR17‐induced oligodendrocyte differentiation. Moreover, we demonstrate, for the first time, that GPR17 activation stimulates OPC migration, suggesting an important role for this receptor after brain injury. Our data indicate that modulation of GPR17 may represent a strategy to potentiate the post‐traumatic response of OPCs under demyelinating conditions, such as multiple sclerosis, stroke, and brain trauma.     

Toward acellular xenogeneic heart valve prostheses: Histological and biomechanical characterization of decellularized and enzymatically deglycosylated porcine pulmonary heart valve matrices

The use of decellularized xenogeneic heart valves might offer a solution to overcome the issue of human valve shortage. The aim of this study was to revise decellularization protocols in combination with enzymatic deglycosylation, in order to reduce the immunogenicity of porcine pulmonary heart valves, in means of cells, carbohydrates, and, primarily, Galα1-3Gal (α-Gal) epitope removal. In particular, the valves were decellularized with sodium dodecylsulfate/sodium deoxycholate (SDS/SD), Triton X-100 + SDS (Tx + SDS), or Trypsin + Triton X-100 (Tryp + Tx) followed by enzymatic digestion with PNGaseF, Endoglycosidase H, or O-glycosidase combined with Neuraminidase. Results showed that decellularization alone reduced carbohydrate structures only to a limited extent, and it did not result in an α-Gal free scaffold. Nevertheless, decellularization with Tryp + Tx represented the most effective decellularization protocol in means of carbohydrates reduction. Overall, carbohydrates and α-Gal removal could strongly be improved by applying PNGaseF, in particular in combination with Tryp + Tx treatment, contrary to Endoglycosidase H and O-glycosidase treatments. Furthermore, decellularization with PNGaseF did not affect biomechanical stability, in comparison with decellularization alone, as shown by burst pressure and uniaxial tensile tests. In conclusion, valves decellularized with Tryp + Tx and PNGaseF resulted in prostheses with potentially reduced immunogenicity and maintained mechanical stability.     

Focus on HPV Infection and the Molecular Mechanisms of Oral Carcinogenesis

This study is focused on the epidemiological characteristics and biomolecular mechanisms that lead to the development of precancerous and cancerous conditions of oral lesions related to Human Papilloma Virus (HPV) infections. Current evidence from the literature demonstrates the role of HPV in potentially malignant oral disorders. Therefore, the underlying biomolecular processes can give arise, or contribute to, benign lesions as well as to oral carcinogenesis.