Highly sensitive voltammetric determination of hydrochlorothiazide using a glassy carbon electrode modified with Super P carbon black nanoparticles.

Hydrochlorothiazide is an extremely important diuretic that regulates body functions, which can prevent several diseases. However, the abuse of this diuretic is concerning since it does not require a medical prescription, particularly for aesthetic purposes such as weight loss, which can lead to various health problems, including ventricular arrhythmia. The present work aims to use a glassy carbon electrode modified with Super P carbon black (SPCB/GCE) to quantify hydrochlorothiazide through Linear Sweep Adsorptive Stripping Voltammetry (LSAdSV). The modification of the GCE with SPCB significantly improved the response of hydrochlorothiazide. Furthermore, due to the adsorptive nature of charge transport, applying preconcentration time enhanced sensitivity. The optimized system provided a linear range of 0.5 to 30.0 µmol L-1 with a detection limit of 0.083 µmol L-1. Pharmaceutical tablet analyses indicated approximately 25 mg per tablet, which was confirmed by the UV-vis and in agreement with that indicated by the manufacturer. Furthermore, analyses of the tea, synthetic urine, tap water and lake water samples indicated recovery values close to 100%, demonstrating that there was no matrix effect. Therefore, it is possible to infer that the proposed method together with the sensor modified with carbon black nanoparticles presented excellent results, demonstrating that it can be an alternative method of monitoring this drug in different samples.

Discordance Between the Initial Diagnosis of Sarcomas and Subsequent Histopathological Revision and Molecular Analyses in a Sarcoma Reference Center in Brazil.

PURPOSE: To investigate the discordance in sarcoma diagnoses between nonspecialized institutions following revision by dedicated sarcoma pathologists at a reference center in Brazil and the relevance of molecular pathology in this context. METHODS: We conducted a retrospective analysis of sarcoma samples initially analyzed at outside laboratories and subsequently reviewed by two specialized pathologists between January 2014 and December 2020. After obtaining demographic and tumor characteristics, pathology results were matched and classified as complete discordance (CD; benign v malignant, sarcoma v other malignancies), partial concordance (similar diagnosis of connective tumor, but different grade/histological subtype/differentiation), and complete concordance (CC). The concordance for histology or grade, and the role of molecular assessments supporting the diagnosis were also independently determined. Statistical analyses were conducted through the kappa coefficient of agreement and adherence by χ2 test, χ2 test by Person, and Fisher exact test. RESULTS: In total, 197 cases were included, with samples obtained predominately from male patients (57.9%) and localized/primary tumors (86.8%). Following revision, the most frequent final diagnoses were undifferentiated pleomorphic sarcoma (17.8%), well-differentiated/dedifferentiated liposarcoma (8.6%), and leiomyosarcoma (7.6%). CD was found in 13.2%, partial discordance in 45.2%, and CC in 41.6% of reviews (P < .001). We found a concordance for histology or grade of 53.5% (P < .001) and 51.8% (P < .001), respectively. Molecular assessments, comprising next-generation sequencing panels (79.5%) and fluorescent in situ hybridization (20.5%), were performed in 44 (22.3%) cases, with findings classified as of diagnostic relevance in 31.8%. CONCLUSION: In nearly 60% of the cases, the initial sarcoma diagnosis was modified when revised by a reference center and dedicated pathologists, assisted by molecular pathology techniques. These results justify the assembly of referral networks in countries with limited health care resources.

Identification of sialic acid receptors for influenza A virus in snakes.

The tissue tropism and the wide host range of influenza A viruses are determined by the presence of sialic acid (SA) α2,3-Gal and SA α2,6-Gal receptors. Recent studies have shown that animals possessing both receptors allow for the rearrangement and emergence of new viral strains of public health importance. This study aimed to evaluate the expression and distribution of human and avian influenza A receptors in nine Neotropical snake species using lectin immunohistochemistry. We selected 17 snakes that were examined post mortem at the Veterinary Pathology Sector of the Universidade Federal de Minas Gerais between 2019 and 2023. Sections of nasal turbinate, trachea, lung, oral mucosa, stomach and intestine were subjected to immunohistochemical analysis using the lectins Maackia amurensis and Sambucus nigra. This research detected, for the first time, co-expression of SA α2,3-Gal and SA α2,6-Gal receptors in the respiratory and digestive tracts of snakes, indicating the possible susceptibility of these species to influenza A virus of avian and human origin. Consequently, snakes can be considered important species for monitoring influenza A in wild, urban and peri-urban environments. More studies should be conducted to investigate the role of snakes in influenza A epidemiology.

Pathological findings and differential diagnoses of lymph node diseases in slaughtered cattle in Brazil: A study of 2000 samples.

Slaughterhouse inspections play a crucial role in the sanitary control of zoonoses and foodborne diseases. This study aimed to identify and analyze the frequencies of lymph node diseases in cattle slaughtered for human consumption, using the samples sent to the anatomic pathology service of the Federal Laboratory for Agricultural Defense (Laboratório Federal de Defesa Agropecuária), Minas Gerais, Brazil, from January 2015 to September 2022. In total, 2000 lymph node samples were analyzed, and additional information was individually retrieved. Lesions were most frequently identified in thoracic lymph nodes. Bacterial isolation and quantitative polymerase chain reaction (qPCR) were performed using samples suspected of tuberculosis. Tuberculosis cases accounted for 89.3% of the samples. Histopathology was more sensitive than other ancillary tests for diagnosing tuberculosis. Paraffin-embedded tissues from lymphoma cases were subjected to immunophenotyping using anti-CD3 and anti-CD79a immunohistochemistry. Frozen and/or paraffin-embedded tissues from lymphoma cases were used to identify the enzootic bovine leukosis (EBL) retrovirus through qPCR. Other diagnoses included primary (T- and B-cell lymphoma) and metastatic neoplasms (squamous cell carcinoma, pulmonary adenocarcinoma, undifferentiated carcinoma, undifferentiated adenocarcinoma, undifferentiated sarcoma, undifferentiated round cell tumor, mesothelioma, hepatic carcinoid, meningioma, and seminoma), actinogranulomas (pyogranulomatous lymphadenitis [actinobacillosis and actinomycosis]), idiopathic lymphadenitis (neutrophilic and/or histiocytic, granulomatous, and suppurative), and miscellaneous nonspecific lymphadenopathies (depletion/lymphoid atrophy, lymphangiectasia, erythrocyte drainage, parasitic eosinophilic lymphadenitis, follicular hyperplasia, and toxic granulomatous lymphadenitis). The combination of histopathology with complementary techniques is important for successful diagnosis, especially in complex cases of high epidemiological, economic, and zoosanitary importance, such as tuberculosis and EBL.

Exploring the impact of high-energy diets on cattle: Insights into subacute rumen acidosis, insulin resistance, and hoof health.

Cattle lameness remains a significant concern, causing economic losses and compromising animal welfare. Claw horn lesions have been identified as a major cause of lameness in dairy cows, but their correlation with high-energy diets and ruminal acidosis remains unclear. Hence, the primary objective of this study was to assess the effects of a high-starch diet and a conventional diet on the rumen environment, acute-phase proteins, and metabolic alterations, with a particular focus on insulin resistance and the consequent implications for the histology of the hooves in Holstein steers. A total of 16 animals were divided into the high-starch (HS; 37% starch) and conventional (CON; 16.8% starch) groups. Glucose tolerance tests (GTT), blood analyses, rumen fluid analyses, and histological evaluations of the hoof tissue were conducted over a 102-d experimental period. The HS group showed a lower ruminal pH than the CON group, and with values indicating SARA. The plasma glucose and IGF-1 concentrations were higher in the HS group, suggesting an anabolic state. Both groups exhibited an increase in the insulin area under the curve (AUC) after the GTT on d 102. Histological analysis of the hooves showed a reduction in the length and width of the epidermal lamella in both groups. We found a significant negative correlation between the insulin AUC and the length and width of the epidermal lamella. Because both groups were similarly affected, the hypothesis that histological alterations were caused by the experimental diets still needs confirmation. Additionally, the development of SARA was not essential for the observed histological changes in the hoof. Further studies are warranted to thoroughly investigate the role of insulin and IGF-1 imbalances in claw health.

Pediatric nephrologist-intensivist interaction in acute kidney injury / Interação nefro-intensivista pediátrica na lesão renal aguda

ABSTRACT Introduction: Acute Kidney Injury (AKI) in the Intensive Care Unit (ICU) have concepts of diagnosis and management have water balance as their main point of evaluation. In our ICU, from 2004 to 2012, the nephrologist's participation was on demand only; and as of 2013 their participation became continuous in meetings to case discussion. The aim of this study was to establish how an intense nephrologist/intensivist interaction influenced the frequency of dialysis indication, fluid balance and pRIFLE classification during these two observation periods. Methods: Retrospective study, longitudinal evaluation of all children with AKI undergoing dialysis (2004 to 2016). Parameters studied: frequency of indication, duration and volume of infusion in the 24 hours preceding dialysis; diuresis and water balance every 8 hours. Non-parametric statistics, p ≤ 0.05. Results: 53 patients (47 before and 6 after 2013). There were no significant differences in the number of hospitalizations or cardiac surgeries between the periods. After 2013, there was a significant decrease in the number of indications for dialysis/year (5.85 vs. 1.5; p = 0.000); infusion volume (p = 0.02), increase in the duration of dialysis (p = 0.002) and improvement in the discrimination of the pRIFLE diuresis component in the AKI development. Conclusion: Integration between the ICU and pediatric nephrology teams in the routine discussion of cases, critically approaching water balance, was decisive to improve the management of AKI in the ICU.

RESUMO Introdução: Os conceitos sobre diagnóstico e conduta da Lesão Renal Aguda (LRA) na Unidade de Terapia Intensiva (UTI) tem como ponto primordial a avaliação do balanço hídrico. Em nossa UTI, de 2004 a 2012, a participação do nefrologista era sob demanda. A partir de 2013, a participação passou a ser contínua em reunião de discussão de casos. O objetivo deste estudo foi determinar como a maior interação nefrologista/intensivista influenciou a frequência de indicação de diálise, no balanço hídrico e na classificação pRIFLE durante esses dois períodos de observação. Método: Estudo retrospectivo, avaliação longitudinal de todas as crianças com LRA em diálise (2004 a 2016). Parâmetros estudados: frequência de indicação, tempo de duração e volume de infusão nas 24 horas precedendo a diálise; diurese e balanço hídrico a cada 8 horas. Estatística não paramétrica, p ≤ 0,05. Resultado: 53 pacientes (47 antes e 6 após 2013). Sem diferença significativa no número de internações e nem de cirurgias cardíacas entre os períodos. Após 2013, houve diminuição significativa no número de indicação de diálise/ano (5,85 vs. 1,5; p = 0,000); no volume de infusão (p = 0,02), aumento do tempo de duração da diálise (p = 0,002) e melhora da discriminação do componente diurese do pRIFLE na indicação de LRA. Conclusão: Integração entre equipes de UTI e nefrologia pediátrica na discussão rotineira de casos, abordando criticamente o balanço hídrico, foi determinante para a melhora na conduta da LRA na UTI.

Pediatric nephrologist-intensivist interaction in acute kidney injury.

INTRODUCTION: Acute Kidney Injury (AKI) in the Intensive Care Unit (ICU) have concepts of diagnosis and management have water balance as their main point of evaluation. In our ICU, from 2004 to 2012, the nephrologist's participation was on demand only; and as of 2013 their participation became continuous in meetings to case discussion. The aim of this study was to establish how an intense nephrologist/intensivist interaction influenced the frequency of dialysis indication, fluid balance and pRIFLE classification during these two observation periods. METHODS: Retrospective study, longitudinal evaluation of all children with AKI undergoing dialysis (2004 to 2016). PARAMETERS STUDIED: frequency of indication, duration and volume of infusion in the 24 hours preceding dialysis; diuresis and water balance every 8 hours. Non-parametric statistics, p ≤ 0.05. RESULTS: 53 patients (47 before and 6 after 2013). There were no significant differences in the number of hospitalizations or cardiac surgeries between the periods. After 2013, there was a significant decrease in the number of indications for dialysis/year (5.85 vs. 1.5; p = 0.000); infusion volume (p = 0.02), increase in the duration of dialysis (p = 0.002) and improvement in the discrimination of the pRIFLE diuresis component in the AKI development. CONCLUSION: Integration between the ICU and pediatric nephrology teams in the routine discussion of cases, critically approaching water balance, was decisive to improve the management of AKI in the ICU.

Desconstruindo a "pedagogia da virilidade": conversação sobre masculinidades de professores homens na educação infantil / Deconstruyendo la "pedagogía de la virilidad": conversación sobre las masculinidades de los docentes hombres en la educación infantil / Deconstructing the "pedagogy of virility": a conversation about male teachers masculinities in early childhood education

Resumo: O objetivo deste estudo foi escutar as narrativas de masculinidades de professores homens atuantes na educação infantil na região sul do Brasil. Apoiados nos Estudos das Masculinidades e Psicanálise, analisamos o mal-estar ao qual são submetidos nas suas vidas profissionais ao tensionarem a "Pedagogia da Virilidade". A partir de uma pesquisa qualitativa, realizaram-se encontros grupais utilizando a Conversação como dispositivo metodológico. Participaram do estudo oito professores homens que atuam na educação infantil, diretamente nas salas de aula. Da análise dos dados, realizada a partir da escuta clínica, emergiram três eixos que versam sobre os significantes: "problema", "diferença" e "potência". Os resultados apontam para a necessidade de uma formação em Pedagogia que acolha as masculinidades, para uma desgenirificação do cuidado e para a potência de seus corpos e fazeres pedagógicos nos espaços educacionais voltados à primeira infância.

Resumen: El objetivo de este estudio fue escuchar las narrativas de masculinidad de docentes hombres que trabajan en educación infantil en la región Sur de Brasil. Apoyados en los Estudios de Masculinidades y el Psicoanálisis, analizamos el malestar al que se ven sometidos en su vida profesional cuando enfatizan la "Pedagogía de la Virilidad". A partir de una investigación cualitativa, se realizaron reuniones grupales utilizando como dispositivo metodológico la Conversación. Participaron del estudio ocho profesores hombres que trabajan en educación infantil, directamente en clase. Del análisis de los datos, realizado a partir de la escucha clínica, surgieron tres ejes que abordan los significantes: "problema", "diferencia" y "poder". Los resultados apuntan a la necesidad de una formación en Pedagogía que abarque las masculinidades, por una desgenrificación del cuidado y por la potenciación de sus cuerpos y prácticas pedagógicas en espacios educativos dirigidos a la primera infancia.

Abstract: The objective of this study was to listen to the narratives of masculinity from male teachers working in early childhood education in the southern region of Brazil. Based on Masculinity Studies and Psychoanalysis, we analyzed the discomfort to which they are subjected in their professional lives when they put the "Pedagogy of Virility" into tension. Based on qualitative research, group meetings were held using Conversation as a methodological device. Eight male teachers who work in early childhood education, directly in classrooms, participated in the study. From data analysis, carried out through clinical listening, three axes emerged that deal with the signifiers: "problem", "difference" and "power". The results point to the need for training in Pedagogy that embraces masculinities, for a degenderification of care and for the power of their bodies and pedagogical practices in educational spaces focused on early childhood.

The Clinical and Molecular Profile of Lung Cancer Patients Harboring the TP53 R337H Germline Variant in a Brazilian Cancer Center: The Possible Mechanism of Carcinogenesis.

In southern and southeastern Brazil, the TP53 founder variant c.1010G>A (R337H) has been previously documented with a prevalence of 0.3% within the general population and linked to a heightened incidence of lung adenocarcinomas (LUADs). In the present investigation, we cover clinical and molecular characterizations of lung cancer patients from the Brazilian Li-Fraumeni Syndrome Study (BLISS) database. Among the 175 diagnosed malignant neoplasms, 28 (16%) were classified as LUADs, predominantly occurring in females (68%), aged above 50 years, and never-smokers (78.6%). Significantly, LUADs manifested as the initial clinical presentation of Li-Fraumeni Syndrome in 78.6% of cases. Molecular profiling was available for 20 patients, with 14 (70%) revealing EGFR family alterations. In total, 23 alterations in cancer driver genes were identified, comprising 7 actionable mutations and 4 linked to resistance against systemic treatments. In conclusion, the carriers of TP53 R337H demonstrate a predisposition to LUAD development. Furthermore, our results indicate that environmental pollution potentially impacts the carcinogenesis of lung tumors in the carriers of TP53 R337H.

Comparison of Different Pneumorrhaphy Methods after Partial Pulmonary Lobectomy in Dogs.

Pulmonary loborraphy can be performed using manual sutures and staples, although other methods, such as tissue adhesives, are also cited in the veterinary literature. Although the surgery is well tolerated in the canine species, failure in pulmonary aerostasis is still a reality since all the methods described so far eventually lead to air leakage after the use of the partial lobectomy technique in the lungs. Within this context, the aim of this research was to compare the effectiveness of different hermetic sealing methods after partial lobectomy of the right caudal lung lobe (RCLL) in dogs. 30 cadavers models were divided in 6 groups: G1-cobbler suture associated with simple continuous; G2-overlapping continuous suture associated with simple continuous suture; G3-Ford interlocking suture; G4-Stapling device; G5-Tissue glue (cyanoacrylate). After performing the sealing techniques, the lungs were submerged in water and inflated with oxygen at positive ventilatory pressures at physiological (up to 14.7 mmHg, which is equivalent to up to 20 cmH2O) and supraphysiological levels (above 14.7 mmHg) to evaluate the performance of the sealing methods. At physiological ventilatory pressure levels, there was no difference between groups. Sealing with surgical glue was superior to interlocking sutures and stapling devices at supraphysiological levels of ventilatory pressure.

The importance of morphological changes in neutrophils in the diagnosis of bacterial infections in dogs with confirmed urinary tract infections in a Veterinary Care Service, Rio de Janeiro, Brazil.

Neutrophils (PMNs) are cellular markers used for diagnosing inflammation and/or infections. In this study, the objective was to highlight the importance of recording the toxic morphological alterations of the PMNs as markers of infection in 10 cases, positive bacterial isolation by culture due to dysuria, hematuria and/or fetid urine, as manifestations of urinary tract disease. Smear observations were performed by immersion for counting and morphological evaluations of 3,000 leukocytes in smears and in leukocyte concentrate. One (10.0%) of the dogs had leukocytosis, and two (20.0%) dogs had leukopenia. All animals showed toxic PMNs with positive bacterial culture. None of the cases in the study showed any quantitative alterations in PMNs such as: neutropenia or neutrophilia, where 100% had nuclear displacement of the regenerative type of PMNs to the left. 100% cases had toxic morphological changes: 90.0% had PMNs with toxic granulations, 80.0% had giant rod neutrophils, 70.0% had target PMNs, in 50.0% of those with vacuolation in the cytoplasm, in 40.0% of the animals, the presence of giant PMNs, 10.0% with Döhle bodies, and another animal 10.0% with karyorrhexis. All case studies had at least one association of two types of toxic changes. Toxic morphological alterations observed in PMNs through cystoscopy proved to be more reliable and sensitive in evidencing the diagnosis of infections than the quantitative alterations of absolute values of total leukocytes; therefore, they were essential in the laboratory diagnosis by blood count in the course of infections in dogs.

Os neutrófilos (PMNs) são marcadores celulares para o diagnóstico de inflamação e/ou infecções. Neste estudo, o objetivo foi apresentar a importância das alterações morfológicas tóxicas dos PMNs envolvidos como marcadores de infecção, em 10 casos com isolamento bacteriano positivo por cultura devido à disúria, hematúria e/ou urina fétida, como manifestações clínicas de doença do trato urinário. As observações de esfregaço foram realizadas para contagens e avaliações morfológicas de 3.000 leucócitos, em esfregaços e em concentrado de leucócitos. Um (10,0%) dos cães teve leucocitose e dois (20,0%) cães apresentaram leucopenia. Todos os animais tiveram alterações tóxicas em PMNs (100% dos casos) e com cultura bacteriana positiva. Nenhum dos casos do estudo apresentou qualquer alteração quantitativa nos PMNs como: neutropenia ou neutrofilia onde 10 (100%) tiveram deslocamento nuclear do tipo regenerativo de PMNs para a esquerda. 10 (100%) casos apresentaram alterações morfológicas tóxicas: nove (90,0%) tinham PMNs com granulações tóxicas, oito (80,0%) tinham neutrófilos de bastonetes gigantes, sete (70,0%) tinham PMNs-alvo, em cinco (50,0%) daqueles com vacuolização no citoplasma, em quatro (40,0%) dos animais a presença de PMNs gigantes, um (10,0%) com corpos de Döhle e outro animal (10,0%) com cariorrexia. Todos os casos observados tiveram pelo menos uma associação de dois tipos de alterações tóxicas. As alterações morfológicas tóxicas, observadas nos PMNs através da cistoscopia, foram mais confiáveis, e sensíveis em evidenciar o diagnóstico de infecções, do que as alterações dos valores absolutos de leucócitos totais e mesmo de PMNs em exames de rotina no curso de infecções em cães.

Lab-made 3D-printed electrochemical sensors for tetracycline determination.

Antibiotics such as tetracycline (TC) are widely prescribed to treat humans or dairy animals. Therefore, it is important to establish affordable devices in laboratories with minimal infrastructure. 3D printing has proven to be a powerful and cost-effective tool that revolutionizes many applications in electrochemical sensing. In this work, we employ a conductive filament based on graphite (Gr) and polylactic acid (PLA) (40:60; w/w; synthesized in our lab) to manufacture 3D-printed electrodes. This electrode was used "as printed" and coupled to batch injection analysis with amperometric detection (BIA-AD) for TC sensing. Preliminary studies by cyclic voltammetry and differential pulse voltammetry revealed a mass transport governed by adsorption of the species and consequent fouling of the redox products on the 3D printed surface. Thus, a simple strategy (solution stirring and application of successive potentials, +0.95 V followed by +1.2 V) was associated with the BIA-AD system to solve this effect. The proposed electrode showed analytical performance comparable to costly conventional electrodes with linear response ranging from 0.5 to 50 µmol L-1 and a detection limit of 0.19 µmol L-1. Additionally, the developed method was applied to pharmaceutical, tap water, and milk samples, which required minimal sample preparation (simple dilution). Recovery values of 92-117% were obtained for tap water and milk samples, while the content found of TC in the capsule was close to the value reported by the manufacturer. These results indicate the feasibility of the method for routine analysis involving environmental, pharmaceutical, and food samples.

Elexacaftor/tezacaftor/ivacaftor-real-world clinical effectiveness and safety. A single-center Portuguese study.

OBJECTIVE: To evaluate the effectiveness of treatment with elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) and to characterize its safety profile in cystic fibrosis (CF) patients in a real-world clinical setting. METHODS: This was a prospective observational study carried out in a CF referral center in Portugal involving adult CF patients who started treatment with ELX/TEZ/IVA. Clinical characteristics of the patients were collected, and effectiveness and safety data were evaluated. RESULTS: Of the 56 patients followed in the center at the time of the study, 28 were eligible for ELX/TEZ/IVA treatment in accordance with the Portuguese National Authority for Medicines and Health Products at the time of the study. Of these, 24 met the follow-up time requirement to be included in the clinical effectiveness analysis. The mean follow-up time was 167.3 ± 96.4 days. Adverse events were generally mild and self-limited. Significant improvements in lung function, BMI, sweat chloride concentration, and number of pulmonary exacerbations were observed. No significant differences in outcomes between F508del homozygous and heterozygous patients were found. The effectiveness of this new CFTR modulator combination also applied to patients with advanced lung disease. CONCLUSIONS: Treatment with ELX/TEZ/IVA showed effective improvement in real-world clinical practice, namely in lung function, BMI, sweat chloride concentration, and number of pulmonary exacerbations, with no safety concerns.

Elexacaftor/tezacaftor/ivacaftor-real-world clinical effectiveness and safety. A single-center Portuguese study / Elexacaftor/tezacaftor/ivacaftor-efetividade clínica e segurança no mundo real. Estudo unicêntrico português

ABSTRACT Objective: To evaluate the effectiveness of treatment with elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) and to characterize its safety profile in cystic fibrosis (CF) patients in a real-world clinical setting. Methods: This was a prospective observational study carried out in a CF referral center in Portugal involving adult CF patients who started treatment with ELX/TEZ/IVA. Clinical characteristics of the patients were collected, and effectiveness and safety data were evaluated. Results: Of the 56 patients followed in the center at the time of the study, 28 were eligible for ELX/TEZ/IVA treatment in accordance with the Portuguese National Authority for Medicines and Health Products at the time of the study. Of these, 24 met the follow-up time requirement to be included in the clinical effectiveness analysis. The mean follow-up time was 167.3 ± 96.4 days. Adverse events were generally mild and self-limited. Significant improvements in lung function, BMI, sweat chloride concentration, and number of pulmonary exacerbations were observed. No significant differences in outcomes between F508del homozygous and heterozygous patients were found. The effectiveness of this new CFTR modulator combination also applied to patients with advanced lung disease. Conclusions: Treatment with ELX/TEZ/IVA showed effective improvement in real-world clinical practice, namely in lung function, BMI, sweat chloride concentration, and number of pulmonary exacerbations, with no safety concerns.

RESUMO Objetivo: Avaliar a efetividade do tratamento com elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) e caracterizar seu perfil de segurança em pacientes com fibrose cística (FC) em um cenário clínico de mundo real. Métodos: Estudo observacional prospectivo realizado em um centro de referência em FC de Portugal com pacientes adultos com FC que iniciaram o tratamento com ELX/TEZ/IVA. As características clínicas dos pacientes foram coletadas, e os dados de efetividade e segurança, avaliados. Resultados: Dos 56 pacientes acompanhados no centro na época do estudo, 28 eram elegíveis para o tratamento com ELX/TEZ/IVA de acordo com a Autoridade Nacional do Medicamento e Produtos de Saúde. Destes, 24 atenderam ao requisito de tempo de acompanhamento para inclusão na análise de efetividade clínica. O tempo médio de acompanhamento foi de 167,3 ± 96,4 dias. Os eventos adversos foram geralmente leves e autolimitados. Foram observadas melhoras significativas na função pulmonar, no IMC, na concentração de cloreto no suor e no número de exacerbações pulmonares. Não foram encontradas diferenças significativas nos resultados entre os pacientes homozigotos e heterozigotos para F508del. A efetividade dessa nova combinação de moduladores da CFRT em fibrose cística também se aplica a pacientes com doença pulmonar avançada. Conclusões: O tratamento com ELX/TEZ/IVA demonstrou melhora efetiva na prática clínica real, a saber, na função pulmonar, no IMC, na concentração de cloreto no suor e no número de exacerbações pulmonares, sem preocupações de segurança.

O conceito de "lugar de fala": das possibilidades de delimitação aos riscos de esvaziamento conceitual / The concept of "lugar de fala": from the possibilities of delimitation to the risks of conceptual emptying / El concepto de "lugar de fala": de las posibilidades de delimitación a los riesgos de vaciamiento conceptual

O objetivo deste estudo foi mapear os usos do conceito de lugar de fala em artigos acadêmicos, avaliando eventuais delimitações propostas nessa literatura. Para tanto, foi realizada uma revisão integrativa, na qual a palavra-chave "lugar de fala" foi buscada no Portal de Periódicos da Capes e na Scielo. Dos 142 artigos recuperados, 66% utilizou a expressão sem referências bibliográficas ou definições explícitas, mantendo, portanto, os riscos de esvaziamento conceitual. No demais dos artigos (34%), cinco apresentaram um uso negativo, com críticas mais ou menos explícitas ao conceito. Os artigos que fizeram um uso positivo do conceito de lugar de fala foram agrupados em campos de investigação mais ou menos específicos, com destaque para o feminismo negro, feminismo e estudos pós-coloniais. Nesses campos o conceito de lugar de fala tem um uso francamente político, abordando criticamente as relações de poder que permeiam as produções discursivas e silenciam grupos marginalizados.

This study aimed to map the uses of the concept "lugar de fala" (place of speech) in academic articles, in order to evaluate eventual delimitations proposed in this literature. For that, an integrative review was carried out in Portal de Periódicos da CAPES and in Scielo databases, using the keyword "lugar de fala" in Portuguese. 66% of 142 recovered articles used the expression without bibliographical references or explicit definitions, thus maintaining the risks of conceptual emptying. Five of the remaining 34 % of the articles presented a negative use, showing more or less explicit criticism of the concept. Articles that made positive use of the concept were grouped into more or less specific fields of investigation, with emphasis on black feminism, feminism and postcolonial studies. In these fields, the concept of "local de fala" has a frankly political use, critically approaching the power relations that permeate discursive productions and that silence marginalized groups.

El objetivo de este estudio fue mapear los usos del concepto de "lugar de fala" en artículos académicos, evaluando eventuales delimitaciones propuestas en esta literatura. Para eso, se realizó una revisión integradora, en la que se buscó la palabra clave "lugar de fala" en Portugués en el Portal de Periódicos de CAPES y en Scielo. De los 142 artículos recuperados, el 66% utilizó la expresión sin referencias bibliográficas ni definiciones explícitas, manteniendo así los riesgos de vaciamiento conceptual. En los demás artículos (34%), cinco presentaron un uso negativo, con críticas más o menos explícitas al concepto. Los artículos que hicieron un uso positivo del concepto de "lugar de fala" fueron agrupados en campos de investigación más o menos específicos, con énfasis en el feminismo negro, el feminismo y los estudios poscoloniales. En estos campos, el concepto tiene un uso francamente político, abordando críticamente las relaciones de poder que permean las producciones discursivas y silencian grupos marginados.

Interplay between Tumor Mutational Burden and Mutational Profile and Its Effect on Overall Survival: A Pilot Study of Metastatic Patients Treated with Immune Checkpoint Inhibitors.

Purpose: Solid tumors harboring tumor mutational burden (TMB) ≥10 mutations per megabase (mut/Mb) received agnostic approval for pembrolizumab. This work aims to analyze the somatic mutational profile's influence on the outcomes of patients with TMB-high tumors treated with immune checkpoint inhibitors (ICIs). Methods: This post-hoc analysis evaluated clinical and molecular features of patients with solid tumors treated with ICIs that could be either monoclonal antibody directed against programmed cell death protein-1 or monoclonal antibody directed against programmed cell death ligand 1 (anti-PD-1/anti-PD-L1), monoclonal antibody directed against cytotoxic T lymphocyte-associated antigen (anti-CTLA-4) or a combined treatment regimen including one anti-PD-1/anti-PD-L1 and one anti-CTLA-4 (ICIs combination). We performed OS analysis for TMB thresholds of ≥10, ≥20, and <10 mut/Mb. We assessed OS according to the mutational profile for a TMB ≥ 10 mut/Mb cutoff. For genes correlated with OS at the univariate assessment, we conducted a Cox multivariate analysis adjusted by median TMB, sex, age, microsatellite instability (MSI), and histology. Results: A total of 1661 patients were investigated; 488 with a TMB ≥10 mut/Mb (29.4%). The median OS was 42 months for TMB ≥10 or 20 mut/Mb, and 15 months for TMB <10 mut/Mb (p < 0.005). Among TMB ≥10 mut/Mb patients, mutations in E2F3 or STK11 correlated with worse OS, and mutations in NTRK3, PTPRD, RNF43, TENT5C, TET1, or ZFHX3 with better OS. These associations were confirmed with univariate and multivariate analyses (p < 0.05). Melanoma histology and TMB above the median endowed patients with better OS (p < 0.05), while MSI status, age, and gender did not have a statistically significant effect on OS. Conclusion: Combining TMB and mutation profiles in key cancer genes can better qualify patients for ICI treatment and predict their OS.

Postvaccinal pyogranulomas in cattle

Clinical History: The carcasses of seven 30-month-old female cows slaughtered in a local abattoir for meat production were totally condemned during meat inspection due to disseminated gross abnormalities. Gross findings: On internal examination, several skeletal muscles (pectoralis superficialis and profundus, transversus abdominis, diaphragm, obliquus internus abdominis, and rectus abdominis) and random areas of the peritoneal cavity had multifocal to coalescing nodules (1-3 cm in diameter). The nodules were firmly adhered (fibrous adherences) to the adjacent tissues and surface of portions of the forestomach serosa and splenic capsule. On the cut surface of the nodules, there was a central accumulation of a friable and yellow exudate surrounded by a fibrous capsule. No external lesions were seen in any of the cows.(AU)

Outbreak of canine distemper and coinfections in a maned wolf (Chrysocyon brachyurus) and in three giant anteaters (Myrmecophaga tridactyla).

Canine distemper outbreak and coinfections in three giant anteaters and in a maned wolf has been described. Three giant anteaters developed respiratory and digestive clinical signs after the introduction of a maned wolf to a Wildlife Rehabilitation Center. The maned wolf and two anteaters died, and one anteater was euthanized. Post mortem and histopathologic exams revealed lesions associated with numerous intraepithelial inclusion bodies, mainly in the respiratory and digestive systems. Infection by distemper virus was confirmed in all animals by RT-PCR and gene sequencing, which revealed the Europe 1/ South America 1 strain, closely related to the strain from Canis familiaris. In addition to distemper, the animals had other comorbidities, such as toxoplasmosis and salmonellosis in the maned wolf and cutaneous candidiasis in an anteater. Considering the chronology of clinical manifestation in both species and the viral characterization, it is possible that the maned wolf was the source of infection to the anteaters. This study demonstrates the importance of implementing biosecurity measures in enclosures that house animals of different species, highlighting the importance of quarantine before introduction of new animals into the same environment.

Unique SLC12A2-ROS1 fusion is associated with marked response to crizotinib in lung adenocarcinoma.

Chromosomal rearrangements involving the c-ros oncogene 1 (ROS1) gene define a subset of non-small cell lung cancers highly sensitive to small-molecule tyrosine kinase inhibitors. However, little is known about the impact of different fusion partners on tyrosine kinase inhibitor efficacy. We herein describe a case of a 26-year-old never-smoker patient from southern Africa with metastatic lung adenocarcinoma driven by SLC12A2-ROS1 fusion, who had a pronounced and durable response to crizotinib. The present case underscores the importance of pursuing actionable alterations in patients with similar clinical and epidemiological characteristics. In addition, provides the second report of crizotinib activity against lung malignancies harboring the unique SLC12A2-ROS1 fusion and highlights the importance of a deeper understanding of molecular alterations in underrepresented subgroups of patients to tailor the decision-making in daily practice.

Exacerbated Renal and Hematologic Toxicities to Ifosfamide and Doxorubicin-Based Chemotherapy in a Patient with Retroperitoneal Liposarcoma Harboring a Germline Mutation in the WRN Gene.

Werner's syndrome is caused by the inactivation of both WRN alleles and is characterized by premature aging and increased risk of neoplasms, especially those of mesenchymal origins, such as sarcomas. Given the characteristic genomic instability, patients with this syndrome are more susceptible to develop toxicities when exposed to cytotoxic agents, such as alkylators and anthracyclines. The impact of the monoallelic WRN mutation on treatment-associated toxicities is poorly understood. Here, we report a patient with locally advanced dedifferentiated liposarcoma of the retroperitoneum harboring a heterozygous germline inactivation mutation in the WRN gene, who was treated with a classic regimen of ifosfamide and doxorubicin and developed exacerbated and prolonged hematological and renal toxicities.