Same-day discharge (SDD) in patients undergoing percutaneous coronary intervention (PCI) of a chronic total occlusion (CTO) is appealing because of the increased patient comfort. However, data on SDD ...following large-bore vascular access are scarce.
We investigated the feasibility and safety of SDD in patients undergoing large-bore CTO PCI.
Between 2013 and 2023, 948 patients were prospectively enrolled in a single-centre CTO registry and underwent CTO PCI. SDD was pursued in all patients. Large-bore access was defined as the use of ≥7 French (Fr) sheaths in ≥1 access site. A logistic regression analysis was used to identify predictors for non-SDD. Clinical follow-up was obtained at 30 days.
SDD was observed in 62% of patients. Large-bore access was applied in 99% of the cohort. SDD patients were younger and more often male, with lower rates of renal insufficiency and prior coronary artery bypass grafting. Local access site bleeding (odds ratio OR 8.53, 95% confidence interval CI: 5.24-13.87) and vascular access complications (OR 7.23, 95% CI: 1.98-26.32) made hospitalisation more likely, with vascular access complications occurring in 3%. At 30 days, the hospital readmission rate was low in both SDD and non-SDD patients (5% vs 7%; p=non-significant). Finally, SDD was not a predictor for major adverse cardiovascular events (MACE) at follow-up.
Same-day discharge can be achieved in the majority of patients undergoing CTO PCI with large-bore (≥7 Fr) access. Similar low hospital readmission and MACE rates between SDD and non-SDD patients at 30 days demonstrate the feasibility and safety of SDD.
Human metapneumovirus (hMPV) is a respiratory virus, first reported the year 2001. Since then, it has been described as one of the main etiological agents that causes acute lower respiratory tract ...infections (ALRTIs), which is characterized by symptoms such as bronchiolitis, wheezing and coughing. Susceptible population to hMPV-infection includes newborn, children, elderly and immunocompromised individuals. This viral agent is a negative-sense, single-stranded RNA enveloped virus, that belongs to the
family and
genus. Early reports-previous to 2001-state several cases of respiratory illness without clear identification of the responsible pathogen, which could be related to hMPV. Despite the similarities of hMPV with several other viruses, such as the human respiratory syncytial virus or influenza virus, mechanisms used by hMPV to avoid the host immune system are still unclear. In fact, evidence indicates that hMPV induces a poor innate immune response, thereby affecting the adaptive immunity. Among these mechanisms, is the promotion of an anergic state in T cells, instead of an effective polarization or activation, which could be induced by low levels of cytokine secretion. Further, the evidences support the notion that hMPV interferes with several pattern recognition receptors (PRRs) and cell signaling pathways triggered by interferon-associated genes. However, these mechanisms reported in hMPV are not like the ones reported for hRSV, as the latter has two non-structural proteins that are able to inhibit these pathways. Several reports suggest that viral glycoproteins, such as G and SH, could play immune-modulator roles during infection. In this work, we discuss the state of the art regarding the mechanisms that underlie the poor immunity elicited by hMPV. Importantly, these mechanisms will be compared with those elicited by other common respiratory viruses.
Ruthenium (II) complexes are promising anticancer molecules due its pharmacological properties and selectivity to cells tumor. The aim of this work was to study the cytotoxic activity, and apoptosis ...induction of two new ruthenium complexes on a human gastric cancer cell line.
Two ruthenium(II) complexes were synthesized: (H2pbbzim)Ru(tpy-Ph-COOCH3)(Cl)2 (Ru-UCN1), and (tpy)Ru(tpy-Ph-bzH)(Cl)2 (Ru-UCN3), and their anticancer capacity determined by cytotoxic assays, gene expression analysis, caspase activation and confocal microscopy.
Ru-UCN3 is more notably cytotoxic than cisplatin in human gastric cancer cells AGS at 24 h, while Ru-UCN1 is more active against gastric cancer cells than cisplatin at 48 h. The complexes induce apoptosis as shown by RT-qPCR, protease activity, and confocal microscopy. Ru-UCN1 induces the overexpression of pro-apoptotic genes at 3 and 6 h, whereas Ru-UCN3 induces overexpression of these genes at 12 and 24 h. Ru-UCN1 treatment shows a strong activation of caspases 3/7 at 24 h, which was not observed for Ru-UCN3 treatment in the same timeframe.
Taken together, this data suggests that Ru-UCN1 and to a lesser extent, Ru-UCN3, may be interesting anticancer agents for gastric cancer.
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IDO is an enzyme that participates in the degradation of tryptophan (Trp), which is an essential amino acid necessary for vital cellular processes. The degradation of Trp and the metabolites ...generated by the enzymatic activity of IDO can have immunomodulating effects, notably over T cells, which are particularly sensitive to the absence of Trp and leads to the inhibition of T cell activation, cell death, and the suppression of T cell effector functions. Noteworthy, T cells participate in the cellular immune response against the human respiratory syncytial virus (hRSV) and are essential for viral clearance, as well as the total recovery of the host. Furthermore, inadequate or non‐optimal polarization of T cells is often seen during the acute phase of the disease caused by this pathogen. Here, we discuss the capacity of hRSV to exploit the immunosuppressive features of IDO to reduce T cell function, thus acquiring relevant aspects during the biology of the virus. Additionally, we review studies on the influence of IDO over T cell activation and its relationship with hRSV infection.
Review of the capacity of hRSV to exploit the immunosuppressive features of IDO to reduce T cell function and activation.
Vaccine-induced protection against pathogens, especially subunit-based vaccines, are related to antigen properties but mainly in their ability to stimulate the immune system by the use of an ...adjuvant. Modern vaccines are formulated with a high level of antigen purity, where an efficient adjuvant is necessary. In this context, the use of protein Toll-Like Receptor (TLR) agonists as vaccine adjuvants has been highlighted because of their optimal immunogenicity and minimal toxicity. The Surface Immunogenic Protein (SIP) from Group B
(GBS) has gained importance as a new potential protein-based vaccine. Recently, we reported that recombinant SIP (rSIP) expressed by E. coli and purified by High Performance Liquid Chromatography (HPLC) alone induces a protective humoral immune response. In this study, we present the immunomodulatory properties of rSIP as a protein-based adjuvant, as an agonist of TLR. To this end, we showed that C57BL/6 bone marrow-derived dendritic cells pulsed by rSIP resulted in enhanced CD40, CD80, CD86, and Major Histocompatibility Complex (MHC) class II as well as increased secretion proinflammatory cytokines Interleukin (IL)-6, Interferon (IFN)-γ, Tumor Necrosis Factor (TNF)-α, and IL-10. Next, we investigated the in vivo effect of rSIP in the absence or presence of ovalbumin (OVA) on antigen-specific antibody secretion in C57BL/6 mice. Immunization with rSIP plus OVA showed that anti-OVA IgG2a and IgG1a increased significantly compared with OVA alone in C57BL/6 mice. Also, the immunization of rSIP plus OVA generates increased serum cytokines levels characterized by IL-12p70, IL-10, IL-4, and IFN-γ. Interestingly, we observed that rSIP stimulate Toll Like Receptor (TLR)2 and TLR4, individually expressed by Human embryonic kidney (HEK) 293-derived TLR reporter cells. These findings suggest that rSIP is a new potential protein TLR agonist adjuvant and may be employed in the development of new vaccines.
Glucose metabolism is critical for the African trypanosome, Trypanosoma brucei, as an essential metabolic process and regulator of parasite development. Little is known about the cellular responses ...generated when environmental glucose levels change. In both bloodstream and procyclic form (insect stage) parasites, glycosomes house most of glycolysis. These organelles are rapidly acidified in response to glucose deprivation, which likely results in the allosteric regulation of glycolytic enzymes such as hexokinase. In previous work, localizing the chemical probe used to make pH measurements was challenging, limiting its utility in other applications. This paper describes the development and use of parasites that express glycosomally localized pHluorin2, a heritable protein pH biosensor. pHluorin2 is a ratiometric pHluorin variant that displays a pH (acid)-dependent decrease in excitation at 395 nm while simultaneously yielding an increase in excitation at 475 nm. Transgenic parasites were generated by cloning the pHluorin2 open reading frame into the trypanosome expression vector pLEW100v5, enabling inducible protein expression in either lifecycle stage. Immunofluorescence was used to confirm the glycosomal localization of the pHluorin2 biosensor, comparing the localization of the biosensor to the glycosomal resident protein aldolase. The sensor responsiveness was calibrated at differing pH levels by incubating cells in a series of buffers that ranged in pH from 4 to 8, an approach we have previously used to calibrate a fluorescein-based pH sensor. We then measured pHluorin2 fluorescence at 405 nm and 488 nm using flow cytometry to determine glycosomal pH. We validated the performance of the live transgenic pHluorin2-expressing parasites, monitoring pH over time in response to glucose deprivation, a known trigger of glycosomal acidification in PF parasites. This tool has a range of potential applications, including potentially being used in high-throughput drug screening. Beyond glycosomal pH, the sensor could be adapted to other organelles or used in other trypanosomatids to understand pH dynamics in the live cell setting.
Introduction
The prevalence of high levels of stress as well as its multilevel consequences is well documented amongst students in the health sciences, and particularly in dentistry. However, ...investigations of perceived stress amongst Spanish‐speaking student groups are sparse. This study aimed to (i) describe the translation, adaptation and psychometric properties of a Spanish version of the Dental Environment Stressors questionnaire and (ii) to examine the perceived sources of stress and their associations with the students' study year and gender in two dental schools in Latin America.
Materials and methods
All students officially registered in the dental schools of the University of San Sebastian (USS) in Chile and the Catholic University of Cordoba (CUC) in Argentina were invited to participate in the study. The DES30 questionnaire was adapted in Spanish using translation/back‐translation, an expert bilingual committee, and consensus building. Cronbach's alpha was used to measure the instrument's internal consistency, and iterated principal factor analysis with promax rotation was employed to explore its underlying factor structure. Descriptive, bivariate and multivariate methods were used to examine the patterns of association between individual stressors, factor scores and students' characteristics.
Results
Three hundred and four students comprised the study's analytical sample, with two‐thirds of those being female. The DES30‐Sp demonstrated good internal consistency (Cronbach's α = 0.89). A four‐factor solution emerged and included ‘academic workload’, ‘clinical training’, ‘time constraints’ and ‘self‐efficacy beliefs’ factors. ‘Fear of failing a course or a year’, ‘examinations and grades’ and ‘lack of time for relaxation’ were amongst the top individual‐item stressors reported by students in both schools. Amongst this group of undergraduate dental students, those in Argentina, in higher study year, and females reported higher perceived stress.
Conclusions
Increased workload, time constraints and some aspects of clinical training were the top stressors of approximately 300 Chilean and Argentinean dental undergraduates. Some variations between schools, males and females and study years were noted. The Spanish version of the DES30 questionnaire performed well, but future studies should evaluate the instrument's properties in larger and more diverse dental student populations.
Shortly after activation by either thrombin or the tethered ligand domain peptide SFLLRN, thrombin receptors undergo homologous desensitization, temporarily losing their ability to respond to both ...agonists. We have examined the role of receptor internalization and recycling in this process using receptor-directed antibodies as probes. The results show within 1 min of activation > 85% of the approximately 200,000 thrombin receptors on megakaryoblastic human erythroleukemia (HEL) and CHRF-288 cells are sequestered into endosomes via coated pits, after which the majority are transferred to lysosomes. This process does not require proteolysis of the receptor and occurs with sufficient speed to play a major role in the regulation of thrombin receptor function. Although most of the internalized receptors are ultimately degraded, approximately 25% return to the cell surface. These recycled receptors are in a state in which they can respond to SFLLRN but not thrombin; nor do they self-activate despite the apparent continued presence of the tethered ligand. In contrast to other G protein-coupled receptors, which are internalized and then recycled in an activatable state, recovery of the thrombin response occurs only after the expression on the cell surface of adequate numbers of newly synthesized receptors.
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