Single-shot observation of nonlinear pulse splitting in a Kerr medium.

We report single-shot, time-resolved observation of self-steepening and temporal splitting of near-infrared, 50 fs, micro-joule pulses propagating nonlinearly in flint (SF11) glass. A coherent, smooth-profiled, 60-nm-bandwidth probe pulse that propagated obliquely to the main pulse through the Kerr medium recorded a time sequence of longitudinal projections of the main pulse's induced refractive index profile in the form of a phase-shift "streak," in which frequency-domain interferometry recovered with ∼10 fs temporal resolution. A three-dimensional simulation based on a unidirectional pulse propagation equation reproduced observed pulse profiles.

Blood-based Proteomic Signatures Associated With MEN1-related Duodenopancreatic Neuroendocrine Tumor Progression.

PURPOSE: Patients with multiple endocrine neoplasia type 1 (MEN1) are predisposed to develop duodenopancreatic neuroendocrine tumors (dpNETs), and metastatic dpNET is the primary cause of disease-related mortality. Presently, there is a paucity of prognostic factors that can reliably identify patients with MEN1-related dpNETS who are at high risk of distant metastasis. In the current study, we aimed to establish novel circulating molecular protein signatures associated with disease progression. EXPERIMENTAL DESIGN: Mass spectrometry-based proteomic profiling was conducted on plasmas procured through an international collaboration between MD Anderson Cancer Center, the National Institutes of Health, and the University Medical Center Utrecht from a cohort of 56 patients with MEN1 [14 with distant metastasis dpNETs (cases) and 42 with either indolent dpNETs or no dpNETs (controls)]. Findings were compared to proteomic profiles generated from serially collected plasmas from a mouse model of Men1-pancreatic neuroendocrine tumors (Men1fl/flPdx1-CreTg) and control mice (Men1fl/fl). RESULTS: A total of 187 proteins were found to be elevated in MEN1 patients with distant metastasis compared to controls, including 9 proteins previously associated with pancreatic cancer and other neuronal proteins. Analyses of mouse plasmas revealed 196 proteins enriched for transcriptional targets of oncogenic MYCN, YAP1, POU5F1, and SMAD that were associated with disease progression in Men1fl/flPdx1-CreTg mice. Cross-species intersection revealed 19 proteins positively associated with disease progression in both human patients and in Men1fl/flPdx1-CreTg mice. CONCLUSIONS: Our integrated analyses identified novel circulating protein markers associated with disease progression in MEN1-related dpNET.

International differences and inaccuracies in the public advertising about calcaneal apophysitis: an audit of websites originating in Australia, UK and USA.

BACKGROUND: Calcaneal apophysitis is a common condition in childhood. Parents often seek online information for children's' health care concerns prior to seeking care. Therefore, we aimed to evaluate the credibility, readability, and accuracy of calcaneal apophysitis advertising on popular websites in three countries. METHODS: We used content analysis of publicly accessible data. This involved identifying the top 50 websites in each country from their hit rates. We used elements of validated tools to audit and determine frequencies relevant to credibility (e.g. publisher), readability (e.g. literacy score) and accuracy (e.g. alignment with evidence). Data were analysed quantitatively and reported against each element. RESULTS: Websites were predominantly hosted by private health services (n = 118, 79%). The mean (SD) SMOG (readability) score was 9.3 (4.5). The majority of websites (n = 140, 93%) provided at least one treatment recommendation, and less than 10% (n = 11) of websites advertised treatments fully aligned with evidence. Use of treatment modalities without evidence and with high risk to children were also found including surgery, extracorporeal shock wave therapy and laser. CONCLUSIONS: Calcaneal apophysitis online advertising is mostly curated by clinicians. Clinicians should consider revising online advertising to increase understandability and accuracy to reduce health care wastage, risk, and low value care.

Phenotypic Profiling and Molecular Mechanisms in Hyperparathyroidism-jaw Tumor Syndrome.

CONTEXT: Hyperparathyroidism-jaw tumor (HPT-JT) syndrome is a heritable form of primary hyperparathyroidism caused by germline inactivating mutations in CDC73 encoding parafibromin and is associated with an increased risk of parathyroid cancer. There is little evidence to guide the management of patients with the disease. OBJECTIVE: (1) Characterize the natural history of HPT-JT, (2) correlate genotype and histology of parathyroid tumors with parafibromin immunostaining, (3) understand molecular changes downstream to CDC73 loss. DESIGN: Retrospective study of patients with HPT-JT syndrome (genetically confirmed or affected first-degree relatives). Independent review of uterine tumor from 2 patients and staining for parafibromin on parathyroid tumors from 19 patients (13 adenomas, 6 carcinomas) was performed. RNA-sequencing was performed in 21 parathyroid samples (8 HPT-JT-related adenomas, 6 HPT-JT-related carcinomas, and 7 sporadic carcinomas with wild-type CDC73). RESULTS: We identified 68 patients from 29 kindreds with HPT-JT with median age at last follow-up of 39 [interquartile range, 29-53] years. A total of 55/68 (81%) developed primary hyperparathyroidism; 17/55 (31%) had parathyroid carcinoma. Twelve of 32 (38%) females developed uterine tumors. Of the 11 patients who had surgical resection for uterine tumors, 12/24 (50%) tumors were rare mixed epithelial mesenchymal polypoid lesions. Four of 68 patients (6%) developed solid kidney tumors; 3/4 had a CDC73 variant at p.M1 residue. Parafibromin staining of parathyroid tumors did not correlate with tumor histology or genotype. RNA-sequencing showed a significant association of HPT-JT-related parathyroid tumors with transmembrane receptor protein tyrosine kinase signaling pathway, mesodermal commitment pathway, and cell-cell adhesion. CONCLUSIONS: Multiple, recurrent atypical adenomyomatous uterine polyps appear to be enriched in women with HPT-JT and appear characteristic of the disease. Patients with CDC73 variants at p.M1 residue appear predisposed to kidney tumors. CLINICAL TRIAL NUMBER: NCT04969926.

Germline- and Somatic-Inactivating FLCN Variants in Parathyroid Cancer and Atypical Parathyroid Tumors.

CONTEXT: Parathyroid cancer (PC) is a rare endocrine neoplasm with high mortality. While surgery is the treatment for patients with the disease, recurrence rates are high, and patients usually succumb to severe hypercalcemia. There is no effective systemic therapy for the disease. OBJECTIVE: To investigate for novel genes causing parathyroid cancer. METHODS: We analyzed the germline DNA of 17 patients with "sporadic" PC and 3 with atypical parathyroid tumors (APTs) who did not have germline CDC73 or MEN1 pathogenic variants. Sequencing of available tumor tissue from 14 patients with PC and 2 with APT was also performed (including 2 patients with no available germline DNA). In addition, sporadic parathyroid adenomas from 74 patients were analyzed for FLCN variants. RESULTS: We identified germline FLCN variants in 3 unrelated patients with PC. The 2 frameshift variants have been described in patients with Birt-Hogg-Dubé (BHD) syndrome, while the pathogenicity of the missense variant c.124G > C (p.G42R) has not been definitively established. Functional analysis of the missense variant showed a potential effect on posttranslational modification. All 3 patients with germline FLCN variants were noted to have renal cysts and 2 had lung cysts, features associated with BHD syndrome. Somatic FLCN variants were identified in tumors from 2 (1 APT) of 16 patients with PC/APT and in none of the 74 sporadic parathyroid adenomas. No second hits in FLCN were noted on sequencing; however, loss of heterozygosity at the locus was demonstrated in 2 of 3 patients with the identified germline FLCN variant. CONCLUSION: The finding of FLCN variants associated with PC may provide the foundation for the development of therapy for this malignancy.

Nutritional profile of indigenous children under five years of age in the Upper Solimões River, Amazonas, Brazil (2013) / Perfil nutricional de crianças indígenas menores de cinco anos de idade no Alto Rio Solimões, Amazonas, Brasil (2013)

Abstract Objectives: to characterize the nutritional status of indigenous children underfive years of age living in rural communities in the Upper Solimões River region, inhabited by seven ethnic groups, based on data of december 2013. Methods: weight and height data extracted from SISVAN-I (Indigenous Food and Nutritional Surveillance System) forms filled in 2013 for 7,520 children (86.0% of the estimated children in this age group). The indices height-for-age (H/A), weight-for-age (W/A), weight-for-height(W/H), and body mass index-for-age (BMI/A) were calculated. Growth reference curves proposed by the World Health Organization were used to calculate z-scores. Results: the height-for-age (H/A) index presented the lowest mean z-score values, reaching -1.95 among children between 36 and 60 months. Mean z-score values for the weight-for-age (W/A) index also remained below zero. Mean z-score values for the indices weight-for-height (W/H) and body mass index-for-age (BMI/A) remained slightly above zero, reaching a maximum value of 0.5. Of all children, 45.7% presented low H/A, 9.6% presented low W/A, 4.5% presented low W/H, and 10.7% presented overweight based on BMI/A. Conclusion: our analysis show that in 2013 poor nutritional status persisted as an important health issue among these rural indigenous children.

Resumo Objetivos: caracterizar o estado nutricional de crianças indígenas menores de cinco anos, de comunidades rurais na região do Alto Solimões, habitada por sete etnias, com base em dados de dezembro de 2013. Métodos: foram extraídos dos formulários do SISVAN Indígena dados de peso e estatura, coletados em 2013, de 7.520 crianças (86,0% das crianças estimadas nesta faixa etária). Foram calculados os índices estatura-para-idade (E/I), peso-para-idade (P/I), peso-para-estatura (P/E) e índice de massa corporal para idade (IMC/I). Curvas de referência para crescimento propostas pela Organização Mundial da Saúde foram utilizadas para calcular escores z. Resultados: o índice estatura-para-idade (E/I) apresentou os menores valores médios de escore z, chegando a -1,95 nas crianças entre 36 e 60 meses. Os valores médios do escore z do índice peso-para-idade (P/I) também permaneceram abaixo de zero. Os valores médios do escore z para os índices P/E e índice de massa corporal para idade (IMC/I) mantiveram-se ligeiramente acima de zero, atingindo valor máximo de 0,5. Do total de crianças, 45,7% apresentaram baixa E/I, 9,6%, baixo P/I, 4,5% baixo P/E e 10,7% de excesso de peso de acordo com o IMC/I. Conclusão: em 2013 a desnutrição persistia como um importante agravo à saúde nessas crianças.

Temporal analysis and contextual factors associated with HIV/AIDS in Brazil from 2000 to 2019 / Análise temporal e fatores contextuais associados ao HIV/aids no Brasil entre 2000 e 2019

ABSTRACT OBJECTIVE: To describe the profile of the HIV/AIDS epidemic in Brazil and its Federation Units by gender, identify its associated contextual factors, and track changes in its epidemiological pattern from 2000 to 2019. METHODS: This is an ecological study with epidemiological data from DATASUS and population data from the Brazilian Institute of Geography and Statistics. Time-series analyses of incidence rates by gender and trends were performed by joinpoint regressions, obtaining the average annual percent change (AAPC). Then, all genders were analyzed regarding the association between AAPC and the following contextual indicators: Municipal Human Development Index (HDI-M), Gini Index, Social Vulnerability Index, illiteracy rates, proportion of late diagnosis, and proportion of test distribution. RESULTS: Incidence rates in men showed a linear decreasing trend (AAPC = −0.6; 95%CI −1.1 to 0.0). Rates in women increased from 2000 to 2009 and decreased from 2010 to 2019, tending upward throughout the period (AAPC = 1.4; 95%CI 0.8 to 1.9). Analyses by gender ratio showed a downward trend (AAPC = −1.8; 95%CI −2.3 to −1.3), indicating a reduction in the rates in men when compared to women. Indicators and the AAPC showed an inverse association for all genders, in which the HDI-M was the variable with the most pronounced association, showing that higher human development indices are associated with lower variations in HIV/AIDS rates. CONCLUSION: Case distribution differ across genders, with an upward incidence trend in women and a possible association with gender-related vulnerabilities. It is important to think about public policies that consider these dimensions.

RESUMO OBJETIVO: Descrever o perfil da epidemia de HIV/aids no Brasil e nas unidades da federação de acordo com o sexo, identificar os fatores contextuais associados e acompanhar mudanças no padrão epidemiológico entre 2000 e 2019. MÉTODOS: Estudo ecológico utilizando dados epidemiológicos do Datasus, e populacionais do Instituto Brasileiro de Geografia e Estatística (IBGE). Inicialmente foram realizadas análises de séries temporais das taxas de incidência por sexo e de tendências por regressões joinpoint, com obtenção da média da variação percentual das taxas (average annual percent change - AAPC). Posteriormente procedeu-se a uma análise, para ambos os sexos, da associação da AAPC com os indicadores contextuais Índice de Desenvolvimento Humano Municipal (IDH-M), Índice de Gini, Índice de Vulnerabilidade Social, taxa de analfabetismo, proporção de diagnóstico tardio e proporção de distribuição de testes. RESULTADOS: Observa-se tendência linear de redução nas taxas de incidência para o sexo masculino (AAPC = −0,6; IC95% −1,1 a 0,0). Para o sexo feminino, houve aumento nas taxas entre 2000 e 2009 e declínio entre 2010 e 2019, com uma tendência de incremento no período completo (AAPC = 1,4; IC95% 0,8 a 1,9). As análises por razão entre os sexos indicaram tendência de declínio (AAPC = −1,8; IC95% −2,3 a −1,3), apontando redução nas taxas para o sexo masculino em relação ao sexo feminino. Verificou-se associação inversa dos indicadores com a AAPC para ambos os sexos, sendo IDH-M a variável com associação mais pronunciada, evidenciando que maiores índices de desenvolvimento humano estão associados a menores variações nas taxas de HIV/aids. CONCLUSÃO: Os casos se distribuem de formas distintas entre os sexos, com tendência de incremento na incidência em mulheres e possível associação com vulnerabilidades relacionadas ao gênero, sendo importante pensar em políticas públicas que considerem essas dimensões.

Metastatic Grade 3 Neuroendocrine Tumor in Multiple Endocrine Neoplasia Type 1 Expressing Somatostatin Receptors.

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) may occur in 30% to 90% of patients with multiple endocrine neoplasia type 1 (MEN1). However, only 1% of GEP-NETs are grade 3 (G3). Given the rarity of these aggressive tumors, treatment of advanced G3 GEP-NETs in MEN1 is based on the treatment guidelines for sporadic GEP-NETs. We report a 43-year-old male with germline MEN1 followed at our institution, with clinical features including hyperparathyroidism, a nonfunctional pancreatic NET, and Zollinger-Ellison syndrome. On routine surveillance imaging at age 40, computed tomography/positron emission tomography imaging showed 2 arterially enhancing intraluminal masses on the medial aspect of the gastric wall. Anatomical imaging confirmed 2 enhancing masses within the pancreas and a rounded mass-like thickening along the lesser curvature of the stomach. The gastric mass was resected, and pathology reported a well-differentiated G3 NET with a Ki-67 >20%. The patient continued active surveillance. Eighteen months later cross-sectional imaging studies showed findings consistent with metastatic disease within the right hepatic lobe and bland embolization was done. On follow-up scans, including 68Ga-DOTATATE (68Ga-DOTA(0)-Tyr(3)-octreotate) imaging, interval increase in number and avidity of metastatic lesions were compatible with disease progression. Given a paucity of treatment recommendations for G3 tumors in MEN1, the patient was counseled based on standard NET treatment guidelines and recommended 177Lu-DOTATATE treatment. PRRT (peptide receptor radionuclide therapy) with 177Lu-DOTATATE (177Lu-tetraazacyclododecanetetraacetic acid-octreotide) is an important therapeutic modality for patients with somatostatin receptor-positive NETs. However, prospective studies are needed to understand the role of PRRT in G3 NETs.

Can Researchers Assess the Suitability of Datasets to Answer Their Research Questions, with Access to Metadata Only?

Health research increasingly requires effective ways to identify existing datasets and assess their suitability for research. We sought to test whether researchers could use an existing metadata catalogue to assess the suitability of datasets for addressing specified research questions. Five datasets were described in the National Institute for Health Research Health Informatics Collaborative metadata catalogue, and for each dataset five associated research questions were formulated, some of which were answerable with the dataset while others were not. Thirteen researchers each assessed whether the ten questions associated with two randomly selected datasets were answerable with the described datasets. After removing instances where participants misunderstood the question or lacked subject matter knowledge to make the assessment, we found that 87 out of 109 assessments (80%) were correct. Participants particularly struggled with one dataset which consisted of EHR data. The most common reason for incorrect assessments was the inability to find the relevant information in the metadata catalogue.

A'uwe (Xavante) views of food security in a context of monetarization of an indigenous economy in Central Brazil.

Following boom-and-bust economic cycles provoked by Brazilian governmental attempts to integrate Indigenous peoples into national society, it is approximately since the beginning of the 2000s that Brazilian Indigenous peoples came to be viewed officially as "poor" and victims of "hunger." Consequently, the national indigenist agency and other State entities started to conceive and implement diverse initiatives that ultimately injected money and resources into Indigenous communities. In 2019 we undertook an ethnographic study in three A'uwe (Xavante) communities in the Pimentel Barbosa Indigenous Reserve, Central Brazil, with the objective of analyzing how people understand and pursue food security. We propose that in the studied communities the complex network of A'uwe food reciprocity is a fundamental strategy for mitigating hunger and acute lack of food. We show that among the A'uwe, the hybrid economy that developed since the 1970s has proved resilient to dramatic transformations and uncertainty in the availability and characteristics of external government inputs.

Coping with Hypertension among Indigenous Peoples in Brazil and the Role of the Primary Care Nurse: A Critical Review from a Transcultural Perspective.

Our objective is to critically review the literature addressing the strategic role of nurses in the daily primary care of arterial hypertension in Indigenous communities in Brazil. We selected studies based on an initial keyword search of major bibliographic indexing databases for the years 2000 to 2020 and manual search. Further selection was based on topical, methodological, and thematic relevance, as well as evaluation of scholarship quality and pertinence to our chosen narrative. The literature demonstrates Indigenous peoples do not receive health services that measure up to national standards in large part due to a marked lack of academic and employer preparation for nurses operating in transcultural settings. Inequities were apparent in recurrent reports of victim-blaming, deficient clinical communication with patients, clinical malpractice, devaluation of hypertension as a problem for Indigenous peoples, insufficient intercultural training for nurses, and discrimination against Indigenous students in nursing education programs. This systemic problem needs to be addressed by universities and the Indigenous Health Care Subsystem in Brazil.

Indigenous migration patterns in Brazil based on the 2010 national demographic census: analysis and critical reflection.

Research in several Latin American countries points to violence, loss of traditional territories, and seeking education, health, and wage labor as key variables in triggering rural-urban migration among Indigenous people. This study presents an analysis of the migration patterns of Indigenous people in Brazil, compared to non-indigenous people, based on data from the most recent national census, conducted in 2010. Migration characteristics related to lifetime migration and recent migration were investigated by means of descriptive and multivariable logistic regression analyses. The findings pointed to complex mobility scenarios according to migrants' Indigenous status and geographical regions of origin and destination. Indigenous people living in urban areas presented high levels of mobility (approximately 50% lived in different municipalities from those where they were born), which were more pronounced than those of non-Indigenous people. Indigenous people living in rural areas presented the lowest levels of migration (approximately 90% residing in their municipality of birth). Statistical modeling confirmed the patterns observed in descriptive analysis, highlighting the marked mobility of Indigenous subjects in urban areas. We emphasize the limitations of using census data for characterizing Indigenous mobility profiles, although no other nationally representative data are available. The finding that the Indigenous population living in urban areas presents rates of migration higher than their non-Indigenous counterparts is particularly important for the planning and implementation of a broad range of public policies aimed at ethnic minorities in the country, including health, education, and housing initiatives.

Parathyroid Hormone Resistance and Autoantibodies to the PTH1 Receptor.

We describe two cases of acquired parathyroid hormone (PTH) resistance consequent to the development of serum PTH type 1 receptor (PTH1R) autoantibodies, which block PTH binding and signaling. Both cases were associated with other autoimmune manifestations, and one case was associated with atypical membranous glomerulonephritis. In vitro binding and signaling assays identified the presence of PTH1R-blocking IgG autoantibodies, which were not present in serum samples from patients with other renal or autoimmune disorders. (Funded by the Intramural Research Programs of the National Institute of Diabetes and Digestive and Kidney Diseases and others.).

Two distinct classes of thymic tumors in patients with MEN1 show LOH at the MEN1 locus.

Patients with the multiple endocrine neoplasia type 1 (MEN1) syndrome carry germline heterozygous loss-of-function mutations in the MEN1 gene which predisposes them to develop various endocrine and non-endocrine tumors. Over 90% of the tumors show loss of heterozygosity (LOH) at chromosome 11q13, the MEN1 locus, due to somatic loss of the wild-type MEN1 allele. Thymic neuroendocrine tumors (NETs) or thymic carcinoids are uncommon in MEN1 patients but are a major cause of mortality. LOH at the MEN1 locus has not been demonstrated in thymic tumors. The goal of this study was to investigate the molecular aspects of MEN1-associated thymic tumors including LOH at the MEN1 locus and RNA-sequencing (RNA-Seq) to identify genes associated with tumor development and potential targeted therapy. A retrospective chart review of 294 patients with MEN1 germline mutations identified 14 patients (4.8%) with thymic tumors (12 thymic NETs and 2 thymomas). LOH at the MEN1 locus was identified in 10 tumors including the 2 thymomas, demonstrating that somatic LOH at the MEN1 locus is also the mechanism for thymic tumor development. Unsupervised principal component analysis and hierarchical clustering of RNA-Seq data showed that thymic NETs formed a homogenous transcriptomic group separate from thymoma and normal thymus. KSR2 (kinase suppressor of Ras 2), that promotes Ras-mediated signaling, was abundantly expressed in thymic NETs, a potential therapeutic target. The molecular insights gained from our study about thymic tumors combined with similar data from other MEN1-associated tumors may lead to better surveillance and treatment of these rare tumors.

A'uwe (Xavante) Social Constructions of Well-Being in Central Brazil.

Well-being is a heterogeneous idea with inconsistent applicability to real-world circumstances. In this article, I explore A'uwe (Xavante) notions of social well-being from an ethnographic perspective. My data indicate many members of this Indigenous group understand wellness to involve not only health and harmony, but also certain modes of strife and inequality that are also viewed as desirable. A'uwe understandings of social wellness, including linkages to the environment, suggest that a broader and more locally contingent concept of social well-being than is evident in mainstream literature would benefit transcultural health efforts and policy involving Indigenous and other culturally distinct communities.

[Nutritional status and factors associated with stunting in children under five years of age in maroon communities in Northeast Brazil]. / Estado nutricional e fatores associados ao déficit estatural em crianças menores de cinco anos de comunidades remanescentes de quilombos do Nordeste brasileiro.

Quilombolas, or members of maroon communities in Brazil, are part of the country's ethnic/racial minorities exposed to health inequities, reflecting a historical process of harsh socioeconomic disadvantages. The study aimed to assess nutritional status and factors associated with stunting in quilombola children under five years of age living in land-deeded quilombola communities in Northeast Brazil. The study used secondary data from the Survey on Food and Nutritional Security in Land-Deeded Quilombola Communities (2011). The target outcomes were stunting (height-for-age < -2z), excess weight (weight-for-height > 2z), and underweight (weight-for-age < -2z). Chi-square test was used to assess the significance of differences between prevalence rates. Multivariate analysis used a hierarchical conceptual model on stunting. Prevalence rates for excess weight and underweight were 2.8% and 6,1%, respectively. Stunting was diagnosed in 14.1% of the sample. The hierarchical model for stunting evidenced higher prevalence rates among children without access to primary healthcare (PR = 1.63; 95%CI: 1.11; 2.41) and safe water (PR = 2.09; 95%CI: 1.42; 3.08) and those with a history of low birthweight (PR = 2.19; 95%CI: 1.33; 3.61). The high prevalence of stunting showed that the quilombola' population in the Northeast experiences unfavorable health condition, reflecting lack of access to primary healthcare and precarious sanitation.

Os quilombolas constituem parte das minorias étnico-raciais do país que apresentam iniquidades em saúde, reflexo de um processo histórico de grandes desvantagens socioeconômicas. O objetivo foi avaliar o estado nutricional e fatores associados ao déficit estatural em crianças quilombolas menores de cinco anos residentes em comunidades quilombolas tituladas na Região Nordeste do Brasil. Utilizaram-se dados secundários provenientes da Pesquisa de Avaliação da Situação de Segurança Alimentar e Nutricional em Comunidades Quilombolas Tituladas (2011). Os desfechos de interesse foram o déficit estatural (estatura-para-idade < -2z), excesso de peso (peso-para-estatura > 2z) e o déficit ponderal (peso-para-idade < -2z). Foi empregado o teste qui-quadrado para avaliar a significância das diferenças entre as prevalências. A análise multivariada considerou um modelo conceitual hierárquico sobre o déficit estatural. As prevalências de excesso de peso e déficit ponderal foram 2,8% e 6,1%, respectivamente. O déficit estatural foi diagnosticado em 14,1% da amostra. O modelo hierárquico de déficit estatural evidenciou maiores prevalências do agravo entre crianças que não tinham acesso à atenção básica (RP = 1,63; IC95%: 1,11; 2,41), à água tratada (RP = 2,09; IC95%: 1,42; 3,08) e que nasceram com baixo peso (RP = 2,19; IC95%: 1,33; 3,61). A elevada prevalência de déficit estatural mostra que a população quilombola no Nordeste apresenta condições de saúde desfavoráveis, sendo reflexo da falta de acesso à atenção básica e das precárias condições de saneamento.

Los quilombolas constituyen parte de las minorías étnico-raciales del país que presentan inequidades en salud, reflejo de un proceso histórico que implicó grandes desigualdades socioeconómicas. El objetivo del trabajo fue evaluar el estado nutricional y los factores asociados con el déficit de estatura en niños quilombolas, menores de 5 años, residentes en comunidades quilombolas, ubicadas en la Región Nordeste del Brasil. Se utilizaron datos secundarios provenientes de la Pesquisa de Avaliação da Situação de Segurança Alimentar e Nutricional em Comunidades Quilombolas Tituladas (2011). Los resultados de interés fueron: déficit de estatura (estatura-para-edad < -2z), exceso de peso (peso-para-estatura > 2z) y insuficiencia ponderal (peso-para-edad < -2z). Se empleó la prueba chi-cuadrado para evaluar la significancia de las diferencias entre las prevalencias. El análisis multivariado consideró un modelo conceptual jerárquico sobre la insuficiencia de estatura. Las prevalencias de exceso de peso y déficit ponderal fueron 2,8%, 6,1%, respectivamente. El déficit de estatura fue diagnosticado en un 14,1% de la muestra. El modelo jerárquico de déficit de estatura evidenció mayores prevalencias de enfermedades entre niños que no tenían acceso a la atención básica (RP = 1,63; IC95%: 1,11; 2,41), al agua tratada (RP = 2,09; IC95%: 1,42; 3,08) y que nacieron con bajo peso (RP = 2,19; IC95%: 1,33; 3,61). La elevada prevalencia de déficit de estatura muestra que la población quilombola en el Nordeste presenta condiciones de salud desfavorables, siendo reflejo de la falta de acceso a la atención básica en salud y de las precarias condiciones de saneamiento.

Co-Occurrence of Familial Non-Medullary Thyroid Cancer (FNMTC) and Hereditary Non-Polyposis Colorectal Cancer (HNPCC) Associated Tumors-A Cohort Study.

Familial non-medullary thyroid cancer (FNMTC) is a form of endocrine malignancy exhibiting an autosomal dominant mode of inheritance with largely unknown germline molecular mechanism. Hereditary nonpolyposis colorectal cancer syndrome (HNPCC) is another hereditary autosomal dominant cancer syndrome which, if proven to be caused by germline mutations in mismatch repair genes (MMR)-MLHL, MSH2, MSH6, PMS2, and EPCAM-is called Lynch syndrome (LS). LS results in hereditary predisposition to a number of cancers, especially colorectal and endometrial cancers. Tumors in LS are characterized by microsatellite instability (MSI) and/or loss of MMR protein expression in immunohistochemistry (IHC). MSI is a rare event in thyroid cancer (TC), although it is known to occur in up to 2.5% of sporadic follicular TC cases. There are limited data on the role of germline MMR variants FNMTC. The goal of this study was to analyze the potential clinical and molecular association between HNPCC and FNMTC. We performed a cohort study analyzing the demographic, clinical, and pathologic data of 43 kindreds encompassing 383 participants (104 affected, 279 unaffected), aged 43.5 [7-99] years with FNMTC, and performed high-throughput whole-exome sequencing (WES) of peripheral blood DNA samples of selected 168 participants (54 affected by FNMTC and 114 unaffected). Total affected by thyroid cancer members per family ranged between 2 and 9 patients. FNMTC was more prevalent in women (68.3%) and characterized by a median tumor size of 1.0 [0.2-5.0] cm, multifocal growth in 44%, and gross extrathyroidal extension in 11.3%. Central neck lymph node metastases were found in 40.3% of patients at presentation, 12.9% presented with lateral neck lymph node metastases, and none had distant metastases. Family history screening revealed one Caucasian family meeting the clinical criteria for FNMTC and HNPCC, with five members affected by FNMTC and at least eight individuals reportedly unaffected by HNPCC-associated tumors. In addition, two family members were affected by melanoma. Genome Analysis Tool Kit (GATK) pipeline was used in variant analysis. Among 168 sequenced participants, a heterozygous missense variant in the MSH2 gene (rs373226409; c.2120G>A; p.Cys707Tyr) was detected exclusively in FNMTC- HNPCC- kindred. In this family, the sequencing was performed in one member affected by FNMTC, HPNCC-associated tumors and melanoma, one member affected solely by HNPCC-associated tumor, and one member with FNMTC only, as well as seven unaffected family members. The variant was present in all three affected adults, and in two unaffected children of the affected member, under the age of 18 years, and was absent in non-affected adults. This variant is predicted to be damaging/pathogenic in 17/20 in-silico models. However, immunostaining performed on the thyroid tumor tissue of two affected by FNMTC family members revealed intact nuclear expression of MSH2, and microsatellite stable status in both tumors that were tested. Although the MSH2 p.Cys707Tyr variant is rare with a minor allele frequency (MAF) of 0.00006 in Caucasians; it is more common in the South Asian population at 0.003 MAF. Therefore, the MSH2 variant observed in this family is unlikely to be an etiologic factor of thyroid cancer and a common genetic association between FNMTC and HNPCC has not yet been identified. This is the first report known to us on the co-occurrence of FNMTC and HNPCC. The co-occurrence of FNMTC and HNPCC-associated tumors is a rare event and although presented in a single family in our large FNMTC cohort, a common genetic background between the two comorbidities could not be established.