Abstract Background Oncostatin M (OSM) is a pleiotropic cytokine which, after arterial injury, has proven to be to be rapidly expressed. Objectives To correlate the serum levels of OSM, soluble OSM receptor (sOSMR), and soluble fraction of glycoprotein 130 (sgp130) in patients with coronary artery disease (CAD) with clinical parameters. Methods Levels of sOSMR and sgp130 were evaluated by ELISA and OSM by Western Blot, in patients with CCS (n=100), patients with ACS (n=70), and 64 control volunteers without clinical manifestations of the disease. P-values < 0.05 were considered to be statistically significant. Results CAD patients exhibited significantly lower levels of sOSMR and sgp130 and higher levels of OSM when compared to the controls (both p < 0.0001). Clinical analysis displayed, lower levels of sOSMR in men ([OR] = 2.05, p = 0.026), youth (OR = 1.68, p = 0.0272), hypertensives (OR = 2.19, p = 0.041), smokers (OR = 2.19, p = 0.017), patients that did not present dyslipidemia (OR = 2.32, p = 0.013), patients with Acute Myocardial Infarction [AMI] (OR = 3.01, p = 0.001) and patients not treated with statin (OR = 1.95, p = 0.031), antiplatelet agent (OR = 2.46, p = 0.005), inhibitors of calcium channels (OR = 3.15, p = 0.028), and antidiabetic drugs (OR = 2.97, p = 0.005). The levels of sOSMR were also correlated with gender, age, hypertension, and use of medications in multivariate analysis. Conclusions Our data suggest that the enhanced serum levels of OSM, and decreased levels of sOSMR and sGP130 in patients with cardiac injury may play an important role in the pathophysiological mechanism of the disease. Furthermore, lower levels of sOSMR were associated with gender, age, hypertension, and the use of medications. (OSM which expressed sOSMR, , (sOSMR) 13 sgp (sgp130 (CAD parameters sgp13 Blot n=100, n100 n n=100 100 (n=100) n=70, n70 n=70 70 (n=70) 6 Pvalues P values 005 0 05 0.0 significant both 0.0001. 00001 0.0001 . 0001 0.0001) displayed OR ([OR 205 2 2.05 0.026, 0026 0.026 026 0.026) 168 1 68 1.68 0.0272, 00272 0.0272 0272 0.0272) 219 19 2.19 0.041, 0041 0.041 041 0.041) 0.017, 0017 0.017 017 0.017) 232 32 2.32 0.013, 0013 0.013 013 0.013) AMI [AMI 301 3 01 3.01 0.001 001 195 95 1.95 0.031, 0031 0.031 031 0.031) 246 46 2.46 0.005, 0005 0.005 0.005) 315 15 3.15 0.028, 0028 0.028 028 0.028) 297 97 2.97 0.005. gender age hypertension sGP sGP13 Furthermore (sOSMR (sgp13 sgp1 n10 n=10 10 (n=100 n7 n=7 7 (n=70 00 0. 0000 0.000 000 20 2.0 002 0.02 02 16 1.6 0027 0.027 027 21 2.1 004 0.04 04 0.01 23 2.3 30 3.0 0.00 9 1.9 003 0.03 03 24 4 2.4 31 3.1 29 2.9 sGP1 (sgp1 n1 n=1 (n=10 n= (n=7 2. 1. 3. (sgp (n=1 (n= (n

Resumo Fundamento A oncostatina M (OSM) é uma citocina pleiotrópica que, após lesão arterial, demonstra ser expressa rapidamente. Objetivos Correlacionar os níveis séricos da OSM, do receptor solúvel de oncostatina M (sOSMR) e da fração solúvel de glicoproteína 130 (sgp130) em pacientes com doença arterial coronariana (DAC) a parâmetros clínicos. Métodos Os níveis de sOSMR e sgp130 foram avaliados por ELISA, enquanto os de OSM foram avaliados por Western Blot, em pacientes com SCC (n=100), pacientes com SCA (n=70) e 64 voluntários do grupo de controle sem manifestações clínicas da doença. Valores de p <0,05 foram considerados estatisticamente significativos. Resultados Pacientes com DAC exibiram níveis significativamente mais baixos de sOSMR e sgp130 e níveis mais altos de OSM em comparação ao grupo de controle (ambos p <0,0001). A análise clínica mostrou níveis mais baixos de sOSMR em homens ([OR] = 2,05, p = 0,026), jovens (OR = 1,68, p = 0,0272), hipertensos (OR = 2,19, p = 0,041), fumantes (OR = 2,19, p = 0,017), pacientes que não apresentavam dislipidemia (OR = 2,32, p = 0,013), pacientes com infarto agudo do miocárdio [IAM] (OR = 3,01, p = 0,001) e pacientes não tratados com estatina (OR = 1,95, p = 0,031), antiplaquetário (OR = 2,46, p = 0,005), inibidores dos canais de cálcio (OR = 3,15, p = 0,028) e antidiabéticos (OR = 2,97, p = 0,005). Os níveis de sOSMR também foram correlacionados a sexo, idade, hipertensão e uso de medicamentos na análise multivariada. Conclusões Nossos dados sugerem que o aumento dos níveis séricos de OSM e a diminuição dos níveis de sOSMR e sGP130 em pacientes com injúria cardíaca podem desempenhar um papel importante no mecanismo fisiopatológico da doença. Além disso, níveis mais baixos de sOSMR foram associados a sexo, idade, hipertensão e uso de medicamentos. (OSM rapidamente (sOSMR 13 sgp (sgp130 (DAC clínicos sgp13 ELISA Blot n=100, n100 n n=100 , 100 (n=100) n=70 n70 70 (n=70 6 005 0 05 <0,0 significativos ambos <0,0001. 00001 <0,0001 . 0001 <0,0001) OR ([OR 205 2 2,05 0,026, 0026 0,026 026 0,026) 168 1 68 1,68 0,0272, 00272 0,0272 0272 0,0272) 219 19 2,19 0,041, 0041 0,041 041 0,041) 0,017, 0017 0,017 017 0,017) 232 32 2,32 0,013, 0013 0,013 013 0,013) IAM [IAM 301 3 01 3,01 0,001 001 195 95 1,95 0,031, 0031 0,031 031 0,031) 246 46 2,46 0,005, 0005 0,005 0,005) 315 15 3,15 0,028 0028 028 297 97 2,97 0,005. sexo idade multivariada sGP sGP13 disso (sgp13 sgp1 n10 n=10 10 (n=100 n=7 n7 7 (n=7 00 <0, 0000 <0,000 000 20 2,0 002 0,02 02 16 1,6 0027 0,027 027 21 2,1 004 0,04 04 0,01 23 2,3 30 3,0 0,00 9 1,9 003 0,03 03 24 4 2,4 31 3,1 29 2,9 sGP1 (sgp1 n1 n=1 (n=10 n= (n= <0 <0,00 2, 0,0 1, 3, (sgp (n=1 (n < 0,

Abstract Osteoarthritis (OA) encompasses degeneration of articular cartilage, subchondral bone erosions and sclerosis. Chondrocyte apoptosis and an oxygen-deprived microenvironment are essential factors in OA pathogenesis. PAR-4 (Prostate apoptosis response-4) is a pro-apoptotic protein implicated in many pathologies as well as in chondrocyte cell death mechanism. Vitamin D supplementation has been identified as a therapeutic tool for a variety of inflammatory pathologies. In the present manuscript, we investigated whether first, PAR-4 expression is influenced by chondrocytes in a model of OA, in vitro, and second, whether vitamin D modulates PAR-4 expression in the same model. To test our hypothesis, we used the primary culture of murine chondrocytes isolated from the femoral and tibial condyles of wistar rats. The expression of the pro-inflammatory effect interleukin IL-1β was evaluated in the presence and absence of vitamin D. Western blot and immunofluorescence analysis confirmed protein expression. In the normoxia condition, the chondrocytes expressed PAR-4 in the cell nucleus, and in the hypoxic condition, PAR-4 was expressed in the cell cytoplasm. We disclosed that the treatment with Vitamin D decreased PAR-4 (p= 0.0137) and caspase-3 (p= 0.0007) expression. Thus, the results suggested that PAR-4 and caspase-3 proteins could be potential targets for OA.However, we believe that research is needed to identify the mechanisms implicated in the regulation of PAR-4 in OA.

Abstract Biopharmaceuticals, mainly monoclonal antibodies, and fusion proteins are drugs that have gained notoriety in the treatment of various chronic and inflammatory diseases and have high prices. The study aimed to verify which monoclonal antibodies and fusion proteins were most incorporated into the Unified Health System (SUS), which therapeutic indication most benefited from them and to analyze public spending on these biopharmaceuticals from January 2012 to September 2019. This study performed a qualitative and quantitative analysis of biopharmaceuticals incorporated by SUS. The data were collected on the websites of CONITEC and the Health Price Bank. The results demonstrated that subcutaneous adalimumab was most frequently incorporated, and the most requested therapeutic indication was rheumatoid arthritis. Public spending on biopharmaceuticals exceeded R$ 28 billion (more than US$ 140 billion). However, a downward trend was confirmed (-266.7%) in the period evaluated. Despite the increase in demand and public spending on biologics in general, in Brazil and worldwide, the results of this research show that there was a drop in public spending on the biopharmaceuticals studied in the last seven years.

RESUMO As tecnologias em saúde têm revolucionado a assistência médica e a gestão em saúde. A Comissão Nacional de Incorporação de Tecnologias no SUS (Conitec) é o órgão do Ministério da Saúde que assessora na incorporação, exclusão ou alteração de novas tecnologias no Sistema Único de Saúde (SUS). O presente estudo objetivou descrever o perfil das tecnologias incorporadas no SUS de 1 de janeiro de 2012 a 30 de setembro de 2019. Os dados foram coletados no site da Conitec. Na análise estatística, foi utilizado o teste Qui-quadrado de Pearson e o Teste Exato de Fisher. Os resultados demonstram que foram incorporadas 380 tecnologias, prevalecendo os medicamentos (46,6%). Em relação aos demandantes, os de origem interna superaram os demais (82,4%), principalmente secretarias do Ministério da Saúde (p<0,001). As Doenças Infecciosas e Parasitárias (DIPs) foram as mais beneficiadas (20,3%), com destaque para o HIV (Vírus da Imunodeficiência Humana). A maioria das tecnologias incorporadas passou por consulta pública (p<0,001). Conclui-se que o perfil das tecnologias incorporadas são principalmente medicamentos, por demanda interna, com indicação para DIPs e, sobretudo para o HIV. Os medicamentos continuam sendo o foco das solicitações e as demandas internas passaram a ter mais espaço nesse cenário.

ABSTRACT Health technologies have revolutionized medical care and health management. The National Commission for the Incorporation of Technologies in the SUS (Conitec) is the Ministry of Health’s body that advises on the incorporation, exclusion or alteration of new technologies in the Unified Health System (SUS). This study aimed to describe the profile of technologies incorporated in the SUS between January 1, 2012 and September 30, 2019. Data were collected on the Conitec website. Statistical analysis used Pearson’s chi-square test and Fisher’s exact test. The results show that 380 technologies were incorporated, with medication prevailing (46.6%). In relation to the plaintiffs, those of internal origin surpassed the others (82.4%), mainly secretariats of the Ministry of Health (p<0.001). Infectious and Parasitic Diseases (PIDs) were the most benefited (20.3%), with emphasis on HIV (Human Immunodeficiency Virus). Most of the incorporated technologies underwent public consultation (p<0.001). It is concluded that the profile of the incorporated technologies are mainly medicines, by internal demand, with indication for PIDs and, above all, for HIV. Medicines continue to be the focus of requests and internal demands have gained more space in this scenario.

ABSTRACT Health technologies have revolutionized medical care and health management. The National Commission for the Incorporation of Technologies in the SUS (Conitec) is the Ministry of Health’s body that advises on the incorporation, exclusion or alteration of new technologies in the Unified Health System (SUS). This study aimed to describe the profile of technologies incorporated in the SUS between January 1, 2012 and September 30, 2019. Data were collected on the Conitec website. Statistical analysis used Pearson’s chi-square test and Fisher’s exact test. The results show that 380 technologies were incorporated, with medication prevailing (46.6%). In relation to the plaintiffs, those of internal origin surpassed the others (82.4%), mainly secretariats of the Ministry of Health (p<0.001). Infectious and Parasitic Diseases (PIDs) were the most benefited (20.3%), with emphasis on HIV (Human Immunodeficiency Virus). Most of the incorporated technologies underwent public consultation (p<0.001). It is concluded that the profile of the incorporated technologies are mainly medicines, by internal demand, with indication for PIDs and, above all, for HIV. Medicines continue to be the focus of requests and internal demands have gained more space in this scenario.

RESUMO As tecnologias em saúde têm revolucionado a assistência médica e a gestão em saúde. A Comissão Nacional de Incorporação de Tecnologias no SUS (Conitec) é o órgão do Ministério da Saúde que assessora na incorporação, exclusão ou alteração de novas tecnologias no Sistema Único de Saúde (SUS). O presente estudo objetivou descrever o perfil das tecnologias incorporadas no SUS de 1 de janeiro de 2012 a 30 de setembro de 2019. Os dados foram coletados no site da Conitec. Na análise estatística, foi utilizado o teste Qui-quadrado de Pearson e o Teste Exato de Fisher. Os resultados demonstram que foram incorporadas 380 tecnologias, prevalecendo os medicamentos (46,6%). Em relação aos demandantes, os de origem interna superaram os demais (82,4%), principalmente secretarias do Ministério da Saúde (p<0,001). As Doenças Infecciosas e Parasitárias (DIPs) foram as mais beneficiadas (20,3%), com destaque para o HIV (Vírus da Imunodeficiência Humana). A maioria das tecnologias incorporadas passou por consulta pública (p<0,001). Conclui-se que o perfil das tecnologias incorporadas são principalmente medicamentos, por demanda interna, com indicação para DIPs e, sobretudo para o HIV. Os medicamentos continuam sendo o foco das solicitações e as demandas internas passaram a ter mais espaço nesse cenário.

Abstract INTRODUCTION Herein, the authors describe a simple enhancement to a commercial rapid DNA extraction kit based on simple viral lysis for detecting COVID-19 via RT-qPCR. METHODS After testing several different modifications, the adapted protocol with the best results in preliminary experiments was statistically evaluated in comparison with an automated robotic protocol. RESULTS Processing and testing of 119 nasopharyngeal samples ultimately yielded near-perfect agreement with the automated protocol (κ = 0.981 [95% confidence interval 0.943-1.000]). CONCLUSIONS The low cost and rapidity of the enhanced protocol makes it suitable for adoption in laboratories diagnosing COVID-19, especially those with high demand for examinations.

Allergic asthma is a chronic, complex inflammatory disease of the airway. Despite extensive studies on the immunomodulation of T helper (Th) cell pathways (i.e., Th1 and Th2) in asthma, little is known about the effects of Th17 pathway modulation, particularly that involving peroxisome proliferator-activated receptors (PPARs). In response, two new thiazolidinedione derivatives-namely, LPSF-GQ-147 and LPSF-CR-35 were synthesized and evaluated for their immunomodulatory effects on Th17-related cytokines, including interferon γ (IFNγ), interleukin IL-6, IL-17, and IL-22 in the peripheral blood mononuclear cells of asthmatic children. Both compounds were nontoxic even at high concentrations (i.e., 100 µM). The LPSF-CR-35 compound significantly reduced the levels of IL-17A (p = .039) and IFNγ (p = .032) at 10 µM. For IL-22 and IL-6, significant reduction occurred at 100 µM (p = .039 and p = .02, respectively). Conversely, LPSF-GQ-147 did not significantly inhibit the production of the tested cytokines, the levels of all of which were more efficiently reduced by LPSF-CR-35 than methylprednisolone, the standard compound. Real-time polymerase chain reaction assay confirmed that LPSF-GQ-147 has significant PPARγ modulatory activity. Such data indicate that both LPSF-CR-35 and LPSF-GQ-147 are promising candidates as drugs for treating inflammation and asthma.