The coronary artery disease equivalent revisited

(1) To study the prevalence and severity of coronary artery disease (CAD) in diabetic patients. (2) To provide a detailed characterization of the coronary atherosclerotic burden, including the localization, degree of stenosis and plaque composition by coronary computed tomography angiography (CCTA). Single center prospective registry including a total of 581 consecutive stable patients (April 2011-March 2012) undergoing CCTA (Dual-source CT) for the evaluation of suspected CAD without previous myocardial infarction or revascularization procedures. Different coronary plaque burden indexes and plaque type and distribution patterns were compared between patients with (n = 85) and without diabetes (n = 496). The prevalence of CAD (any plaque; 74.1 vs. 56 %; p = 0.002) and obstructive CAD (≥50 % stenosis; 31.8 vs. 10.3 %; p<0.001) were significantly higher in diabetic patients. The remaining coronary atherosclerotic burden indexes evaluated (plaque in LM-3v-2v with prox. LAD; SIS; SSS; CT-LeSc) were also significantly higher in diabetic patients. In the per segment analysis, diabetics had a higher percentage of segments with plaque in every vessel (2.6/13.1/7.5/10.5 % for diabetics vs. 1.4/7.1/3.3/4.4 % for nondiabetics for LM, LAD, LCx, RCA respectively; p<0.001 for all) and of both calcified (19.3 vs. 9.2 %, p<0.001) and noncalcified or mixed types (14.4 vs. 7.0 %; p<0.001); the ratio of proximal-to-distal relative plaque distribution (calculated as LM/proximal vs. mid/distal/branches) was lower for diabetics (0.75 vs. 1.04; p = 0.009). Diabetes was an independent predictor of CAD and was also associated with more advanced CAD, evaluated by indexes of coronary atherosclerotic burden. Diabetics had a significantly higher prevalence of plaques in every anatomical subset and for the different plaque composition. In this report, the relative geographic distribution of the plaques within each subgroup, favored a more mid-to-distal localization in the diabetic patients.publishersversionpublishe

Diabetes as an independent predictor of high atherosclerotic burden assessed by coronary computed tomography angiography: The coronary artery disease equivalent revisited

(1) To study the prevalence and severity of coronary artery disease (CAD) in diabetic patients. (2) To provide a detailed characterization of the coronary atherosclerotic burden, including the localization, degree of stenosis and plaque composition by coronary computed tomography angiography (CCTA). Single center prospective registry including a total of 581 consecutive stable patients (April 2011-March 2012) undergoing CCTA (Dual-source CT) for the evaluation of suspected CAD without previous myocardial infarction or revascularization procedures. Different coronary plaque burden indexes and plaque type and distribution patterns were compared between patients with (n = 85) and without diabetes (n = 496). The prevalence of CAD (any plaque; 74.1 vs. 56 %; p = 0.002) and obstructive CAD (≥50 % stenosis; 31.8 vs. 10.3 %; p<0.001) were significantly higher in diabetic patients. The remaining coronary atherosclerotic burden indexes evaluated (plaque in LM-3v-2v with prox. LAD; SIS; SSS; CT-LeSc) were also significantly higher in diabetic patients. In the per segment analysis, diabetics had a higher percentage of segments with plaque in every vessel (2.6/13.1/7.5/10.5 % for diabetics vs. 1.4/7.1/3.3/4.4 % for nondiabetics for LM, LAD, LCx, RCA respectively; p<0.001 for all) and of both calcified (19.3 vs. 9.2 %, p<0.001) and noncalcified or mixed types (14.4 vs. 7.0 %; p<0.001); the ratio of proximal-to-distal relative plaque distribution (calculated as LM/proximal vs. mid/distal/branches) was lower for diabetics (0.75 vs. 1.04; p = 0.009). Diabetes was an independent predictor of CAD and was also associated with more advanced CAD, evaluated by indexes of coronary atherosclerotic burden. Diabetics had a significantly higher prevalence of plaques in every anatomical subset and for the different plaque composition. In this report, the relative geographic distribution of the plaques within each subgroup, favored a more mid-to-distal localization in the diabetic patients

Effect of surgical experience and spine subspecialty on the reliability of the {AO} Spine Upper Cervical Injury Classification System

OBJECTIVE The objective of this paper was to determine the interobserver reliability and intraobserver reproducibility of the AO Spine Upper Cervical Injury Classification System based on surgeon experience (&lt; 5 years, 5–10 years, 10–20 years, and &gt; 20 years) and surgical subspecialty (orthopedic spine surgery, neurosurgery, and "other" surgery). METHODS A total of 11,601 assessments of upper cervical spine injuries were evaluated based on the AO Spine Upper Cervical Injury Classification System. Reliability and reproducibility scores were obtained twice, with a 3-week time interval. Descriptive statistics were utilized to examine the percentage of accurately classified injuries, and Pearson’s chi-square or Fisher’s exact test was used to screen for potentially relevant differences between study participants. Kappa coefficients (κ) determined the interobserver reliability and intraobserver reproducibility. RESULTS The intraobserver reproducibility was substantial for surgeon experience level (&lt; 5 years: 0.74 vs 5–10 years: 0.69 vs 10–20 years: 0.69 vs &gt; 20 years: 0.70) and surgical subspecialty (orthopedic spine: 0.71 vs neurosurgery: 0.69 vs other: 0.68). Furthermore, the interobserver reliability was substantial for all surgical experience groups on assessment 1 (&lt; 5 years: 0.67 vs 5–10 years: 0.62 vs 10–20 years: 0.61 vs &gt; 20 years: 0.62), and only surgeons with &gt; 20 years of experience did not have substantial reliability on assessment 2 (&lt; 5 years: 0.62 vs 5–10 years: 0.61 vs 10–20 years: 0.61 vs &gt; 20 years: 0.59). Orthopedic spine surgeons and neurosurgeons had substantial intraobserver reproducibility on both assessment 1 (0.64 vs 0.63) and assessment 2 (0.62 vs 0.63), while other surgeons had moderate reliability on assessment 1 (0.43) and fair reliability on assessment 2 (0.36). CONCLUSIONS The international reliability and reproducibility scores for the AO Spine Upper Cervical Injury Classification System demonstrated substantial intraobserver reproducibility and interobserver reliability regardless of surgical experience and spine subspecialty. These results support the global application of this classification system

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure &lt;= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Anti-neoplastic properties of hydralazine in prostate cancer

Prostate cancer (PCa) is a major cause of cancer-related morbidity and mortality worldwide. Although early disease is often efficiently managed therapeutically, available options for advanced disease are mostly ineffective. Aberrant DNA methylation associated with gene-silencing of cancer-related genes is a common feature of PCa. Therefore, DNA methylation inhibitors might constitute an attractive alternative therapy. Herein, we evaluated the anti-cancer properties of hydralazine, a non-nucleoside DNA methyltransferases (DNMT) inhibitor, in PCa cell lines. In vitro assays showed that hydralazine exposure led to a significant dose and time dependent growth inhibition, increased apoptotic rate and decreased invasiveness. Furthermore, it also induced cell cycle arrest and DNA damage. These phenotypic effects were particularly prominent in DU145 cells. Following hydralazine exposure, decreased levels of DNMT1, DNMT3a and DNMT3b mRNA and DNMT1 protein were depicted. Moreover, a significant decrease in GSTP1, BCL2 and CCND2 promoter methylation levels, with concomitant transcript re-expression, was also observed. Interestingly, hydralazine restored androgen receptor expression, with upregulation of its target p21 in DU145 cell line. Protein array analysis suggested that blockage of EGF receptor signaling pathway is likely to be the main mechanism of hydralazine action in DU145 cells. Our data demonstrate that hydralazine attenuated the malignant phenotype of PCa cells, and might constitute a useful therapeutic tool

High-Quality Draft Genome Sequence of Pantanalinema sp. GBBB05, a Cyanobacterium From Cerrado Biome

Peer reviewe

Geographic Information Systems and Applied Spatial Statistics Are Efficient Tools to Study Hansen's Disease (Leprosy) and to Determine Areas of Greater Risk of Disease

Applied Spatial Statistics used in conjunction with geographic information systems (GIS) provide an efficient tool for the surveillance of diseases. Here, using these tools we analyzed the spatial distribution of Hansen's disease in an endemic area in Brazil. A sample of 808 selected from a universe of 1,293 cases was geocoded in Mossoró, Rio Grande do Norte, Brazil. Hansen's disease cases were not distributed randomly within the neighborhoods, with higher detection rates found in more populated districts. Cluster analysis identified two areas of high risk, one with a relative risk of 5.9 (P = 0.001) and the other 6.5 (P = 0.001). A significant relationship between the geographic distribution of disease and the social economic variables indicative of poverty was observed. Our study shows that the combination of GIS and spatial analysis can identify clustering of transmissible disease, such as Hansen's disease, pointing to areas where intervention efforts can be targeted to control disease

Proteomic Analysis Reveals a Predominant NFE2L2 (NRF2) Signature in Canonical Pathway and Upstream Regulator Analysis of Leishmania-Infected Macrophages

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2019-07-16T11:56:06Z No. of bitstreams: 1 Menezes, J.P. Proteomic Analysi...2019.pdf: 2216682 bytes, checksum: 42cced00b8b12eaae7f24baeecf4ae90 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2019-07-16T12:33:35Z (GMT) No. of bitstreams: 1 Menezes, J.P. Proteomic Analysi...2019.pdf: 2216682 bytes, checksum: 42cced00b8b12eaae7f24baeecf4ae90 (MD5)Made available in DSpace on 2019-07-16T12:33:35Z (GMT). No. of bitstreams: 1 Menezes, J.P. Proteomic Analysi...2019.pdf: 2216682 bytes, checksum: 42cced00b8b12eaae7f24baeecf4ae90 (MD5) Previous issue date: 2019Fundação de Amparo à Pesquisa do Estado da Bahia (PV http://www.fapesb.ba.gov.br), Conselho Nacional de Pesquisa e Desenvolvimento Científico (PV http://www.cnpq.br) and National Institute of Science and Technology of Tropical Disease (PV http://inct.cnpq.br/ web/inct-dt). VB, PV, and UL are senior investigators funded by CNPq.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Interação Hospedeiro-Parasita e Epidemiologia. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Doenças Infecciosas de Vetores. Salvador, BA, Brasil / Federal University of Bahia. Faculty of Medicine. Legal Medicine. Salvador, BA, Brazil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Interação Hospedeiro-Parasita e Epidemiologia. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Interação Hospedeiro-Parasita e Epidemiologia. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Interação Hospedeiro-Parasita e Epidemiologia. Salvador, BA, Brasil / Federal University of Rio de Janeiro. Laboratory of Physiopathology. Department of Pathology. Macaé, RJ, Brazil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Interação Hospedeiro-Parasita e Epidemiologia. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Interação Hospedeiro-Parasita e Epidemiologia. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Interação Hospedeiro-Parasita e Epidemiologia. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Inflamação e Biomarcadores. Salvador, BA, Brasil.Federal University of the Western of Bahia. Centro de Ciências Biológicas e da Saúde. Barreiras, BA, Brazil.Fundação Oswaldo Cruz. Centro de Integração de Dados e Conhecimento para a Saúde. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto René Rachou. Minas Gerais, BH, Brasil.Fundação Oswaldo Cruz. Instituto René Rachou. Minas Gerais, BH, Brasil.Virginia Commonwealth University. Department of Microbiology and Immunology. Richmond, VA, United States.Fundação Oswaldo Cruz. Instituto Carlos Chagas. Paraná, PR, Brasil.Federal University of Rio de Janeiro. Carlos Chagas Filho Biophysics Institute. Laboratory of Molecular Parasitology. Center of Health Science. Rio de Janeiro, RJ, Brazil.Federal University of Rio de Janeiro. Carlos Chagas Filho Biophysics Institute. Laboratory of Molecular Parasitology. Center of Health Science. Rio de Janeiro, RJ, Brazil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Doenças Infecciosas de Vetores. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Interação Hospedeiro-Parasita e Epidemiologia. Salvador, BA, Brasil / National Institute of Science and Technology of Tropical Disease. Patos, Brazil.CBA mice macrophages (MØ) control infection by Leishmania major and are susceptive to Leishmania amazonensis, suggesting that both parasite species induce distinct responses that play important roles in infection outcome. To evaluate the MØ responses to infection arising from these two Leishmania species, a proteomic study using a Multidimensional Protein Identification Technology (MudPIT) approach with liquid chromatography tandem mass spectrometry (LC-MS/MS) was carried out on CBA mice bone-marrow MØ (BMMØ). Following SEQUEST analysis, which revealed 2,838 proteins detected in BMMØ, data mining approach found six proteins significantly associated with the tested conditions. To investigate their biological significance, enrichment analysis was performed using Ingenuity Pathway Analysis (IPA). A three steps IPA approach revealed 4 Canonical Pathways (CP) and 7 Upstream Transcriptional Factors (UTFs) strongly associated with the infection process. NRF2 signatures were present in both CPs and UTFs pathways. Proteins involved in iron metabolism, such as heme oxigenase 1 (HO-1) and ferritin besides sequestosome (SQSMT1 or p62) were found in the NRF2 CPs and the NRF2 UTFs. Differences in the involvement of iron metabolism pathway in Leishmania infection was revealed by the presence of HO-1 and ferritin. Noteworty, HO-1 was strongly associated with L. amazonensis infection, while ferritin was regulated by both species. As expected, higher HO-1 and p62 expressions were validated in L. amazonensis-infected BMMØ, in addition to decreased expression of ferritin and nitric oxide production. Moreover, BMMØ incubated with L. amazonensis LPG also expressed higher levels of HO-1 in comparison to those stimulated with L. major LPG. In addition, L. amazonensis-induced uptake of holoTf was higher than that induced by L. major in BMMØ, and holoTf was also detected at higher levels in vacuoles induced by L. amazonensis. Taken together, these findings indicate that NRF2 pathway activation and increased HO-1 production, together with higher levels of holoTf uptake, may promote permissiveness to L. amazonensis infection. In this context, differences in protein signatures triggered in the host by L. amazonensis and L. major infection could drive the outcomes in distinct clinical forms of leishmaniasis