Distinct effects of intravenous bone marrow-derived mesenchymal stem cell therapy on ischemic and non-ischemic lungs after ischemia-reperfusion injury.

BACKGROUND: The preclinical efficacy of mesenchymal stem cell (MSC) therapy after intravenous infusion has been promising, but clinical studies have yielded only modest results. Although most preclinical studies have focused solely on the ischemic lung, it is crucial to evaluate both lungs after ischemia-reperfusion injury, considering the various mechanisms involved. This study aimed to bridge this gap by assessing the acute effects of bone marrow MSC(BM) infusion before ischemic insult and evaluating both ischemic and non-ischemic lungs after reperfusion. METHODS: Eighteen male Wistar rats (403 ± 23 g) were anesthetized and mechanically ventilated using a protective strategy. After baseline data collection, the animals were randomized to 3 groups (n = 6/group): (1) SHAM; (2) ischemia-reperfusion (IR), and (3) intravenous MSC(BM) infusion followed by IR. Ischemia was induced by complete clamping of the left hilum, followed by 1 h of reperfusion after clamp removal. At the end of the experiment, the right and left lungs (non-ischemic and ischemic, respectively) were collected for immunohistochemistry and molecular biology analysis. RESULTS: MSC(BM)s reduced endothelial cell damage and apoptosis markers and improved markers associated with endothelial cell integrity in both lungs. In addition, gene expression of catalase and nuclear factor erythroid 2-related factor 2 increased after MSC(BM) therapy. In the ischemic lung, MSC(BM) therapy mitigated endothelial cell damage and apoptosis and increased gene expression associated with endothelial cell integrity. Conversely, in the non-ischemic lung, apoptosis gene expression increased in the IR group but not after MSC(BM) therapy. CONCLUSION: This study demonstrates distinct effects of MSC(BM) therapy on ischemic and non-ischemic lungs after ischemia-reperfusion injury. The findings underscore the importance of evaluating both lung types in ischemia-reperfusion studies, offering insights into the therapeutic potential of MSC(BM) therapy in the context of lung injury.

High prevalence of intracranial arterial stenosis among acute ischemic stroke patients in a Brazilian center: a transcranial color-coded duplex sonography study.

BACKGROUND: There is limited data available regarding the prevalence of intracranial arterial stenosis (ICAS) among acute ischemic stroke (AIS) patients in Brazil and Latin America. OBJECTIVE: The present study sought to investigate the frequency and predictors of ICAS among patients with AIS or transient ischemic attack (TIA) in a Brazilian center, with transcranial color-coded duplex sonography (TCCS) technique. METHODS: Consecutive AIS and TIA patients, admitted to an academic public comprehensive stroke center in Brazil from February to December 2014, evaluated by TCCS were prospectively selected. Vascular narrowings > 50% were considered as ICAS, based on ultrasound criteria previously defined in the literature. RESULTS: We assessed 170 consecutive patients with AIS or TIA, of whom 27 (15.9%) were excluded due to an inadequate transtemporal acoustic bone window. We confirmed ICAS in 55 patients (38.5%). The most common location was the proximal segment of the middle cerebral artery (28.2%), followed by the vertebral (15.4%), posterior cerebral (13.6%), terminal internal carotid (9.1%) and basilar (8.2%) arteries. On multivariate models adjusting for potential confounders, systolic blood pressure (OR: 1.03, 95%CI: 1.01-1.04; p = 0.008) was independently associated with ICAS. CONCLUSION: We found significant ICAS in approximately ⅓ of patients admitted with symptoms of AIS or TIA in a public tertiary academic stroke center in Brazil. The TCCS is an accessible and noninvasive technique that can be used to investigate the presence of moderate and severe ICAS, especially in patients who cannot be exposed to more invasive exams, such as the use of intravenous contrast agents.

ANTECEDENTES: Dados acerca da prevalência da estenose arterial intracraniana (EAIC) entre os pacientes com acidente vascular isquêmico (AVCi) agudo no Brasil e América Latina são limitados. OBJETIVO: O presente estudo pretendeu investigar a frequência e os preditores da EAIC nos pacientes AVCi ou ataque isquêmico transitório (AIT) em um centro brasileiro utilizando o Doppler transcraniano colorido (duplex transcraniano). MéTODOS: Pacientes consecutivos com AVCi ou AIT, admitidos entre fevereiro e dezembro de 2014 em um centro acadêmico brasileiro especializado em doenças cerebrovasculares, foram avaliados prospectivamente com duplex transcraniano. Os estreitamentos vasculares > 50% foram considerados como EAIC, baseado em critérios ultrassonográficos definidos previamente na literatura. RESULTADOS: Foram avaliados 170 pacientes com AVCi ou AIT, dos quais 27 (15,9%) foram excluídos em decorrência da janela óssea transtemporal acústica inadequada. Confirmamos EAIC em 55 pacientes (38,5%). A localização mais comum foi o segmento proximal da artéria cerebral média (28,2%), seguida pelas artérias vertebral (15,4%), cerebral posterior (13,6%), carótida interna terminal (9,1%) e basilar (8,2%). No modelo multivariado, ajustado para os potenciais confundidores, a pressão arterial sistólica aumentada (OR: 1,03; IC 95%: 1,01­1,04; p = 0,008) foi independentemente associada a EAIC. CONCLUSãO: Foi identificada EAIC significativa em quase ⅓ dos pacientes admitidos com sintomas de AVCi ou AIT em um serviço acadêmico público de atendimento especializado em doenças cerebrovasculares. O Doppler transcraniano colorido é uma ferramenta acessível e não invasiva que pode ser utilizada com segurança para a investigação da presença de EAIC moderada ou grave, especialmente nos pacientes que não podem ser expostos a exames complementares mais invasivos com uso de contraste intravenoso.

Phenolic composition and encapsulation of Brazilian grape seed extracts: evaluating color stabilizing capacity in grape juices.

The color of grape juice is an important acceptance attribute by consumers, but it suffers losses during storage. The use of commercial antioxidants has limitations because the concept of a "100% natural drink" of Brazilian legislation. This work characterized Brazilian grape seeds, and the cultivar extract with the greatest potential was encapsulated in arabic-gum (encapsulated extract-EE) to evaluate the color stabilizing capacity. The EE used in the grape juice was compared with the commercial antioxidants sulphite and enological tannin during storage (150 days). The BRS Magna and BRS Violeta grape seeds had the highest phenolic content, and the EE showed high catechin (4108 mg/kg), epicatechin (1161 mg/kg) and procyanidin-B2 (905 mg/kg) values. Sulfite was found to be the best color stabilizer. The use of EE (0.5 g/L) in grape juice improved color stability and anthocyanin stability. It was demonstrated that encapsulated grape seed extract has color stabilizing potential and that Brazilian grape seeds are a raw material of high technological value. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-024-05956-8.

Exploring mood disorders and treatment options using human stem cells.

Despite their global prevalence, the mechanisms for mood disorders like bipolar disorder and major depressive disorder remain largely misunderstood. Mood stabilizers and antidepressants, although useful and effective for some, do not have a high responsiveness rate across those with these conditions. One reason for low responsiveness to these drugs is patient heterogeneity, meaning there is diversity in patient characteristics relating to genetics, etiology, and environment affecting treatment. In the past two decades, novel induced pluripotent stem cell (iPSC) research and technology have enabled the use of human-derived brain cells as a new model to study human disease that can help account for patient variance. Human iPSC technology is an emerging tool to better understand the molecular mechanisms of these disorders as well as a platform to test novel treatments and existing pharmaceuticals. This literature review describes the use of iPSC technology to model bipolar and major depressive disorder, common medications used to treat these disorders, and novel patient-derived alternative treatment methods for non-responders stemming from past publications, as well as presenting new data derived from these models.

Hydroxychloroquine is associated with lower seroconversion upon 17DD-Yellow fever primovaccination in patients with primary Sjögren's syndrome.

The present study aimed at investigating whether the hydroxychloroquine (HCQ) treatment would impact the neutralizing antibody production, viremia levels and the kinetics of serum soluble mediators upon planned 17DD-Yellow Fever (YF) primovaccination (Bio-Manguinhos-FIOCRUZ) of primary Sjögren's syndrome (pSS). A total of 34 pSS patients and 23 healthy controls (HC) were enrolled. The pSS group was further categorized according to the use of HCQ (HCQ and Non-HCQ). The YF-plaque reduction neutralization test (PRNT ≥1:50), YF viremia (RNAnemia) and serum biomarkers analyses were performed at baseline and subsequent time-points (Day0/Day3-4/Day5-6/Day7/Day14-D28). The pSS group showed PRNT titers and seropositivity rates similar to those observed for HC (GeoMean = 238 vs 440, p = .11; 82% vs 96%, p = .13). However, the HCQ subgroup exhibited lower seroconversion rates as compared to HC (GeoMean = 161 vs 440, p = .04; 69% vs 96%, p = .02) and Non-HQC (GeoMean = 161 vs 337, p = .582; 69% vs 94%, p = .049). No differences in YF viremia were observed amongst subgroups. Serum biomarkers analyses demonstrated that HCQ subgroup exhibited increased levels of CCL2, CXL10, IL-6, IFN-γ, IL1-Ra, IL-9, IL-10, and IL-2 at baseline and displayed a consistent increase of several biomarkers along the kinetics timeline up to D14-28. These results indicated that HCQ subgroup exhibited a deficiency in assembling YF-specific immune response elicited by 17DD-YF primovaccination as compared to Non-HCQ subgroup. Our findings suggested that hydroxychloroquine is associated with a decrease in the humoral immune response after 17DD-YF primovaccination.

Testicular damage without clinical manifestations in BALB/c mice experimentally infected with Zika virus.

In 2015-2016, the Zika virus (ZIKV) caused a major epidemic in the Americas, increasing cases of microcephaly and Guillain-Barré syndrome. During this period, the discovery of ZIKV sexual transmission intensified studies on the impact of this virus on the reproductive organs. For this study, 2-month-old male BALB/c mice were infected with 1.26 x 106 PFU/mL of ZIKV in solution via the intravenous route. After three, seven, and fourteen days post-infection (DPI), blood and testicle samples were obtained to detect ZIKV RNA. The authors observed that the infected animals had slower weight gain than the control group. Viremia occurred only at 3DPI, and the ZIKV RNA was detected in one testis sample at 7DPI. The histopathological analysis of this organ revealed intense disorganization of the seminiferous tubules' structure, inflammatory infiltrate, necrosis, hemorrhage, fluid accumulation, congestion of blood vessels, and reduced sperm count. Ultrastructural analysis showed nuclear changes in tubule cells, activation of interstitial cells, and morphological changes in spermatozoa, in addition to fragmentation and decreased electron density of the genetic material of these cells. Thus, despite causing predominantly asymptomatic infections, ZIKV can cause significant subclinical and transient damage, including to male reproductive organs.

Accuracy of arch expansion with two thermoplastic materials in Invisalign® patients: EX30® and SmartTrack®.

OBJECTIVE: The purpose of this retrospective study was to compare accuracy of arch expansion using two different thermoplastic materials in Invisalign aligners: EX30® (Polyethylene Terephthalate Glycol, or PETG) and SmartTrack® (polyurethane). METHODS: The study sample comprised 65 adult patients consecutively treated with Invisalign from two private practices: group 1 - treated with EX30® (358 teeth) and group 2 - treated with SmartTrack® (888 teeth). Six hundred and twenty-three measurements were assessed in three digital models throughout treatment: model 1 - initial, model 2 - predicted tooth position, and model 3 - achieved position. Sixteen reference points per arch were marked and, after best alignment, 2 points per tooth were copied from one digital model to another. Linear values of both arches were measured for canines, premolars, and first molars: on lingual gingival margins and cusp tips of every tooth. Comparisons were performed by Wilcoxon and Mann-Whitney test. RESULTS: Both termoplastic materials presented significant differences between predicted and achieved values for all measurements, except for the lower molar cusp tip in the SmartTrack® group. There is no statistical difference in the accuracy of transverse expansion between these two materials. Overall accuracy for EX30® aligners in maxilla and mandible were found to be 37 and 38%, respectively; and Smarttrack® presented an overall accuracy of 56.62% in the maxilla and 68.72% in the mandible. CONCLUSIONS: It is not possible to affirm one material expands better than the other. Further controlled clinical studies should be conducted comparing SmartTrack® and EX30® under similar conditions.

Estimation of economic losses due to leptospirosis in dairy cattle.

There are few studies that effectively quantify the economic losses resulting from problems caused by leptospirosis in naturally infected dairy cattle. Given this gap, the objective of this study was to propose and apply a method to quantify the economic losses resulting from productive and reproductive problems in a commercial dairy herd naturally infected by Leptospira spp. For this study, the zootechnical and economic indicators at a property with Jersey cattle were analyzed during the period from 2014 to 2017. The leptospirosis outbreak occurred in 2014, and the therapeutic approach was carried out between 2015 and 2017, with the latter considered the year of control of the outbreak. The adopted integrated control strategy consisted of dividing the herd according to the serological results obtained through the microscopic agglutination test, the treatment of reagents with streptomycin, and vaccination against leptospirosis of non-reagent heifers and cows. The method used to evaluate the economic indicators of the property was the calculation of the gross margin by taking into account the implicit and explicit cost parameters associated with the manifestation of leptospirosis. The prevalence rate of leptospirosis decreased from 49.4 % in 2015 to 21.6 % in 2017. There was a reduction in the abortion rate (from 40.00 % in 2014 to 9.00 % in 2017), in the stillborn rate (from 2.63 % in 2014 to 1.69 % in 2017) and an increase in the calving rate (from 65.00 % in 2014 to 86.00 % in 2017). In addition, there were increases in the number of lactating cows (from 38 in 2014-57 in 2017) and the mean times of lactation duration, which increased from 275 days in 2014-295 days in 2017. As a result, the average annual production of milk increased from 164,655 liters in 2014-248,521 liters in 2017. In 2014, when treatment hadn't yet started, the gross margin per liter of milk sold, considering implicit and explicit costs, was US$0.00. In 2015 and 2016, US$0.27 and US$0.30 were obtained, respectively, for this variable. In 2017, with the disease under control on the property, the gross margin per liter of milk reached US$0.36. The gross margin per liter of milk sold was higher in the period when the disease was controlled, showing losses of up to 84 % of the gross margin during the outbreak. Immediate treatment of positive cows and preventive measures had a significant impact on improving the productive and economic efficiency of the property.

[Adequacy of provision of procedures for early detection of breast cancer in the Brazilian Unified National Health System: a cross-sectional study conducted in Brazil and its regions, 2019]. / Adequação da oferta de procedimentos para a detecção precoce do câncer de mama no Sistema Único de Saúde: um estudo transversal, Brasil e regiões, 2019.

Early detection is a major strategy in breast cancer control and, for this reason, it is important to ensure access to investigation of suspected cases for care continuity and timely treatment. This study aimed to estimate the need for procedures of breast cancer early detection and assess their adequacy for providing care to screened and symptomatic women in the Brazilian Unified National Health System (SUS) in 2019. A descriptive cross-sectional study was conducted to analyze the provision of tests for breast cancer early detection, comparing the estimated need with the procedures performed in the SUS. Parameters provided by the Brazilian National Cancer Institute were used to estimate the population and the need for early detection tests. The number of procedures performed in 2019 was obtained from the Outpatient Information System of the SUS. A deficit in screening mammograms was observed in the country (-45.1%), ranging from -31.4% in the South Region to -70.5 % in the North Region. If this test was offered to the target population, the deficit in the country would reduce to -14.8% and there would be an oversupply in the South Region (6.2%). Diagnostic investigation procedures varied between the regions, with higher deficits in coarse needle biopsy (-90.8%) and breast lump biopsy/excision (-80.6%) observed in the Central-West Region, and the highest deficit in anatomopathological exams in the North Region (-88.5%). The comparison between the production and need for procedures of breast cancer early detection in Brazil and its regions identified deficits and inadequacies that must be better understood and addressed at the state and municipal levels.

A detecção precoce é uma das estratégias para o controle do câncer de mama e, para tanto, é fundamental garantir o acesso à investigação dos casos suspeitos para continuidade do cuidado e tratamento oportuno. Este estudo tem por objetivo estimar a necessidade de procedimentos para detecção precoce dessa neoplasia e avaliar a sua adequação no atendimento às mulheres rastreadas e sintomáticas no Sistema Único de Saúde (SUS), no ano de 2019. Foi realizado um estudo descritivo transversal para analisar a oferta de exames de detecção precoce do câncer de mama, comparando a necessidade estimada com os procedimentos realizados no SUS. Foram utilizados os parâmetros disponibilizados pelo Instituto Nacional de Câncer para estimar a população e a necessidade de exames para a detecção precoce. No Sistema de Informações Ambulatoriais do SUS, obteve-se o número de procedimentos realizados em 2019. Observou-se um déficit de mamografias de rastreamento no país (-45,1%), variando entre -31,4% na Região Sul a -70,5% na Região Norte. Se a oferta desse exame fosse direcionada para a população-alvo do rastreamento, o déficit no país reduziria para -14,8% e haveria sobreoferta no Sul (6,2%). Os procedimentos de investigação diagnóstica apresentaram variações entre as regiões, com maiores déficits de punção por agulha grossa (-90,8%) e biópsia/exérese de nódulo da mama (-80,6%) observados no Centro-oeste, e o maior déficit de exames anatomopatológicos no Norte (-88,5%). A comparação entre a produção e a necessidade de procedimentos para detecção precoce do câncer de mama no Brasil identificou déficits e inadequações que devem ser melhor conhecidos e equacionados em nível estadual e municipal.

La detección temprana es una de las estrategias para el control del cáncer de mama y, para ello, es fundamental garantizar el acceso a la investigación de los casos sospechosos para la continuidad del cuidado y el tratamiento oportuno. El presente estudio tiene como objetivo estimar la necesidad de procedimientos para la detección temprana de esta neoplasia y evaluar su adecuación en la atención a las mujeres rastreadas y sintomáticas en el Sistema Único de Salud (SUS) brasileño, en el año 2019. Se realizó un estudio descriptivo transversal para analizar la oferta de pruebas para la detección temprana del cáncer de mama, comparando la necesidad estimada con los procedimientos realizados en el SUS. Se utilizaron los parámetros proporcionados por el Instituto Nacional del Cáncer para estimar la población y la necesidad de pruebas para la detección temprana. El número de procedimientos realizados en el 2019 se obtuvo del Sistema de Información Ambulatoria del SUS. Se observó un déficit de mamografías de tamizaje en el país (-45,1%), oscilando entre el -31,4% en la Región Sur y el -70,5% en la Región Norte. Si la oferta de esta prueba se dirigiera a la población objetivo del rastreo, el déficit en el país se reduciría al -14,8% y habría una sobreoferta en el Sur (6,2%). Los procedimientos de investigación diagnóstica presentaron variaciones entre regiones, observándose mayores déficits en punción con aguja gruesa (-90,8%) y biopsia/escisión de nódulo mamario (-80,6%) en el Centro-Oeste, y el mayor déficit de pruebas anatomopatológicas en el Norte (-88,5%). La comparación entre la producción y la necesidad de procedimientos para la detección temprana del cáncer de mama en Brasil y en las regiones identificó déficits e insuficiencias que deben ser mejor conocidos y abordados a nivel estatal y municipal.

Accuracy of Invisalign® aligners in adult patients: a retrospective study of angular tooth movements.

OBJECTIVE: This retrospective study aimed to assess the predictability of Invisalign® aligners regarding rotational, mesio-distal and buccal-lingual tip movements. METHODS: Two materials were included in the analysis - EX30, used until 2013; and SmartTrack, in current use. The study comprised 56 adult patients treated with Invisalign Comprehensive. Data sample were assessed on three sets of digital models; model 1 - initial, model 2 - predicted, and model 3 - achieved. Sixty reference points were marked in each dental arch, and two reference planes assisted the superimposition. The degree of rotation, mesio-distal and buccal-lingual tip was obtained via trigonometric calculations, through a previously published validated method. The accuracy of outcomes was compared according to the types of tooth movement and teeth groups,and the influence of predetermined variables on movement accuracy was also investigated. RESULTS: Rotation and mesio-distal tip did not present any significant difference when comparing EX30 and SmartTrack groups. Only buccal-lingual tip presented a significant difference, incisor and canine groups treated with EX30 aligners presented an increase in accuracy (p= 0.007 and p = 0.007, respectively). For each additional degree planned for rotation movements, there was an increase of 0.35° in the discrepancy, and an increase of 0.40° and 0.41° for mesio-distal and buccal-lingual tip, respectively. EX30 and SmartTrack discrepancies were compared by multilevel linear regression. CONCLUSION: EX30 aligners reached higher accuracy for buccal-lingual tip in anterior teeth. However, for rotation and mesio-distal tip, SmartTrack and EX30 are similarly accurate. The total amount of planned movement has a significant impact on accuracy rates, with a decrease in accuracy for every additional degree.

Induction of SK-MEL-28 Invasion by Brain Cortical Cell-Conditioned Medium Through CXCL10 Signaling.

Melanoma, an infrequent yet significant variant of skin cancer, emerges as a primary cause of brain metastasis among various malignancies. Despite recognizing the involvement of inflammatory molecules, particularly chemokines, in shaping the metastatic microenvironment, the intricate cellular signaling mechanisms underlying cerebral metastasis remain elusive. In our pursuit to unravel the role of cytokines in melanoma metastasis, we devised a protocol utilizing mixed cerebral cortical cells and SK-MEL-28 melanoma cell lines. Contrary to expectations, we observed no discernible morphological change in melanoma cells exposed to a cerebral conditioned medium (CM). However, a substantial increase in both migration and proliferation was quantitatively noted. Profiling the chemokine secretion by melanoma in response to the cerebral CM unveiled the pivotal role of interferon gamma-induced protein 10 (CXCL10), inhibiting the secretion of interleukin 8 (CXCL8). Furthermore, through a transwell assay, we demonstrated that knockdown CXCL10 led to a significant decrease in the migration of the SK-MEL-28 cell line. In conclusion, our findings suggest that a cerebral CM induces melanoma cell migration, while modulating the secretion of CXCL10 and CXCL8 in the context of brain metastases. These insights advance our understanding of the underlying mechanisms in melanoma cerebral metastasis, paving the way for further exploration and targeted therapeutic interventions.

Smoking Cessation Is Associated With Short-Term Improvement of Vascular Health in a Cohort of People Living With HIV in Rio de Janeiro, Brazil.

Smoking is highly prevalent in people living with HIV/AIDS (PLHA), leading to detrimental effects in different tissues. We examined the effects of nicotine replacement therapy (NRT) on smoking cessation and vascular health. From December 2019 to October 2021, we prospectively enrolled PLHA who were actively smoking. The primary outcome was endothelial function measured by brachial artery flow-mediated dilatation (FMD). We evaluated the percent change in FMD compared to the baseline measure (Δ%FMD) to detect improvements among participants who quit smoking. To confirm the results, we used linear regression models to account for classical cardiovascular (CV) confounders. We included 117 participants with median age of 45.5 years (IQR= 36.4-54.8); 22 (20.4%) had hypertension, 9 (8.3%) had diabetes, almost half were smoking 20+ cigarettes/day (41.7%). After 12 weeks 30.76% participants quit smoking. Comparison of Δ%FMD change from baseline to week 12 showed that among participants adherent to therapy, there has been an increase in Δ%FMD when compared to those who relapsed (1.17% [0.29-2.98] vs -0.19% [-1.95-0.91], p<0.001). After adjustment for CV factors, multiple linear regression showed that Δ%FMD in participants who quit smoking presented a 2.54 mean increase in comparison to those who continued smoking (p=0.007). In conclusion, this study provides evidence that a strategy of NRT and counseling is modestly effective for smoking cessation in PLHA and improves vascular health in a short period of time. This reinforces the importance of the widespread anti-tobacco programs in HIV clinics and the expected impact lowering the incidence of future cardiovascular events.

Adequação da oferta de procedimentos para a detecção precoce do câncer de mama no Sistema Único de Saúde: um estudo transversal, Brasil e regiões, 2019 / Adequacy of provision of procedures for early detection of breast cancer in the Brazilian Unified National Health System: a cross-sectional study conducted in Brazil and its regions, 2019 / Adecuación de la oferta de procedimientos para la detección precoz del cáncer de mama en el Sistema Único de Salud: un estudio transversal, Brasil y regiones, 2019

Resumo: A detecção precoce é uma das estratégias para o controle do câncer de mama e, para tanto, é fundamental garantir o acesso à investigação dos casos suspeitos para continuidade do cuidado e tratamento oportuno. Este estudo tem por objetivo estimar a necessidade de procedimentos para detecção precoce dessa neoplasia e avaliar a sua adequação no atendimento às mulheres rastreadas e sintomáticas no Sistema Único de Saúde (SUS), no ano de 2019. Foi realizado um estudo descritivo transversal para analisar a oferta de exames de detecção precoce do câncer de mama, comparando a necessidade estimada com os procedimentos realizados no SUS. Foram utilizados os parâmetros disponibilizados pelo Instituto Nacional de Câncer para estimar a população e a necessidade de exames para a detecção precoce. No Sistema de Informações Ambulatoriais do SUS, obteve-se o número de procedimentos realizados em 2019. Observou-se um déficit de mamografias de rastreamento no país (-45,1%), variando entre -31,4% na Região Sul a -70,5% na Região Norte. Se a oferta desse exame fosse direcionada para a população-alvo do rastreamento, o déficit no país reduziria para -14,8% e haveria sobreoferta no Sul (6,2%). Os procedimentos de investigação diagnóstica apresentaram variações entre as regiões, com maiores déficits de punção por agulha grossa (-90,8%) e biópsia/exérese de nódulo da mama (-80,6%) observados no Centro-oeste, e o maior déficit de exames anatomopatológicos no Norte (-88,5%). A comparação entre a produção e a necessidade de procedimentos para detecção precoce do câncer de mama no Brasil identificou déficits e inadequações que devem ser melhor conhecidos e equacionados em nível estadual e municipal.

Abstract: Early detection is a major strategy in breast cancer control and, for this reason, it is important to ensure access to investigation of suspected cases for care continuity and timely treatment. This study aimed to estimate the need for procedures of breast cancer early detection and assess their adequacy for providing care to screened and symptomatic women in the Brazilian Unified National Health System (SUS) in 2019. A descriptive cross-sectional study was conducted to analyze the provision of tests for breast cancer early detection, comparing the estimated need with the procedures performed in the SUS. Parameters provided by the Brazilian National Cancer Institute were used to estimate the population and the need for early detection tests. The number of procedures performed in 2019 was obtained from the Outpatient Information System of the SUS. A deficit in screening mammograms was observed in the country (-45.1%), ranging from -31.4% in the South Region to -70.5 % in the North Region. If this test was offered to the target population, the deficit in the country would reduce to -14.8% and there would be an oversupply in the South Region (6.2%). Diagnostic investigation procedures varied between the regions, with higher deficits in coarse needle biopsy (-90.8%) and breast lump biopsy/excision (-80.6%) observed in the Central-West Region, and the highest deficit in anatomopathological exams in the North Region (-88.5%). The comparison between the production and need for procedures of breast cancer early detection in Brazil and its regions identified deficits and inadequacies that must be better understood and addressed at the state and municipal levels.

Resumen: La detección temprana es una de las estrategias para el control del cáncer de mama y, para ello, es fundamental garantizar el acceso a la investigación de los casos sospechosos para la continuidad del cuidado y el tratamiento oportuno. El presente estudio tiene como objetivo estimar la necesidad de procedimientos para la detección temprana de esta neoplasia y evaluar su adecuación en la atención a las mujeres rastreadas y sintomáticas en el Sistema Único de Salud (SUS) brasileño, en el año 2019. Se realizó un estudio descriptivo transversal para analizar la oferta de pruebas para la detección temprana del cáncer de mama, comparando la necesidad estimada con los procedimientos realizados en el SUS. Se utilizaron los parámetros proporcionados por el Instituto Nacional del Cáncer para estimar la población y la necesidad de pruebas para la detección temprana. El número de procedimientos realizados en el 2019 se obtuvo del Sistema de Información Ambulatoria del SUS. Se observó un déficit de mamografías de tamizaje en el país (-45,1%), oscilando entre el -31,4% en la Región Sur y el -70,5% en la Región Norte. Si la oferta de esta prueba se dirigiera a la población objetivo del rastreo, el déficit en el país se reduciría al -14,8% y habría una sobreoferta en el Sur (6,2%). Los procedimientos de investigación diagnóstica presentaron variaciones entre regiones, observándose mayores déficits en punción con aguja gruesa (-90,8%) y biopsia/escisión de nódulo mamario (-80,6%) en el Centro-Oeste, y el mayor déficit de pruebas anatomopatológicas en el Norte (-88,5%). La comparación entre la producción y la necesidad de procedimientos para la detección temprana del cáncer de mama en Brasil y en las regiones identificó déficits e insuficiencias que deben ser mejor conocidos y abordados a nivel estatal y municipal.

Accuracy of arch expansion with two thermoplastic materials in Invisalign® patients: EX30® and SmartTrack®

ABSTRACT Objective: The purpose of this retrospective study was to compare accuracy of arch expansion using two different thermoplastic materials in Invisalign aligners: EX30® (Polyethylene Terephthalate Glycol, or PETG) and SmartTrack® (polyurethane). Methods: The study sample comprised 65 adult patients consecutively treated with Invisalign from two private practices: group 1 - treated with EX30® (358 teeth) and group 2 - treated with SmartTrack® (888 teeth). Six hundred and twenty-three measurements were assessed in three digital models throughout treatment: model 1 - initial, model 2 - predicted tooth position, and model 3 - achieved position. Sixteen reference points per arch were marked and, after best alignment, 2 points per tooth were copied from one digital model to another. Linear values of both arches were measured for canines, premolars, and first molars: on lingual gingival margins and cusp tips of every tooth. Comparisons were performed by Wilcoxon and Mann-Whitney test. Results: Both termoplastic materials presented significant differences between predicted and achieved values for all measurements, except for the lower molar cusp tip in the SmartTrack® group. There is no statistical difference in the accuracy of transverse expansion between these two materials. Overall accuracy for EX30® aligners in maxilla and mandible were found to be 37 and 38%, respectively; and Smarttrack® presented an overall accuracy of 56.62% in the maxilla and 68.72% in the mandible. Conclusions: It is not possible to affirm one material expands better than the other. Further controlled clinical studies should be conducted comparing SmartTrack® and EX30® under similar conditions.

RESUMO Objetivo: O objetivo deste estudo retrospectivo foi comparar a acurácia na expansão da arcada utilizando alinhadores Invisalign com dois tipos de material termoplástico: EX30® (Polietileno Tereftalato Glicol, ou PETG) e SmartTrack® (poliuretano). Método: A amostra desse estudo incluiu 65 pacientes adultos tratados consecutivamente em dois consultórios particulares: grupo 1 - tratado com EX30® (358 dentes), e grupo 2 - tratado com SmartTrack® (888 dentes). Foram avaliadas 623 medidas em três pares de modelos digitais, ao longo do tratamento: modelo 1 - inicial, modelo 2 - posição dentária planejada, modelo 3 - posição alcançada. Foram marcados 16 pontos de referência por arcada e, após o bestfit, 2 pontos por arcada foram copiados de um modelo digital para o outro. Medidas lineares de ambas as arcadas foram aferidas para caninos, pré-molares e primeiros molares, localizadas na margem gengival lingual e ponta de cúspide de todos os dentes. Foram realizadas comparações usando os testes Wilcoxon e Mann-Whitney. Resultados: Ambos os materiais termoplásticos apresentaram diferenças significativas entre os valores planejados e alcançados em todas as medidas, exceto na ponta de cúspide dos primeiros molares inferiores do grupo SmartTrack®. Não houve diferença estatística entre esses dois materiais quanto à acurácia da expansão transversa. Em termos gerais, a acurácia dos alinhadores EX30® na maxila e mandíbula foi de 37% e 38%, respectivamente. O grupo SmartTrack® apresentou acurácia de 56,62% e 68,72% na maxila e mandíbula, respectivamente. Conclusões: Não foi possível afirmar que um material expande melhor que o outro. Estudos clínicos controlados futuros devem ser conduzidos comparando SmartTrack® e EX30® sob condições similares.

Accuracy of Invisalign® aligners in adult patients: a retrospective study of angular tooth movements

ABSTRACT Objective: This retrospective study aimed to assess the predictability of Invisalign® aligners regarding rotational, mesio-distal and buccal-lingual tip movements. Methods: Two materials were included in the analysis - EX30, used until 2013; and SmartTrack, in current use. The study comprised 56 adult patients treated with Invisalign Comprehensive. Data sample were assessed on three sets of digital models; model 1 - initial, model 2 - predicted, and model 3 - achieved. Sixty reference points were marked in each dental arch, and two reference planes assisted the superimposition. The degree of rotation, mesio-distal and buccal-lingual tip was obtained via trigonometric calculations, through a previously published validated method. The accuracy of outcomes was compared according to the types of tooth movement and teeth groups,and the influence of predetermined variables on movement accuracy was also investigated. Results: Rotation and mesio-distal tip did not present any significant difference when comparing EX30 and SmartTrack groups. Only buccal-lingual tip presented a significant difference, incisor and canine groups treated with EX30 aligners presented an increase in accuracy (p= 0.007 and p = 0.007, respectively). For each additional degree planned for rotation movements, there was an increase of 0.35° in the discrepancy, and an increase of 0.40° and 0.41° for mesio-distal and buccal-lingual tip, respectively. EX30 and SmartTrack discrepancies were compared by multilevel linear regression. Conclusion: EX30 aligners reached higher accuracy for buccal-lingual tip in anterior teeth. However, for rotation and mesio-distal tip, SmartTrack and EX30 are similarly accurate. The total amount of planned movement has a significant impact on accuracy rates, with a decrease in accuracy for every additional degree.

RESUMO Objetivo: Esse estudo retrospectivo teve como objetivo aferir a previsibilidade dos alinhadores Invisalign em relação aos movimentos de rotação e inclinações mesiodistal e vestibulolingual. Material e Métodos: Foram incluídos dois materiais nessa análise: EX30®, utilizado até 2013; e SmartTrack®, atualmente em uso. Esse estudo avaliou 56 pacientes tratados com Invisalign Comprehensive. Os dados foram avaliados em três pares de modelos digitais; modelo 1 - inicial, modelo 2 - planejado, e modelo 3 - alcançado. Foram marcados 60 pontos de referência em cada arcada, sendo a sobreposição realizada com auxílio de planos de referência. O grau de rotação e inclinações mesiodistal e vestibulolingual foi obtido por cálculos de trigonometria, usando um método validado publicado anteriormente. Os resultados foram comparados de acordo com os tipos de movimento dentário e grupos de dentes, também foi investigada a influência de variáveis predeterminadas na confiabilidade dos movimentos. Resultados: Os movimentos de rotação e inclinação mesiodistal não apresentaram diferença estatística, quando comparados os grupos EX30® e SmartTrack®. Somente a inclinação vestibulolingual apresentou diferença estatisticamente significativa, sendo que os grupos de incisivos e caninos tratados com alinhadores EX30® apresentaram um aumento na previsibilidade(p= 0,007 e p= 0,007, respectivamente). Para cada grau adicional planejado para movimento de rotação, ocorreu um aumento de 0,35° na discrepância, e aumentos de 0,40° e 0,41° para as inclinações mesiodistal e vestibulolingual, respectivamente. As discrepâncias entre EX30® e SmartTrack® foram comparadas por regressão linear multinível. Conclusão: Os alinhadores EX30® alcançaram maior previsibilidade para a inclinação vestibulolingual em dentes anteriores. No entanto, para rotação e inclinação mesiodistal, SmartTrack® e EX30® apresentaram previsibilidade similar. A quantidade total de movimento planejado apresenta influência significativa nas taxas de previsibilidade, com diminuição na acurácia para cada grau adicional.

Adapting lean management to prevent healthcare-associated infections: a low-cost strategy involving Kamishibai cards to sustain bundles' compliance.

Lean healthcare visual management has been successfully integrated into infection control programs, leading to lower healthcare-associated infection (HAI) rates and greater provider compliance with evidence-based prevention practices; however, its implementation during quality improvement (QI) initiatives in limited-resource settings has not yet been well exploited. We aimed to describe a low-cost strategy involving Kamishibai cards to sustain bundles' adherence to prevent HAIs in a middle-income country. This descriptive case study evaluated the implementation of a lean healthcare visual management tool-Kamishibai board (K-board)-during a nationwide QI collaborative preventing three critical HAIs in 189 adult and pediatric/neonatal intensive care units (ICUs) from September 2021 to January 2023. Considering a limited-resource setting, our team adapted a K-board using simple, cheap, and easy-to-handle materials for routine monitoring of QI procedures, including safety bundles' compliance. After test prototypes, the final K-board version was implemented. The chart materials and assembly cost BRL 80.00 (USD 15.48). Before launching, expert working group meetings were held to shape the contents, refine technical issues, and prepare the ICU teams for implementation. After starting, plan-do-study-act cycles were conducted according to the Breakthrough Series model. Participating ICU teams, including leaders and front-line health workers, performed bedside audits following a weekly chronogram. Two indicators were calculated: the percentage of ICUs in which K-boards were being implemented and whether bundles' compliance was addressed in the K-board. Audit data were recorded in 'SimpleQI'. After 17 months of this initiative, 177 (93.7%) participating ICUs had included this visual management tool in their daily care routines. When more than 94 (>50%) ICUs posted K-board data, the mean compliance for the bundles for each HAI was sustained above 85%. A lean healthcare visual management tool can be adapted to local settings, including healthcare facilities with limited resources. K-board seems to be a feasible method for auditing evidence-based practices in medical care, including safety bundles to simultaneously prevent three types of HAIs.

Pharmacological Agents and Potential New Therapies in Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a progressive disease characterized by an imbalance between vasoactive mediators, which causes vascular remodeling, increased pulmonary vascular resistance, and right ventricular overload, ultimately leading to heart failure and death. A metabolic theory has been suggested to explain the pathophysiology of PAH whereby abnormalities in mitochondrial biogenesis can trigger a hyperproliferative and apoptosis-resistant phenotype in cardiopulmonary and malignant cells, leading to mitochondrial dysfunction, which in turn causes the Warburg effect. This can culminate in the mitophagy of pulmonary vessels and cardiomyocytes. The present narrative review focuses on the pathophysiology of PAH, the pharmacological agents currently available for its treatment, and promising and challenging areas of therapeutic investigation.

Correlation between ischemic stroke topography and female urinary incontinence.

AIM: To investigate the association between ischemic stroke topography and the onset of urinary incontinence (UI); to evaluate predictors of post-stroke UI in women. METHOD: We prospectively followed up a cohort of women with ischemic stroke confirmed by clinical and computed tomography (CT) or magnetic resonance imaging (MRI) scans findings. Participants were subjected to interview, clinical evaluation, and urodynamic study if needed at 6 months post-stroke and divided in continent and incontinent groups. Non-parametric tests compared the baseline characteristics among the groups and determined association between post-stroke UI and the brain sites of injury. Logistic regression analysis determined predictors of post-stroke UI. Significance level at 5 % was set. RESULTS: 162 S-women were included: 128 (79 %) continent and 34 (21 %) incontinent. Frontal lobe lesions were higher in the incontinent group (82.9 % versus 51.2 %, p = 0.001); lesions in the parietal lobe and the left cerebral hemisphere were higher in the continent group (40.9 % versus 20 %, p = 0.023; and 61.4 % versus 40 %, p = 0.024, respectively). Frontal lobe injury [RR 3.68 (CI 1.2-11.2)], body mass index (BMI) [RR1.16 (CI 1.062-1.266)] and number of vaginal deliveries [RR 1.358 (CI 1.163-1.585)] are risk factors for post-stroke UI. Left parietal lobe injury is less likely to occur in continent women after 6 months [RR 0.168 (CI 0.029-0.981; p = 0.048)]. CONCLUSION: There is a correlation between the topography of the ischemic stroke and the onset of UI. Frontal lobe lesion, BMI and number of vaginal deliveries are predictors of post-stroke UI.

Tales of me: storytelling identity work, authenticity, and impression management during new CEOs' work role transitions.

Introduction: This study aims to understand how new CEOs construct, revise, and maintain in their narrative, repertoire stories that represent their identity as it is associated with their new occupational role. Methods: For this purpose, we conducted a qualitative study using the Grounded Theory method, involving 47 CEOs from different sectors residing in Brazil. Results: Our results allowed for the construction of a central category called Storytelling Identity Work, which refers to stories that individuals tell about themselves, and enable them to propose and redefine who they are during major life transitions. This paper seeks to explain: (a) under what conditions this phenomenon tends to occur; (b) what characterizes the success of Storytelling Identity Work and; (c) what leads to the revision or retention of stories in the self. Our results show that storytelling identity work tends to be used by new CEOs during their transition period into the role, and when their new position involves higher levels of visibility and alteration of prestige levels in comparison to their previous position. They also suggest that storytelling identity work tends to be more successful when the stories are co-constructed and validated with other significant individuals and when they enable new CEOs to feel "sufficiently authentic" and "sufficiently impressive." Finally, we theorize that such feelings, along with a sense of coherence between the story being told and other narratives consciously or unconsciously being narrated by the interviewees throughout their lives, lead to the retention of the story within the individual's self. Discussion: This article innovates by connecting the literature on personal storytelling with identity work and exploring processes that are not only useful during the process of transitioning into the role of new CEOs but also influence the constitution of the narrative repertoire and, consequently, the identity of these individuals.

Network size affects the complexity of activity in human iPSC-derived neuronal populations.

Multi-electrode recording of neural activity in cultures offer opportunities for understanding how the structure of a network gives rise to function. Although it is hypothesized that network size is critical for determining the dynamics of activity, this relationship in human neural cultures remains largely unexplored. By applying new methods for analyzing neural activity to human iPSC derived cultures at either low-densities or high-densities, we uncovered the significant impacts that neuron number has on the individual neurophysiological properties of cells (such as firing rates), the collective behavior of the networks these cultures formed (as measured by entropy), and the relationship between the two. As a result, simply changing the densities of neurons generated dynamics and network behavior that differed not just in degree, but in kind. Beyond revealing the relationship between network structure and function, our findings provide a novel analytical framework to study diseases where network level activity is affected.