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Lung carcinoids are rare tumors representing 1-2% of all invasive lung malignancies. They include typical and atypical carcinoids, whose distinction is made based on the mitotic index and presence or absence of necrosis. The 10-year overall survival for stage IV typical carcinoid is 47% and 18% for atypical carcinoid, reflecting the indolent growth of these tumors. There are limited approved treatment options for them and most of the evidence comes from retrospective analyses, single-arm trials, subgroup analysis of phase II/III trials for metastatic neuroendocrine tumors and extrapolation of data from phase III trials for gastroenteropancreatic neuroendocrine tumors. Management of metastatic lung carcinoids requires a multidisciplinary standardized approach in specialized centers. Treatment should have a dual objective, control of tumor growth and control of symptoms related to hypersecretion syndromes, aiming to improve quality of life and survival. In the continuum of treatment disease, locoregional treatment options need to be considered in parallel with systemic treatments. In this paper, we review the present treatment options and their rational and we give an insight into future alternatives.

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Neuroendocrine breast cancer (NEBC) is a rare and heterogeneous entity. It most commonly presents a luminal phenotype and a worse prognosis. When diagnosed in an advanced stage, metastasis from another neuroendocrine tumor should be excluded. This case features a premenopausal woman with an oligometastatic breast large cell neuroendocrine carcinoma, estrogen receptor (ER) positive, and human epidermal growth factor receptor 2 (HER2) negative. Since the patient was very symptomatic at the presentation of the disease, chemotherapy was started. Complete radiological response of the metastatic disease was achieved, and the patient was then submitted to radical breast surgery and bilateral oophorectomy. She subsequently underwent radiation therapy. Since then and to date, she has been under endocrine therapy (ET) and a CDK4/6 inhibitor (CDK4/6i), with no evidence of malignant disease. Evidence to guide the choice of treatment for these tumors is currently scarce. In cases with oligometastatic disease, radical treatment should be considered. Given that this entity is rare, its reporting should be encouraged.

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The occurrence and severity of osteonecrosis in sickle cell anaemia (SCA) vary due to risk factors, including genetic modifiers. Bone morphogenetic proteins (BMPs), particularly BMP6, and the vitamin D receptor (VDR) play key roles in cartilage and bone metabolism, making them potential contributors to orthopaedic outcomes in SCA. Here, we evaluated the association of polymorphisms in BMP6 (rs3812163, rs270393 and rs449853) and VDR (FokI rs2228570 and Cdx2 rs11568820) genes with osteonecrosis risk in a Brazilian SCA cohort. A total of 177 unrelated SCA patients were selected. The AA genotype of BMP6 rs3812163 was independently associated with a lower osteonecrosis risk (p = 0.015; odds ratio (OR): 0.38; 95% confidence interval (CI): 0.18-0.83) and with the long-term cumulative incidence of osteonecrosis (p = 0.029; hazard ratio: 0.56, 95% CI: 0.34-0.94). The VDR rs2228570 TT genotype was independently associated with a lower osteonecrosis risk (p = 0.039; OR: 0.14; 95% CI: 0.02-0.90). In summary, our results provide evidence that BMP6 rs3812163 and the VDR rs2228570 might be implicated in osteonecrosis pathophysiology in SCA and might help identify individuals at high risk.

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Urothelial carcinoma is a significant global health concern that accounts for a substantial part of cancer diagnoses and deaths worldwide. The tumor microenvironment is a complex ecosystem composed of stromal cells, soluble factors, and altered extracellular matrix, that mutually interact in a highly immunomodulated environment, with a prominent role in tumor development, progression, and treatment resistance. This article reviews the current state of knowledge of the different cell populations that compose the tumor microenvironment of urothelial carcinoma, its main functions, and distinct interactions with other cellular and non-cellular components, molecular alterations and aberrant signaling pathways already identified. It also focuses on the clinical implications of these findings, and its potential to translate into improved quality of life and overall survival. Determining new targets or defining prognostic signatures for urothelial carcinoma is an ongoing challenge that could be accelerated through a deeper understanding of the tumor microenvironment.

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Objetivo: avaliar as consequências da depressão pós-parto no desenvolvimento cognitivo infantil. Métodos: trata-se de uma revisão narrativa, com caráter analítico quantitativo, realizada por meio da busca de artigos científicos publicados, nas plataformas Google Acadêmico, Scielo e PubMed, sobre a relação entre depressão pós-parto e desenvolvimento infantil. Resultados: foi selecionado um total de 23 artigos entre os três bancos de dados. Os resultados apontam que filhos de mães deprimidas são mais propensos a ter alterações no desenvolvimento cognitivo, social e linguístico do que filhos de mães não deprimidas. Entretanto, deve-se lembrar que essa alteração não acontece exclusivamente pela depressão pós-parto, uma vez que ela pode estar associada a outros fatores de risco, como condições socioeconômicas e apoio marital. Conclusão: a depressão pós-parto como fator isolado afeta o bebê de maneira sutil, mas, diante de diversos fatores ambientais e conduta parental, o efeito nocivo pode ser intensificado, o que pode prejudicar os desempenhos nos testes cognitivos, de atenção e aprendizagem. Desse modo, compreende-se que é importante incentivar um acompanhamento pré-natal que valorize a saúde mental das gestantes, para que qualquer manifestação psicológica negativa seja prontamente identificada e receba o apoio necessário o mais rápido possível.

Objective: to evaluate the consequences of postpartum depression on child cognitive development. Methods: this is a narrative review, with a quantitative analytical character, carried out by searching for scientific articles published on the Google Scholar, Scielo and PubMed platforms on the relationship between postpartum depression and child development. Results: a total of 23 articles were selected from the three databases. The results indicate that children of depressed mothers are more likely to have changes in cognitive, social and linguistic development than children of non-depressed mothers. However, it should be remembered that this change does not occur exclusively due to postpartum depression, as it may be associated with other risk factors, such as socioeconomic conditions and marital support. Conclusion: postpartum depression as an isolated factor affects the baby in a subtle way, but, given several environmental factors and parental behavior, the harmful effect can be intensified, which can harm performance in cognitive, attention and learning tests. Therefore, it is understood that it is important to encourage prenatal care that values the mental health of pregnant women, so that any negative psychological manifestations are promptly identified and receive the necessary support as quickyl as possible.

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OBJECTIVES: Stroke is a devastating clinical outcome that significantly contributes to the morbidity and mortality of sickle cell anemia (SCA) patients. Despite its advantages in predicting stroke risk, transcranial Doppler screening has limitations that restrict its applicability, highlighting the need for emerging prognostic tools. Thrombospondin-1 plays a crucial role in endothelial injury, platelet adhesion, and nitric oxide metabolism and may be implicated in stroke pathophysiology. Here, we aimed to evaluate the association of THBS1 genetic variations with the occurrence of stroke in SCA patients MATERIALS AND METHODS: By real-time PCR, 512 SCA patients were fully genotyped for THBS1 A-296G (rs1478605) polymorphism RESULTS: THBS1 GG genotype was associated with a lower risk for stroke occurrence [odds ratio (OR): 0.30; 95% confidence interval (CI): 0.11-0.78; P = 0.011], although these findings were not consistent with multivariate logistic regression analysis (OR: 0.73, 95% CI: 0.12 - 4.37; P = 0.736). In agreement, the cumulative incidence of stroke for patients with AG/AA genotypes was higher when compared to the GG genotype (P = 0.018). However, the association was not maintained in the multivariate proportional hazards model (hazard ratio: 0.67, 95% CI: 0.12-3.61; P = 0.643) CONCLUSIONS: In summary, the present study shows that the THBS1 A-296G (rs1478605) polymorphism may be a potential modifier for stroke in SCA.

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The existence of encrypted fragments with antimicrobial activity in human proteins has been thoroughly demonstrated in the literature. Recently, algorithms for the large-scale identification of these segments in whole proteomes were developed, and the pervasiveness of this phenomenon was stated. These algorithms typically mine encrypted cationic and amphiphilic segments of proteins, which, when synthesized as individual polypeptide sequences, exert antimicrobial activity by membrane disruption. In the present report, the human reference proteome was submitted to the software kamal for the uncovering of protein segments that correspond to putative intragenic antimicrobial peptides (IAPs). The assessment of the identity of these segments, frequency, functional classes of parent proteins, structural relevance, and evolutionary conservation of amino acid residues within their corresponding proteins was conducted in silico. Additionally, the antimicrobial and anticancer activity of six selected synthetic peptides was evaluated. Our results indicate that cationic and amphiphilic segments can be found in 2% of all human proteins, but are more common in transmembrane and peripheral membrane proteins. These segments are surface-exposed basic patches whose amino acid residues present similar conservation scores to other residues with similar solvent accessibility. Moreover, the antimicrobial and anticancer activity of the synthetic putative IAP sequences was irrespective to whether these are associated to membranes in the cellular setting. Our study discusses these findings in light of the current understanding of encrypted peptide sequences, offering some insights into the relevance of these segments to the organism in the context of their harboring proteins or as separate polypeptide sequences.

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ABSTRACT Neuroendocrine breast cancer (NEBC) is a rare and heterogeneous entity. It most commonly presents a luminal phenotype and a worse prognosis. When diagnosed in an advanced stage, metastasis from another neuroendocrine tumor should be excluded. This case features a premenopausal woman with an oligometastatic breast large cell neuroendocrine carcinoma, estrogen receptor (ER) positive, and human epidermal growth factor receptor 2 (HER2) negative. Since the patient was very symptomatic at the presentation of the disease, chemotherapy was started. Complete radiological response of the metastatic disease was achieved, and the patient was then submitted to radical breast surgery and bilateral oophorectomy. She subsequently underwent radiation therapy. Since then and to date, she has been under endocrine therapy (ET) and a CDK4/6 inhibitor (CDK4/6i), with no evidence of malignant disease. Evidence to guide the choice of treatment for these tumors is currently scarce. In cases with oligometastatic disease, radical treatment should be considered. Given that this entity is rare, its reporting should be encouraged.

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Random energy models (REMs) provide a simple description of the energy landscapes that guide protein folding and evolution. The requirement of a large energy gap between the native structure and unfolded conformations, considered necessary for cooperative, protein-like, folding behavior, indicates that proteins differ markedly from random heteropolymers. It has been suggested, therefore, that natural selection might have acted to choose nonrandom amino acid sequences satisfying this particular condition, implying that a large fraction of possible, unselected random sequences, would not fold to any structure. From an informational perspective, however, this scenario could indicate that protein structures, regarded as messages to be transmitted through a communication channel, would not be efficiently encoded in amino acid sequences, regarded as the communication channel for this transmission, since a large fraction of possible channel states would not be used. Here, we use a combined REM for conformations and sequences, with previously estimated parameters for natural proteins, to explore an alternative possibility in which the appropriate shape of the landscape results mainly from the deviation from randomness of possible native structures instead of sequences. We observe that this situation emerges naturally if the distribution of conformational energies happens to arise from two independent contributions corresponding to sequence-dependent and -independent terms. This construction is consistent with the hypothesis of a protein burial folding code, with native structures being determined by a modest amount of sequence-dependent atomic burial information with sequence-independent constraints imposed by unspecific hydrogen bond formation. More generally, an appropriate combination of sequence-dependent and -independent information accommodates the possibility of an efficient structural encoding with the main physical requirement for folding, providing possible insight not only on the folding process but also on several aspects sequence evolution such as neutral networks, conformational coverage, and de novo gene emergence.

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INTRODUCTION: Dengue is the most fatal virus disease spread by mosquito bites and Aedes aegypti is the main transmitting agent. It is an endemic disease in the tropical and subtropical regions, currently affecting more than 100 countries. Although most patients present mild forms of the disease, a considerable proportion of individuals has severe alterations in the blood count. The aim of this study was to evaluate the consumption pattern of blood components in epidemic and non-epidemic periods and to verify if there was an impact on dengue cases and the death rate. METHOD: This is a retrospective cross-sectional study conducted through the collection and analysis of data from the Brazilian Ministry of Health from 2008 to 2019 on new cases and deaths from dengue, as well as the consumption of blood components in the period mentioned by hemovigilance bulletins of the Brazilian authority. RESULTS: Regarding the results, no significant difference was found between the absolute amount of blood components used in years with an epidemic peak. Regarding the relative values, an important variation was shown among the distributive consumption patterns of blood components in the outbreak years. In the univariate linear regression analysis, there was statistical significance between the increase in the number of dengue cases and deaths from dengue with the increase in the consumption of red blood cell concentrates (RBP), platelet concentrates (PP), fresh frozen plasma (FFP) and cryoprecipitate (Cryo) (p-value < 0.05). The increase in dengue cases was related to the increase in Cryo consumption with clinical significance (R² > 0.5), but dengue deaths were not correlated to the same. In multivariate analysis, all regression models had clinical and statistical significance. CONCLUSION: The data obtained in the present study demonstrate that there is a relevant relationship between the increase in cases and deaths from dengue with the blood components usage, especially PP, FFP and cryoprecipitate.

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INTRODUCTION: The aberrant expression of the inhibitor of DNA binding (ID1) gene has been frequently associated with the leukemogenesis and prognostication acute myeloid leukemia (AML), although its clinical importance has never been investigated in patients treated outside well-controlled clinical trials. METHODS: Using quantitative real-time polymerase chain reaction, we investigated the role of the ID1 expression in the clinical outcomes of non-selected patients with acute myeloid leukemia treated in a real-life setting. RESULTS: Overall, 128 patients were enrolled. Patients with high ID1 expression had a lower 3-year overall survival (OS) rate of 9%, with the 95% confidence interval (95%CI) at 3 to 20%, compared to patients with a low ID1 expression (22%, 95%CI: 11 - 34%) (p = 0.037), although these findings did not retain significance after adjustment (hazard ratio (HR): 1.5, 95%CI: 0.98 - 2.28; p = 0.057). The ID1 expression had no impact on post-induction outcomes (disease-free survival, p = 0.648; cumulative incidence of relapse, p = 0.584). CONCLUSIONS: Although we are aware thar our data are confronted with many variables that cannot be fully controlled, including drug unavailability, risk-adapted treatment, comorbidities and the time from diagnosis to treatment initiation, we are firm believers that such an initiative can provide more realistic data on understudied populations, in particular those from low- and middle-income countries.

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Background: Harvey Cushing and collaborators created the first society of neurosurgeons in 1920, in the United States of America, the Society of Neurological Surgeons. In 1955, the World Federation of Neurosurgical Societies (WFNS) was created in Switzerland to improve neurosurgical care globally through the scientific cooperation of members. The performance of neurosurgical associations today is fundamental to discuss diagnostic methods and therapeutic approaches, transforming modern medicine. Although most neurosurgical associations are recognized worldwide, there are some societies that are not recognized internationally due to a lack of regulatory bodies and lack of official digital channels, among other reasons. The main objective of the article is to list the neurosurgical societies and to provide a more integrated view of the interactions between neurosurgical societies in different countries. Methods: We developed a table summarizing the countries recognized by the United Nations, the continents, capitals, name of the present societies, and social networks. We utilized "Country AND (Neurosurgery OR Neurological Surgery) AND (Society OR Association)," in English, and in the native language of the country. Our search included: PubMed, Scopus, Google, Google Scholar, and the WFNS website, without filters. Results: We found 189 neurosurgery associations, from 131 countries and territories; 77 countries did not have their own neurosurgical societies. Conclusion: There is a difference between the number of internationally recognized societies, and the number of societies found in this study. In the future, we should better organize neurosurgical societies in countries that have neurosurgical activity with those without such resources.

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The nanostructured lanthanide-silica materials of the Ln-SiO2 type (Ln = La, Ce, Pr, Nd, Eu, Gd, Dy, Yb, Lu) were synthesized by the hydrothermal method at 100 °C, using cetyltrimethylammonium as a structural template, silica gel and sodium silicate as a source of silicon, and lanthanide oxides, with Si/Ln molar ratio = 50. The resulting materials were calcined at 500 °C using nitrogen and air, and characterized by X-ray diffraction (XRD), Fourier-Transform infrared absorption spectroscopy, scanning electron microscopy, thermogravimetry (TG), surface area by the BET method and acidity measurements by n-butylamine adsorption. The XRD and chemical analysis indicated that the SiO2 presented a hexagonal structure and the incorporation of lanthanides in the structure changes the properties of the Ln-SiO2 materials. The heavier the lanthanide element, the higher the Si/Ln ratio. The TG curves showed that the decomposition of the structural template occurs in the materials at temperatures below 500 °C. The samples showed variations in specific surface area, mean pore diameter and silica wall thickness, depending on the nature of the lanthanide. The incorporation of different lanthanides in the silica generated acid sites of varied strength. The hydrothermal stability of the Ln-SiO2 materials evaluated at high temperatures, evidenced that the properties can be controlled for application in adsorption and catalysis processes.

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OBJECTIVES: To evaluate MRI with gadoxetic acid to quantify liver function in cirrhotic patients using the relative enhancement index (REI) compared with Child-Pugh score (CPS), MELD score, and indocyanine green plasma disappearance rate (ICG-PDR) and to establish cutoffs for REI to stratify cirrhotic patients into good and poor liver function groups. METHODS: We prospectively evaluated 60 cirrhotic patients and calculated CPS, MELD score, ICG-PDR, and REI for each patient. Spearman's correlation coefficient was used to assess correlation between REI, CPS, MELD, and ICG-PDR. Good and poor liver function groups were created by k-means clustering algorithm using CPS, MELD, and ICG-PDR. ROC curve analysis was performed and optimal cutoff was identified for group differentiation. RESULTS: Good correlations were found between REI and other liver function biomarkers: REI and CPS (rho = - 0.816; p < 0.001); REI and MELD score (rho = - 0.755; p < 0.001); REI and ICG-PDR (rho = 0.745; p < 0.001)]. REI correlation was stronger for patients with Child-Pugh A (rho = 0.642, p = 0.002) and B (rho = 0.798, p < 0.001) than for those with Child-Pugh C (rho = 0.336, p = 0.148). REI is significantly lower in patients with poor liver function (p < 0.001). ROC curve showed an AUC 0.94 to discriminate patients with poor liver function (REI cutoff < 100; 100% sensitivity; 76% specificity). CONCLUSIONS: REI is a valuable non-invasive index for liver function quantification that has good correlations with other liver function biomarkers. REI can be easily calculated and can be used to estimate liver function in clinical practice in the routine evaluation of cirrhotic patients that undergo MR imaging with gadoxetic acid contrast. KEY POINTS: • REI is a valuable non-invasive index for liver function quantification that has good correlations with other liver function biomarkers. • REI can be easily calculated in the routine evaluation of cirrhotic patients that undergo gadoxetic acid-enhanced MRI. • The REI enables stratification of cirrhotic patients into good and poor liver function groups and can be used as additional information, together with morphological and focal liver lesion evaluation.

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BACKGROUND: Sickle cell anemia (SCA) is a genetic disease with great clinical heterogeneity and few viable strategies for treatment; hydroxyurea (HU) is the only widely used drug. Thus, the study of single nucleotide polymorphisms (SNPs) and the gene expression of MMPs 1, 2, 9, 7 and TIMPs 1 and 2, which are involved in the regulation of extracellular matrix, inflammation, and neuropathies, may provide further insights into the pathophysiology of the disease and elucidate biomarkers and molecules as potential therapeutic targets for patients with SCA. METHODS AND RESULTS: We evaluated 251 young individuals with SCA from northeastern Brazil. The groups were divided according to vaso-occlusive crisis (VOC) and cerebrovascular disease (CVD), compared to control individuals. SNP detection and gene expression assays were performed by real-time PCR, TaqMan system®. Both the expression levels of MMP1 gene, and the SNP MMP1-1607 1G/2G were associated with the risk of cerebral ischemic stroke (IS), and the expression of MMP1 was also associated with a higher frequency of VOC/year. Expression levels of MMP7, TIMP1, and TIMP2 were increased in patients conditioned to IS. The SNP 372T>C (rs4898) TIMP1 T alleles were more frequent in patients with > 5 VOC events/year. The SNP rs17576 of MMP9 showed differences in gene expression levels; it was increased in the genotypes AG, and AG+GG. CONCLUSION: The findings of this study, the SNPs, and expression provide initial support for understanding the role of MMPs-TIMPs in the pathophysiology of SCA in young patients.

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