Systemic lupus erythematosus induced by anti-tumor necrosis factor α therapy in inflammatory rheumatic diseases: a case series.

This case series aims to characterize the development of systemic lupus erythematosus (SLE) induced by anti-tumor necrosis factor α (anti-TNFα) therapy in patients with inflammatory rheumatic diseases, namely rheumatoid arthritis (RA), spondylarthritis (SpA), and psoriatic arthritis (PsA). Patients with a diagnosis of SLE induced by anti-TNFα therapy and registered on the Rheumatic Diseases Portuguese Register (Reuma.pt) who started their first anti-TNFα between 2001 and 2020 were included. Demographic, clinical, and laboratory data were obtained by consulting Reuma.pt. The diagnosis of SLE induced by anti-TNFα was considered if there was a temporal relationship between the onset of anti-TNFα therapy and manifestations (clinical and immunological) in accordance with the American College of Rheumatology/European League Against Rheumatism criteria (2019). A total of 607 patients with inflammatory rheumatic diseases and six cases of SLE induced by anti-TNF-α therapy were reviewed: two patients were affected by RA, three patients by SpA, and one by PsA. All these patients had articular and constitutional symptoms that improved after discontinuation of the anti-TNFα agent. After switching to a second anti-TNFα agent, there was no recurrence of SLE over time. The development of SLE secondary to anti-TNFα agents in inflammatory rheumatic patients is rare. In this case series, all patients had a mild disease that improved after therapy discontinuation without recurrence of the disease. SLE induced by anti-TNFα should be considered in the follow-up of RA, SpA, and PsA patients.

A medication reconciliation failure: A case report and incident analysis.

BACKGROUND: Medication reconciliation is advocated to ensure the continuity, safety, and effective use of medicines across transitions of care. CASE REPORT: In this report, we describe the case of a 90-year-old female with previous diagnoses of atrial fibrillation and cutaneous metastatic breast cancer presenting with bilateral ulcerative lesions on the chest wall. The patient was diagnosed with Deep Vein Thrombosis at the Emergency Department and started on rivaroxaban, although the patient was already taking edoxaban. This therapeutic duplication was noticed only one week later, even though she was already experiencing significant bleeding managed through a prescribing cascade. Despite the technical error (action-based), it is possible to identify several weaknesses in the organisation's structure, which provided a trajectory of accident opportunity. CONCLUSION: Anticoagulants are ranked first for the highest priority to receive a medication reconciliation. To achieve an optimal level of medication reconciliation, we ought to recognise and correct latent failures.

Burden of non-communicable diseases and the achievement of the sustainable development goals in 2030 in Mercosur countries.

OBJECTIVES: The aims of this article were to analyse the burden of NCDs and their RFs in the Mercosur countries between 1990 and 2019 and to project mortality trends for 2030. STUDY DESIGN: Epidemiological study of time series. METHODS: The present study used data from the Global Burden of Disease study. The absolute number of deaths, mortality rates, disability-adjusted life years, years of life lost, years lived with disability and the burden of premature mortality by NCD attributable to the RFs were evaluated. Projections were made up to 2030. Age-standardised rates were used to draw comparisons by years and by countries. The analysis was conducted using the RStudio software. RESULTS: Between 1990 and 2019, a decrease was found in the premature mortality rates caused by NCDs in all the countries, except for Paraguay, which remained stable. When analysing premature mortality rates due to NCDs up to 2030, it was predicted that none of the countries would achieve the sustainable development goal of a one-third reduction in premature mortality by NCDs. Regarding the impacts of the RFs for NCDs, smoking, dietary risks, high blood pressure (BP) and high body mass index (BMI) were the main risks attributable to premature deaths due to NCDs. CONCLUSIONS: The results showed that mortality rates are declining in Mercosur countries; however, none of the countries are predicted to achieve the sustainable development goal of a one-third reduction in mortality due to NCDs by 2030. In addition to access to adequate treatment, progress is required in public regulation actions to reduce RFs, such as smoking, dietary risks, high BP and high BMI.

Evaluating H295R steroidogenesis assay data for robust interpretation.

The in vitro H295R steroidogenesis assay (OECD TG 456) is used to determine a chemical's potential to interfere with steroid hormone synthesis/metabolism. As positive outcomes in this assay can trigger significant higher tiered testing, we compiled a stakeholder database of reference and test item H295R data to characterize assay outcomes. Information concerning whether a Level 5 reproductive toxicity study was triggered due to a positive outcome in the H295R assay was also included. Quality control acceptance criteria were not always achieved, suggesting this assay is challenging to conduct within the guideline specifications. Analysis of test item data demonstrated that pairwise significance testing to controls allowed for overly sensitive statistically significant positive outcomes, which likely contribute to the assay's high positive hit rate. Complementary interpretation criteria (e.g., 1.5-fold change threshold) markedly reduced the rate of equivocal and positive outcomes thus improving identification of robust positive effects in the assay. Finally, a case study (positive H295R outcome and no endocrine adversity in vivo) is presented, which suggests that stricter data interpretation criteria could refine necessary in vivo follow-up testing. Overall, the described additional criteria could improve H295R data interpretation and help inform on how to best leverage this assay for regulatory purposes.

Management and outcomes of obturator hernias: a systematic review and meta-analysis.

PURPOSE: Obturator Hernia (OH) is a rare type of abdominal wall hernia. It usually occurs in elderly women with late symptomatic presentation, increasing mortality rates. Surgery is the standard of care for OH, and laparotomy with simple suture closure of the defect is commonly used. Given the rarity of this disease, large studies are lacking, and data to drive management are still limited. This systematic review and meta-analysis aimed to describe current surgical options for OHs, with a focus on comparing the effectiveness and safety of mesh use with primary repair. METHODS: PubMed, EMBASE, and Cochrane were searched for studies comparing mesh and non-mesh repair for OH. Postoperative outcomes were assessed by pooled analysis and meta-analysis. Statistical analysis was performed using RevMan 5.4. RESULTS: One thousand seven hundred and sixty studies were screened and sixty-seven were thoroughly reviewed. We included 13 observational studies with 351 patients surgically treated for OH with mesh or non-mesh repair. One hundred and twenty (34.2%) patients underwent mesh repair and two hundred and thirty-one (65.81%) underwent non-mesh repair. A total of 145 (41.3%) underwent bowel resection, with the majority having a non-mesh repair performed. Hernia recurrence was significantly higher in patients who underwent hernia repair without mesh (RR 0.31; 95% CI 0.11-0.94; p = 0.04). There were no differences in mortality (RR 0.64; 95% CI 0.25-1.62; p = 0.34; I2 = 0%) or complication rates (RR 0.59; 95% CI 0.28-1.25; p = 0.17; I2 = 50%) between both groups. CONCLUSION: Mesh repair in OH was associated with lower recurrence rates without an increase in postoperative complications. While mesh in clean cases is more likely to offer benefits, an overall recommendation regarding its use in OH repair cannot be made due to potential bias across studies. Given that many OH patients are frail and present emergently, the decision to use mesh is complex and should consider the patient's clinical status, comorbidities, and degree of intraoperative contamination.

Bone density and proximal support effects on dental implant stability - Finite element analysis and in vitro experiments.

OBJECTIVES: The application of dental implants presents the occurrence of implant failures associated with bone proximal support. This study aims to assess implant behavior, in particular implant stability and strain distribution in the bone at different bone densities, and the effect of proximal bone support. MATERIAL AND METHODS: Three bone densities (D20, D15, and D10) were considered in the experimental in vitro study, represented by solid rigid polyurethane foam and two conditions of bone support in the proximal region. A finite element model was developed and validated experimentally and a Branemark model at a 3:1 scale was implanted in the experiments; the model was loaded and extracted. RESULTS: The results of the experimental models validate the finite element models with a correlation R2 equal to 0.899 and NMSE of 7%. The implant extraction tests for the effect of bone properties in the maximum load were 2832 N for D20 and 792 N for D10. The effect of proximal bone support changes the implant stability was observed experimentally; at 1 mm less bone support decreases by 20% of stability and at 2 mm by 58% for D15 density. CONCLUSIONS: Bone properties and bone quantity are important for the initial stability of the implant. A bone volume fraction of less than 24 g/cm3 exhibits poor behavior and is not indicated for implantation. Proximal bone support reduces the primary stability of the implant and the effect is critical in lower bone density.

Hyperphosphatemia is associated with cardiac valve calcification in chronic hypoparathyroidism.

PURPOSE: To evaluate the association between metabolic abnormalities and cardiovascular risk factors in patients with chronic hypoparathyroidism (HPP). PATIENTS AND METHODS: Patients 18 years and older, glomerular filtration > 30 mL/min/1.73 m2 and no documented coronary artery disease were selected. Serum calcium, phosphorus, glucose, lipids, PTH, 25(OH)D and FGF23 were measured. Cardiovascular risk was estimated by the European Society of Cardiology (ESC) calculator. Transthoracic echocardiogram and carotid ultrasound were performed to detect carotid plaques (CP), carotid intima-media thickness (IMT), cardiac valve calcification (CVC), and left ventricular hypertrophy (LVH). RESULTS: Thirty-seven patients (94.6% female), aged 56.0 ± 13.5 years and HPP duration 7.0 (4.0; 11.3) years, were included. Fifteen were classified as low cardiovascular risk, 9 as intermediate risk, 9 as high risk and none as very high risk. The prevalence of CP, CVC and LVH was 24.3%, 24.3% and 13.5%, respectively. IMT values were within normal ranges in all cohort. FGF23 were not associated with CP, IMT, CVC or LVH. After logistic regression, phosphorus was the only significant metabolic variable impacting CVC in univariate analysis (OR 2.795; 95% CI 1.132-6.905; p = 0.026), as well as in the multivariate analysis (OR 3.572; 95% CI 1.094-11.665; p = 0.035). Analysis by ROC curve showed serum phosphorus > 5.05 mg/dL (AUC 0.748; CI 0.584-0.877; p = 0.05) as the best cutoff point associated with valve heart calcification (sensitivity 78%; negative predictive value 91.3%). CONCLUSION: Hyperphosphatemia was associated with CVC in HPP patients. Further studies are needed to investigate whether the control of hyperphosphatemia may reduce cardiovascular risk in this population.

Osimertinib and anti-HER3 combination therapy engages immune dependent tumor toxicity via STING activation in trans.

Over the past decade, immunotherapy delivered novel treatments for many cancer types. However, lung cancer still leads cancer mortality, and non-small-cell lung carcinoma patients with mutant EGFR cannot benefit from checkpoint inhibitors due to toxicity, relying only on palliative chemotherapy and the third-generation tyrosine kinase inhibitor (TKI) osimertinib. This new drug extends lifespan by 9-months vs. second-generation TKIs, but unfortunately, cancers relapse due to resistance mechanisms and the lack of antitumor immune responses. Here we explored the combination of osimertinib with anti-HER3 monoclonal antibodies and observed that the immune system contributed to eliminate tumor cells in mice and co-culture experiments using bone marrow-derived macrophages and human PBMCs. Osimertinib led to apoptosis of tumors but simultaneously, it triggered inositol-requiring-enzyme (IRE1α)-dependent HER3 upregulation, increased macrophage infiltration, and activated cGAS in cancer cells to produce cGAMP (detected by a lentivirally transduced STING activity biosensor), transactivating STING in macrophages. We sought to target osimertinib-induced HER3 upregulation with monoclonal antibodies, which engaged Fc receptor-dependent tumor elimination by macrophages, and STING agonists enhanced macrophage-mediated tumor elimination further. Thus, by engaging a tumor non-autonomous mechanism involving cGAS-STING and innate immunity, the combination of osimertinib and anti-HER3 antibodies could improve the limited therapeutic and stratification options for advanced stage lung cancer patients with mutant EGFR.

HIV-related non-Hodgkin lymphomas affecting the oral cavity: a clinicopathologic study of 11 cases.

BACKGROUND: HIV-related non-Hodgkin lymphomas of the oral cavity are rare lesions with aggressive clinical behaviour. The aim of this study is to describe the clinicopathological features of a series of HIV-related oral non-Hodgkin lymphomas. MATERIAL AND METHODS: Eleven cases of oral lymphomas affecting HIV-positive patients were retrieved from 2012 to 2019. Clinicopathological features regarding age, sex, tumour location, clinical presentation, laboratory findings, disease stage and follow-up were obtained. Histologic, immunohistochemical and in situ hybridization for EBV detection were done for diagnosis confirmation. Overall survival was estimated by Kaplan-Meier curve. RESULTS: Males predominated, with a mean age of 40.3 years-old. Maxilla and mandible were the mostly affected. Plasmablastic lymphoma and diffuse large B-cell lymphoma not otherwise specified (NOS) were the main histological types. Lesions presented as reddish ulcerated swellings, representing the first sign of AIDS in six cases. Stage IV were common (7 cases) and the mean HIV viral load was 10,557 copies/mL, with a mean of 266 CD4+ cells/mm3, 1,278 CD8+ cells/mm3 and a CD4+/CD8+ ratio of 0.26. Eight patients died of the disease (72.7%). Overall survival revealed that 78.2% of the patients died after 21 months of follow-up. CONCLUSIONS: HIV-related oral lymphomas present a poor prognosis usually diagnosed in advanced stages and in our series plasmablastic lymphoma was the most common subtype.

Cherubism: a systematic literature review of clinical and molecular aspects.

The purpose of this review was to integrate the clinical, radiological, microscopic, and molecular data of published cherubism cases, in addition to therapeutic approaches, to provide more concise information about the disease. An electronic search was undertaken in September 2019. Eligibility criteria included publications having enough clinical, radiological, and histological information to confirm the diagnosis. A total of 260 publications reporting 513 cherubism cases were included. Familial history was observed in 310/458 cases (67.7%). SH3BP2 mutations were reported in 101/108 cases (93.5%) and mainly occurred at protein residues 415, 418, 419, and 420. Retrospective clinical grading was possible in 175 cases. Advanced clinical grading was associated with tooth agenesis, but not with other clinical, radiological, and genetic features. Specific amino acid substitutions of SH3BP2 mutations were not associated with the clinical grading of the disease. 'Wait and see' was the most common therapeutic approach. In a small number of cases, drugs were used in the treatment, with variable response. In conclusion, there is no clear correlation between the genotype and the phenotype of the disease, but additional genomic and gene expression regulation information is necessary for a better understanding of cherubism.

Comparison of cell invasion, macrophage survival and inflammatory cytokines profiles between Salmonella enterica serovars Enteritidis and Dublin from Brazil.

AIMS: This study compared the capacity of strains of Salmonella enterica serovars Enteritidis and Dublin isolated in Brazil to invade epithelial cells, to be internalized by and survive within macrophages, and to stimulate cytokine release in vitro. METHODS AND RESULTS: Both serovars infected 75 and 73% Caco-2 (human) and MDBK (bovine) epithelial cells respectively. Salmonella Dublin and S. Enteritidis (i) were internalized at the respective rates of 79·6 and 65·0% (P ≤ 0·05) by U937 (human) macrophages, and 70·4 and 66·9% by HD11 (chicken) macrophages; and (ii) multiplied at the respective rates of 3·2- and 2·7-fold within U937 cells, and 1·9- and 1·1-fold (P ≤ 0·05) within HD11 cells respectively. Seventy per cent of 10 S. Dublin strains stimulated IL-8 production, while 70% of S. Enteritidis strains enhanced production of IL-1ß, IL-6, IL-8, IL-10, IL-12p70 and TNF in Caco-2 cells. CONCLUSIONS: Compared with S. Enteritidis, S. Dublin had stronger ability to survive within macrophages and induced weak cytokine production, which may explain the higher incidence of invasive diseases caused by S. Dublin in humans. SIGNIFICANCE AND IMPACT OF THE STUDY: This study compared S. enterica serovars Enteritidis and Dublin to provide comparative data about the profile of the two serovars in cells from humans, the common host and their respective natural animal hosts and vice versa in order to check the differences between these two phylogenetically closely related serovars that share antigenic properties but present different phenotypic behaviours.

Desenvolvendo o pensamento crítico no ensino de Enfermagem: um desafio em tempos de pandemia de Covid-19 / Developing critical thinking in the teaching of Nursing: a challenge in times of Covid-19 pandemic / Desarrollando el pensamiento crítico en la enseñanza en Enfermería: un desafío en tiempos de la pandemia Covid-19

Objetivo: Refletir sobre o desenvolvimento do pensamento crítico no ensino de enfermagem em tempos de pandemia de Covid-19. Método: Estudo teórico-reflexivo baseado nas experiencias dos pesquisadores do Programa de Pós Graduação em Enfermagem da Universidade Federal de Santa Catarina em parceria com os pesquisadores do Programa de Graduação em Enfermagem da Faculdade diaconisa Lovisenberg (Lovisenberg Diakonale Høgskole), Noruega e com a Faculdade de Enfermagem do Hospital Israelita Albert Einstein. Resultados e Discussão: Essa discussão categorizou dois pontos teóricos reflexivos: A importância do pensamento crítico na educação de enfermagem e Inovação para estimular o pensamento crítico. O atual momento de calamidade assume caráter pedagógico porque ensina sobre a necessidade de mudanças nos modos de fazer atenção, gestão e pesquisa, bem como sinaliza para o campo da educação em saúde a necessidade de adaptação dos processos de ensino e aprendizagem à realidade das condições de vida dos estudantes. Conclusão e implicação para a prática: Espera-se despertar nos formadores a reflexão em torno do compromisso com o ato de ensinar em tempos de mudanças, adaptando suas práticas pedagógicas com criatividade, inovação tecnológica e desenvolvimento do pensamento crítico nos estudantes

Objective: Reflect on the development of critical thinking in nursing education in times of Covid-19 pandemic. Method: Theoreticalreflective study based on the experiences of researchers in the Postgraduate Program in Nursing at the Federal University of Santa Catarina in partnership with researchers in the Graduate Program in Nursing at the Faculty of Deaconess Lovisenberg (Lovisenberg diakonale høgskole), Norway and the Faculty Nursing at Hospital Israelita Albert Einstein. Results and Discussion: This discussion categorized two reflective theoretical points: The importance of critical thinking in nursing education and Innovation to stimulate critical thinking. The current moment of calamity assumes a pedagogical character because it teaches about the need for changes in the ways of doing care, management and research, as well as signals to the field of health education the need to adapt teaching and learning processes to the reality of the conditions students life. Conclusion and implication for the practice: It is expected to awaken in the trainers the reflection around the commitment to the act of teaching in times of change, adapting their pedagogical practices with creativity, technological innovation and the development of critical thinking in students

Objetivo: Reflexionar sobre el desarrollo del pensamiento crítico en la educación de enfermería en tiempos de la pandemia Covid-19. Método: Estudio teórico-reflexivo basado en las experiencias de investigadores del Programa de Posgrado en Enfermería de la Universidad Federal de Santa Catarina en asociación con investigadores del Programa de Posgrado en Enfermería de la Facultad de Diaconisa Lovisenberg (Lovisenberg diakonale høgskole), Noruega y la Facultad Enfermería del Hospital Israelita Albert Einstein. Resultados y Discusión: Esta discusión categorizó dos puntos teóricos reflexivos: La importancia del pensamiento crítico en la educación de enfermería y la Innovación para estimular el pensamiento crítico. El momento actual de calamidad asume un carácter pedagógico porque enseña sobre la necesidad de cambios en las formas de hacer el cuidado, la gestión y la investigación, además de señalar al campo de la educación en salud la necesidad de adecuar los procesos de enseñanza y aprendizaje a la realidad de las condiciones de salud. vida de los estudiantes. Conclusión e implicación para la práctica: Se espera despertar en los formadores la reflexión en torno al compromiso con el acto de enseñar en tiempos de cambio, adaptando sus prácticas pedagógicas con creatividad, innovación tecnológica y el desarrollo del pensamiento crítico en los estudiantes

Immunoexpression of bone resorption biomarkers in apical periodontitis in diabetics and normoglycaemics.

AIM: To compare the immunoexpression of RANK, MMP-9 and PTHrP in apical periodontitis lesions of diabetic and normoglycaemic individuals. METHODOLOGY: Primary chronic apical periodontitis lesions associated with teeth indicated for extraction in 13 type 2 diabetic individuals and 13 normoglycaemic individuals who were screened for the glycaemic index and glycated haemoglobin (HbA1c) were analysed. Individuals with other systemic diseases and users of anti-inflammatories and/or antibiotics in the previous 3 months were excluded. Silanized slides with paraffin sections were used for immunohistochemical reactions and stained with haematoxylin and eosin for histopathological classification. The images were analysed with an optical microscope, and the slides were subdivided into five large fields assigning scores (0-2), according to the number of positive markings for each antibody. Fisher's exact test evaluated the parameters: gender, type of lesion, location and position in the arch. Nonparametric Mann-Whitney test was used for age, HbA1c values and comparison of marker expression. The chi-squared test was used to associate the expression of the markers. And the Spearman's coefficient correlated the markers with the size of the periapical lesion. RESULTS: The samples consisted of 69% periapical granulomas and 31% periapical cysts in each group. RANK expression was considered weak/moderate and strong in, respectively, 62% and 38% of the cases in both groups. MMP-9 expression was weak/moderate and strong in, respectively, 38% and 62% of the cases from the diabetic group, in comparison with 38% and 38% in the normoglycaemics (24% cases from this group were negative). In contrast, PTHrP expression was negative, weak/moderate and strong in, respectively, 46%, 46% and 8% of the cases from the diabetic group, in comparison with 38% negative and 62% weak/moderate in normoglycaemics. Quantitative analysis revealed that there were no significant differences in the immunoexpression of RANK (P = 0.26), MMP-9 (P = 0.17) and PTHrP (P = 0.43) between the groups. There was no significant correlation between the expression of bone resorption markers and the macroscopic size of the periapical lesions (P > 0.05). CONCLUSIONS: The bone resorption mediators analysed had similar immunoexpression in the periapical lesions of diabetic and normoglycaemic individuals.

Severe acute pancreatitis: eight fundamental steps revised according to the 'PANCREAS' acronym.

Severe acute pancreatitis remains a life-threatening condition, responsible for many disorders of homeostasis and organ dysfunction. By means of a mnemonic 'PANCREAS', eight important steps in the management of severe acute pancreatitis are highlighted. These steps follow the principle of goal-directed therapy and should be borne in mind after diagnosis and during clinical treatment. The first step is perfusion: the goal is to reach a central venous pressure of 12-15mmHg, urinary output 0.5-1ml/kg/hour and inferior vena cava collapse index greater than 48%. Next is analgesia: multimodal, systemic and combined pharmacological agent and epidural block are possibilities. Third is nutrition: precocity, enteral feeding in gastric or post-pyloric position. Parenteral nutrition works best in difficult cases to achieve the individual total caloric value. Fourth is clinical: mild, moderate or severe pancreatitis according to the Atlanta criteria. Radiology is fifth: abdominal computed tomography on the fourth day for prognosis or to modify management. Endoscopy is sixth: endoscopic retrograde cholangiopancreatography (cholangitis, unpredicted clinical course and ascending jaundice); management of pancreatic fluid collection and 'walled-off necrosis'. Antibiotics come next: infectious complications are common causes of morbidity. The only rational indication for antibiotics is documented pancreatic infection. The last step is surgery: the dogma is represented by the 'three Ds' (delay, drain, debride). The preferred method is a minimally invasive step-up approach, which allows for gradually more invasive procedures when the previous treatment fails.

Uveal melanoma: physiopathology and new in situ-specific therapies.

Uveal melanoma is the most common primary intraocular tumor in adults. It can arise from melanocytes in the anterior (iris) or posterior uveal tract (choroid and ciliary body). Uveal melanoma has a particular molecular pathogenesis, being characterized by specific chromosome alterations and gene mutations (e.g., GNAQ/GNA11; BAP1), which are considered promising targets for molecular therapy. Primary treatment of uveal melanoma includes radiotherapy (brachytherapy and charged-particle therapy), phototherapy (photocoagulation, transpupillary thermal therapy, and photodynamic therapy) and surgery (local resection, enucleation and exenteration). Approximately half of patients with uveal melanoma will, however, develop metastasis, especially in the liver. The treatment of metastatic uveal melanoma includes systemic chemotherapy, immunotherapy and molecular targeted therapy. Liver-directed therapies, such as resection, chemoembolization, immunoembolization, radioembolization, isolated hepatic perfusion and percutaneous hepatic perfusion, are also available to treat metastatic uveal melanoma. Several clinical trials are being developed to study new therapeutic options to treat uveal melanoma, mainly for those with identified liver metastases. The present work discusses the physiopathology and new in situ-specific therapies for the treatment of uveal melanoma.

Parâmetros fisiológicos e bioquímicos de equinos em treinamento de três tambores: pós-condicionamento, pós-percurso e pós-descanso / Physiological and biochaemical parameters of horses in three-barrel training: post-warm-up, post-exercise and post-rest

Foram avaliados parâmetros fisiológicos e bioquímicos em equinos Quarto de Milha durante treinamento de três tambores, antes do condicionamento (T0), após o condicionamento (T1), após um percurso (T2), após descanso do percurso, por 20 minutos (T3) e após descanso do percurso, por 40 minutos (T4). Os parâmetros físicos avaliados foram: frequência cardíaca (FC), frequência respiratória (FR), temperatura retal (TR) e tempo de enchimento capilar (TEC); e os bioquímicos: sódio, potássio, cloreto, cálcio total, ureia, creatinina, osmolaridade, creatinaquinase, aspartato transaminase, proteínas totais (PT), glicose e lactato. A FC, a FR e a TR aumentaram após o percurso (T2), mas foram recompostas após 40 minutos de descanso. A concentração do lactato pouco aumentou após o condicionamento, mas altas concentrações ocorreram após o percurso (T2), e embora ele tenha diminuído após 20 (T3) e 40 minutos (T4) do percurso, ainda permaneceu acima dos limites normais. Nos demais parâmetros, não houve variações significativas. Concluiu-se que, ao final de um percurso de três tambores, o exercício sob máxima intensidade não ocasionou variações bioquímicas significativas nos equinos, exceto para o lactato, pois gerou uma hiperlactatemia que não foi restaurada até 40 minutos de descanso pós-percurso, mesmo com os parâmetros físicos já recompostos do esforço.(AU)

Physiological and biochemical parameters were evaluated in Quarter Horse during three-barrel training, in three times: T0 (before warm-up), T1 (after warm-up), T2 (after completing the exercise, performing only one course), T3 (after resting for 20 minutes of the course), and T4 (after resting for 40 minutes of the course). The parameters evaluated were: heart rate (HR), respiratory rate (RR), rectal temperature (RT) and capillary filling time (ECT); Serum concentrations of sodium, potassium, chloride, total calcium, BUN, creatinine, osmolarity, creatine kinase, aspartate transaminase; Plasma concentrations of total protein (PT), glucose, and lactate. HR, RR and RT increased shortly after the course (T2) but were restored after 40 minutes of rest. Lactate concentration increased after conditioning, but at low concentrations, but high levels occurred after the course (T2), and although decreased after 20 (T3) and 40 minutes (T4) of the course, it was still above normal limits. There were no significant changes in the other parameters. At the end of a single course of three-barrel, the exercise of maximum intensity did not cause significant biochemical variations in horses, except for lactate, which increased to levels of hyperlactatemia, and was not restored until 40 minutes of rest, even with the physical parameters already recovered.(AU)

Accuracy of qPCR for quantifying Leishmania kDNA in different skin layers of patients with American tegumentary leishmaniasis.

OBJECTIVES: Superficial swab sampling of American tegumentary leishmaniasis (ATL) lesions shows higher amounts of Leishmania than those from biopsy. Subcutaneous involvement is also important in ATL, but parasite quantification according to lesion depth has not been evaluated. We aim to present the best depth at which sampling should be performed for molecular exams of ATL. METHODS: Patients with a clinical presentation compatible with ATL were allocated to ATL and control groups. Qualitative and quantitative qPCR assays were performed using SYBR Green and primers amplifying the kDNA minicircle of Leishmania spp. in different skin layers, including the epidermis, the superior dermis, the inferior dermis, and the hypodermis. RESULTS: Fifty-nine patients were included in this study, including 40 who had been diagnosed with ATL and 19 controls. The number of parasites was greater in samples of the epidermis and superior dermis (159.1 × 106, range 4.0-781.7, and 75.4 × 106, range 8.0-244.5, mean Leishmania parasite equivalents per µg of tissue DNA, respectively) than those in samples of the inferior dermis and hypodermis (54.6, range 8.0-256.6, and 16.8 × 106, range 8.0-24.1, mean Leishmania parasite equivalents per µg of tissue DNA, respectively). The best diagnostic accuracy was achieved in the superior dermis (77.9%) and was significantly greater than that in the hypodermis (63.3%; p 0.039). CONCLUSIONS: We conclude that superficial sampling can retrieve a greater quantity of parasites. Future studies of the role of transepidermal elimination as a mechanism of host defence in ATL must be performed as there is a considerable quantity of Leishmania kDNA in the epidermis.