Infection with SARS-COV-2 is the cause of COVID-19 and has generated an unprecedented health crisis worldwide. While most of the patients experience mild symptoms, around 20% develop severe disease, ...characterized by pneumonia and in the worst cases by acute respiratory distress syndrome (ARDS).1 The analysis and understanding of the immune responses arising in the course of SARS-COV-2 infection may help to propose therapeutic solutions. Due to the crucial role of Natural Killer (NK) cells in antiviral immune responses,2 we analyzed NK cells in blood from a cohort of 82 individuals: 10 healthy controls (HC), 10 paucisymptomatic COVID-19 patients (pauci), 34 patients with pneumonia (pneumo) and 28 patients with ARDS due to SARS-CoV-2 infection. The absolute numbers of peripheral blood NK cells, B, CD4+, and CD8+ T lymphocytes were lower in the pneumonia and ARDS groups than in healthy controls, consistent with previously published results3 (Fig. 1a). We investigated the NK cell subsets further and found that among CD45+CD3−CD56+ total NK cells the proportion of mature NK cells, a subset defined on the basis of its expression of the CD16 and CD57 cell surface receptors, was markedly lower in patients with ARDS (Fig. 1b). Given their role in viral infection, the loss of mature NK cells may contribute to the pulmonary complications occurring in the most severe cases of COVID-19. We then focused our analysis on molecular pathways likely to improve NK cell antiviral activity to promote SARS-CoV-2 clearance, and analyzed the expression of several immune checkpoints. Given the availability of therapeutic monoclonal antibodies blocking the immunosuppressive functions of PD-1,4 NKG2A,5 and CD396 initially developed for cancer therapies, we analyzed the expression of these molecules on NK cells in our cohort. PD-1 and NKG2A are cell surface receptors, and their engagement with their ligands, PD-L1 and HLA-E, respectively, inhibits the function of T and NK cells. CD39 is an ectoenzyme that cleaves extracellular ATP and ADP, which can be released from dead cells upon viral infection, leading to the generation of adenosine, which has strong immunosuppressive effects on T and NK cells.
Although there is evidence that redox regulation has an essential role in malignancies, its impact on tumor prognosis remains unclear. Here we show crosstalk between oxidative stress and the miR-200 ...family of microRNAs that affects tumorigenesis and chemosensitivity. miR-141 and miR-200a target p38α and modulate the oxidative stress response. Enhanced expression of these microRNAs mimics p38α deficiency and increases tumor growth in mouse models, but it also improves the response to chemotherapeutic agents. High-grade human ovarian adenocarcinomas that accumulate miR-200a have low concentrations of p38α and an associated oxidative stress signature. The miR200a-dependent stress signature correlates with improved survival of patients in response to treatment. Therefore, the role of miR-200a in stress could be a predictive marker for clinical outcome in ovarian cancer. In addition, although oxidative stress promotes tumor growth, it also sensitizes tumors to treatment, which could account for the limited success of antioxidants in clinical trials.
The miR-200 family members have been implicated in stress responses and ovarian tumorigenesis. Here, we find that miR-200c/141 transcription is intimately linked to the transcription of the proximal ...upstream gene PTPN6 (SHP1) in all physiological conditions tested. PTPN6 and miR-200c/141 are transcriptionally co-regulated by two complementary mechanisms. First, a bypass of the regular PTPN6 polyadenylation signal allows the transcription of the downstream miR-200c/141. Second, the promoters of the PTPN6 and miR-200c/141 transcription units physically interact through a 3-dimensional DNA loop and exhibit similar epigenetic regulation. Our findings highlight that transcription of intergenic miRNAs is a novel outcome of transcriptional read-through and reveal a yet unexplored type of DNA loop associating two closely located promoters. These mechanisms have significant relevance in ovarian cancers and stress response, pathophysiological conditions in which miR-200c/141 exert key functions.
The aim of this review was to assess the evidence regarding the most commonly used chelating agents in terms of efficacy, erosive potential, cytotoxicity, interaction, antimicrobial effect, impact on ...sealers adhesion, and release of growth factors.
MEDLINE (PubMed) database, Cochrane Library and Scopus were searched up to January 14, 2023, including studies with one or more of the following chelating agents: 17% EDTA, 9% and 18% HEDP, 10% and 20% citric acid, 2%-2.25% peracetic acid and 7% maleic acid. In addition, the reference lists of all selected articles were also checked to identify additional relevant studies. Articles published in English and available in full-text were selected. The quality of studies was assessed using the modified CONSORT checklist guide and the Cochrane Collaboration tool.
The electronic search yielded 538 citations, 56 of which were included. The articles included had moderate and low evidence values. Among 56 articles included, 55 were in vitro studies and one was a randomized clinical trial. Among the in vitro studies, 15 evaluated efficacy and dentin erosion, 12 evaluated interaction with other endodontic irrigants, 9 tested antimicrobial effect, 4 evaluated cytotoxicity in hamster and rat lung cells, 9 evaluated intervention in adhesion of filling materials and 8 focused on release of growth factors and on behavior of stem cells in regenerative endodontic. The RCT tested antimicrobial effect.
17% EDTA is the most effective in smear layer removal and in releasing growth factors on regenerative endodontics. However, the current incorporation of 9% and 18% etidronic acid has shown optimal results due to its compatibility with sodium hypochlorite and its capability on avoiding smear layer formation through a continuous chelation action. Despite these preliminary findings, methodological standardization between studies is required and in vivo studies are necessary to confirm in vitro studies.
Chelating Agents, Smear Layer, Systematic Review, Endodontics, Root Canal Irrigants.
BackgroundNew and fully validated tests need to be brought into clinical practice to improve the estimation of recurrence risk in patients with colon cancer. The aim of this study was to assess the ...analytical performances of the Immunoscore (IS) and show its contribution to prognosis prediction.MethodsImmunohistochemical staining of CD3+ and CD8+ T cells on adjacent sections of colon cancer tissues were quantified in the core of the tumor and its invasive margin with dedicated IS modules integrated into digital pathology software. Staining intensity across samples collected between 1989 and 2016 (n=595) was measured. The accuracy of the IS workflow was established by comparing optical and automatic counts. Analytical precision of the IS was evaluated within individual tumor block on distant sections and between eligible blocks. The IS interlaboratory reproducibility (n=100) and overall assay precision were assessed (n=3). Contribution of the IS to prediction of recurrence based on clinical and molecular parameters was determined (n=538).ResultsOptical and automatic counts for CD3+ or CD8+ were strongly correlated (r=0.94, p<0.001 and r=0.92, p<0.001, respectively). CD3 and CD8 staining intensities were not altered by the age of the tumor block over a period of 30 years. Neither the position of tested tissue sections within a tumor block nor the selection of the tissue blocks affected the IS. Reproducibility of the IS was not affected by multiple variables (eg, antibody lots, DAB revelation kits, immunohistochemistry automates and operators). Interassay repeatability of the IS was 100% and interlaboratory reproducibility between two testing centers was 93%. Finally, in a case series of patients with stage II–III colon cancer, the relative proportion of variance for time to recurrence was greatest for the IS (53% of prognostic variability) in a model that included IS, T-stage, microsatellite instability status and total number of lymph nodes.ConclusionIS is a robust and validated clinical assay leveraging immune scoring to predict recurrence risk of patient with localized colon cancer. The strong and independent prognostic value of IS should pave the way for it use in clinical practice.
Human beings, monkeys from the Old and New World, make up the mammals belonging to the Primate Order, the latter being exclusive to the American continent and of arboreal habits. With the advances in ...research in the areas of medicine and biomedicine, the demand for raising primates in captivity has increased significantly, so the well-being of non-human primates has become the target of studies by the scientific community. The skeleton is made up of bones and their joints. It is divided into two portions: the axial portion, formed by the skull, vertebrae, ribs and sternum, and the appendicular portion, formed by the thoracic and pelvic limbs. The cells responsible for the formation and integration of these matrices are osteoblasts. However, when they are coated by the matrices, they are called osteocytes, which are responsible for maintaining healthy bone tissue and ensuring isocalcemia (calcium balance). Metabolic bone diseases result from the imbalance between some of these elements and can affect human and non-human primates, as well as other species such as birds, reptiles, amphibians and, of course, other mammals. If calcium levels become unbalanced, the body can develop osteodystrophies over time, that is, lesions in bone tissue caused by an exacerbated increase in bone resorption and consequent weakening of the skeleton. The present case report aims to describe a condition of osteodystrophy secondary to failure in nutritional management in a female Callithrix jacchus (Linnaeus, 1758).
Os seres humanos, macacos do velho e do novo mundo compõem os mamíferos pertencentes a ordem Primates, sendo os últimos exclusivos do continente americano e de hábitos arborícolas. Com os avanços das pesquisas nas áreas da medicina e biomedicina, a demanda da criação de primatas em cativeiro aumentou significantemente. Desta forma, o bem-estar dos primatas não humanos passou a ser alvo de estudos pela comunidade científica. O esqueleto é constituído pelos ossos e suas respectivas articulações. É dividido em duas porções: a porção axial, formada pelo crânio, vértebras, costelas e esterno e a porção apendicular pelos membros torácicos e pélvicos. As células responsáveis pela formação e integração dessas matrizes são os osteoblastos. Todavia, quando os mesmos estão revestidos pelas matrizes, são denominados de osteócitos, que têm a responsabilidade de manter o tecido ósseo hígido e assegurar a isocalcemia (equilíbrio de cálcio). Doenças osteometabólicas são resultantes do desequilíbrio entre alguns desses elementos e podem acometer primatas humanos ou não humanos, assim como outras espécies como aves, répteis, anfíbios e demais mamíferos. Caso os níveis de cálcio entrem em desordem, o organismo pode desenvolver com o tempo quadros de osteodistrofias, ou seja, lesões no tecido ósseo causadas pelo aumento exacerbado de reabsorção óssea e consequente fragilização do esqueleto. O presente relato de caso tem como objetivo descrever um quadro de osteodistrofia secundária à falha no manejo nutricional em uma fêmea de Callithrix jacchus (Linnaeus, 1758).
Purpose
The current literature shows a growing interest to assess the feelings and perceptions of students associated with the performance of elective endodontic procedures. This study aimed to ...evaluate the students' anxiety and self‐perceptions related to performing such treatments.
Methods
Forty‐five students participated in the research (G1 = 22 beginners students; G2 = 23 senior students). Demographic data, STAI‐State and Numerical Rating Scale (NRS) for pre‐operative anxiety were completed before the appointment with patient. The STAI‐Trait; NRS for post‐operative anxiety; previous experiences in endodontics; and level of confidence in each stage of endodontic treatments were collected after appointment. Focal groups for qualitative data collection were performed on separate occasion.
Results
Both groups showed higher scores in STAI‐State than for STAI‐Trait scale. G1 showed higher levels of anxiety in the pre‐operative, compared with post‐operative moment in the NRS scale. G2 reported feeling more confidence to insert intracanal medication and to restore teeth between appointments than G1. In both focus groups, participants reported insecurity in performing endodontic procedures due to difficulty in visualisation and to anatomic complexities. G1 reported that all the confidence they had was based in pre‐clinical experience, and G2 mentioned concern about the end of graduation.
Conclusion
The participants' anxiety diminishes as they gain more experience in performing endodontic procedures. However, as they approach the end of the course anxiety levels increase. Greater availability of elective courses in endodontics could be a valuable alternative to provide students with more exposure to and experience with these procedures.
Parasitic diseases are frequently diagnosed infections in wild animals, among which are gastrointestinal parasites that affect several species. Animals kept in captivity are susceptible to these ...diseases due to stress, poor sanitary and nutritional management, inadequate facilities and overcrowding of individuals in enclosures. However, endoparasitoses can occur clinically or subclinically, with or without a zoonotic character. The present work traced the parasitological profile of captive Nasua nasua (Linnaeus, 1766) specimens from the Arruda Câmara Zoobotanical Park (PZAC) in João Pessoa, Paraíba (Brazil), through the performance of coproparasitological exams, chosen because they are low-cost, fast and minimally invasive techniques requiring little equipment for their execution, in addition to being effective diagnostic methods. Simple flotation techniques and direct examination were used as qualitative means of the samples, thus enabling the visualization and identification of parasites found in the feces.
As doenças parasitárias são infecções frequentemente diagnosticadas em animais selvagens, dentre estas estão as parasitoses gastrointestinais que afetam diversas espécies. Os animais mantidos em cativeiro estão susceptíveis à estas enfermidades devido ao estresse, manejos sanitários e nutricionais deficientes, instalações inadequadas e superlotação de indivíduos em recintos. No entanto, as endo parasitoses podem cursar de maneira clínica ou subclínica, possuindo ou não caráter zoonótico. O presente trabalho traçou o perfil parasitológico de espécimes de Nasua nasua (Linnaeus, 1766) cativos do parque zoobotânico de Arruda Câmara (PZAC) em João Pessoa, Paraíba por meio da realização de exame coproparasitológico, escolhidos por serem métodos de baixo custo, rápidos e pouco invasivos, necessitando de poucos equipamentos para a sua execução, além de ser um eficaz exame diagnóstico. Foram utilizadas técnicas de flutuação simples e exame direto como meio qualitativo das amostras, possibilitando assim a visualização e identificação dos parasitos encontrados nas fezes.
Purpose
This study aims to evaluate the experience of dental students and assess their anxiety levels when performing emergency endodontic treatments.
Methods
Undergraduate students completed the ...STAI‐Trait/State and a questionnaire to assess their confidence level to perform each step of an emergency endodontic procedure. They also answered a numerical scale (NRS) for anxiety before and after emergency care. Ten randomly selected students from the same sample further participated in a focus group aimed at obtaining qualitative data on their perception of endodontic treatments’ conduction and the learning process necessary to perform them.
Results
A total of 23 students joined the study. The majority of the participants reported feeling “confident” when performing local anaesthesia (57.6%), rubber dam placement (57.6%) and coronal sealing (72.7%). However, a small number reported feeling “little confident” to perform access cavity (15.2%) or pulpotomy/pulpectomy (24.2%). Students who scored above the 3rd quartile of STAI‐Trait/State were classified as “highly anxious,” and comprised 26.1% of the sample. The values of NRS scale were higher in the preoperative when compared with the post‐operative assessment. All students classified as “highly anxious” reported low confidence in performing “access cavity” and “pulpotomy/pulpectomy.”
Conclusion
Both quantitative and qualitative analysis showed different anxiety levels in dental students. It can possibly contribute to a reduction in confidence prior to emergency endodontic procedures. The current findings suggest it might be important to rearrange activities in order to allow for more practical classes in Endodontics.
This work aims to study the synthesis and characterization of Ho and HoZr bioglass seeds, in addition to radiological response with the contrast agent Zr incorporated. The cylindrical seeds, ...identified also as Si:Ca:Ho and Si:Ca:Ho:Zr, were synthesized by the sol–gel method and coated with acrylic resin and polyvinyl alcohol membrane . Analysis of the mass attenuation coefficients of Ho and Zr according to the medical X-ray spectrum was performed. The synthesized bioglasses were characterized by quantitatively and qualitatively evaluating the main elemental composition. The following characterization techniques were performed: UV–Vis spectrometry, energy-dispersive X-ray fluorescence (EDS) and X-ray fluorescence with CdTe detector and americium excitation source (Am-241). As results, seeds were synthesized and coated within the two established dimensions of 0.35 ± 0.05 and 0.65 ± 0.05 mm diameters and 1.50 ± 0.10 and 1.57 ± 0.05 mm lengths. The Ho composition was 30.7 % and Zr 22.2 % on Si:Ca:Ho:Zr seeds. The mass attenuation coefficient of zirconium showed to be eightfold superior to the holmium within the medical diagnosis spectra. Radiological response of Si:Ca:Ho:Zr seeds showed 20 % higher contrast compared to Si:Ca:Ho, within a background equivalent to breast glandular tissue, resulting in an appropriate radiological visibility of Si:Ca:Ho:Zr. As conclusion, the characterization methods have identified their elemental composition. Insertion of Zr in the synthesis has increased the radiological contrast, allowing implant’s monitoring by conventional X-ray or mammogram.
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