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Summary: Rho GTPases are molecular switches regulating multiple cellular processes. To investigate the role of RhoA in normal intestinal physiology, we used a conditional mouse model overexpressing a dominant negative RhoA mutant (RhoAT19N) in the intestinal epithelium. Although RhoA inhibition did not cause an overt phenotype, increased levels of nuclear β-catenin were observed in the small intestinal epithelium of RhoAT19N mice, and the overexpression of multiple Wnt target genes revealed a chronic activation of Wnt signaling. Elevated Wnt signaling in RhoAT19N mice and intestinal organoids did not affect the proliferation of intestinal epithelial cells but significantly interfered with their differentiation. Importantly, 17-month-old RhoAT19N mice showed a significant increase in the number of spontaneous intestinal tumors. Altogether, our results indicate that RhoA regulates the differentiation of intestinal epithelial cells and inhibits tumor initiation, likely through the control of Wnt signaling, a key regulator of proliferation and differentiation in the intestine.

IntroductionHIV late presentation (LP) remains excessive in Europe. We aimed to analyze the factors associated with late presentation in the MSM population newly diagnosed with HIV in Portugal between 2014 and 2019.MethodsWe included 391 newly HIV-1 diagnosed Men who have Sex with Men (MSM), from the BESTHOPE project, in 17 countrywide Portuguese hospitals. The data included clinical and socio-behavioral questionnaires and the viral genomic sequence obtained in the drug resistance test before starting antiretrovirals (ARVs). HIV-1 subtypes and epidemiological surveillance mutations were determined using different bioinformatics tools. Logistic regression was used to estimate the association between predictor variables and late presentation (LP).ResultsThe median age was 31 years, 51% had a current income between 501–1,000 euros, 28% were migrants. 21% had never been tested for HIV before diagnosis, with 42.3% of MSM presenting LP. 60% were infected with subtype B strains. In the multivariate regression, increased age at diagnosis, higher income, lower frequency of screening, STI ever diagnosed and higher viral load were associated with LP.ConclusionOur study suggests that specific subgroups of the MSM population, such older MSM, with higher income and lower HIV testing frequency, are not being targeted by community and clinical screening services. Overall, targeted public health measures should be strengthened toward these subgroups, through strengthened primary care testing, expanded access to PrEP, information and promotion of HIV self-testing and more inclusive and accessible health services.

ABSTRACT BACKGROUND: The prevalence of chronic kidney disease (CKD) has increased in the recent decades, along with the number of patients in the terminal stages of this disease, requiring transplantation. Some skin disorders are more frequent in patients with CKD and in renal transplant recipients (RTR). OBJECTIVES: To evaluate the frequency of skin diseases in RTR and patients with CKD receiving conservative treatment. DESIGN AND SETTING: This observational cross-sectional study recruited consecutive patients with CKD and RTR from a nephrology clinic at a teaching hospital in Brazil between 2015 and 2020. METHODS: Quantitative, descriptive, and analytical approaches were used. The sample was selected based on convenience sampling. Data were collected from dermatological visits and participants’ medical records. RESULTS: Overall, 308 participants were included: 206 RTR (66.9%, median age: 48 years, interquartile range [IQR] 38.0–56.0, 63.6% men) and 102 patients with CKD (33.1%, median age: 61.0 years, IQR 50.0–71.2, 48% men). The frequency of infectious skin diseases (39.3% vs. 21.6% P = 0.002) were higher in RTR than in patients with CKD. Neoplastic skin lesions were present in nine (4.4%) RTR and in only one (1.0%) patient with CKD. Among the RTR, the ratio of basal cell carcinoma to squamous cell carcinoma was 2:1. CONCLUSIONS: This study revealed that an increased frequency of infectious skin diseases may be expected in patients who have undergone kidney transplantation. Among skin cancers, BCC is more frequently observed in RTR, especially in those using azathioprine.

Introduction. High variation in the low-level proprieties of visual stimuli and varying degrees of familiarity with famous faces may have caused a bias in the results of investigations that tried to disentangle the processes involved in familiar and unfamiliar face processing (e.g., temporal differences in the detection of the first event-related potentials specialized in face processing may have been caused by different methods of controlling variance in the low-level proprieties of visual stimuli). Objective. To address these problems, we developed a freely available database of 183 famous faces whose low-level proprieties (brightness, size, resolution) have been homogenized and the level of familiarity established. Method. The brightness of the stimuli was standardized by a custom-developed algorithm. The size and the resolution of the pictures were homogenized in Gimp. The familiarity level of the famous faces was established by a group of 48 Portuguese college students. Results. Our results suggest that the brightness of each image did not differ significantly from the mean brightness value of the stimuli set, confirming the standardizing ability of the algorithm. Forty-one famous faces were classified as highly familiar. Main findings and implications. This study provides two important resources, as both the algorithm and the database are freely available for research purposes. The homogenization of the low-level features and the control of the level of familiarity of the famous faces included in our database should ensure that they do not elicit confounding effects such as the ones verified in past studies.

Summary: Lineage switching can induce therapy resistance in cancer. Yet, how lineage fidelity is maintained and how it can be lost remain poorly understood. Here, we have used CRISPR-Cas9-based genetic screening to demonstrate that loss of SMARCB1, a member of the SWI/SNF chromatin remodeling complex, can confer an advantage to clear cell renal cell carcinoma (ccRCC) cells upon inhibition of the renal lineage factor PAX8. Lineage factor inhibition-resistant ccRCC cells formed tumors with morphological features, but not molecular markers, of neuroendocrine differentiation. SMARCB1 inactivation led to large-scale loss of kidney-specific epigenetic programs and restoration of proliferative capacity through the adoption of new dependencies on factors that represent rare essential genes across different cancers. We further developed an analytical approach to systematically characterize lineage fidelity using large-scale CRISPR-Cas9 data. An understanding of the rules that govern lineage switching could aid the development of more durable lineage factor-targeted and other cancer therapies.

Primary and metastatic tumours have different metabolic phenotypes due to changes in nutrient availability. Here the authors perform multi-omic analyses of primary and metastatic renal cancer cells grown in a physiological medium and show that the reprogramming of the branched-chain amino acid catabolism and urea cycle through re-expression of ASS1 allows metabolic flexibility during renal cancer progression.

Abstract The present cross-sectional study aimed to analyze the relationship between awake bruxism and fatigue of masticatory muscles in healthy young adults. For this purpose, 121 graduate students participated in this study. Frequency of awake bruxism was collected for 7 consecutive days by ecological momentary assessment (EMA) using an online survey (mentimeter). Muscle fatigue was tested one day after EMA assessment, which consisted of voluntarily and continuously clenching at 30% (kgf/cm2) of maximum bite force (MBF) until exhaustion. The percentage of change in MBF after the clenching task, as compared to the MBF before the clenching task was measured. The average frequency of awake bruxism was 45.5% during 7 days. Sustained clenching resulted in a significant reduction in MBF values in the total sample (p < 0.05). Nevertheless, no significant correlation was found between frequency of awake bruxism behaviors and percent of change in MBF and endurance time during the fatigue test. Therefore, it can be concluded that young healthy adults present a relatively high frequency of awake bruxism behaviors that do not seem to impact the degree of masticatory muscle fatigue.

Leprosy is a chronic disease and also a global health issue, with a high number of new cases per year. Toll-like receptors can respond to mycobacterial molecules in the early stage of infection. As important components of the innate immune response, alterations in genes coding for these receptors may contribute to susceptibility/protection against diseases. In this context, we used a case-control study model (183 leprosy cases vs. 185 controls) to investigate whether leprosy patients and the control group, in southern Brazil, have different frequencies in TLR1 (TLR1 G>T; rs5743618), TLR2 (TLR2 T>C, rs1816702 and rs4696483), and TLR4 (TLR4 A>G, rs1927911) polymorphisms. Analysis of the TLR1 1805G>T polymorphism presented the G/G genotype more frequently in the control group. TLR2 T>C rs1816702 and TLR2 T>C rs4696483, the T/T and C/T genotype, respectively, were more frequent in the control group than in leprosy patients, suggesting protection from leprosy when the T allele is present (rs4696483). Haplotype analyses between TLR1 (rs5743618) and TLR2 (rs1816702 and rs4696483) polymorphisms suggest risk for the presence of the TCC haplotype and protection in the presence of the TCT haplotype. This study suggests that polymorphisms in TLR1 and TLR2 are factors that may contribute to development/resistance of leprosy.

Limitations in the accuracy of brain pathways reconstructed by diffusion MRI (dMRI) tractography have received considerable attention. While the technical advances spearheaded by the Human Connectome Project (HCP) led to significant improvements in dMRI data quality, it remains unclear how these data should be analyzed to maximize tractography accuracy. Over a period of two years, we have engaged the dMRI community in the IronTract Challenge, which aims to answer this question by leveraging a unique dataset. Macaque brains that have received both tracer injections and ex vivo dMRI at high spatial and angular resolution allow a comprehensive, quantitative assessment of tractography accuracy on state-of-the-art dMRI acquisition schemes. We find that, when analysis methods are carefully optimized, the HCP scheme can achieve similar accuracy as a more time-consuming, Cartesian-grid scheme. Importantly, we show that simple pre- and post-processing strategies can improve the accuracy and robustness of many tractography methods. Finally, we find that fiber configurations that go beyond crossing (e.g., fanning, branching) are the most challenging for tractography. The IronTract Challenge remains open and we hope that it can serve as a valuable validation tool for both users and developers of dMRI analysis methods.

Abstract Background Preterm birth (PTB) is one of the major causes of neonatal morbidity and mortality worldwide. It is commonly accepted that the act of giving birth is the final step in a proinflammatory signaling cascade, orchestrated by an intrauterine milieu coupled to hormonal cues. Consequently, the inflammatory process plays a pivotal role during the pathogenesis of human labor, both in term and preterm deliveries. The ability of innate lymphoid cells (ILCs) to act as pro-inflammatory mediators arose the interest to study their role in normal and pathological pregnancies. The aim of this work was to analyze the relative frequencies of ILCs subsets in pregnancy and the levels of IL-4, IL-17, IL-22, and IFN-γ as inflammatory mediators. Accordingly, we hypothesized that changes in the proportions of ILCs subpopulations could be related to preterm birth. Methods We analyzed 15 full-term delivery samples and six preterm delivery samples. In the full-term group (FTB) peripheral blood was taken during routine blood analysis, on 3 occasions: 1st, 2nd and 3rd trimester. After delivery, peripheral blood, cord blood and placenta were collected. In PTB group, peripheral blood samples were obtained on two occasions: before and 24 h after treatment with progesterone. We used flow cytometry to analyze ILCs in maternal peripheral blood, placenta, and cord blood samples. Maternal peripheral blood and cord blood samples were analyzed by enzyme-linked immunosorbent assay for IL-4, IL-17, IL-22, and IFN-γ plasma levels at the time of labor. Results We observed significantly increased relative frequencies of ILC2 and ILC3 in the decidua, as well as an increase of ILC2 in cord blood samples in PTB group, compared to FTB samples. We also found a decrease in IFN-γ in peripheral blood samples of the PTB group, suggesting a functional withdrawal. Additionally, IL-4, IL-17, IL-22 levels were similar in PTB and FTB groups, denoting a relevant role in mediating labor. Conclusion Our results suggest that ILC2 and ILC3 play a role in PTB by mediating an inflammatory response. Further work is necessary to evaluate the importance of ILCs in the regulation of labor.

PurposeTear fluid biomarkers may offer a non-invasive strategy for detecting diabetic patients with increased risk of developing diabetic retinopathy (DR) or increased disease progression, thus helping both improving diagnostic accuracy and understanding the pathophysiology of the disease. Here, we assessed the tear fluid of nondiabetic individuals, diabetic patients with no DR, and diabetic patients with nonproliferative DR (NPDR) or with proliferative DR (PDR) to find putative biomarkers for the diagnosis and staging of DR.MethodsTear fluid samples were collected using Schirmer test strips from a cohort with 12 controls and 54 Type 2 Diabetes (T2D) patients, and then analyzed using mass spectrometry (MS)-based shotgun proteomics and bead-based multiplex assay. Tear fluid-derived small extracellular vesicles (EVs) were analyzed by transmission electron microscopy, Western Blotting, and nano tracking.ResultsProteomics analysis revealed that among the 682 reliably quantified proteins in tear fluid, 42 and 26 were differentially expressed in NPDR and PDR, respectively, comparing to the control group. Data are available via ProteomeXchange with identifier PXD033101. By multicomparison analyses, we also found significant changes in 32 proteins. Gene ontology (GO) annotations showed that most of these proteins are associated with oxidative stress and small EVs. Indeed, we also found that tear fluid is particularly enriched in small EVs. T2D patients with NPDR have higher IL-2/-5/-18, TNF, MMP-2/-3/-9 concentrations than the controls. In the PDR group, IL-5/-18 and MMP-3/-9 concentrations were significantly higher, whereas IL-13 was lower, compared to the controls.ConclusionsOverall, the results show alterations in tear fluid proteins profile in diabetic patients with retinopathy. Promising candidate biomarkers identified need to be validated in a large sample cohort.

RESUMO Este artigo apresenta o tema da prostituição em publicações do campo dos Estudos Organizacionais. Foi realizada uma leitura interpretativa das publicações encontradas em periódicos nacionais e internacionais do campo, que resultou na organização de três conjuntos de textos. o primeiro compreende publicações que analisam a prostituição considerando aspectos relacionados à psicodinâmica; o segundo inclui textos que abordam os corpos e seus papeis em trocas que ocorrem em serviços comerciais de sexo, nos quais a prostituição está incluída; e o terceiro que compreende publicações que buscam analisar a relação da prostituição com as estruturas sociais e econômicas. Seguem as considerações finais, nas quais indicamos lacunas e potenciais desenvolvimentos.

CD56+ T cells are generally recognized as a distinct population of T cells and are categorized as NKT-like cells. Although our understanding of NKT-like cells is far from satisfactory, it has been shown that aging and a number of disease situations have impacted these cells. To construct an overview of what is currently known, we reviewed the literature on human NKT-like cells. NKT-like cells are highly differentiated T cells with “CD1d-independent” antigen recognition and MHC-unrestricted cell killing. The genesis of NKT-like cells is unclear; however, it is proposed that the acquisition of innate characteristics by T cells could represent a remodeling process leading to successful aging. Additionally, it has been shown that NKT-like cells may play a significant role in several pathological conditions, making it necessary to comprehend whether these cells might function as prognostic markers. The quantification and characterization of these cells might serve as a cutting-edge indicator of individual immune health. Additionally, exploring the mechanisms that can control their killing activity in different contexts may therefore result in innovative therapeutic alternatives in a wide range of disease settings.

Since the 1990s Conservation Agriculture (CA) has been presented to smallholders in Laikipia (Kenya) as a strategy to improve both soil fertility and productivity. In this paper, we provide a historical and social analysis of categories used to define soil management practices and farmers by agricultural programmes in colonial and post-colonial Kenya. For this purpose, we have conducted archive research, recorded the social memory of agricultural policies and farming techniques, and examined contemporary conceptual frameworks and institutional networks around CA in Ethi and Umande in Laikipia County, Central Kenya. We identified evidence of historical continuity in the strategies and methods of agricultural promotional practices. CA networks have broadly advertised the advantages of CA as a means to revert soil degradation and improve livelihoods. However, farmer categorizations based on engagement with CA, promotional strategies, and unclear operational definitions have all prevented CA from being understood by farmers as a technological farming proposal. Instead its adoption is linked with social status and occasional free access to agricultural inputs. Additionally, information about the potential risks and limitations of CA should be explicitly made available to farmers in Laikipia in order to promote transparency and informed decision-making.

ObjectiveTo describe and analyze transmitted drug resistance (TDR) between 2014 and 2019 in newly infected patients with HIV-1 in Portugal and to characterize its transmission networks.MethodsClinical, socioepidemiological, and risk behavior data were collected from 820 newly diagnosed patients in Portugal between September 2014 and December 2019. The sequences obtained from drug resistance testing were used for subtyping, TDR determination, and transmission cluster (TC) analyses.ResultsIn Portugal, the overall prevalence of TDR between 2014 and 2019 was 11.0%. TDR presented a decreasing trend from 16.7% in 2014 to 9.2% in 2016 (pfor–trend = 0.114). Multivariate analysis indicated that TDR was significantly associated with transmission route (MSM presented a lower probability of presenting TDR when compared to heterosexual contact) and with subtype (subtype C presented significantly more TDR when compared to subtype B). TC analysis corroborated that the heterosexual risk group presented a higher proportion of TDR in TCs when compared to MSMs. Among subtype A1, TDR reached 16.6% in heterosexuals, followed by 14.2% in patients infected with subtype B and 9.4% in patients infected with subtype G.ConclusionOur molecular epidemiology approach indicates that the HIV-1 epidemic in Portugal is changing among risk group populations, with heterosexuals showing increasing levels of HIV-1 transmission and TDR. Prevention measures for this subpopulation should be reinforced.

ABSTRACT: Key performance indicators (KPI) are essential to decision-making in an organization, but the approach to analysis and composition used in the formulation of the KPIs can lead to errors. Analysis based only on averages does not allow for discriminating between variations that are natural to the process or special cases which require investigation. The use of control charts can identify this differentiation. However, when several charts are presented encompassing different measurement units and scales, systemic interpretation can be impaired. To assist in this interpretation, this research study aimed at proposing a method to facilitate the analysis of control charts when multiple indicators are employed in the monitoring of agricultural operations. Based on the data obtained over 26 weeks from a mechanized sugarcane (Saccharum officinarum L.) harvesting front, six indicators were defined and analyzed through individual control charts and, systemically, through a standardized group control chart. Results show that the points identified as being outside the control zone (special causes of variation) according to the standardized group control chart were the same as those identified by the six individual charts, which demonstrates the potential of this method to summarize the information with no loss of quality of analysis.

Across Sub-Saharan Africa, agricultural practices for sustainable intensification need to be up-scaled from project interventions to institutional mainstreaming. However, several constraints, including a general lack of resources and knowledge, limited institutional support and challenging market conditions hamper this process. The objective of this study was to develop region-specific options to promote Conservation Agriculture (CA) in the Laikipia region, Kenya. We applied the Transformative Learning Approach (TLA) to stimulate and nurture a joint learning process around CA, to diagnose hindering and supporting factors for up-scaling of CA and to develop options for change promotion. Through a series of field visits, we collected and analyzed data using elements of the TLA approach: i.e. agro-ecosystem health check, stakeholder mapping, participatory videos and the Qualitative Assessment tool for CA adoption (QAToCA). Our findings reveal that up-scaling of CA is hindered by inefficient agricultural market structures, limited access to CA specific biological (residue, seeds), and technical inputs (e.g. machinery), a lack of finances, and absence of knowledge. We recommend four options for further CA promotion in the region: localised expertise (e.g. crop-livestock integration), unbiased facilitation (e.g. careful choice of multipliers), subsidized inputs (e.g. micro-credits) and robust institutional system support (e.g. stable agricultural policies).

A recent model coupling the shear-Alfvén and acoustic continua, which depends strongly on the equilibrium shaping and on elongation in particular, is employed to explain the properties of Alfvénic activity observed on JET plasmas below but close to the typical frequency of toroidicity-induced Alfvén eigenmodes (TAEs). The frequency gaps predicted by the model result from high-order harmonics of the geodesic field-line curvature caused by plasma shaping (as opposed to lower-order toroidicity) and give rise to high-order geodesic acoustic eigenmodes (HOGAEs), their frequency value being close to one-half of the TAEs one. The theoretical predictions of HOGAE frequency and radial location are found to be in fair agreement with measurements in JET experiments, including magnetic, reflectometry and soft x-ray data. The stability of the observed HOGAEs is evaluated with the linear hybrid magnetohydrodynamic/drift-kinetic code CASTOR-K , taking into account the energetic-ion populations produced by neutral beam injection and ion cyclotron resonance heating systems. Wave-particle resonances, along with drive/damping mechanisms, are also discussed in order to understand the conditions leading to HOGAEs destabilisation in JET plasmas.

Diffusion MRI (dMRI) has become an invaluable tool to assess the microstructural organization of brain tissue. Depending on the specific acquisition settings, the dMRI signal encodes specific properties of the underlying diffusion process. In the last two decades, several signal representations have been proposed to fit the dMRI signal and decode such properties. Most methods, however, are tested and developed on a limited amount of data, and their applicability to other acquisition schemes remains unknown. With this work, we aimed to shed light on the generalizability of existing dMRI signal representations to different diffusion encoding parameters and brain tissue types. To this end, we organized a community challenge - named MEMENTO, making available the same datasets for fair comparisons across algorithms and techniques. We considered two state-of-the-art diffusion datasets, including single-diffusion-encoding (SDE) spin-echo data from a human brain with over 3820 unique diffusion weightings (the MASSIVE dataset), and double (oscillating) diffusion encoding data (DDE/DODE) of a mouse brain including over 2520 unique data points. A subset of the data sampled in 5 different voxels was openly distributed, and the challenge participants were asked to predict the remaining part of the data. After one year, eight participant teams submitted a total of 80 signal fits. For each submission, we evaluated the mean squared error, the variance of the prediction error and the Bayesian information criteria. The received submissions predicted either multi-shell SDE data (37%) or DODE data (22%), followed by cartesian SDE data (19%) and DDE (18%). Most submissions predicted the signals measured with SDE remarkably well, with the exception of low and very strong diffusion weightings. The prediction of DDE and DODE data seemed more challenging, likely because none of the submissions explicitly accounted for diffusion time and frequency. Next to the choice of the model, decisions on fit procedure and hyperparameters play a major role in the prediction performance, highlighting the importance of optimizing and reporting such choices. This work is a community effort to highlight strength and limitations of the field at representing dMRI acquired with trending encoding schemes, gaining insights into how different models generalize to different tissue types and fiber configurations over a large range of diffusion encodings.

O panorama de arquivamento digital da pandemia da Covid-19 no Brasil é um eixo argumentativo que possibilita a reflexão sobre temas como: as possibilidades de escrita da história da Covid-19 em escala global; a infraestrutura de arquivos digitais; a construção coletiva de acervos por uma rede de projetos paralelos no país; as características da produção social e do teor documental dos registros preservados nessas iniciativas. O cenário pandêmico catalisa e desnuda problemas concernentes à memória, aos arquivos e à história que não são novos, mas se veem diante de uma ocasião profícua para avanços teóricos e práticos relevantes — que vão do aprimoramento infraestrutural à revisão das balizas epistemológicas para a construção da memória e da história em escala global.

Objetivou-se com este estudo comparar funções matemáticas no ajuste da curva de lactação média e individual de caprinos e estimar parâmetros genéticos e ambientais para medidas repetidas de produção de leite. Foram utilizadas 183 lactações, sendo 121 de cabras Saanen e 62 de cabras Alpinas, de animais pertencentes ao Laboratório de Caprinocultura e Ovinocultura da UFPB/CCHSA. O controle leiteiro foi realizado em intervalos de sete dias. O ajuste foi feito para curva média utilizando-se seis funções matemáticas: polinomial inversa, linear hiperbólica, gama incompleta, quadrática logarítmica, linear e quadrática, sendo ajustada por processos interativos, através de regressão não linear. Os critérios utilizados para verificar a qualidade do ajuste para cada função foram: coeficiente de determinação ajustado (R2a), percentuais de desvio entre as produções totais observadas e estimadas, percentuais de curvas típicas, desvio médio absoluto e quadrado médio dos resíduos. Verificou-se que qualquer um dos modelos testados pode ser utilizado para estimativas da curva média, porém, para o estudo das curvas individuais, o modelo Gama Incompleto deve ser preferido por apresentar melhores estimativas dos componentes da curva de lactação. Palavras-chave: cabras leiteiras; curva de lactação; modelos matemáticos

Super enhancers are frequently involved in the dysregulation of gene expression in cancer. Here, in kidney cancer, a super enhancer is shown to drive the expression of KLF6, which alters the expression of lipid metabolism genes and promotes tumorigenesis.

Innate lymphoid cells (ILCs) are a new set of cells considered to be a part of the innate immune system. ILCs are classified into five subsets (according to their transcription factors and cytokine profile) as natural killer cells (NK cells), group 1 ILCs, group 2 ILCs, group 3 ILCs, and lymphoid tissue inducers (LTi). Functionally, these cells resemble the T helper population but lack the expression of recombinant genes, which is essential for the formation of T cell receptors. In this work, the authors address the distinction between peripheral and decidual NK cells, highlighting their diversity in ILC biology and its relevance to human pregnancy. ILCs are effector cells that are important in promoting immunity, inflammation, and tissue repair. Recent studies have directed their attention to ILC actions in pregnancy. Dysregulation or expansion of pro-inflammatory ILC populations as well as abnormal tolerogenic responses may directly interfere with pregnancy, ultimately resulting in pregnancy loss or adverse outcomes. In this review, we characterize these cells, considering recent findings and addressing knowledge gaps in perinatal medicine in the context of ILC biology. Moreover, we discuss the relevance of these cells not only to the process of immune tolerance, but also in disease.

The role of the immune system, and hence inflammation, in the pathophysiology of hypertensive patients is not clear. Until now, most clinical and biochemical parameters have failed to predict a positive response to renal denervation (RDN). Our aim was to evaluate the immune response in a cohort of patients treated by RDN, through the analysis of cytokine, chemokine, and growth factor behavior. A population of 21 resistant hypertension patients, treated by RDN, was evaluated at six months and one year. Response was defined as a drop of ≥5 mmHg in ambulatory blood pressure monitoring. Sixty-seven percent and 81% of patients clinically responded after six months and one year, respectively. There were no complications or safety issues. Plasmatic levels of 45 cytokine, chemokine, and growth factors were quantified at four different times, pre- and post-procedure. Baseline characteristics were similar between groups, except that active smoking was more frequent in non-responders at one year. Regulated on activation, normal T cell expressed, and secreted (RANTES/CCL5) levels were significantly lower in responders, both at baseline and at 30 days (p = 0.037), and a level ≤15,496 pg/mL was the optimal cutoff, for prediction of a response. IL-15, IL-17A, IL-27, and leukemia inhibitory factor varied significantly in time, with an acute rise being observed 24 h after RDN. Our group has previously showed that HLA-DR+ double-negative (DN) T cells were significantly lower in responders. There was a positive correlation between IL-13, -27, and -4, and DN T cells, and a negative correlation between the latter and SDF-1α and TNF-α, at baseline. Low plasmatic levels of the chemokine RANTES/CCL5 was the most significant result associated with RDN response and may help to identify the best candidates among patients with true resistant hypertension. Pro-inflammatory cytokines correlated negatively with DN T cells in responders, a finding compatible with an enhanced inflammatory milieu present in this extremely high cardiovascular risk cohort.

Gastrointestinal stromal tumors (GISTs) represent about 80% of the mesenchymal neoplasms of the gastrointestinal tract. Most GISTs contain oncogenic KIT (85%) or PDGFRA (5%) receptors. The kinase inhibitor imatinib mesylate is the preferential treatment for these tumors; however, the development of drug resistance has highlighted the need for novel therapeutic strategies. Recently, we reported that the adaptor molecule SH3 Binding Protein 2 (SH3BP2) regulates KIT expression and signaling in human mast cells. Our current study shows that SH3BP2 is expressed in primary tumors and cell lines from GIST patients and that SH3BP2 silencing leads to a downregulation of oncogenic KIT and PDGFRA expression and an increase in apoptosis in imatinib‐sensitive and imatinib‐resistant GIST cells. The microphthalmia‐associated transcription factor (MITF), involved in KIT expression in mast cells and melanocytes, is expressed in GISTs. Interestingly, MITF is reduced after SH3BP2 silencing. Importantly, reconstitution of both SH3BP2 and MITF restores cell viability. Furthermore, SH3BP2 silencing significantly reduces cell migration and tumor growth of imatinib‐sensitive and imatinib‐resistant cells in vivo. Altogether, SH3BP2 regulates KIT and PDGFRA expression and cell viability, indicating a role as a potential target in imatinib‐sensitive and imatinib‐resistant GISTs.

Osteosarcoma (OST) is the most common type of high-grade primary bone tumor, which mainly affects young adults. The current standard of care for OST combines surgical resection with chemotherapy. The clinical outcomes and the current options to treat OST patients are unsatisfactory and novel treatment strategies are needed. The crosstalk between tumor cells and immune cells is essential to the OST microenvironment. Despite the efforts that have been made to address the importance of immune-related factors in OST, there is still a lot to understand. The purpose of the current study was to evaluate the tumor-infiltrating lymphocytes (TIL), the expression of proteins involved in tumor biology, and their impact on the clinical outcome of OST patients. We studied 93 samples of OST patients using immunohistochemistry and histomorphometry. We looked for the infiltration of CD3+, CD4+, CD8+, TIA1+ and CD20+ cells and for the expression of CD44 standard (CD44s) and variant 6 (CD44v6), CD95/Fas, Fas-L, p53 and p-glycoprotein. All the parameters were analyzed for the influence on the occurrence of death and metastasis, plus patient overall survival (OS) and progression-free survival (PFS). The effect of sex, age, tumor location (distal femur or proximal tibia) and the combination with neoadjuvant chemotherapy was also assessed. Our results suggest that the presence of tumor-infiltrating CD4+ cells provides protection to OST patients, and that CD8+ cells have a significant impact on the patient’s overall survival (OS) and progression-free survival (PFS), which is more evident in male patients. In addition, a strong association between tumor-infiltrating CD4+ cells and the presence of CD44s expression in tumor samples was observed. Analysis of TIL and tumor markers related to tumor biology could be useful to stratify patients and monitor the response to therapy, as well as to assist with the development of immunotherapy strategies to improve the effects of cytotoxic TIL to eradicate the tumor cells.

Soft Tissue Sarcomas (STS) are a heterogeneous and rare group of tumors. Immune cells, soluble factors, and immune checkpoints are key elements of the complex tumor microenvironment. Monitoring these elements could be used to predict the outcome of the disease, the response to therapy, and lead to the development of new immunotherapeutic approaches. Tumor-infiltrating B cells, Natural Killer (NK) cells, tumor-associated neutrophils (TANs), and dendritic cells (DCs) were associated with a better outcome. On the contrary, tumor-associated macrophages (TAMs) were correlated with a poor outcome. The evaluation of peripheral blood immunological status in STS could also be important and is still underexplored. The increased lymphocyte-to-monocyte ratio (LMR) and neutrophil-to-lymphocyte ratio (NLR), higher levels of monocytic myeloid-derived suppressor cells (M-MDSCs), and Tim-3 positive CD8 T cells appear to be negative prognostic markers. Meanwhile, NKG2D-positive CD8 T cells were correlated with a better outcome. Some soluble factors, such as cytokines, chemokines, growth factors, and immune checkpoints were associated with the prognosis. Similarly, the expression of immune-related genes in STS was also reviewed. Despite these efforts, only very little is known, and much research is still needed to clarify the role of the immune system in STS.

Soft-tissue sarcomas (STS) represent about 80% of sarcomas, and are a heterogeneous group of rare and malignant tumors. STS arise from mesenchymal tissues and can grow into structures such as adipose tissue, muscles, nervous tissue and blood vessels. Morphological evaluation has been the standard model for the diagnosis of sarcomas, and even in samples with similar characteristics, they present a diversity in cytogenetic and genetic sequence alterations, which further increases the diversity of sarcomas. This variety is one of the main challenges for the classification and understanding of STS patterns, as well as for their respective treatments, which further decreases patient survival (

Change is a word which characterizes the transition of the industrial society to the knowledge one. In this sense it is necessary to reevaluate the educational processes as well as the needing of nowadays society. In such scenery, it appears as a possibility the model proposed by Eric Mazur, during the 90ties, called inverted classroom. This model uses technology as a support to teaching. This article aims to describe the effects of the inverted classroom methodology in a Private IES. The methodology was based on a qualitative and quantitative research and used questionnaires available in google docs and/or printed matter, applied to the students of the Faculdade Pitágoras located in the Metropolitan area of Belo Horizonte, and also in interviews with teachers and a participating observation. Results show that the students’ profile is favorable to the use of inverted classroom model: they are young and in permanent contact with technology. Nevertheless, their daily routine, a deficient formation basis and the necessity to work in order to bear the cost of a private IES make quite complex the application of this model.

Therapy with Tyrosine Kinase Inhibitors (TKI) aiming stable deep molecular response is the gold standard to treat Chronic Myeloid Leukemia (CML). NKT-like cells (CD3+CD56+) combine characteristics of T and NK cells. The physiopathological role of these cells remains unknown although the literature refers their association with inflammation, autoimmune diseases, and cancer. Since the information regarding the role of NKT-like cells in CML is rare, we aimed at the characterization of these cells in CML patients treated with TKIs. Peripheral blood NKT-like cells from 48 CML patients and 40 healthy donors were analyzed by multiparametric flow cytometry. Functional tests consisting of co-culture with leukemic target cells (K562 cell line) were used to measure degranulation and cytokine production. Our results revealed that NKT-like cells are decreased in treated CML patients, although they present increased expression of activation markers (CD69 and HLA-DR), increased degranulation (CD107a) and impaired IFN-γ production. Significantly alterations on the expression of tumor recognition (NCRs and NKp80), and immune regulation receptors (LAG-3, TIM-3, and CD137) by NKT-like cells were observed in CML patients. Second generation TKIs increased cell activation (CD69) and decreased expression of NKp44 and NKp80 by NKT-like cells from CML patients when compared to Imatinib. CML patients that achieved deep molecular response (MR4.5) presented downregulation of NKp44 and LAG-3. Further studies are needed to clarify the role of these cells as biomarkers of therapy response and also to evaluate their value for discrimination of better candidates for sustained treatment-free remission after TKI discontinuation.

Natural killer (NK) cells are a very important component of the innate immune response involved in the lysis of virus infected and tumor cells. Aging has a profound impact in the frequency, phenotype and function of NK cells. Chronic Myeloid Leukemia (CML) is caused by the BCR-ABL gene formation encoding aberrant oncoprotein tyrosine kinase. Treatment with tyrosine kinase inhibitors (TKIs) induces durable deep molecular response. The response to treatment and life expectancy is lower in older patients with chronic phase of CML than in younger patients. In this work we analyse NK cells from TKI-treated CML patients and healthy controls stratified according to age. We have analyzed the expression of NK receptors, activation markers, NK cell differentiation in CD56bright and CD56dim NK cell subsets and the expression of CD107a and IFN-γ in NK cells stimulated with K562. Whereas significant differences on the phenotype and function of NK cells were found between middle-aged (35–65 years old) and elderly (older than 65) healthy individuals, NK cells from TKI-treated CML patients do not show significant differences related with age in most parameters studied, indicating that age is not a limitation of the NK cell recovery after treatment with TKI. Our results also revealed differences in the expression of NK receptors, activation markers and functional assays in NK cells from TKI-treated CML patients compared with age-matched healthy controls. These results highlight the relevance of NK cells in TKI-treated patients and the need of an extensive analysis of the effect of aging on NK cell phenotype and function in these patients in order to define new NK-cell based strategies directed to control CML progression and achieve long-term disease remission after TKI cessation.

3,4-Methylenedioxypyrovalerone (MDPV), a widely available synthetic cathinone, is a popular substitute for classical controlled drugs of abuse, such as methamphetamine (METH). Although MDPV poses public health risks, its neuropharmacological profile remains poorly explored. This study aimed to provide evidence on that direction. Accordingly, C57BL/6J mice were exposed to a binge MDPV or METH regimen (four intraperitoneal injections every 2 h, 10 mg/kg). Locomotor, exploratory, and emotional behavior, in addition to striatal neurotoxicity and glial signature, were assessed within 18–24 h, a known time-window encompassing classical amphetamine dopaminergic neurotoxicity. MDPV resulted in unchanged locomotor activity (open field test) and emotional behavior (elevated plus maze, splash test, tail suspension test). Additionally, striatal TH (METH neurotoxicity hallmark), Iba-1 (microglia), GFAP (astrocyte), RAGE, and TLR2/4/7 (immune modulators) protein densities remained unchanged after MDPV-exposure. Expectedly, and in sheer contrast with MDPV, METH resulted in decrease general locomotor activity paralleled by a significant striatal TH depletion, astrogliosis, and microglia arborization alterations (Sholl analysis). This comparative study newly highlights that binge MDPV-exposure comes without evident behavioral, neurochemical, and glial changes at a time-point where METH-induced striatal neurotoxicity is clearly evident. Nevertheless, neuropharmacological MDPV signature needs further profiling at different time-points, regimens, and brain regions.

O artigo, em caráter exploratório, trata da influência da obra da banda Los Hermanos na configuração de uma estrutura de sentimentos que fundamenta uma ética da delicadeza. Partindo da reconhecida importância da banda para uma nova geração na música popular, exploramos particularidades da contribuição musical de Los Hermanos a partir de uma correlação entre a forma estética e a ética. O trabalho da banda permitiu a construção de uma referência que ressoaria em outras bandas, com variações significativas: em especial, entre a manutenção do caráter conflituoso da ética delicadeza e uma estilização da delicadeza que apaziguaria os atritos com um mundo hostil a ela. Por fim, explora-se também ressonâncias políticas dessa estrutura de sentimentos.

The central vocal pathway of the African clawed frog, Xenopus laevis, is a powerful vertebrate model to understand mechanisms underlying central pattern generation. However, fast and efficient methods of introducing exogenous genes into the neurons of adult X. laevis are currently not available. Here, we systematically tested methods of transgene delivery into adult X. laevis neurons. Although successfully used for tadpole neurons for over a decade, electroporation was not efficient in transfecting adult neurons. Similarly, adeno-associated virus (AAV) was not reliable, and lentivirus (LV) failed to function as viral vector in adult Xenopus neurons. In contrast, vesicular stomatitis virus (VSV) was a fast and robust vector for adult X. laevis neurons. Although toxic to the host cells, VSV appears to be less virulent to frog neurons than they are to mice neurons. At a single cell level, infected neurons showed normal physiological properties up to 7 days post infection and vocal circuits that included infected neurons generated normal fictive vocalizations up to 9 days post infection. The relatively long time window during which the physiology of VSV-infected neurons can be studied presents an ideal condition for the use of optogenetic tools. We showed that VSV does not gain entry into myelinated axons, but is taken up by both the soma and axon terminal; this is an attractive feature that drives transgene expression in projection neurons. Previous studies showed that VSVs can spread across synapses in anterograde or retrograde directions depending on the types of glycoprotein that are encoded. However, rVSV did not spread across synapses in the Xenopus central nervous system. The successful use of VSV as a transgene vector in amphibian brains not only allows us to exploit the full potential of the genetic tools to answer questions central to understanding central pattern generation, but also opens the door to other research programs that focus on non-genetic model organisms to address unique questions.

Photodynamic therapy (PDT) relies on the administration of a photosensitizer (PS) that is activated, after a certain drug-to-light interval (DLI), by the irradiation of the target tumour with light of a specific wavelength absorbed by the PS. Typically, low light doses are insufficient to eradicate solid tumours and high fluence rates have been described as poorly immunogenic. However, previous work with mice bearing CT26 tumours demonstrated that vascular PDT with redaporfin, using a low light dose delivered at a high fluence rate, not only destroys the primary tumour but also reduces the formation of metastasis, thus suggesting anti-tumour immunity. This work characterizes immune responses triggered by redaporfin-PDT in mice bearing CT26 tumours. Our results demonstrate that vascular-PDT leads to a strong neutrophilia (2−24 h), systemic increase of IL-6 (24 h), increased percentage of CD4+ and CD8+ T cells producing IFN-γ or CD69+ (2−24 h) and increased CD4+/CD8+ T cell ratio (2−24 h). At the tumour bed, T cell tumour infiltration disappeared after PDT but reappeared with a much higher incidence one day later. In addition, it is shown that the therapeutic effect of redaporfin-PDT is highly dependent on neutrophils and CD8+ T cells but not on CD4+ T cells.

O artigo analisa algumas manifestações sociais que surgiram pelo mundo a partir de 2008, em especial no Egito, na Espanha, nos EUA, no Chile e no Brasil. O nosso interesse está no impacto, nessas manifestações, do uso das redes sociais, já razoavelmente inseridas num contexto de intensa mediação na comunicação entre manifestantes e na opinião pública em geral. Analisamos dois aspectos: o impacto na organização desses movimentos e o uso cada vez mais central das imagens como forma de comunicação. Com a preocupação de identificar pontos de novidade mais do que analisá-los profundamente, indicamos que há interessantes possibilidades de luta contra-hegemônica a partir do uso extensivo e intensivo das mídias sociais, o que se dá pela busca da democracia radical e pelo uso crítico da imagem.

Objectives Determine what happens to patients after unsuccessful SUI operations and to explore the reasons why these patients change doctors. Materials and Methods One hundred consecutive failed patients treated for SUI were interviewed about the exams requested after persistence of the incontinence as well as the reasons they abandoned their primary doctors through a structured questionnaire. Results Among the patients with cases of anterior colporrhaphy, bladder suspensions or slings, 34.3%, 13.7% and 8.3%, respectively, were not offered any further type of investigative procedures to clarify the failure. Urodynamic evaluations were recommended in 75% of failed slings, and 66.6% of the patients proceeded with these tests. In contrast, only 31% of patients with bladder suspensions and 40% of patients with anterior colporrhaphy were recommended for urodynamic investigations, and only 44.4% and 28.5% of them, respectively, proceeded with the option. Patients´ delusions were reinforced by the doctors’ attitude toward the investigations. Vacuous justifications and the lack of intention to seek improvement were the driving forces causing the patients to change doctors. Conclusion Unsuccessful patients are evaluated in a non-protocol form. Difficulty in clarifying the reasons for surgical failure and the disruption of the doctor-patient relationship are the main reasons why patients abandon them.

Cyclosporin A (CsA), a calcineurin inhibitor, remain the cornerstone of immunosuppressive regimens, regardless of nephrotoxicity, which depends on the duration of drug exposure. The mechanisms and biomarkers underlying the transition from CsA-induced renal dysfunction to nephrotoxicity deserve better elucidation, and would help clinical decisions. This study aimed to clarify these issues, using a rat model of short- and long-term CsA (5 mg/kg bw/day) treatments (3 and 9 weeks, respectively). Renal function was assessed on serum and urine; kidney tissue was used for histopathological characterization and gene and/or protein expression of markers of proliferation, fibrosis and inflammation. In the short-term, creatinine and blood urea nitrogen (BUN) levels increased and clearances decreased, accompanied by glomerular filtration rate (GFR) reduction, but without kidney lesions; at that stage, CsA exposure induced proliferating cell nuclear antigen (PCNA), transforming growth factor beta 1 (TGF-β1), factor nuclear kappa B (NF-κβ) and Tumor Protein P53 (TP53) kidney mRNA up-regulation. In the long-term treatment, renal dysfunction data was accompanied by glomerular and tubulointerstitial lesions, with remarkable kidney mRNA up-regulation of the mammalian target of rapamycin (mTOR) and the antigen identified by monoclonal antibody Ki-67 (Mki67), accompanied by mTOR protein overexpression. Transition from CsA-induced renal dysfunction to nephrotoxicity is accompanied by modification of molecular mechanisms and biomarkers, being mTOR one of the key players for kidney lesion evolution, thus suggesting, by mean of molecular evidences, that early CsA replacement by mTOR inhibitors is indeed the better therapeutic choice to prevent chronic allograft nephropathy.

Os estudos sobre sexualidade têm sido influenciados pelas abordagens culturais e pela analítica queer, compartilhando a exclusão do tema classes sociais. Neste contexto, abordamos os conflitos que ocorrem, há mais de cinco anos, pela definição de quem pode usar o espaço de um centro comercial e sua vizinhança, em Porto Alegre. As informações foram obtidas de fontes secundárias, entrevistas e observação não-participante. A análise indicou que a estratégia do centro comercial se orientou pelo consumo da diferença. No entanto, quando o público de homossexuais de classe média foi substituído por um público mais jovem e com menor poder aquisitivo, passaram a ocorrer episódios de violência por parte de seguranças e da Brigada Militar. Propomos articular identidade sexual, classe social e consumo com as noções de espaço e território, de modo a compreender as ações sociais destes jovens que, indesejados em um território de consumo, produzem um território de luta.

Resenha do livro - LUKÁCS, György. Prolegômenos para uma ontologia do ser social. São Paulo: Boitempo, 2010.

The mechanized harvest of sugar cane (Saccharum officinarum L.) in Brazil is an irreversible trend and it comes with a great concern about the quality of the cane delivered to the industry. A key component to quality is the billet length which affects the processing of raw material, cane deterioration, invisible losses and load density of transport vehicles. Thus, due to the importance of the billet standard in quality and cost of raw material, this study aimed to evaluate if the mechanized harvesting of sugar cane can supply the quality requirements for the crushing process, regarding the billet length. A plot with burnt sugar cane (3.2 ha) and another one with green sugar cane (8.0 ha) were selected to be harvested by two (2) self-propelled sugar cane harvesters. For each harvested 0.4 ha a sample from each infield wagon was collected. The sample was composed by ten billets. The variability in burnt sugar cane was higher than in green sugar cane, and both harvesters did not present the capacity of keeping the billets with similar lengths when operating either in burnt or green conditions.A colheita mecanizada de cana-de-açúcar (Saccharum officinarum L.) no Brasil é uma tendência irreversível e junto a ela vem à preocupação com a qualidade da matéria-prima que chega à indústria. O tamanho de rebolos tem influência nessa qualidade por afetar o processo de deterioração da cana, perdas invisíveis e a densidade de carga no transbordo e transporte. Considerando-se a importância do padrão do rebolo na qualidade e custo da matéria-prima, avaliou-se se a colheita mecanizada de cana-de-açúcar pode atender às exigências de qualidade da moagem no que se refere ao indicador tamanho de rebolo. Para tanto, uma área de cana queimada (3,2 ha) e outra de cana crua (8,0 ha) foram selecionadas. As áreas foram colhidas por duas colhedoras automotrizes. Para cada colhedora e área, uma amostra a cada 0,4 ha colhidos foi coletada, junto ao conjunto de transbordo e cada amostra era composta por dez rebolos. Os resultados foram analisados por meio de gráficos de controle, e a capacidade do processo de corte foi determinada. Houve maior variabilidade na condição de cana queimada em relação à cana crua, e que ambas as colhedoras não têm a capacidade de manter os rebolos em tamanhos semelhantes, quando operando nessas duas condições diferentes.

OBJETIVO: Dezoito anos atrás, dois jovens pacientes, do sexo masculino, com 8 meses e 13 anos de vida, ambos com coarctação da aorta torácica associada à hipoplasia da aorta, entre a artéria subclávia esquerda e a área coarctada, foram submetidos à correção cirúrgica destas lesões por meio de uma nova e pioneira técnica cirúrgica desenvolvida por nós. MÉTODO: A técnica consiste na secção do canal arterial e ressecção de todo tecido coarctado da aorta, seguida por uma aortoplastia, utilizando-se de um retalho longitudinal de pericárdio vascularizado autógeno, implantado desde a saída da artéria subclávia até 2,0 cm abaixo da área coarctectomizada. Em ambos os casos, a pressão arterial sistêmica e os pulsos arteriais dos membros superiores e inferiores ficaram normais, imediatamente após a cirurgia até os dias de hoje. RESULTADOS: Os exames clínicos e de medidas com Doppler mostraram, respectivamente, nenhum gradiente pressórico braço/perna, assim como, demonstraram fluxo sanguíneo arterial normal e não gradiente arterial pressórico através da área coartectomizada. Ambos foram submetidos a rigorosas avaliações 18 anos após a cirurgia, incluindo cateterismo cardíaco e torácico aórtico, com aortografia, testes ergométricos e angiotomografia computadorizada aórtica. Essas avaliações mostraram uma configuração aórtica normal, com diâmetros transversos normais, inclusive nas regiões acima e abaixo da área coartectomizada. Não houve demonstração de qualquer forma de lesão degenerativa do retalho pericárdico pediculado implantado ao longo dos anos, assim como nenhuma identificação de lesão aneurismática, de sinais de lesão aterosclerótica no mesmo, ou de recoarctação. Mais importante, é que ficou evidente que o retalho pericárdico pediculado totalmente vascularizado, assim utilizado, é mantido vivo, e cresceu ao longo dos anos, tanto em seu diâmetro como em seu comprimento. CONCLUSÃO: A técnica do emprego do retalho pericárdico pediculado, vascularizado e autógeno é a mais adequada e a mais completa em comparação com todas as outras técnicas cirúrgicas existentes para correção dos diferentes tipos de coarctação da aorta torácica, nas suas formas simples ou associadas a outras lesões aórticas. É indicada em todas as faixas etárias, inclusive em recém-natos.OBJECTIVE: Eighteen years ago, two young male patients of 8 months and 13 years with aortic coarctation associated to aortic hypoplasia between the left subclavian artery and the coarctated area, were submitted to surgical correction using a new world-pioneering surgical technique developed in our service. METHOD: This technique consists of sectioning the patent ductus arteriosus, followed by resection of all the coarctated tissue in the aortic wall and aortoplasty correction by means of the lengthwise implantation of a pediculated autogenous pericardial flap. This flap is inserted into the thoracic aorta, from the root of the left subclavian artery to 2.0 cm below the coarctated area. RESULTS: For both patients, the blood pressure and arterial pulses of both arms and legs have been normal since the surgery until the present moment. Clinical examination and Doppler evaluation evidenced no pressure gradient between arms and legs, normal blood flow and no pressure gradient through the coarctated area. Both patients were submitted to other evaluations 18 years after surgery, including cardiac and thoracic aortic catheterization followed by aortography. These evaluations demonstrated normal aortic configuration, with normal diameter, including the areas above and below the coarctated site. There was no evidence of any kind of degenerative lesions of the vascularized pericardial flap or re-coarctation of the lesion and no signs of aneurysms forming or the presence of atherosclerosis of the flap. Moreover, and very importantly, it was evident that the pediculated completely vascularized autologous pericardial flap had been kept alive and had grown in diameter as well as in length. CONCLUSION: The surgical technique using a pediculated vascularized autologous pericardial flap is the most complete and adequate for the correction of the different types of simple or complex forms of thoracic aortic coarctation in all age groups, including newborn babies when compared to all the existing techniques.

Acromegalia é entidade clínica resultante do aumento da produção do hormônio de crescimento (GH) em virtude da existência de um tumor hipofisário secretor deste hormônio, ou de tumores de localização extra-hipofisária com influência nas células produtoras de GH. O reconhecimento dos sinais e sintomas, tamanho e comportamento biológico são de fundamental importância para a introdução de um tratamento eficaz, antes da instalação de danos ou distúrbios fisiológicos irreversíveis. Trabalhos atuais mostram que é inadequada a conotação de “curados” ou “não curados” aos pacientes acromegálicos tratados, sendo recomendado considerá-los como “controlados”, “inadequadamente controlados” e “não controlados”. Os autores buscam, no presente trabalho, uma maneira simples de identificar, diferenciar, diagnosticar clinicamente e por imagens essas lesões, resumindo uma proposta lógica para abordagem na condução terapêutica e introdução de medidas coadjuvantes.