Efficacy and safety of induction chemotherapy in oral cavity cancer: An eight-year experience at a Portuguese reference center.

BACKGROUND: Induction chemotherapy has been described as an option in locally advanced oral cavity squamous cell carcinoma when the surgical morbidity is expected to be high. This work aimed to evaluate the outcome and safety of induction chemotherapy in this setting. METHODS: We performed a retrospective and observational study including patients with oral cavity squamous cell carcinoma, treated with induction chemotherapy between January 2010 and December 2018. Outcomes included induction chemotherapy toxicity, treatment response, disease-free survival and overall survival. RESULTS: A total of 108 oral cavity squamous cell carcinoma patients were included. Ninety-six (88.9%) had stage IV disease, while 12 (11.1%) had stage III. Eighty-four patients (80.8%) achieved at least a partial response to induction chemotherapy at clinical evaluation, and 75 (72.1%) at radiological evaluation. Seventy-eight patients have been proposed for subsequent definitive treatments, with no differences obtained in prognosis, when comparing surgical to non-surgical approaches. In patients treated with definitive treatments, improved five-year disease-free survival was obtained if at least a clinical (56.3%; p=0.001) or radiological (52.9%; p=0.001) partial response was achieved after induction chemotherapy. Similarly, superior five-year overall survival was verified for those achieving at least clinical (51.1%; p<0.0001) or radiological (52.6%; p=0.001) partial response. Also, accomplishing a pathologic complete response (n=22.6%) significantly improved disease-free survival (p=0.039) and overall survival (p=0.005). Grade 3 and 4 toxicities were observed in 52 patients (41.8%). CONCLUSION: Responses to induction chemotherapy predicted prognosis in our population, however important toxicities were observed. Further studies are necessary to identify induction chemotherapy response predictors and subgroups who may benefit from this approach.

Beyond the GRACE ACS Score: Do We Need a Different Model for Men and Women after STEMI? / Além do Escore GRACE SCA: É Necessário um Modelo Diferente para Homens e Mulheres após IAMCSST?

BACKGROUND: Women, in comparison to men, experience worse outcomes after acute coronary syndrome (ACS). However, whether the female sex per se is an independent predictor of such adverse events remains unclear. OBJECTIVE: This study aims to assess the association between the female sex and in-hospital mortality after ST-elevation myocardial infarction (STEMI). METHODS: We conducted a retrospective cohort study by enrolling consecutive STEMI patients admitted to a tertiary hospital from January 2018 to February 2019. All patients were treated per current guideline recommendations. Multivariable logistic regression models were applied to evaluate in-hospital mortality using GRACE variables. Model accuracy was evaluated using c-index. A p-value < 0.05 was statistically significant. RESULTS: Out of the 1678 ACS patients, 709 presented with STEMI. The population consisted of 36% women, and the median age was 61 years. Women were older (63.13 years vs. 60.53 years, p = 0.011); more often presented with hypertension (75.1% vs. 62.4%, p = 0.001), diabetes (42.2% vs. 27.8%, p < 0.001), and hyperlipidemia (34.1% vs. 23.9%, p = 0.004); and were less likely to undergo percutaneous coronary intervention (PCI) via radial access (23.7% vs. 46.1%, p < 0.001). In-hospital mortality rate was significantly higher in women (13.2% vs. 5.6%, p = 0.001), and the female sex remained at higher risk for in-hospital mortality (OR 2.79, 95% CI 1.15-6.76, p = 0.023). A multivariate model including age, sex, systolic blood pressure, cardiac arrest, and Killip class was 94.1% accurate in predicting in-hospital mortality, and the c-index was 0.85 (95% CI 0.77-0.93). CONCLUSION: After adjusting for the risk factors in the GRACE prediction model, women remain at higher risk for in-hospital mortality.

FUNDAMENTO: As mulheres, em comparação aos homens, apresentam piores resultados após a síndrome coronariana aguda (SCA). No entanto, ainda não está claro se o sexo feminino em si é um preditor independente de tais eventos adversos. OBJETIVO: Este estudo tem como objetivo avaliar a associação entre o sexo feminino e a mortalidade hospitalar após infarto do miocárdio com supradesnivelamento do segmento ST (IAMCSST). MÉTODOS: Conduzimos um estudo de coorte retrospectivo, recrutando pacientes consecutivos com IAMCSST, internados em um hospital terciário de janeiro de 2018 a fevereiro de 2019. Todos os pacientes foram tratados de acordo com as recomendações das diretrizes atuais. Modelos de regressão logística multivariada foram aplicados para avaliar a mortalidade hospitalar utilizando variáveis de GRACE. A precisão do modelo foi avaliada usando o índice c. Um valor de p < 0,05 foi estatisticamente significativo. RESULTADOS: Dos 1.678 pacientes com SCA, 709 apresentaram IAMCSST. A população era composta por 36% de mulheres e a idade média era de 61 anos. As mulheres tinham maior idade (63,13 anos vs. 60,53 anos, p = 0,011); apresentavam hipertensão (75,1% vs. 62,4%, p = 0,001), diabetes (42,2% vs. 27,8%, p < 0,001) e hiperlipidemia (34,1% vs. 23,9%, p = 0,004) mais frequentemente; e apresentaram menor probabilidade de serem submetidas a intervenção coronária percutânea (ICP) por acesso radial (23,7% vs. 46,1%, p < 0,001). A taxa de mortalidade hospitalar foi significativamente maior em mulheres (13,2% vs. 5,6%, p = 0,001), e o sexo feminino permaneceu em maior risco de mortalidade hospitalar (OR 2,79, IC de 95% 1,15­6,76, p = 0,023). Um modelo multivariado incluindo idade, sexo, pressão arterial sistólica, parada cardíaca e classe de Killip atingiu 94,1% de precisão na previsão de mortalidade hospitalar, e o índice c foi de 0,85 (IC de 95% 0,77­0,93). CONCLUSÃO: Após ajuste para os fatores de risco no modelo de previsão do GRACE, as mulheres continuam em maior risco de mortalidade hospitalar.

A rare case of epithelioid angiosarcoma.

Epithelioid angiosarcoma is a rare high-grade vascular neoplasm with a poor prognosis. We present an anticoagulated 77-year-old man, with a history of popliteal/soleal vein thrombosis in the previous month, complaining of ipsilateral persistent lower limb pain and claudication. Absent popliteal/distal pulses prompted an arterial doppler ultrasound (DUS), revealing thrombosis of the distal superficial femoral artery and a popliteal mass. As the arterial wall's integrity could not be appropriately evaluated by DUS, adventitial cystic disease of the popliteal artery was suspected. Computed tomography angiography and magnetic resonance imaging findings were also suggestive. Due to refractory pain, he was submitted to a popliteal mass excision along with a femoral-posterior tibial bypass. Pathology revealed an epithelioid angiosarcoma. He was referred to a Sarcoma Center, requiring hospitalization for agitation and fever. A positron emission tomography (PET) scan revealed extensive lower limb disease persistence and distant metastases. He died on the 56th day after surgery. To our knowledge, there are only 15 cases of angiosarcoma of the popliteal artery described in the literature. Ours stands out as the first one unrelated to a popliteal aneurysm. Being a highly-aggressive tumor, an early diagnosis is challenging but essential to a successful treatment, warranting the need for suspicion of this neoplasm. An early core biopsy or surgical sample may expedite the diagnosis.

Mechanisms involved in the cytoprotective effects of Lonomia obliqua venom on human endometrial stromal cells.

The pathophysiology of recurrent pregnancy loss (RPL) involves deficiencies in the proliferation and migration capacities of endometrial stromal cells (hESCs), which impair embryo implantation and development. Since animal venoms are rich source of bioactive molecules, we aimed to characterize the cytoprotective effects of Lonomia obliqua venom on hESCs. hESCs were isolated from endometrial biopsies and the mechanisms of L. obliqua venomous secretions on cell viability, proliferation and migration were characterized. Venom components were identified by chromatography and proteomic analyses. L. obliqua venom induced hESC proliferation, viability and migration in a dose-dependent manner, both in the presence and absence of serum. By ion-exchange chromatography, one fraction enriched in cytoprotective components and devoid of hemotoxins was obtained. Venom proteome identified at least six protein classes with potential cytoprotective properties (hemolins, lipocalins, hemocyannins, antiviral proteins, antimicrobial peptides, and protease inhibitors). L. obliqua venom protected hESCs from oxidative insult. Cytoprotection was also related to nitric oxide and PKC-ERK-activation and down-regulation of cAMP-PKA-dependent pathways that control cell proliferation. L. obliqua venom-induced hESC viability, proliferation and migration occurs mainly by protecting against oxidative damage and activating ERK. Thus, L. obliqua venom components are promising pharmacological tools to understand the underlying mechanisms of hESC deficiency in RPL.

Proteomic profile of Cryptococcus gattii biofilm: Metabolic shift and the potential activation of electron chain transport.

Cryptococcus gattii is a primary pathogenic fungus that causes pneumonia. This species is also responsible for an outbreak in Vancouver, Canada, and spreading to the mainland and United States. The use of medical devices is often complicated by infections with biofilm-forming microbes with increased resistance to antimicrobial agents and host defense mechanisms. This study investigated the comparative proteome of C. gattii R265 (VGIIa) grown under planktonic and biofilm conditions. A brief comparison with C. neoformans H99 biofilm and the use of different culture medium and surface were also evaluated. Using Multidimensional Protein Identification Technology (MudPIT), 1819 proteins were identified for both conditions, where 150 (8.2%) were considered differentially regulated (up- or down-regulated and unique in biofilm cells). Overall, the proteomic approach suggests that C. gattii R265 biofilm cells are maintained by the induction of electron transport chain for reoxidation, and by alternative energy metabolites, such as succinate and acetate. SIGNIFICANCE: Since C. gattii is considered a primary pathogen and is one of the most virulent and less susceptible to antifungals, understanding how biofilms are maintained is fundamental to search for new targets to control this important mode of growth that is difficult to eradicate.

Metarhizium anisopliae E6 secretome reveals molecular players in host specificity and toxicity linked to cattle tick infection.

Although Metarhizium anisopliae is one of the most studied fungal biocontrol agents, its infection mechanism is far from being completely understood. Using multidimensional protein identification technology (MudPIT), we evaluated the differential secretome of M. anisopliae E6 induced by the host Rhipicephalus microplus cuticle. The proteomic result showed changes in the expression of 194 proteins after exposure to host cuticle, such as proteins involved in adhesion, penetration, stress and fungal defense. Further, we performed a comparative genomic distribution of differentially expressed proteins of the M. anisopliae secretome against another arthropod pathogen, using the Beauveria bassiana ARSEF2860 protein repertory. Among 47 analyzed protein families, thirty were overexpressed in the M. anisopliae E6 predicted genome compared to B. bassiana. An in vivo toxicity assay using a Galleria mellonella model confirmed that the M. anisopliae E6 secretome was more toxic in cattle tick infections compared to other secretomes, including B. bassiana with cattle ticks and M. anisopliae E6 with the insect Dysdereus peruvianus, which our proteomic results had also suggested. These results help explain molecular aspects associated with host infection specificity due to genetic differences and gene expression control at the protein level in arthropod-pathogenic fungi.

The role of glial cells in Zika virus-induced neurodegeneration.

Zika virus (ZIKV) is a strongly neurotropic flavivirus whose infection has been associated with microcephaly in neonates. However, clinical and experimental evidence indicate that ZIKV also affects the adult nervous system. In this regard, in vitro and in vivo studies have shown the ability of ZIKV to infect glial cells. In the central nervous system (CNS), glial cells are represented by astrocytes, microglia, and oligodendrocytes. In contrast, the peripheral nervous system (PNS) constitutes a highly heterogeneous group of cells (Schwann cells, satellite glial cells, and enteric glial cells) spread through the body. These cells are critical in both physiological and pathological conditions; as such, ZIKV-induced glial dysfunctions can be associated with the development and progression of neurological complications, including those related to the adult and aging brain. This review will address the effects of ZIKV infection on CNS and PNS glial cells, focusing on cellular and molecular mechanisms, including changes in the inflammatory response, oxidative stress, mitochondrial dysfunction, Ca2+ and glutamate homeostasis, neural metabolism, and neuron-glia communication. Of note, preventive and therapeutic strategies that focus on glial cells may emerge to delay and/or prevent the development of ZIKV-induced neurodegeneration and its consequences.

Differential proteomics of Zika virus (ZIKV) infection reveals molecular changes potentially involved in immune system evasion by a Brazilian strain of ZIKV.

Zika virus (ZIKV) is an arbovirus that was responsible for multiple outbreaks from 2007 to 2015. It has been linked to cases of microcephaly in Brazil in 2015, among other neurological disorders. Differences among strains might be the reason for different clinical outcomes of infection. To evaluate this hypothesis, we performed a comparative proteomic analysis of Vero cells infected with the African strain MR766 (ZIKVAFR) and the Brazilian strain 17 SM (ZIKVBR). A total of 550 proteins were identified as differentially expressed in ZIKVAFR- or ZIKVBR-infected cells compared to the control. The main findings included upregulation of immune system pathways (neutrophil degranulation and adaptive/innate immune system) and potential activation of immune-system-related pathways by ZIKVAFR (mTOR, JAK-STAT, NF-κB, and others) compared with the ZIKVBR/control. In addition, phagocytosis by macrophages and engulfment of leukocytes were activated in ZIKVAFR infection. An in vivo analysis using an immunocompetent C57BL/6N mouse model identified interstitial pneumonia with neutrophil infiltration in the lungs only in mice infected with ZIKVBR at 48 hours postinfection, with a significant amount of virus detected. Likewise, only animals infected with ZIKVBR had viral material in the cytoplasm of lung macrophages. These results suggest that activation of the immune system by ZIKVAFR infection may lead to faster viral clearance by immune cells.

The proteomic and particle composition of human platelet lysate for cell therapy products.

Following health agencies warning, the use of animal origin supplements should be avoided in biological products proposed as therapy in humans. Platelet lysate and several other growth factors sources are alternatives to replace fetal calf serum, the current gold standard in clinical-grade cell culture. However, the platelet supplement's content lacks data due to different production methods. The principle behind these products relays on the lysis of platelets that release several proteins, some of which are contained in heterogeneous granules and coordinate biological functions. This study aims to analyze the composition and reproducibility of a platelet lysate produced with a standardized method, by describing several batches' protein and particle content using proteomics and dynamic light scattering. Proteomics data revealed a diversified protein content, with some related to essential cellular processes such as proliferation, morphogenesis, differentiation, biosynthesis, adhesion, and metabolism. It also detected proteins responsible for activation and binding of transforming growth factor beta, hepatocyte growth factor, and insulin-like growth factor. Total protein, biochemical, and growth factors quantitative data showed consistent and reproducible values across batches. Novel data on two major particle populations is presented, with high dispersion level at 231 ± 96 d.nm and at 30 ± 8 d.nm, possibly being an important way of protein trafficking through the cellular microenvironment. This experimental and descriptive analysis aims to support the content definition and quality criteria of a cell supplement for clinical applications.

The influence of protective psychosocial factors on the incidence of dental pain.

OBJECTIVE: To investigate the influence of protective psychosocial factors on the incidence of dental pain in the last six months among 12-year-old children living in Manaus (AM). METHODS: A prospective school-based cohort study was conducted with 210 12-year-old students enrolled in public schools in the eastern zone of Manaus (AM). Students were followed up for two years. Validated questionnaires were used to assess sociodemographic characteristics, protective psychosocial factors, including sense of coherence, social support, and self-esteem at baseline and after two years. Calibrated examiners clinically assessed dental caries and gingival bleeding. Multivariate multilevel Poisson regression was used to estimate the relative risk (RR) and 95% confidence interval (95%CI) between the changes on psychosocial factors scores and incidence of dental pain, adjusted for psychosocial factors scores at baseline, dental health insurance, frequency of tooth brushing, and dental caries. RESULTS: Mean scores for sense of coherence and social support reduced significantly from baseline to 2-year follow-up. The incidence of dental pain along the two-year follow-up was 28.6%. The risk of dental pain was 14% higher for every 10 points in the mean reduction of sense of coherence score (RR = 1.14; 95%CI: 1.02-1.20), and 6% higher for every 10 points of the mean reduction in social support score (RR = 1.06; 95%CI: 1.01-1.11). Change on self-esteem was not associated with risk of dental pain. CONCLUSION: Change on sense of coherence and social support over the two-year period influenced the incidence of dental pain among children, suggesting that protective psychosocial factors, health behaviours, dental health insurance, and clinical oral condition have an important role in the incidence of dental pain.

Neurodevelopment in Children Exposed to Zika in utero: Clinical and Molecular Aspects.

Five years after the identification of Zika virus as a human teratogen, we reviewed the early clinical manifestations, collectively called congenital Zika syndrome (CZS). Children with CZS have a very poor prognosis with extremely low performance in motor, cognitive, and language development domains, and practically all feature severe forms of cerebral palsy. However, these manifestations are the tip of the iceberg, with some children presenting milder forms of deficits. Additionally, neurodevelopment can be in the normal range in the majority of the non-microcephalic children born without brain or eye abnormalities. Vertical transmission and the resulting disruption in development of the brain are much less frequent when maternal infection occurs in the second half of the pregnancy. Experimental studies have alerted to the possibility of other behavioral outcomes both in prenatally infected children and in postnatal and adult infections. Cofactors play a vital role in the development of CZS and involve genetic, environmental, nutritional, and social determinants leading to the asymmetric distribution of cases. Some of these social variables also limit access to multidisciplinary professional treatment.

In vitro and in vivo anti-inflammatory and anticoagulant activities of Myrciaria plinioides D. Legrand ethanol leaf extract.

Myrciaria plinioides D. Legrand (Myrtaceae) is a native plant of Southern Brazil, which have potential in the food industry due to its edible fruits. Many plants belonging to this genus have been used for a variety of illnesses, including inflammatory disorders due to antioxidant properties. However, therapeutic uses of M. plinioides have been poorly studied. The aim of study was to assess the anti-inflammatory and anticoagulant activities of the ethanol leaf extract of M. plinioides. In M. plinioides extract-treated RAW 264.7 cells, assessments of cell viability, TNF-α release and p38 MAPK pathway-dependent protein expression were detected. In addition, rat paw edema models were used to analyze the anti-inflammatory effect of the extract. Macrophages cell line treated with M. plinioides extract showed a slight decrease in cell viability. In LPS-stimulated macrophages treated with different concentrations of the extract for 24 h, TNF-α release was inhibited, while modulation of p38 signaling pathway and inhibition of NF-κB p65 protein expression were dose-dependent. In rats, the extract inhibited the formation of paw edema, while an inhibitory effect on trypsin-like enzymes derived from mast cells was seen. Furthermore, the extract presented anticoagulant activity via extrinsic pathway, being able to block specifically factor Xa and thrombin. The study suggests that extract possess potent anti-inflammatory and anticoagulant effects. M. plinioides present great biological potential as a source for the development of anti-inflammatory and anticoagulant drugs. Additional studies can be proposed to better elucidate the mechanism by which M. plinioides exerts its effects.

The influence of protective psychosocial factors on the incidence of dental pain / A influência de fatores psicossociais protetores sobre a incidência de dor dentária

ABSTRACT OBJECTIVE To investigate the influence of protective psychosocial factors on the incidence of dental pain in the last six months among 12-year-old children living in Manaus (AM). METHODS A prospective school-based cohort study was conducted with 210 12-year-old students enrolled in public schools in the eastern zone of Manaus (AM). Students were followed up for two years. Validated questionnaires were used to assess sociodemographic characteristics, protective psychosocial factors, including sense of coherence, social support, and self-esteem at baseline and after two years. Calibrated examiners clinically assessed dental caries and gingival bleeding. Multivariate multilevel Poisson regression was used to estimate the relative risk (RR) and 95% confidence interval (95%CI) between the changes on psychosocial factors scores and incidence of dental pain, adjusted for psychosocial factors scores at baseline, dental health insurance, frequency of tooth brushing, and dental caries. RESULTS Mean scores for sense of coherence and social support reduced significantly from baseline to 2-year follow-up. The incidence of dental pain along the two-year follow-up was 28.6%. The risk of dental pain was 14% higher for every 10 points in the mean reduction of sense of coherence score (RR = 1.14; 95%CI: 1.02-1.20), and 6% higher for every 10 points of the mean reduction in social support score (RR = 1.06; 95%CI: 1.01-1.11). Change on self-esteem was not associated with risk of dental pain. CONCLUSION Change on sense of coherence and social support over the two-year period influenced the incidence of dental pain among children, suggesting that protective psychosocial factors, health behaviours, dental health insurance, and clinical oral condition have an important role in the incidence of dental pain.

RESUMO OBJETIVO Investigar a influência de fatores psicossociais protetores sobre a incidência de dor dentária nos últimos seis meses em crianças de 12 anos residentes em Manaus (AM). MÉTODOS Um estudo de coorte prospectivo de base escolar foi realizado com 210 alunos de 12 anos, matriculados em escolas públicas da zona leste de Manaus (AM) que foram acompanhados por dois anos. Questionários validados foram usados para avaliar características sociodemográficas, fatores psicossociais protetores, incluindo senso de coerência, apoio social e autoestima na linha de base e após dois anos. Examinadores calibrados avaliaram clinicamente cárie dentária e sangramento gengival. Regressão de Poisson multinível multivariada foi usada para estimar o risco relativo (RR) e o intervalo de confiança de 95% (IC95%) entre a variação dos escores dos fatores psicossociais e a incidência de dor dentária, ajustada para os escores dos fatores psicossociais na linha de base, plano de saúde odontológico, frequência de escovação dentária e cárie dentária. RESULTADOS As médias dos escores do senso de coerência e do apoio social reduziram significativamente entre linha de base e seguimento de dois anos. A incidência de dor dentária no seguimento de dois anos foi 28,6%. O risco de dor dentária foi 14% maior para cada 10 pontos na redução média do escore do senso de coerência (RR = 1,14; IC95% 1,02-1,20), e 6% maior para cada 10 pontos na redução média do escore do apoio social (RR = 1,06; IC95% 1,01-1,11). A mudança na autoestima não foi associada ao risco de dor dentária. CONCLUSÃO A variação do senso de coerência e do apoio social no período de dois anos influenciou a incidência de dor dentária em crianças, sugerindo que fatores psicossociais protetores, comportamentos em saúde, plano odontológico e a condição clínica bucal desempenham um papel importante na incidência da dor dentária.

Effect of Lonomia obliqua Venom on Human Neutrophils.

The significant incidence of deforestation in South America culminates in the contact of humans with typical forests species. Among these species, one may highlight Lonomia obliqua caterpillar, which, when touched by humans, can poison them through their bristles. Therefore, better acknowledging the mechanisms involved in envenomation caused by Lonomia obliqua caterpillar bristle extract (LOCBE) may contribute to further treatments. Recently, we demonstrated that LOCBE induces a pro-inflammatory profile in endothelial cells; thus, we decided to investigate the effects of LOCBE on human polymorphonuclear neutrophils (PMN), which are the first leukocytes that migrate to the inflammatory focus. Our results showed that treatment with LOCBE induced PMN chemotaxis together with alterations in actin cytoskeleton and focal adhesion kinase (FAK) activation, favoring migration. Concurrently, LOCBE induced PMN adhesion to matrix proteins, such as collagen IV, fibronectin, and fibrinogen. Moreover, we observed that LOCBE attenuated PMN apoptosis and increased reactive oxygen species (ROS) production together with nuclear factor kB (NF-κB) activation-a redox-sensitive transcription factor-as well as interleukin (IL)-1ß and IL-8 release. We call attention to the ROS-dependent effect of LOCBE on increased cell migration once an antioxidant treatment reverted it. In summary, we report that LOCBE activates PMN, inducing pro-inflammatory responses modulated by ROS.

Zika Virus Infection Associated with Autism Spectrum Disorder: A Case Report.

INTRODUCTION: The aim of this case was to investigate the association of the Zika virus infection in utero with the autism spectrum disorder (ASD) as clinical outcome that presented no congenital anomalies. METHODS: ASD was diagnosed in the second year of life by different child neurologists and confirmed by DSM-5 and ASQ. After that, an extensive clinical, epidemiological, and genetic evaluations were performed, with main known ASD causes ruled out. RESULTS: An extensive laboratorial search was done, with normal findings. SNP array identified no pathogenic variants. Normal neuroimaging and EEG findings were also obtained. ZIKV (Zika virus) IgG was positive, while IgM was negative. Other congenital infections were negative. The exome sequencing did not reveal any pathogenic variant in genes related to ASD. CONCLUSION: Accordingly, this report firstly associates ZIKV exposure to ASD.

SARSCOVIDB-A New Platform for the Analysis of the Molecular Impact of SARS-CoV-2 Viral Infection.

The COVID-19 pandemic caused by the new coronavirus (SARS-CoV-2) has become a global emergency issue for public health. This threat has led to an acceleration in related research and, consequently, an unprecedented volume of clinical and experimental data that include changes in gene expression resulting from infection. The SARS-CoV-2 infection database (SARSCOVIDB: https://sarscovidb.org/) was created to mitigate the difficulties related to this scenario. The SARSCOVIDB is an online platform that aims to integrate all differential gene expression data, at messenger RNA and protein levels, helping to speed up analysis and research on the molecular impact of COVID-19. The database can be searched from different experimental perspectives and presents all related information from published data, such as viral strains, hosts, methodological approaches (proteomics or transcriptomics), genes/proteins, and samples (clinical or experimental). All information was taken from 24 articles related to analyses of differential gene expression out of 5,554 COVID-19/SARS-CoV-2-related articles published so far. The database features 12,535 genes whose expression has been identified as altered due to SARS-CoV-2 infection. Thus, the SARSCOVIDB is a new resource to support the health workers and the scientific community in understanding the pathogenesis and molecular impact caused by SARS-CoV-2.

COVID-19 impacts the expression of molecular markers associated with neuropsychiatric disorders.

Coronavirus disease 2019 (COVID-19) was initially characterized due to its impacts on the respiratory system; however, many recent studies have indicated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) significantly affects the brain. COVID-19 can cause neurological complications, probably caused by the induction of a cytokine storm, since there is no evidence of neurotropism by SARS-CoV-2. In line with this, the COVID-19 outbreak could accelerate the progression or affect the clinical outcomes of neuropsychiatric conditions. Thus, we analyzed differential gene expression datasets for clinical samples of COVID-19 patients and identified 171 genes that are associated with the pathophysiology of the following neuropsychiatric disorders: alcohol dependence, autism, bipolar disorder, depression, panic disorder, schizophrenia, and sleep disorder. Several of the genes identified are associated with causing some of these conditions (classified as elite genes). Among these elite genes, 9 were found for schizophrenia, 6 for autism, 3 for depression/major depressive disorder, and 2 for alcohol dependence. The patients with the neuropsychiatric conditions associated with the genes identified may require special attention as COVID-19 can deteriorate or accelerate neurochemical dysfunctions, thereby aggravating clinical outcomes.

Urine proteomic analysis reveals alterations in heme/hemoglobin and aminopeptidase metabolism during Lonomia obliqua venom-induced acute kidney injury.

AIMS: Accidental contact with the Lonomia obliqua caterpillar is a common event in southern Brazil. Envenomed victims present consumption coagulopathy, which can evolve to acute kidney injury (AKI). In the present study, we searched for AKI biomarkers and changes in molecular pathway signatures through urine proteomic analysis. METHODOLOGY: Male Wistar rats were injected with L. obliqua venom (1.5 mg/kg, via s.c.) or 0.9 % NaCl and distributed into metabolic cages. After 24 h, urine was obtained, and the set of differentially regulated proteins was analyzed by MudPIT technology in an OrbiTRAP mass spectrometer. RESULTS: L. obliqua venom leads to an increase in urine output and water and electrolyte excretion and to an increase in the albumin to creatine ratio in urine. The proteomic analysis revealed an up-regulation of tubular injury biomarkers, such as neutrophil-gelatinase associated lipocalin (NGAL) and cystatin C, in urine from envenomed rats. Several components related to the heme scavenging system were up-regulated or exclusively identified in urine from envenomed animals. There was an increase in urinary heme levels and hemoglobin subunits, hemopexin, haptoglobin, and biliverdin reductase. Similarly, kinin- and angiotensin-generating/degrading peptidases, such as kallikreins, neprilysin, plasmin, dipeptidyl peptidase IV, cathepsin D, kininogen, and neutral, basic, glutamyl, and acidic aminopeptidases, were also up-regulated in urine. CONCLUSIONS: L. obliqua envenomation induced tubular and glomerular injury, probably involving heme/hemoglobin toxicity and an imbalance in the kinin/angiotensin generating/degrading system.

Avaliação do Seguimento de 1 Ano dos Pacientes Incluídos no Registro da Prática Clínica em Pacientes de Alto Risco Cardiovascular (REACT) / Evaluation of 1-Year Follow-up of Patients Included in the Registry of Clinical Practice in Patients at High Cardiovascular Risk (REACT)

Resumo Fundamento Na prática clínica, há evidências de falhas na prescrição de terapias baseadas em evidências para pacientes de alto risco cardiovascular. Entretanto, no Brasil, ainda são insuficientes os dados sobre a evolução ao longo de 1 ano desses pacientes. Objetivos Descrição no acompanhamento de 12 meses da utilização de terapias baseadas em evidência e da ocorrência de desfechos cardiovasculares maiores e seus principais preditores em um registro brasileiro multicêntrico de pacientes de alto risco cardiovascular. Métodos Estudo observacional prospectivo que documentou a prática clínica ambulatorial de indivíduos acima de 45 anos e de alto risco cardiovascular tanto em prevenção primária como secundária. Os pacientes foram seguidos por 1 ano e avaliou-se a prescrição de terapias baseadas em evidência e a ocorrência de eventos cardiovasculares maiores (infarto agudo do miocárdio [IAM], acidente vascular cerebral [AVC], parada cardíaca e mortalidade por causa cardiovascular). Valores de p < 0,05 foram considerados estatisticamente significantes. Resultados De julho de 2010 até agosto de 2014, 5.076 indivíduos foram incluídos em 48 centros, sendo 91% dos 4.975 pacientes elegíveis acompanhados em centros de cardiologia e 68,6% em prevenção secundária. Em 1 ano, o uso concomitante de antiplaquetários, estatinas e inibidores da enzima conversora de angiotensina (IECA) reduziu de 28,3% para 24,2% (valor de p < 0,001). A taxa de eventos cardiovasculares maiores foi de 5,46%, e os preditores identificados foram: idade, pacientes em prevenção secundária e nefropatia diabética. Conclusões Neste grande registro nacional de pacientes de alto risco cardiovascular, foram identificados preditores de risco semelhantes aos registros internacionais, porém a adesão da prescrição médica a terapias baseadas em evidência esteve abaixo dos dados da literatura internacional e apresentou piora significativa em 1 ano. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0)

Abstract Background In clinical practice, there is evidence of failure to prescribe evidence-based therapies for patients at high cardiovascular risk. However, in Brazil, data on 1-year outcomes of these patients remain insufficient. Objectives To describe the use of evidence-based therapies and the occurrence of major cardiovascular outcomes and their major predictors in a 12-month follow-up of a Brazilian multicenter registry of patients at high cardiovascular risk. Methods This prospective observational study documented the outpatient clinical practice of managing patients over 45 years of age and of high cardiovascular risk in both primary and secondary prevention. Patients were followed-up for 1 year, and the prescription of evidence-based therapies and the occurrence of major cardiovascular events (myocardial infarction, stroke, cardiac arrest, and cardiovascular death) were assessed. P-values < 0.05 were considered statistically significant. Results From July 2010 to August 2014, a total of 5076 individuals were enrolled in 48 centers, 91% of the 4975 eligible patients were followed-up in cardiology centers, and 68.6% were in secondary prevention. At 1 year, the concomitant use of antiplatelet agents, statins, and angiotensin-converting enzyme inhibitors reduced from 28.3% to 24.2% (p < 0.001). Major cardiovascular event rate was 5.46%, and the identified predictors were age, patients in secondary prevention, and diabetic nephropathy. Conclusions In this large national registry of patients at high cardiovascular risk, risk predictors similar to those of international registries were identified, but medical prescription adherence to evidence-based therapies was inferior and significantly worsened at 1 year. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0)

Evaluation of 1-Year Follow-up of Patients Included in the Registry of Clinical Practice in Patients at High Cardiovascular Risk (REACT). / Avaliação do Seguimento de 1 Ano dos Pacientes Incluídos no Registro da Prática Clínica em Pacientes de Alto Risco Cardiovascular (REACT).

BACKGROUND: In clinical practice, there is evidence of failure to prescribe evidence-based therapies for patients at high cardiovascular risk. However, in Brazil, data on 1-year outcomes of these patients remain insufficient. OBJECTIVES: To describe the use of evidence-based therapies and the occurrence of major cardiovascular outcomes and their major predictors in a 12-month follow-up of a Brazilian multicenter registry of patients at high cardiovascular risk. METHODS: This prospective observational study documented the outpatient clinical practice of managing patients over 45 years of age and of high cardiovascular risk in both primary and secondary prevention. Patients were followed-up for 1 year, and the prescription of evidence-based therapies and the occurrence of major cardiovascular events (myocardial infarction, stroke, cardiac arrest, and cardiovascular death) were assessed. P-values < 0.05 were considered statistically significant. RESULTS: From July 2010 to August 2014, a total of 5076 individuals were enrolled in 48 centers, 91% of the 4975 eligible patients were followed-up in cardiology centers, and 68.6% were in secondary prevention. At 1 year, the concomitant use of antiplatelet agents, statins, and angiotensin-converting enzyme inhibitors reduced from 28.3% to 24.2% (p < 0.001). Major cardiovascular event rate was 5.46%, and the identified predictors were age, patients in secondary prevention, and diabetic nephropathy. CONCLUSIONS: In this large national registry of patients at high cardiovascular risk, risk predictors similar to those of international registries were identified, but medical prescription adherence to evidence-based therapies was inferior and significantly worsened at 1 year. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0).

FUNDAMENTO: Na prática clínica, há evidências de falhas na prescrição de terapias baseadas em evidências para pacientes de alto risco cardiovascular. Entretanto, no Brasil, ainda são insuficientes os dados sobre a evolução ao longo de 1 ano desses pacientes. OBJETIVOS: Descrição no acompanhamento de 12 meses da utilização de terapias baseadas em evidência e da ocorrência de desfechos cardiovasculares maiores e seus principais preditores em um registro brasileiro multicêntrico de pacientes de alto risco cardiovascular. MÉTODOS: Estudo observacional prospectivo que documentou a prática clínica ambulatorial de indivíduos acima de 45 anos e de alto risco cardiovascular tanto em prevenção primária como secundária. Os pacientes foram seguidos por 1 ano e avaliou-se a prescrição de terapias baseadas em evidência e a ocorrência de eventos cardiovasculares maiores (infarto agudo do miocárdio [IAM], acidente vascular cerebral [AVC], parada cardíaca e mortalidade por causa cardiovascular). Valores de p < 0,05 foram considerados estatisticamente significantes. RESULTADOS: De julho de 2010 até agosto de 2014, 5.076 indivíduos foram incluídos em 48 centros, sendo 91% dos 4.975 pacientes elegíveis acompanhados em centros de cardiologia e 68,6% em prevenção secundária. Em 1 ano, o uso concomitante de antiplaquetários, estatinas e inibidores da enzima conversora de angiotensina (IECA) reduziu de 28,3% para 24,2% (valor de p < 0,001). A taxa de eventos cardiovasculares maiores foi de 5,46%, e os preditores identificados foram: idade, pacientes em prevenção secundária e nefropatia diabética. CONCLUSÕES: Neste grande registro nacional de pacientes de alto risco cardiovascular, foram identificados preditores de risco semelhantes aos registros internacionais, porém a adesão da prescrição médica a terapias baseadas em evidência esteve abaixo dos dados da literatura internacional e apresentou piora significativa em 1 ano. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0).