Uma nova variante de splicing STK3/MST2 que exibe atividade de quinase reduzida e potencial clínico / A novel STK3/MST2 splicing variant displays impaired kinase activity and clinical potential

A via Hippo consiste em uma cascata de serina-treonina quinases que desempenha um papel central na transdução de sinais mecânicos. Em mamíferos, o eixo canônico da via consiste na ativação das quinases MST1 e MST2 (codificadas pelos genes STK4 e STK3, respectivamente) e LATS1 e LATS2. A ativação dos dois últimos culmina na fosforilação, retenção citoplasmática e inativação dos coativadores transcricionais YAP e TAZ. A inativação de Hippo resulta na localização nuclear de YAP/TAZ, aumento da proliferação e contribui para a transformação maligna em células epiteliais. No presente trabalho, identificamos que o exon 7, que codifica um segmento do domínio quinase de MST2, estava ausente em células malignas da glândula mamária humana, T4-2, mas não na linhagem não maligna, S1. A exclusão do exon 7 compromete a interação de MST2 com MOB1, um dos principais substratos de MST2. Ao contrário da proteína completa, a superexpressão de MST2 sem o exon 7 não resultou em aumento da morte celular, bem como, não diminuiu a proliferação celular. Esta nova variante de STK3/MST2, a qual denominamos STK3Δ7/MST2Δ7 é produto de um exon skipping e foi encontrada em amostras de tumores de pacientes, mas pouco predominante em amostras de tecidos normais. Além disso, em pacientes com câncer pancreático, a expressão STK3Δ7 resultou em menor sobrevida específica da doença. A retenção do exon 7 foi menor em tumores mais agressivos e com alto grau histológico. Em ensaio 3D, células não malignas com expressão ectópica de MST2Δ7 não respondem aos sinais inibitórios da membrana basal reconstituída e formam estruturas tumor-like. Esta nova variante perde sua atividade quinase e pode perturbar a homeostase tecidual pela incapacidade de ativar morte e inibir a proliferação celular, mesmo em microambientes repressores desses processos em células normais, como na presença membrana basal. Esses achados podem avançar o nosso conhecimento sobre progressão tumoral com possível relevância clínica

The Hippo pathway consists of a cascade of serine-threonine kinases that plays a central role in the transduction of mechanical signals. In mammals, the canonical axis of the pathway consists of the activation of the kinases MST1 and MST2 (encoded by the genes STK4 and STK3, respectively) and LATS1 and LATS2 and their activation culminates in the phosphorylation, cytoplasmic retention and inactivation of the transcriptional coactivators YAP and TAZ. Hippo inactivation results in nuclear localization of YAP/TAZ, increased cell proliferation, and contributes to malignant transformation in epithelial cells. In the present work, we identified that exon 7, which encodes a segment of the kinase domain of MST2, was absent in malignant cells of the human mammary gland, T4-2, but not in the non-malignant S1 cell line. Exclusion of exon 7 compromises the interaction of MST2 with one of its main substrates, MOB1. Unlike the full-length protein, overexpression of MST2 without exon 7 did not result in increased cell death, nor decreased cell proliferation. This new variant of STK3/MST2, which we named STK3Δ7/MST2Δ7, is the product of an exon skipping and was found in tumor samples, but seldomly found in samples of normal tissues. Furthermore, in patients with pancreatic cancer, STK3Δ7 expression resulted in lower disease-specific survival. Exon 7 retention was reduced in aggressive tumors with a high histological grade. In a 3D assay, non-malignant cells with ectopic expression of MST2Δ7, even at low concentrations, do not respond to inhibitory signals from a reconstituted basement membrane and form tumor-like structures. This new variant loses its kinase activity and may disturb the tissue homeostasis due to its inability to activate death and to inhibit cell proliferation, even in microenvironments that repress these processes in normal cells, such as the basement membrane. These findings may advance our knowledge about tumor progression and might be clinically relevant

Uma análise do projeto de educação nos documentos do MST (1990-2014): a cultura corporal em debate / n analysis of the education project in the MST documents (1990-2014): corporal culture in debate / Un análisis del proyecto educativo en los documentos del MST (1990-2014): cultura corporal en debate

No presente estudo, referenciamos o debate sobre Educação e Movimentos Sociais, através das contribuições do Movimento dos Trabalhadores Rurais Sem Terra (MST). Desse modo, buscamos apresentar mediações entre o Projeto de Educação do MST e a Cultura Corporal, a partir do seguinte problema: Se e como a Cultura Corporal está retratada no projeto de Educação do MST? O objetivo é caracterizar a concepção de Cultura Corporal com base nos textos/documentos sobre Educação sistematizados pelo MST. Para subsidiar a análise, trazemos as contribuições teóricas de Antonio Gramsci, sobre cultura, princípio educativo, escola unitária e o conceito de intelectual, bem como o Coletivo de Autores sobre a perspectiva de Cultura Corporal (AU).

In the present study, we aim to the debate on Education and Social Movements, through the contributions of the Landless Rural Workers Movement (MST). In this way, wes eek to present mediations between the MST Education Project and Corporal Culture, base don't he following problem: I fan dhow is Corporal Culture portrayed in the MST education project? The object ivies to characterize the concept of Corporal Culture from the texts/documents on education systematized by the MST. To support he analysis, we bright et he oretical contributions of Antonio Gramsci, on culture, educational principle, unitary school and the concept of intellectual, as well as the Coletivo de Autores on the perspective of Corporal Culture (AU).

En este estudio nos referimos al debate sobre Educación y Movimientos Sociales, a través de los aportes del Movimiento de Trabajadores Rurales Sin Tierra (MST). Así, buscamos presentar mediaciones entre el Proyecto Educativo MST y la Cultura Corporal, partiendo del siguiente problema: ¿Si y cómo se retrata la Cultura Corporal en el proyecto educativo MST? El objetivo es caracteriza el concepto de Cultura Corporal a partir de los textos/documentos sobre educación sistematizados por el MST. Para sustentar elanálisis, traemoslos aportes teóricos de Antonio Gramsci, sobre cultura, principio educativo, escuela unitaria y el concepto de intelectual, así como el Coletivo de Autores en la perspectiva de la Cultura Corporal (AU).

Uma análise do projeto de educação nos documentos do MST (1990-2014): a cultura corporal em debate / An analysis of the education project in the MST documents (1990-2014): corporal culture in debate / Un análisis del proyecto educativo en los documentos del MST (1990-2014): cultura corporal en debate

No presente estudo, referenciamos o debate sobre Educação e Movimentos Sociais, através das contribuições do Movimento dos Trabalhadores Rurais Sem Terra (MST). Desse modo, buscamos apresentar mediações entre o Projeto de Educação do MST e a Cultura Corporal, a partir do seguinte problema: Se e como a Cultura Corporal está retratada no projeto de Educação do MST? O objetivo é caracterizar a concepção de Cultura Corporal com base nos textos/documentos sobre Educação sistematizados pelo MST. Para subsidiar a análise, trazemos as contribuições teóricas de Antonio Gramsci, sobre cultura, princípio educativo, escola unitária e o conceito de intelectual, bem como o Coletivo de Autores sobre a perspectiva de Cultura Corporal.

In the present study, we aim to the debate on Education and Social Movements, through the contributions of the Landless Rural Workers Movement (MST). In this way, wes eek to present mediations between the MST Education Project and Corporal Culture, base don't he following problem: I fan dhow is Corporal Culture portrayed in the MST education project? The object ivies to characterize the concept of Corporal Culture from the texts/documents on education systematized by the MST. To support he analysis, we bright et he oretical contributions of Antonio Gramsci, on culture, educational principle, unitary school and the concept of intellectual, as well as the Coletivo de Autores on the perspective of Corporal Culture.

En este estudio nos referimos al debate sobre Educación y Movimientos Sociales, a través de los aportes del Movimiento de Trabajadores Rurales Sin Tierra (MST). Así, buscamos presentar mediaciones entre el Proyecto Educativo MST y la Cultura Corporal, partiendo del siguiente problema: ¿Si y cómo se retrata la Cultura Corporal en el proyecto educativo MST? El objetivo es caracterizar el concepto de Cultura Corporal a partir de los textos/documentos sobre educación sistematizados por el MST. Para sustentar el análisis, traemoslos aportes teóricos de Antonio Gramsci, sobre cultura, principio educativo, escuela unitaria y el concepto de intelectual, así como el Coletivo de Autores en la perspectiva de la Cultura Corporal.

Effects of long-term exposure to MST-312 on lung cancer cells tumorigenesis: Role of SHH/GLI-1 axis.

Replicative immortality is a key feature of cancer cells and it is maintained by the expression of telomerase, a promising target of novel therapies. Long-term telomerase inhibition can induce resistance, but the mechanisms underlying this process remain unclear. The Sonic hedgehog pathway (SHH) is an embryogenic pathway involved in tumorigenesis and modulates the transcription of telomerase. We evaluated the effects of long-term treatment of the telomerase inhibitor MST-312 in morphology, proliferation, resistance, and in the SHH pathway molecules expression levels in lung cancer cells. Cells treated for 12 weeks with MST-312 showed changes in morphology, such as spindle-shaped cells, and a shift in the distribution of F-ACTIN from cortical to diffuse. Treatment also significantly reduced cells' efficiency to form spheroids and their clonogenic potential, independently of the cell cycle and telomeric DNA content. Moreover, GLI-1 expression levels were significantly reduced after 12 weeks of MST-312 treatment, indicating a possible inhibition of this signaling axis in the SHH pathway, without hindering NANOG and OCT4 expression. Here, we described a novel implication of long-term treatment with MST-312 functionally and molecularly, shedding new light on the molecular mechanisms of this drug in vitro.

Atomistic insight into the essential binding event of ACE2-derived peptides to the SARS-CoV-2 spike protein.

The pathogenic agent of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters into human cells through the interaction between the receptor binding domain (RBD) of its spike glycoprotein and the angiotensin-converting enzyme 2 (ACE2) receptor. Efforts have been made towards finding antivirals that block this interaction, therefore preventing infection. Here, we determined the binding affinity of ACE2-derived peptides to the RBD of SARS-CoV-2 experimentally and performed MD simulations in order to understand key characteristics of their interaction. One of the peptides, p6, binds to the RBD of SARS-CoV-2 with nM affinity. Although the ACE2-derived peptides retain conformational flexibility when bound to SARS-CoV-2 RBD, we identified residues T27 and K353 as critical anchors mediating the interaction. New ACE2-derived peptides were developed based on the p6-RBD interface analysis and expecting the native conformation of the ACE2 to be maintained. Furthermore, we found a correlation between the helicity in trifluoroethanol and the binding affinity to RBD of the new peptides. Under the hypothesis that the conservation of peptide secondary structure is decisive to the binding affinity, we developed a cyclized version of p6 which had more helicity than p6 and approximately half of its KD value.

Effects of in vitro short- and long-term treatment with telomerase inhibitor in U-251 glioma cells.

BACKGROUND: The inhibition of the enzyme telomerase (TERT) has been widely investigated as a new pharmacological approach for cancer treatment, but its real potential and the biochemical consequences are not totally understood. OBJECTIVE: Here, we investigated the effects of the telomerase inhibitor MST-312 on a human glioma cell line after both short- and long-term (290 days) treatments. METHODS: Effects on cell growth, viability, cell cycle, morphology, cell death and genes expression were assessed. RESULTS: We found that short-term treatment promoted cell cycle arrest followed by apoptosis. Importantly, cells with telomerase knock-down revealed that the toxic effects of MST-312 are partially TERT dependent. In contrast, although the long-term treatment decreased cell proliferation at first, it also caused adaptations potentially related to treatment resistance and tumor aggressiveness after long time of exposition. CONCLUSIONS: Despite the short-term effects of telomerase inhibition not being due to telomere erosion, they are at least partially related to the enzyme inhibition, which may represent an important strategy to pave the way for tumor growth control, especially through modulation of the non-canonical functions of telomerase. On the other hand, long-term exposure to the inhibitor had the potential to induce cell adaptations with possible negative clinical implications.

Novel Approach Sizing and Routing of Wireless Sensor Networks for Applications in Smart Cities.

Citizens are expected to require the growth of multiple Internet of Things (IoT) -based applications to improve public and private services. According to their concept, smart cities seek to improve the efficiency, reliability, and resilience of these services. Consequently, this paper searches for a new vision for resolving problems related to the quick deployment of a wireless sensor network (WSN) by using a sizing model and considering the capacity and coverage of the concentrators. Additionally, three different routing models of these technology resources are presented as alternatives for each WSN deployment to ensure connectivity between smart meters and hubs required for smart metering. On the other hand, these solutions must reduce costs when this type of wireless communication network is deployed. The present work proposes various optimization models that consider the physical and network layers in order to integrate different wireless communication technologies, thus reducing costs in terms of the minimum number of data aggregation points. Using a heterogeneous wireless network can reduce resource costs and energy consumption in comparison to a single cellular technology, as proposed in previous works. This work proposes a sizing model and three different models for routing wireless networks. In each case, constraints are evaluated and can be associated with different real-world scenarios. This document provides an optimization model that encompasses all of the proposed constraints; due to the combinatorial nature of the problem, this would require a heuristic technique.

Multispacer Sequence Typing for Mycobacterium bovis Genotyping.

The molecular typing of Mycobacterium bovis, which causes bovine tuberculosis, can be accomplished by combining different polymorphic markers, contributing to its epidemiological investigation. Multispacer sequence typing (MST) is a sequencing-based method that employs intergenic regions susceptible to higher mutation rates given the low selection pressure. It has been applied to M. tuberculosis, but not to M. bovis. The aim of this study was to evaluate a MST for M. bovis. A total of 58 strains isolated from tissues with lesions suggestive of bovine tuberculosis, coming from cattle herds in six Brazilian states and four standard samples of M. bovis were typified employing the MST technique. Fourteen intergenic regions were used, and four types of genetic events were reported: single nucleotide mutation (SNP), insertion, deletion, and tandem repeat (TR). Seven loci were chosen for typing. Twenty-eight type sequences (ST) were identified, indicating type sequences (ST) were identified, indicating a 92.9% HGDI (Hunter Gaston Discriminatory Index). The data were used to analyze the evolutionary patterns of these isolates and correlate them to phylogeographic lineages based on the formation of clonal complexes generated from eBURST software. Later, we associated the MST with spoligotyping technique, currently considered the gold standard for classification of M. bovis. The results support the MST as an alternative method for genotyping of M. bovis. The method has the advantage of sequencing and the availability of sequences analyzed in public databases, which can be used by professionals around the world as a tool for further analysis. This was the first study to identify the variability of isolates of M. bovis by the MST method.

Capybara and Brush Cutter Involvement in Q Fever Outbreak in Remote Area of Amazon Rain Forest, French Guiana, 2014.

We investigated a Q fever outbreak that occurred in an isolated area of the Amazon Rain Forest in French Guiana in 2014. Capybara fecal samples were positive for Coxiella burnetii DNA. Being near brush cutters in use was associated with disease development. Capybaras are a putative reservoir for C. burnetii.

Fecal pollution source tracking and thalassogenic diseases: The temporal-spatial concordance between maximum concentrations of human mitochondrial DNA in seawater and Hepatitis A outbreaks among a coastal population.

Fecal pollution source tracking (FST) studies the origin of fecal contamination and promotes action to eliminate it to improve human health and environmental sustainability. This work presents the temporal and spatial relations of human mitochondrial DNA (HmtDNA), fecal coliforms (FC) and live microbial biomass (ATP) in seawater during a hepatitis A outbreak among a human coastal population. The study area is approximately 100 km along the coastline of the Biobío Region in the southeastern Pacific (Humboldt Current System, Chile). Total data from the swash zone from summer 2015 to autumn 2016 show there were significant positive log-log correlations between FC and HmtDNA (R = 0.32) and ATP (R = 0.31). These correlations were highest during the austral spring of 2015 (R = 0.53 and 0.58 respectively), when HmtDNA also correlated significantly with ATP (R = 0.86). Maximum average values of the parameters measured in this season showed a temporal-spatial concordance with the peak in the number of hepatitis A cases among the nearby coastal population. FC correlated significantly with HmtDNA (R = 0.98) in the water column of the coastal zone close to Concepción Bay during the austral summer of 2016 and in the swash zone of the bay (R = 0.68) throughout the study period. Hepatitis A virus (HAV) has also been detected in organisms and seawater in Concepción Bay, which is consistent with the high incidence of hepatitis A among the coastal population. The concordance between human fecal pollution in the study area and a seasonal hepatitis A outbreak strongly suggests that HmtDNA and its relation with FC and ATP in the coastal zone of marine environments can be used as a proxy to evaluate the risk of outbreaks of thalassogenic diseases.

Microbial Source Tracking Analysis Using Viral Indicators in Santa Lucía and Uruguay Rivers, Uruguay.

The aim of this study was to determine the origin (human, bovine or porcine) and the concentration of the fecal sources of contamination in waters from Santa Lucía basin and Uruguay River in Uruguay by using host-specific viral markers (adenoviruses and polyomaviruses) as microbial source tracking (MST). Between June 2015 and May 2016, monthly collections of surface water samples were performed in six sites in Santa Lucía basin and four sites in Uruguay River (n = 120 samples). Viral concentration was carried out using an absorption-elution method. Detection and quantification of human and porcine adenovirus (HAdV and PAdV, respectively) and human and bovine polyomavirus (HPyV and BoPyV, respectively) were performed by quantitative PCR (qPCR). To evaluate the infectivity of circulating HAdV, an integrated cell culture-qPCR (ICC-qPCR) was used. A logistic regression analysis was carried out to estimate the influence of environmental variables on the virus presence in surface waters. Overall, HAdV was the prevalent (18%; 21/120) followed by BoPyV (11%; 13/120) and HPyV (3%; 3/120), whereas PAdV was not detected in this study. The mean concentration ranged from 1.5 × 104 genomic copies/L (gc/L) for HAdV to 1.8 × 102 gc/L for HPyV. Infective HAdVs were observed in two out of ten analyzed samples. A significant effect of environmental temperature (p = 0.001) and river (p = 0.012) on the presence of human viruses was found. These results suggest that fecal contamination could affect the water quality of these rivers, showing deficiencies in the procedure of sewage discharge from regional cities, livestock and dairy farms.

Long-term in vitro treatment with telomerase inhibitor MST-312 induces resistance by selecting long telomeres cells.

Telomerase is a good target for new anticancer drug development because it is present in over 85% of human tumours. However, despite chronic therapy is a condition for anti-telomerase approach, the effects of long-term treatment with telomerase inhibitors remain not well understood. In this work, it was evaluated the effects of long-term treatment of human MDA-MB-231 breast cancer cells with the telomerase inhibitor MST-312. Cells were treated for 72 hours or 140 days, and it was accessed their viability, proliferation rate, morphology, telomeric DNA content, and resistance mechanism. The drug had a clear short-term effect, including chemosensitizing cells for docetaxel and irinotecan, but the chronic exposition led to selection of long telomeres clones, changing characteristics of original cell line. This effect was confirmed in a clonal culture with homogenous karyotype. MRP-1 expression and alternative lengthening of telomeres (ALT) were discarded as additional mechanisms of resistance. This data suggest that, considering the intra-tumour heterogeneity (ITH), what is already a big challenge for treatment of cancer, chronic exposition to telomerase inhibitors can promote tumour adaptations with potential clinical repercussion, drawing attention to ongoing clinical trials and pointing important considerations most times neglected on studies about use of these inhibitors on cancer therapy. SIGNIFICANCE OF THE STUDY: Antitumour action of telomerase inhibitors is well known, but it depends on a long-term exposition because cells will undergo telomere erosion only after many duplication cycles. Recently, the frustrating results of clinical trials with these inhibitors aroused the interest of the scientific community to understand the mechanisms of resistance to anti-telomerase therapy. In this study, we conducted an 18-week experiment to show that telomerase inhibition can lead to cell adaptations and selection of long-telomeres clones, leading to acquisition of resistance. However, we also showed that this inhibitor can sensitize cells to the chemotherapeutic drugs docetaxel and irinotecan.

Clinical and economic outcomes associated with malnutrition in hospitalized patients.

BACKGROUND & AIMS: Hospitalized patients show a high rate of malnutrition, which is associated with poor patient outcomes and high healthcare costs. However, relatively few studies have investigated the association between clinical and economic outcomes and malnutrition in hospitalized patients, particularly those with cardiac and pulmonary conditions. METHODS: This multicenter prospective observational cohort study included 800 patients hospitalized at four Colombian hospitals with a diagnosis of congestive heart failure, acute myocardial infarction, community-acquired pneumonia, or chronic obstructive pulmonary disease. All patients were screened for malnutrition using the Malnutrition Screening Tool (MST). A descriptive analysis of baseline variables was followed by multivariate analysis and inverse probability weighting (IPW) to compare the clinical outcomes, i.e., length of stay (LOS), mortality, and readmission, and hospital costs associated with a positive MST result. RESULTS: The prevalence of a positive MST result was 24.62% (n = 197) and was more common in patients with older age and greater comorbidities. Multivariate analysis controlling for age, gender, healthcare plan, university degree, hospitalization, entrance disease and Charlson co-morbidity index showed that a positive MST result was associated with increased LOS (1.43 ± 0.61 days) and both in-hospital mortality (odds ratio, 2.39) and global mortality (odds ratio, 2.52). IPW analysis confirmed the association between a positive MST result and increased hospital LOS and 30-day mortality, as well as a relative increase of 30.13% in the average cost associated with hospitalization. CONCLUSIONS: This study of hospital inpatients demonstrated a high burden of malnutrition at the time of hospital admission, which negatively impacted LOS and mortality and increased the costs of hospitalization. These findings underscore the need for improved diagnosis and treatment of hospital malnutrition to improve patient outcomes and reduce healthcare costs.

Acute effects of photobiomodulation therapy (PBMT) combining laser diodes, light-emitting diodes, and magnetic field in exercise capacity assessed by 6MST in patients with COPD: a crossover, randomized, and triple-blinded clinical trial.

Chronic obstructive pulmonary disease (COPD) is characterized by dyspnea, as well as musculoskeletal and systemic manifestations. Photobiomodulation therapy (PBMT) with use of low-level laser therapy (LLLT) and/or light-emitting diode therapy (LEDT) is an electrophysical intervention that has been found to minimize or delay muscle fatigue. The aim of this study was to evaluate the acute effect of PBMT with combined use of lasers diodes, light-emitting diodes (LEDs), magnetic field on muscle performance, exercise tolerance, and metabolic variables during the 6-minute stepper test (6MST) in patients with COPD. Twenty-one patients with COPD (FEV1 46.3% predicted) completed the 6MST protocol over 2 weeks, with one session per week. PBMT/magnetic field or placebo (PL) was performed before each 6MST (17 sites on each lower limb, with a dose of 30 J per site, using a cluster of 12 diodes 4 × 905 nm super-pulsed laser diodes, 4 × 875 nm infrared LEDs, and 4 × 640 nm red LEDs; Multi Radiance Medical™, Solon, OH, USA). Patients were randomized into two groups before the test according to the treatment they would receive. Assessments were performed before the start of each protocol. The primary outcomes were oxygen uptake and number of steps, and the secondary outcome was perceived exertion (dyspnea and fatigue in the lower limbs). PBMT/magnetic field applied before 6MST significantly increased the number of steps during the cardiopulmonary exercise test when compared to the results with placebo (129.8 ± 10.6 vs 116.1 ± 11.5, p = 0.000). PBMT/magnetic field treatment also led to a lower score for the perception of breathlessness (3.0 [1.0-7.0] vs 4.0 [2.0-8.0], p = 0.000) and lower limb fatigue (2.0 [0.0-5.0] vs 4.0 [0.0-7.0], p = 0.001) compared to that with placebo treatment. This study showed that the combined application of PBMT and magnetic field increased the number of steps during the 6MST and decreased the sensation of dyspnea and lower limb fatigue in patients with COPD.

New Genotypes of Coxiella burnetii Circulating in Brazil and Argentina.

Coxiella burnetii, the zoonotic agent of Q fever, has a worldwide distribution. Despite the vast information about the circulating genotypes in Europe and North America, there is a lack of data regarding C. burnetii strains in South America. Here, we show the presence of novel multispacer sequence typing (MST) genotypes of C. burnetii in two clusters detected in Brazil and Argentina that seem to be distant in parenthood. Argentinian strains isolated from a tick belongs to a new phylogenetic branch of C. burnetii, and the Brazilians strains may be related to MST 20 and 61. Multilocus variable number tandem repeats analysis (MLVA) typing provided a deeper resolution that may be related to host clusters of bovines, caprine, ovine, and ticks. Our results corroborate with the reports of geotypes of C. burnetii. Thus, we highlight the need for more genotyping studies to understand the genetic diversity of C. burnetii in South America and to confirm the hypothesis of host-related genotypes. We also emphasize the importance of virulence studies for a better understanding of Q fever in the region, which may help in surveillance and disease prevention programs.

Risk of malnutrition and emotional distress as factors affecting health-related quality of life in patients with resected cancer.

INTRODUCTION: This study analyzes the prevalence of malnutrition, depression, anxiety, and somatization and which factor has the biggest effect on quality of life (QoL) in individuals with resected cancer. METHODS: A prospective study was conducted among 747 participants. Participants completed the EORTC-QLQ30, MST, and BSI-18 questionnaires. RESULTS: Prevalence for risk of malnutrition, depression, anxiety, and somatization were 36.4%, 35.5%, 35.2%, and 48.8%, respectively. Hierarchical multiple regression analyses revealed that malnutrition risk, somatization, depression, and anxiety accounted for 50.8% of the variance in functional scale, 45.3% in symptom scale, and 52.2% in global health. Malnutrition, somatization, depression, and anxiety displayed high explanatory power on all health-related QoL (HRQoL) scales. CONCLUSION: The risk of malnutrition and psychological symptoms is strongly associated with HRQoL in cancer patients; thus, medical oncologists should develop effective interventions that contribute to lowering the risk of malnutrition and psychological distress, thereby improving subjects' HRQoL before initiating adjuvant chemotherapy.

A ciranda infantil na visão de crianças de um assentamento rural vinculado ao MST / The children’s ciranda by the view of children from a rural settlement linked to the landless workers’ movement (MST) / La ciranda infantil desde la mirada de niños de un asentamiento rural del MST

A pesquisa objetivou compreender as significações de crianças de um assentamento rural vinculado ao MST, na região de Ribeirão Preto-SP, acerca de um espaço/tempo especificamente a elas destinado, denominado Ciranda Infantil. Utilizamos como instrumentos diário de campo, fotografias realizadas pelas crianças, conversas baseadas em fotografias, fantoches. Participaram seis crianças de 10 a 12 anos. Os resultados indicam que a Ciranda tem sido significada pelas crianças como um espaço de socialização e aprendizagens variadas entre adultos e crianças, marcadas pela construção de relações afetivas, socioambientais e geracionais, com destaque para a ludicidade. Conclui-se que as crianças percebem que existe para elas um projeto intencional e apropriam-se desse espaço como sujeitos críticos que colaboram em sua construção e, ou, disputam-no com os adultos. Esse sentimento de ter a Ciranda como espaço próprio os autoriza a propor melhorias para sua realização.

This research aimed to understand the meanings yielded by children of a rural settlement linked to the Landless Workers’ Movement (MST), in the region of Ribeirão Preto (SP, Brazil), about a space/time assigned specifically to them, called Children’s Ciranda. As methodological instruments, we used field diary, photographs taken by the children; conversations based on the photographs; and puppets. Six children aged from ten to twelve years participated. The results indicate that "Ciranda" has been signified by children as a space of socialization and varied learnings among adults and children, marked by the construction of affective, socio-environmental and generational relations, highlighting playfulness. We conclude that children realize that there is an intentional project for them and they take property of this space as critical subjects who collaborate in its construction and / or compete with adults. This feeling of having the “Ciranda” as their own space authorizes them to propose improvements to its realization.

La investigación tuvo como objetivo comprender los significados de los niños de un asentamiento rural vinculado al MST, en Ribeirão Preto (SP), acerca de un espacio / tiempo destinado específicamente hacia ellos, llamado "Ciranda Infantil". Se utilizó como instrumentos: diario de campo; fotografías tomadas por los niños; conversaciones acerca de las fotografías y marionetas. Participaron seis niños de diez a doce años. Los resultados indican que la "Ciranda" ha sido significada por los niños como un espacio de socialización y aprendizajes variados entre adultos y niños, así como marcada por la construcción de relaciones afectivas, ambientales y generacionales, destacando su carácter lúdico. Llegamos a la conclusión de que los niños perciben que este espacio fue creado para ellos y se apropian de ello como sujetos críticos que colaboran en su construcción y / o la disputan con los adultos. Y esta sensación de tener la "Ciranda" como un espacio suyo les autoriza a proponer mejoras para su realización.

Despite Being "Known, Highly Promiscuous and Active": Presumed Heterosexuality in the USPHS's STD Inoculation Study, 1946-48.

The Sexually Transmitted Disease Inoculation Study of the United States Public Health Service (USPHS) was a short-term deliberate exposure experiment into the prevention of venereal diseases. Between 1946 and 1948, over 1,300 Guatemalan prisoners, psychiatric patients, soldiers, and sex workers were exposed to syphilis, gonorrhoea, and chancroid. USPHS researchers initially proposed hiring sex workers to "naturally" transmit venereal diseases to male subjects who would then be given various prophylaxes. The researchers were interested in studying the effectiveness of new preventative measures. In other words, the USPHS study was designed to transmit venereal diseases heterosexually from an "infected" female body to the men who, it was assumed, were sexually isolated subjects. However, the researchers did record instances of male-to-male disease transmission among their subject populations, instances that challenged the presumption of heterosexuality on which the study was based.

Oficinas com adolescentes do MST: sexualidade, diversidade sexual e gênero / Workshops with MST teenagers: sexuality, sexual diversity and gender / Talleres con adolescentes DEL MST: sexualidad, diversidad sexual y género

O objetivo do presente artigo é apresentar as oficinas sobre sexualidade, diversidade sexual e gênero, realizadas em uma escola de agroeocologia do Movimento dos Trabalhadores Rurais Sem Terra (MST). Participaram 36 adolescentes e jovens, com idade entre 15 e 24 anos, da mesma turma do curso de agroecologia. A demanda que nos foi endereçada, tanto pelos educandos como pela coordenação da escola, foi trabalhar com o tema sexualidade. Realizamos 15 encontros semanais no ano de 2015, com 2 horas de duração, com os seguintes temas geradores: gênero e relacionamentos abusivos, diversidade sexual, infecções sexualmente transmissíveis e métodos contraceptivos. As técnicas utilizadas foram variadas: dinâmicas de grupo, mitos e verdades, exibição e discussão de filmes (curtas e longas). Nas oficinas, trabalhamos de uma forma dinâmica, esclarecendo dúvidas, proporcionando experiências e situações que estimulassem a reflexão e a expressão de vivências, para superar o enfoque do binômio saúde-doença.

The aim of this article is to present the workshops about sexuality, sexual diversity and gender, performed in an agroecology school of the Landless Workers' Movement (MST). The participants were 36 adolescents and young, aged 15 to 24 years, from the same class of the agroecology course. The demand addressed to us, both by the students and by the coordination of the school, was approaching the sexuality theme. We performed 15 weekly meetings during the year 2015, with the duration of 2 hours each, about the following generating themes: gender and abusive relationships, sexual diversity, sexually transmitted diseases and contraceptive methods. Different techniques were used, such as: group dynamics, myths and truths, exhibition and discussion of short and long films. In the workshops, we pursued a dynamical working method, clarifying doubts, providing experiences and situations that stimulate reflection and sharing of experiences, in order to overcome the health-disease binomial approach.

El objetivo del presente artículo es presentar los talleres sobre sexualidad, diversidad sexual y género, realizados en una escuela de agroecología del Movimiento de los Trabajadores Rurales Sin Tierra (MST). Los participantes fueron 36 adolescentes y jóvenes, con edades entre 15 a 24 años, de la misma clase del curso de agroecología. La demanda que nos ha sido dirigida, tanto por los alumnos como por la coordinación de la escuela, fue trabajar con el tema sexualidad. Realizamos 15 encuentros semanales en el año 2015, con 2 horas de duración, con los siguientes temas generadores: género y relación abusiva, diversidad sexual, enfermedades sexualmente transmisibles y métodos anticonceptivos. Las técnicas utilizadas fueron variadas: dinámica de grupo, mitos y verdades, exhibición y discusión de películas (corto y largometraje). En los talleres, propusimos trabajar de un modo dinámico, aclarando dudas, proporcionando vivencias y situaciones para fomentar la reflexión y la expresión de experiencias, buscando superar el enfoque del binomio salud-enfermedad.

Characterization of the clonal subpopulation Fiocruz L1-130 of Leptospira interrogans in rats and dogs from Brazil.

PURPOSE: Leptospira interrogans serogroup Icterohaemorrhagiae strains have been described as causing disease in both humans and animals and as being present worldwide. Icterohaemorrhagiae and Copenhageni serovars are known to cause severe disease in their hosts, and zoonotic outbreaks have been described. The genetic similarity among the strains of these serovars is known. However, it has not yet been demonstrated whether major clonal subpopulation in humans, strain Fiocruz L1-130-like, can circulate among other hosts. METHODOLOGY: We performed genetic characterization of Brazilian serogroup Icterohaemorrhagiae strains of dog and rat origin by secY sequencing, variable-number tandem-repeat, multilocus sequence type and multi-spacer typing analysis. RESULTS: The strains were found to be identical among themselves and to strain Fiocruz L1-130. We suggest that the major strain of L. interrogans serogroup Icterohaemorrhagiae, Fiocruz L1-130, is widely distributed in Brazil in different hosts with substantial zoonotic potential. CONCLUSION: Understanding the circulation of strain Fiocruz L1-130 is important for the implementation of appropriate control measures. Its circulation highlights the need to treat leptospirosis caused by L. interrogans serogroup Icterohaemorrhagiae as a zoonosis that acts in the human-animal-environment interface, as per the One Health approach.