Long-term Insights: Histopathological Assessment in Polyurethane Implant Capsules up to 24 Years.

BACKGROUND: Polyurethane (PU)-coated breast implants are known for their strong integration into breast tissue and the formation of capsules around them. However, capsular contracture can pose both aesthetic and clinical challenges. OBJECTIVES: To analyze the biological and morphological characteristics of the capsular tissue surrounding PU-coated implants, irrespective of their contracture status, and to assess their potential suitability as a flap in revision breast surgery for capsular contracture. METHODS: A total of 23 tissue samples were harvested from the capsules surrounding PU-coated breast implants in 12 female patients during replacement or revision surgery. We evaluated collagen abundance, cellular and vascular density, inflammation, collagen band types and alignment, synovial metaplasia, capsule thickness, and the expression of inflammatory biomarkers and myofibroblasts using immunohistochemical techniques. Scanning electron microscopy was used to assess implant surface characteristics over time. RESULTS: We found a significant association of capsule contraction with longer implantation durations and greater implant surface roughness (p = 0.018 and p = 0.033, respectively). Synovial metaplasia was significantly more frequent in noncontracted capsules (p = 0.0049). Both capsule types consisted of paucicellular, type I collagen-rich compact fibrous tissue with low vascularization. There was a marked reduction in inflammatory cells within the foreign body granuloma. The expression of inflammatory biomarkers in the capsular tissue was negligible. CONCLUSIONS: Given the reduced levels of inflammatory and vascular components within the dense, fibrous capsular tissue, we consider them to be viable alternatives for use as capsular flaps in revision surgery. This strategy has the potential to mimic the reconstruction achieved with acellular dermal matrix.

SARS-CoV-2 Rapid Antigen Test Based on a New Anti-Nucleocapsid Protein Monoclonal Antibody: Development and Real-Time Validation.

SARS-CoV-2 diagnostic tests have become an important tool for pandemic control. Among the alternatives for COVID-19 diagnosis, antigen rapid diagnostic tests (Ag-RDT) are very convenient and widely used. However, as SARS-CoV-2 variants may continuously emerge, the replacement of tests and reagents may be required to maintain the sensitivity of Ag-RDTs. Here, we describe the development and validation of an Ag-RDT during an outbreak of the Omicron variant, including the characterization of a new monoclonal antibody (anti-DTC-N 1B3 mAb) that recognizes the Nucleocapsid protein (N). The anti-DTC-N 1B3 mAb recognized the sequence TFPPTEPKKDKKK located at the C-terminus of the N protein of main SARS-CoV-2 variants of concern. Accordingly, the Ag-RDT prototypes using the anti-DTC-N 1B3 mAB detected all the SARS-CoV-2 variants-Wuhan, Alpha, Gamma, Delta, P2 and Omicron. The performance of the best prototype (sensitivity of 95.2% for samples with Ct ≤ 25; specificity of 98.3% and overall accuracy of 85.0%) met the WHO recommendations. Moreover, results from a patients' follow-up study indicated that, if performed within the first three days after onset of symptoms, the Ag-RDT displayed 100% sensitivity. Thus, the new mAb and the Ag-RDT developed herein may constitute alternative tools for COVID-19 point-of-care diagnosis and epidemiological surveillance.

Obtaining a high titer of polyclonal antibodies from rats to the SARS-CoV-2 nucleocapsid protein and its N- and C-terminal domains for diagnostic test development.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is an enveloped, plus-stranded RNA virus responsible for the Coronavirus Disease 2019 (COVID-19). Patients infected with COVID-19 may be asymptomatic or have symptoms ranging from mild manifestations to severe cases of the disease that could lead to death. The SARS-CoV-2 genome encodes 4 structural proteins, including the Spike protein (S), the Nucleocapsid protein (N), Membrane protein (M) and, the Envelope protein (E). The N protein forms a major component of the ribonucleoprotein complex within the virus particle and play a vital role in its transcription and replication. Nevertheless, the S protein was the most important protein in the development of vaccines against COVID-19. However, the decrease in number of registered immunizations against the disease and the rapid drop in neutralizing antibody titers together with looser preventive measures for virus transmission, favored the rapid appearance of new variants of concerns (VOCs) that primarily show mutations in the S protein. This fact makes the N protein a good candidate for the development of diagnostic tests, due to its stability, amino acid conservation, high immunogenicity, and the smaller likelihood of mutation. With the aim of developing a new diagnostic kit based on the N protein, we evaluated the humoral response in female Wistar rats against this target. Three constructions of the N protein were used to inoculate the animals: the full-length protein (Cfull), the N- (NTD), and the C-terminal (CTD) portion of the protein. The immunizations induced the animal's immune response, with specific polyclonal IgG antibodies against the Cfull protein and its fragments. There were not non-specific bind to the protein used as negative control. Anti-Cfull antibodies demonstrated high efficiency in binding to the NTD protein and the antibodies present in the anti-CTD and anti-NTD sera have recognized the Cfull protein, but they were not able to recognize the NTD and CTD proteins, respectively. Our results indicate an efficient protocol for obtaining high antibody titers against the N recombinant protein of SARS-CoV-2 and its fragments highlighting the Cfull protein, which can be used in the development of new diagnostic kits.

Influence of the TAS2R38 Gene Single Nucleotide Polymorphisms in Metabolism and Anthropometry in Thyroid Dysfunction.

The gene TAS2R38 single nucleotide polymorphisms (SNPs-P49A, A262V and V296I) can condition bitter tasting by PAV (proline-alanine-valine) and non-bitter-tasting by AVI (alanine-valine-isoleucine) homozygosity. We evaluated this polymorphisms association with thyroid function, metabolism and anthropometry parameters determined by: Endpoint analysis (SNPs); DXA (fat mass-%, total fat mass-kg, lean mass-kg); Standard methods (lipid metabolism parameters, HbA1c-%, glycemia-mg/dL, insulinemia-µIU/mL, HOMA-IR, uricemia-mg/dL, calcemia-mg/dL and BMI-kg/m2); ELISA (leptinemia-ng/mL); Spectrophotometry (Angiotensin Converting Enzyme activity-UI/L). Statistics: SPSS program; OR [IC95%]; p < 0.05. Sample: 114 hypothyroid, 49 hyperthyroid, and 179 controls. An association between A262V-valine-valine and hypothyroidism/hyperthyroidism was verified (OR = 2.841; IC95% [1.726-4.676]), p < 0.001/OR = 8.915; IC95% [4.286-18.543]), p < 0.001). Protector effect from thyroid dysfunction: A262V-alanine-valine (OR = 0.467; IC95% [0.289-0.757], p = 0.002/OR = 0.132; IC95% [0.056-0.309], p < 0.001) and PAV (OR = 0.456; IC95% [0.282-0.737], p = 0.001/OR = 0.101; IC95% [0.041-0.250], p < 0.001). Higher parameter values associated with genotypes were: fat-mass-% (V296I-valine-isoleucine), lean-mass (P49A-proline-proline; PVI), leptin (AVI), HbA1c (A262V-alanine-valine) and lower values in lean-Mass (AVI; PVV), leptin (A262V-alanine-alanine), HbA1c (PVV), uricemia (V296I-valine-isoleucine), glycemia (A262V-alanine-alanine; AAV) and plasma triglycerides (PVV). In conclusion, TAS2R38 influences thyroid function, body composition and metabolism. Bitter taste perception (PAV) and the genotype A262V-alanine-valine can protect from thyroid dysfunction. AVV, PVV and genotype A262V-valine-valine may confer higher predisposition for thyroid dysfunction, particularly PVV for hyperthyroidism.

Temporal trends of persistent organic pollutant contamination in Franciscana dolphins from the Southwestern Atlantic.

Persistent organic pollutants (POPs) were analyzed in 136 blubber samples of Franciscana dolphins from Brazil (Pontoporia blainvillei), which is the most threatened dolphin in the Southwestern Atlantic. The dolphins were caught by the fishery fleet and collected from 2000 to 2018 in three regions of São Paulo state: northern São Paulo (SPN), central São Paulo (SPC), and southern São Paulo (SPS). The POPs analyzed in this study were polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethane (DDTs), Mirex, hexachlorobenzene (HCB), chlordane compounds (CHLs), hexachlorocyclohexane isomers (HCHs), and polybrominated diphenyl ethers (PBDEs). The concentrations ranged from 36 to 7200 ng g-1 lipid weight (lw) and 113-42200 ng g-1 lw for predominant compounds DDTs and PCBs, respectively. Similar profiles of PCB congeners were observed with a predominance of hexachlorinated compounds, representing approximately 50% of the total PCB amount; the highest PCB concentrations were observed from Baixada Santista (SPC) proximate to a highly urbanized and industrial coastal area. Significant differences were observed between the sexes and maturity of dolphins, mainly for PCBs, DDTs, and Mirex. In general, POPs other than HCB in Franciscana dolphins showed downward temporal trends, matching the regulatory periods for restricting and/or banning these compounds. Although POP concentrations are declining, PCB levels remain high in small dolphins, suggesting adverse health effects on Franciscanas. As organic contaminants are one of the numerous threats Franciscanas have been vulnerable to along the Brazilian coast, we recommend monitoring POPs levels every five years to check for declining (or stabilizing) trends.

Ti3C2 MXene Membranes for Gas Separation: Influence of Heat Treatment Conditions on D-Spacing and Surface Functionalization.

Two-dimensional (2D) MXene materials have recently been the focus of membrane research due to their unique properties, such as their single-atomic-layer thickness, flexibility, molecular filtration abilities and microstructural similarities with graphene, which is currently the most efficient precursor material for gas separation applications. In addition, the potential to process nanoscale channels has motivated investigations of parameters which can improve membrane permeability and selectivity. Interlayer spacing and defects, which are still challenging to control, are among the most crucial parameters for membrane performance. Herein, the effect of heat treatment on the d-spacing of MXene nanosheets and the surface functionalization of nanolayers was shown regarding its impact on the gas diffusion mechanism. The distance of the layers was reduced by a factor of over 10 from 0.345 nm to 0.024 nm, the defects were reduced, and the surface functionalization was maintained upon treatment of the Ti3C2 membrane at 500 °C under an Ar/H2 atmosphere as compared to 80 °C under vacuum. This led to a change from Knudsen diffusion to molecular sieving, as demonstrated by single-gas permeation tests at room temperature. Overall, this work shows a simple and promising way to improve H2/CO2 selectivity via temperature treatment under a controlled atmosphere.

SARS-CoV-2 Nucleocapsid Protein is Associated With Lower Testosterone Levels: An Experimental Study.

The ongoing COVID-19 pandemic represents an extra burden in the majority of public and private health systems worldwide beyond the most pessimistic expectations, driving an urgent rush to develop effective vaccines and effective medical treatments against the SARS-CoV-2 pandemic. The Nucleocapsid structural viral protein is remarkably immunogenic and hugely expressed during infection. High IgG antibodies against Nucleocapsid protein (N protein) levels were detected in the serum of COVID-19 patients, confirming its pivotal antigen role for a T lymphocyte response in a vaccine microenvironment. Currently, adverse events associated with immunizations have raised some degree of concern, irrespective of its huge benefits in dealing with disease severity and decreasing mortality and morbidity. This hitherto study evaluates histological changes in rats' testes, epididymis, prostate, and seminal vesicles and analyzes hormone levels after solely N protein inoculation. Therefore, we exposed a group of Lewis rats to weekly injections of the recombinant N protein for 28 days, while a control group was inoculated with a buffer solution. The N group revealed a more significant number of spermatozoa. Spermatozoa in the seminiferous tubules were counted in twenty 400 × microscopy fields (mean of 9.2 vs. 4.6 in the control group; p < 0,01), but significantly lower testosterone levels (mean of 125.70 ng/dl vs. 309,00 ng/dl in the control group; p < 0,05) were found. No other histological and biochemical changes were displayed. Conclusively, these data suggest testicular hormonal imbalance mediated by the SARS-CoV-2 N protein that could be linked to reported post-COVID-19 syndrome hypogonadism. More relevant research might be performed to confirm this viral antigen's deleterious mechanism in the human testicular microenvironment, particular in Leydig cell function.

Vascular endothelial growth factor (VEGF) and interleukin-1 receptor antagonist (IL-1Ra) as promising biomarkers for distinguishing active from latent tuberculosis in children and adolescents.

Since distinguishing pulmonary (PTB) from latent tuberculosis (LTBI) in pediatric patients remains a challenge, we aimed to investigate the efficacy of immune mediators in diagnosing PTB and LTBI in this population. In this cross-sectional study performed with children and adolescents, serum levels of 20 biomarkers were assessed and data were analyzed according to age groups. We included 65 participants (PTB, n = 28 and LTBI, n = 37). Overall, levels of TNF-α, IL-1Ra, IL-6, IL-17A, VEGF, MMP-1, and procalcitonin were significantly higher (P < 0.05) in adolescents and children <10 years-old with PTB. Also, principal component analysis (PCA) showed that immune mediators were able to distinguish PTB from LTBI. VEGF and IL-1Ra presented the highest area under the curve (AUC) values, both separately (AUC 0.890 and 0.785) and combined (AUC 0.99). Taken together, we showed that VEGF and IL-1Ra are promising biomarkers to distinguish PTB from LTBI in pediatric patients, especially in children <5 years-old.

Toxicity of spike fragments SARS-CoV-2 S protein for zebrafish: A tool to study its hazardous for human health?

Despite the significant increase in the generation of SARS-CoV-2 contaminated domestic and hospital wastewater, little is known about the ecotoxicological effects of the virus or its structural components in freshwater vertebrates. In this context, this study evaluated the deleterious effects caused by SARS-CoV-2 Spike protein on the health of Danio rerio, zebrafish. We demonstrated, for the first time, that zebrafish injected with fragment 16 to 165 (rSpike), which corresponds to the N-terminal portion of the protein, presented mortalities and adverse effects on liver, kidney, ovary and brain tissues. The conserved genetic homology between zebrafish and humans might be one of the reasons for the intense toxic effects followed inflammatory reaction from the immune system of zebrafish to rSpike which provoked damage to organs in a similar pattern as happen in severe cases of COVID-19 in humans, and, resulted in 78,6% of survival rate in female adults during the first seven days. The application of spike protein in zebrafish was highly toxic that is suitable for future studies to gather valuable information about ecotoxicological impacts, as well as vaccine responses and therapeutic approaches in human medicine. Therefore, besides representing an important tool to assess the harmful effects of SARS-CoV-2 in the aquatic environment, we present the zebrafish as an animal model for translational COVID-19 research.

Educação permanente sobre cuidados paliativos para profissionais de enfermagem: revisão integrativa da literatura / Permanent education on palliative care for nursing professionals: an integrative literature review / Educación permanente en cuidados paliativos para profesionales de enfermería: revisión integradora de la literatura

Objetivo: identificar na literatura evidências científicas atuais acerca de educação permanente em cuidados paliativos para profissionais de enfermagem. Método: revisão integrativa da literatura realizada em seis etapas: 1- definição da questão norteadora; 2- busca na literatura nas bases de dados: Latin American and Caribbean Health Sciences Literature, Base de Dados em Enfermagem e Medical Literature Analysis and Retrieval System Online por meio da combinação dos Descritores português: "Cuidados Paliativos", "Enfermagem" e "Educação Continuada"; 3- definição das informações a serem extraídas dos estudos; 4- avaliação crítica; 5- interpretação dos resultados; 6- síntese do conteúdo. Resultados: seis artigos selecionados para leitura na íntegra, emergindo duas categorias para discussão. Conclusão: trata-se de uma temática recente, porém em ascensão. Observou-se um número reduzido de estudos, indicando a necessidade de novas pesquisas no campo dos cuidados paliativos e educação permanente nessa área.

Objective: to identify current scientific evidence in the literature about continuing education in palliative care for nursing professionals. Method: integrative literature review carried out in six steps: 1- definition of the guiding question; 2- Literature search in the databases: Latin American and Caribbean Health Sciences Literature, Database in Nursing and Medical Literature Analysis and Retrieval System Online by combining the Portuguese Descriptors: "Palliative Care", "Nursing" and "Education Continued"; 3- definition of the information to be extracted from the studies; 4- critical evaluation; 5- interpretation of results; 6- content synthesis. Results: six articles selected for full reading, emerging two categories for discussion. Conclusion: this is a recent theme, but on the rise. There was a small number of studies, indicating the need for further research in the field of palliative care and continuing education in this area.

Objetivo: identificar la evidencia científica actual en la literatura sobre la formación continua en cuidados paliativos para profesionales de enfermería. Método: revisión integradora de la literatura realizada en seis pasos: 1- definición de la pregunta orientadora; 2- Búsqueda de literatura en las bases de datos: Literatura Latinoamericana y del Caribe en Ciencias de la Salud, Base de Datos en Enfermería y Sistema de Análisis y Recuperación de Literatura Médica en Línea mediante la combinación de los Descriptores Portugueses: "Cuidados Paliativos", "Enfermería" y "Educación Continuada"; 3- definición de la información a extraer de los estudios; 4- evaluación crítica; 5- interpretación de resultados; 6- síntesis de contenido. Resultados: seis artículos seleccionados para lectura completa, emergiendo dos categorías para discusión. Conclusión: este es un tema reciente, pero en aumento. Hubo un pequeño número de estudios, lo que indica la necesidad de realizar más investigaciones en el campo de los cuidados paliativos y la educación continua en esta área.

Educação permanente sobre cuidados paliativos para profissionais de enfermagem: revisão integrativa da literatura / Permanent education on palliative care for nursing professionals: an integrative literature review / Educación permanente en cuidados paliativos para profesionales de enfermería: revisión integradora de la literatura

Objetivo: identificar na literatura evidências científicas atuais acerca de educação permanente em cuidados paliativos para profissionais de enfermagem. Método: revisão integrativa da literatura realizada em seis etapas: 1- definição da questão norteadora; 2- busca na literatura nas bases de dados: Latin American and Caribbean Health Sciences Literature, Base de Dados em Enfermagem e Medical Literature Analysis and Retrieval System Online por meio da combinação dos Descritores português: "Cuidados Paliativos", "Enfermagem" e "Educação Continuada"; 3- definição das informações a serem extraídas dos estudos; 4- avaliação crítica; 5- interpretação dos resultados; 6- síntese do conteúdo. Resultados: seis artigos selecionados para leitura na íntegra, emergindo duas categorias para discussão. Conclusão: trata-se de uma temática recente, porém em ascensão. Observou-se um número reduzido de estudos, indicando a necessidade de novas pesquisas no campo dos cuidados paliativos e educação permanente nessa área.

Objective: to identify current scientific evidence in the literature about continuing education in palliative care for nursing professionals. Method: integrative literature review carried out in six steps: 1- definition of the guiding question; 2- Literature search in the databases: Latin American and Caribbean Health Sciences Literature, Database in Nursing and Medical Literature Analysis and Retrieval System Online by combining the Portuguese Descriptors: "Palliative Care", "Nursing" and "Education Continued"; 3- definition of the information to be extracted from the studies; 4- critical evaluation; 5- interpretation of results; 6- content synthesis. Results: six articles selected for full reading, emerging two categories for discussion. Conclusion: this is a recent theme, but on the rise. There was a small number of studies, indicating the need for further research in the field of palliative care and continuing education in this area.

Objetivo: identificar la evidencia científica actual en la literatura sobre la formación continua en cuidados paliativos para profesionales de enfermería. Método: revisión integradora de la literatura realizada en seis pasos: 1- definición de la pregunta orientadora; 2- Búsqueda de literatura en las bases de datos: Literatura Latinoamericana y del Caribe en Ciencias de la Salud, Base de Datos en Enfermería y Sistema de Análisis y Recuperación de Literatura Médica en Línea mediante la combinación de los Descriptores Portugueses: "Cuidados Paliativos", "Enfermería" y "Educación Continuada"; 3- definición de la información a extraer de los estudios; 4- evaluación crítica; 5- interpretación de resultados; 6- síntesis de contenido. Resultados: seis artículos seleccionados para lectura completa, emergiendo dos categorías para discusión. Conclusión: este es un tema reciente, pero en aumento. Hubo un pequeño número de estudios, lo que indica la necesidad de realizar más investigaciones en el campo de los cuidados paliativos y la educación continua en esta área.

Toxicity of spike fragments SARS-CoV-2 S protein for zebrafish: a tool to study its hazardous for human health?

Despite the significant increase in the generation of SARS-CoV-2 contaminated domestic and hospital wastewater, little is known about the ecotoxicological effects of the virus or its structural components in freshwater vertebrates. In this context, this study evaluated the deleterious effects caused by SARS-CoV-2 Spike protein on the health of Danio rerio, zebrafish. We demonstrated, for the first time, that zebrafish injected with fragment 16 to 165 (rSpike), which corresponds to the N-terminal portion of the protein, presented mortalities and adverse effects on liver, kidney, ovary and brain tissues. The conserved genetic homology between zebrafish and humans might be one of the reasons for the intense toxic effects followed inflammatory reaction from the immune system of zebrafish to rSpike which provoked damage to organs in a similar pattern as happen in severe cases of COVID-19 in humans, and, resulted in 78,6% of survival rate in female adults during the first seven days. The application of spike protein in zebrafish was highly toxic that is suitable for future studies to gather valuable information about ecotoxicological impacts, as well as vaccine responses and therapeutic approaches in human medicine. Therefore, besides representing an important tool to assess the harmful effects of SARS-CoV-2 in the aquatic environment, we present the zebrafish as an animal model for translational COVID-19 research.

Photobiomodulation therapy increases functional capacity of patients with chronic kidney failure: randomized controlled trial.

Photobiomodulation (PBM) has been used in different populations as a strategy to attenuate muscle fatigue and improve exercise performance. Recent findings demonstrated that a single session with specific PBM doses during hemodialysis (HD) increased the upper limb muscle strength of chronic kidney failure (CKF) patients. Now, the primary objective of this study was to evaluate the chronic effect of PBM on the functional capacity of this population. Secondarily, we aimed at investigating the effects of PBM on the patients' strength, muscle thickness and echogenicity, perception of pain, fatigue, and quality of life. A randomized controlled trial was conducted in which the intervention group (IG, n = 14) received 24 sessions of PBM (810 nm, 5 diodes × 200 mW, 30 J/application site) on lower limb during HD. The control group (CG, n = 14) did not receive any physical therapy intervention, it only underwent HD sessions. As a result, there was an increase in the functional capacity (assessed through the six-minute walk test) for the IG compared with the CG [50.7 m (CI95% 15.63; 85.72), p = 0.01, large effect size, d = 1.12], as well as an improvement on lower limb muscle strength (assessed through the sit-and-stand test) [- 7.4 s (CI95% - 4.54; - 10.37), p = 0.00, large effect size, d = 1.99]. For other outcomes evaluated, no significant difference between-group was observed. Finally, PBM applied as monotherapy for 8 weeks in the lower limb improves functional capacity and muscle strength of CKF patients.

Diagnosis of pulmonary tuberculosis in children and adolescents: comparison of two versions of the Brazilian Ministry of Health scoring system.

The aim of this study was to evaluate the concordance between two versions of the scoring system (2011 and 2019), recommended by the Brazilian Ministry of Health, for the diagnosis of pulmonary tuberculosis (PTB) in children and adolescents. A retrospective descriptive study was performed to assess the medical records of children and adolescents with PTB, in TB units from Brazilian cities located in Rio de Janeiro, Minas Gerais, and Parana States, from January 1 st , 2004, to December 1 st , 2018. Patients aged 0 to 18 years old with a diagnosis of PTB were included. The comparison between the two scoring systems showed a moderate concordance according to the κ coefficient value = 0.625. Fourteen patients showed a reduction in the TB score, going from 30 points in the 2011, to 25 points or less in the 2019 one. Seventy one percent of these 14 patients had radiological changes suggestive of PTB and 86% had tuberculin skin tests greater than 10 mm. The study concluded that a moderate agreement was observed between the 2011 and 2019 scoring systems, with an increase in the number of patients scoring 25 points or less in 2019, which can eventually hinder the diagnosis of PTB.

An association between successful engraftment of osteosarcoma patient-derived xenografts and clinicopathological findings.

Although osteosarcoma is a rare disease, with a global incidence rate estimated at 5.0/million/year, it is the most frequent primary bone sarcoma in children and adolescents. In translational research, the patient-derived xenograft (PDX) model is considered an authentic in vivo model for several types of cancer, as tumorgrafts faithfully retain the biological characteristics of the primary tumors. Our goal was to investigate the association between PDX formation and clinical findings of osteosarcoma patients and the ability of the model to preserve in immunocompromized mice the characteristics of the parental tumor. A fresh sample of the patient tumor obtained from a representative biopsy or from surgical resection was implanted into nude mice. When tumor outgrowths reached ~1,500mm³, fresh PDX fragments were re-transplanted into new hosts. Engraftment in mice was obtained after a latency period of 19-225 days (median 92 days) in 40.54% of the implanted samples. We confirmed the histopathological fidelity between the patient tumor and their respective established PDXs, including the expression of biomarkers. PDX take rate was higher in surgical resection samples, in post-chemotherapy surgical samples and in samples from patients with metastatic disease at presentation. In conclusion, we have shown that the osteosarcoma PDX model reliably recapitulates the morphological aspects of the human disease after serial passage in mice. The observation that more aggressive forms of osteosarcoma, including those with metastatic disease at presentation, have a higher efficiency to generate PDXs provides a promising scenario to address several unanswered issues in clinical oncology.

Serological biomarkers for monitoring response to treatment of pulmonary and extrapulmonary tuberculosis in children and adolescents.

Key measures to halt the spread of tuberculosis (TB) include early diagnosis, effective treatment, and monitoring disease management. We sought to evaluate the use of serum immunoglobulin levels against antigens present in cell envelope of Mycobacterium tuberculosis to monitor TB treatment response in children and adolescents with pulmonary (PTB) or extrapulmonary TB (EPTB). Blood samples were collected prior to and one, two, and six months following treatment initiation. Serum immunoglobulin levels against cardiolipin, sulfatide, mycolic acid and Mce1A protein were measured by ELISA. Serum from 53 TB patients and 12 healthy participants were analyzed. After six months of successful treatment, there was a significant decrease (p < 0.0001) in IgM levels against cardiolipin, sulfatide, mycolic acid and Mce1A protein and IgG levels against Mce1A protein when compared to baseline immunoglobulin levels. There was no significant variation in antibody levels during follow-up between participants with PTB and EPTB, confirmed and unconfirmed TB diagnosis, and HIV infection status. Antibody levels in control participants without TB did not decrease during follow-up. These results suggest that immunoglobulin responses to mycobacterial cell wall products may be a useful tool to monitor treatment response in children and adolescents with PTB or EPTB.

Pediatric tuberculosis in the metropolitan area of Rio de Janeiro.

AIM: To evaluate the clinical characteristics, diagnostic approach, and treatment outcomes of tuberculosis (TB) in children living in a high-burden metropolitan area. METHODS: This was a retrospective study, based on a medical chart review, involving children under 15 years old treated for TB between 2007 and 2016, in four primary health units (PHU) and three reference centers (RC) in five cities of Rio de Janeiro metropolitan area. Factors associated with TB treatment setting, microbiological diagnosis, and treatment outcomes were evaluated. RESULTS: A total of 544 children were enrolled; 71% were treated in PHU, 36% were under 5 years old, and 72% had pulmonary TB (PTB). The HIV prevalence was 10% (31/322). Fifty-three percent had at least one microbiological test for TB, 68% of them (196/287) had TB confirmed. Among 222 children with previous TB contact, information on LTBI was available for 78 (35%), and only 17% (13/78) were treated. Extrapulmonary TB (56% vs 32%), microbiologically confirmed TB (77% vs 60%), and HIV positivity (18.5% vs 4.0%) were significantly more frequent in RC. Treatment in RC (odds ratio (OR) 3.08, 95% confidence interval (CI) 1.74-5.44) and PTB (OR 2.47, 95% CI 1.34-4.56) were independently associated with a microbiological diagnosis of TB. The treatment success rate was 85%. In the logistic regression analysis, HIV-infected children had a 2.5-fold higher risk of an unfavorable outcome (OR 2.53, 95% CI 1.0-6.38; p = 0.05). CONCLUSIONS: Opportunities for TB prevention and early TB treatment are missed due to suboptimal close contact screening. Microbiological diagnosis of TB and drug susceptibility testing in children should be made available through more sensitive and accessible tests.

Home-based inspiratory muscle training in pediatric patients after kidney transplantation: a randomized clinical trial.

BACKGROUND: Chronic kidney disease (CKD) represents the irreversible stages of renal failure and is a growing worldwide public health issue associated with increases in morbidity, mortality, and decreased quality of life. Kidney transplantation is considered one of the best treatment options in this population. However, even after surgery, respiratory muscle strength is below normal values, and inspiratory muscle training (IMT) improves respiratory muscle function, strength, and endurance. This study aimed to evaluate the effects of IMT regarding respiratory muscle strength, functional capacity, and pulmonary function in pediatric kidney transplant recipients with CKD, and secondarily, to assess the biochemical profile of patients after intervention. METHODS: This is a randomized, double-blind, placebo-controlled trial. Patients were randomized into two groups, intervention (IG) and control (CG) and performed IMT home-based training for 6 weeks. In the IG, the load was adjusted to 40% of the maximal inspiratory pressure and in the CG was adjusted to a minimum placebo load (9 cm H2O). RESULTS: Thirty-one patients were randomly allocated to the intervention (n = 16) or control (n = 15) groups. There were no differences at baseline between groups. Increase of 35% in the maximal inspiratory pressure predicted and 26% in the maximal expiratory pressure predicted in the IG were found, compared with 5 and 4% in the CG. There was an increase in hemoglobin and hematocrit values in the IG. CONCLUSIONS: Home-based IMT provides a significant increase in respiratory muscle strength, without changes in functional capacity and pulmonary function. Benefits regarding biochemical markers (hemoglobin and hematocrit) were also observed.

Evolução temporal de exames bioquímicos em mulheres privadas de liberdade / Temporal evolution of biochemical tests in incarcerated women

Objetivo: Investigar a evolução de parâmetros bioquímicos em mulheres privadas de liberdade. Métodos: Estudo observacional, prospectivo, envolvendo a totalidade da população feminina encarcerada em regime fechado de Natal, Rio Grande do Norte, Brasil. Foram comparados exames bioquímicos (glicemia de jejum, colesterol total, triglicerídeos, LDL-c, HDL-c, não-HDL-c), realizados nos anos de 2012 (n=180) e 2015 (n=89), por meio dos testes de Mann-Whitney, Wilcoxon e Qui-quadrado. Resultados: Verificou-se elevada prevalência de HDL-c baixo, de Não HDL-c elevado e de hipertrigliceridemia isolada em ambos os anos do estudo. Após três anos de encarceramento, a coorte de detentas apresentou elevação nas concentrações da glicemia de jejum (62,2mg/dL para 87,9mg/dL, p<0,001), colesterol total (163,3mg/dL para 184,9mg/dL, p=0,007), não-HDL-c (120,8mg/dL para 138,2mg/dL, p=0,023), triglicerídeos (96,7mg/dL para 150,2mg/dL, p=0,024) e HDL-c (42,5mg/dL para 46,7mg/dL, p=0,012). Conclusão: Durante o encarceramento, ocorreram importantes alterações bioquímicas que podem favorecer o desenvolvimento e agravamento de doenças crônicas não transmissíveis, evidenciando a necessidade de intensificar as ações de saúde no ambiente prisional. (AU)

Objective: To investigate the evolution of biochemical parameters in incarcerated women. Methods: An observational prospective study involving the entire incarcerated female population in a closed regime in Natal, Rio Grande do Norte, Brazil. Biochemical tests (fasting blood glucose, total cholesterol, triglycerides, LDL-c, HDL-c, non-HDL-c) performed in the years 2012 (n = 180) and 2015 (n = 89) were compared using the Mann-Whitney, Wilcoxon and Chi-squared tests. Results: There was a high prevalence of low HDL-c, high Non-HDL-c and isolated hypertriglyceridemia in both years of the study. After three years of incarceration, the cohort of inmates showed an increase in fasting blood glucose concentrations (62.2mg/dL to 87.9mg/dL, p<0.001), total cholesterol (163.3mg/dL to 184.9mg/dL, p = 0.007), non-HDL-c (120.8mg/dL to 138.2mg/dL, p = 0.023), triglycerides (96.7mg/dL to 150.2mg/dL, p = 0.024) and HDL-c (42.5mg/dL to 46.7mg/dL, p = 0.012). Conclusion: Important biochemical changes occurred during incarceration which may favor development and worsening of chronic non-communicable diseases, highlighting the need to intensify health actions in the prison environment. (AU)