A Fucose-Containing Sulfated Polysaccharide from Spatoglossum schröederi Potentially Targets Tumor Growth Rather Than Cytotoxicity: Distinguishing Action on Human Melanoma Cell Lines.

Natural substances are strategic candidates for drug development in cancer research. Marine-derived molecules are of special interest due to their wide range of biological activities and sustainable large-scale production. Melanoma is a type of skin cancer that originates from genetic mutations in melanocytes. BRAF, RAS, and NF1 mutations are described as the major melanoma drivers, but approximately 20% of patients lack these mutations and are included in the triple wild-type (tripleWT) classification. Recent advances in targeted therapy directed at driver mutations along with immunotherapy have only partially improved patients' overall survival, and consequently, melanoma remains deadly when in advanced stages. Fucose-containing sulfated polysaccharides (FCSP) are potential candidates to treat melanoma; therefore, we investigated Fucan A, a FCSP from Spatoglossum schröederi brown seaweed, in vitro in human melanoma cell lines presenting different mutations. Up to 72 h Fucan A treatment was not cytotoxic either to normal melanocytes or melanoma cell lines. Interestingly, it was able to impair the tripleWT CHL-1 cell proliferation (57%), comparable to the chemotherapeutic cytotoxic drug cisplatin results, with the advantage of not causing cytotoxicity. Fucan A increased CHL-1 doubling time, an effect attributed to cell cycle arrest. Vascular mimicry, a close related angiogenesis process, was also impaired (73%). Fucan A mode of action could be related to gene expression modulation, in special ß-catenin downregulation, a molecule with protagonist roles in important signaling pathways. Taken together, results indicate that Fucan A is a potential anticancer molecule and, therefore, deserves further investigation.

Strategies to improve the home care of periodontal disease in dogs: A systematic review.

The expected contribution of this study is to have a complete view of the available products used in the prevention of periodontal disease in dogs. The related studies in databases including Web of Science, Science Direct, and Scopus, from 1992 to 2021, were retrieved, and 36 studies were used in the systematic review. Among the continents researched, North America proved to have the most developed research relating to the subject. The active ingredients researched, isolated, or compared to each other, were polyphosphates > phytogenics > chlorhexidine > enzymes > vitamin C > xylitol = adelmidrol = and probiotics. The form of use of active products was chewable > solution via water = via food > biscuits > paste and gels > mucoadhesive. Gingivitis index was the most studied parameter used to assess oral health. According to the evidence recovered in the systematic review was possible to conclude that products with different active agents and forms of use demonstrated positive effects in the prevention of periodontal diseases. The results of this study summarize the most frequently used active ingredients and application forms for cleaning dogs' teeth and provide a roadmap for future research on the maintenance of oral health in dogs.

"Ela não pode ser pai?": um estudo sobre a transparentalidade a partir de três casos de mulheres trans / "Can't she be a father?": a study on transparenting based on three cases of trans women

Este trabalho analisa vivências parentais de mulheres trans, e utiliza a categoria analítica de transparentalidade. As pessoas trans, bem como as suas vidas, as suas percepções de si e os seus relacionamentos, principalmente com seus familiares, são inquestionavelmente marcados por um dos valores hegemonicamente estabelecidos na sociedade brasileira, chamado neste trabalho de cisheteronormatividade compulsória. Em paralelo a isso, o rápido avanço de tecnologias de comunicação das últimas décadas permitiu que cada vez mais pessoas acessassem internet, canais de televisão e outras ferramentas que viabilizam o conhecimento de diversas e diferentes informações e concepções de mundo, portanto de possibilidades de ser e estar no mundo. Essa maior acessibilidade torna mais visíveis as narrativas acerca das experiências de vidas não hegemônicas, como as de pessoas trans, que são representadas até hoje quase que exclusivamente pelos vieses e falas de pessoas cisgêneras. Tais representações são muito recorrentemente pejorativas, reiterando estigmas a elas associados, de abjetas, pecaminosas, doentias, criminosas, sofridas, vítimas, anormais, controversas e desprovidas de autonomia; e salientando vínculos de pessoas trans com temáticas de HIV/AIDS, prostituição, violência, criminalidade e marginalização. No entanto, desde os anos finais do século XX, as pessoas trans estão gozando de alguma possibilidade de falar por conta própria e de si próprias, quando, por exemplo, são convidadas a participar de documentários e programas de auditório de televisão, ou quando publicam vídeos e textos com seus próprios relatos e reflexões na internet. E este trabalho pretende analisar esses registros públicos dessas narrativas sobre mulheres trans que foram feitas por elas mesmas, enaltecendo suas falas. Mais especificamente, serão analisados os registros que tratam de casos de mulheres trans que exercem a parentalidade e em tais registros falam sobre como a transparentalidade afeta suas experiências de vida, suas identidades e seus relacionamentos. Cabe ressaltar que este trabalho é feito a partir da perspectiva de uma pesquisadora que também se configura como uma pessoa trans, que em sua subjetividade se enuncia como uma mulher transgênera não binária. Sem a pretensão de esgotar a discussão do tema com respostas que se presumam universalizantes ou desmistificadoras, busca-se levantar questões que permitam pensar como mulheres trans experimentam a parentalidade, por exemplo, ao enunciar a si mesmas como pais de seus filhos, numa peculiar forma de autoafirmação que foge a uma perspectiva binária de gênero, imposta pela cisheteronormatividade compulsória. Para tanto, será feita uma pesquisa qualitativa que se baseia na análise de registros textuais e audiovisuais que se encontram disponíveis para acesso público acerca de três mulheres trans. Tais registros consistem em documentários, entrevistas, participações em programas de auditório, falas em congressos, publicações textuais e autobiografias, nos quais tais mulheres trans e seus parentes dão relatos de suas vivências e percepções de mundo a respeito da temática da transparentalidade e questões outras que atravessem tal tema. Buscamos verificar a existência de tensão entre a trajetória de construção de identidade de gênero e as vivências parentais dessas mulheres trans que, concluímos, vivenciam uma parentalidade hierarquizada que nomeamos de parentalidade curinga.

This work analyzes parenting experiences of trans women, and uses the analytical category of transparenting. Trans people, as well as their lives, their perceptions of themselves and their relationships, especially with their families, are unquestionably marked by one of the hegemonically established values ​​in Brazilian society, called in this work compulsory cisheteronormativity. In parallel to this, the rapid advancement of communication technologies in recent decades has allowed more and more people to access the internet, television channels and other tools that enable the acquisition of diverse information and worldviews, therefore making it possible to live different lives. This greater accessibility makes narratives about non-hegemonic life experiences more visible, such as those of trans people, which are represented until today almost exclusively by the biases and speeches of cisgender people. Such representations are recurrently pejorative, reiterating stigmas associated with trans people, such as: abject, sinful, sick, criminal, victims and devoid of autonomy. These representations also reiterate the link between trans people and subjects such as HIV/AIDS, prostitution, violence, criminality and marginalization. However, since the final years of the 20th century, trans people have been enjoying some possibility of speaking on their own and about themselves, when, for example, they are invited to participate in documentaries and television auditorium programs, or when they publish videos and texts with their own reports and reflections on the internet. And this work intends to praise the speeches of trans women, by analyzing these public records of these narratives about trans women that were made by themselves. This work will analyze records dealing with cases of trans women who exercise parenthood, in which they talk about how transparenting affects their life experiences, their identities and their relationships. It should be noted that this work is done from the perspective of a researcher who also configures herself as a trans person, who enunciates herself as a non-binary trans woman. Without intending to exhaust the discussion of the subject with answers that are presumed to be universal or demystifying, the aim of this work is to raise questions that allow thinking about how trans women experience parenthood, for example, when enunciating themselves as fathers of their children, in a peculiar way of self-affirmation that escapes a binary perspective of gender, imposed by compulsory cisheteronormativity. A qualitative research will be carried out based on the analysis of textual and audiovisual records that are available for public access about three trans women. Such records consist of documentaries, interviews, participation in auditorium programs, speeches at congresses, textual publications and autobiographies, in which such trans women and their relatives give reports of their experiences and perceptions of the world regarding the theme of transparenting and other themes that relate to this topic. We seek to verify the existence of tension between the trajectory of construction of gender identity and the parenting experiences of these trans women who, we conclude, experience a hierarchical parenting that we call joker parenting.

Motivos para el ingreso en el posgrado stricto sensu - una investigación con estudiantes de una IES pública / Motivos para o ingresso na pós-graduação stricto sensu - uma pesquisa com estudantes de uma ies pública / Reasons for entering the stricto sensu postgraduate course - a survey with students from a public hei

No mundo gerido pelas relações de trabalho, a escolha por realizar um curso após a conclusão da graduação vislumbra possíveis perspectivas em termos profissionais. Fundamentada na Psicologia Histórico-Cultural, a pesquisa aqui apresentada teve como objetivo conhecer os motivos relatados por estudantes de pós-graduação stricto sensu da Universidade Federal de Uberlândia (UFU) para o ingresso no curso. De caráter quali-quanti, o estudo envolveu aplicação de questionário on-line, pela Plataforma SurveyMonkey, respondido por 374 estudantes de 36 programas de mestrado e doutorado. A análise de dados foi realizada por meio do Statistical Package for Social Sciences (SPSS) e da análise de conteúdo e propiciou a organização das respostas em quatro eixos de análise: a) Carreira acadêmica; b) Qualificação profissional para inserção no mercado de trabalho e aumento salarial; c) Aprofundar conhecimentos / Pesquisa, d) Questões pessoais/ Falta de opção. Os processos de aprendizagem e desenvolvimento precisam ser compreendidos e mediados por ações pedagógicas intencionalmente elaboradas e destinadas a esse público na universidade. Além disso, o motivo gerador de sentido para a realização de um mestrado ou doutorado precisa vincular-se ao significado social da pós-graduação de modo ampliado, visando à formação e à emancipação humana.

En el mundo dirigido por las relaciones de trabajo, la elección por realizar un curso tras la conclusión de la graduación vislumbra posibles perspectivas en términos profesionales. Fundamentada en la Psicología Histórico-cultural, la investigación aquí presentada tuvo como objetivo conocer los motivos relatados por estudiantes de posgrado stricto sensu de la Universidad Federal de Uberlândia (UFU) para el ingreso en el curso. De carácter cuali-cuanti, el estudio abarcó aplicación de cuestionario on-line, por la Plataforma SurveyMonkey, contestado por 374 estudiantes de 36 programas de maestría y doctorado. El análisis de datos se realizó por intermedio del Statistical Package for Social Sciences (SPSS) y del análisis de contenido y propició la organización de las respuestas en cuatro ejes de análisis: a) Carrera académica; b) Cualificación profesional para inserción en el mercado laboral y aumento salarial; c) Profundizar conocimientos / Pesquisa, d) Cuestiones personales/ Falta de opción. Los procesos de aprendizaje y desarrollo necesitan ser comprendidos y mediados por acciones pedagógicas intencionalmente elaboradas y destinadas a ese público en la universidad. Además de eso, el motivo generador de sentido para la realización de un curso de maestría o doctorado necesita vincularse al significado social del posgrado de modo ampliado, visando la formación y a la emancipación humana.

In the world managed by labor relations, choosing to take a course after completing graduation envisions possible perspectives in professional terms. Based on Historical-Cultural Psychology, the research presented here aimed to know the reasons reported by stricto sensu graduate students at the Federal University of Uberlândia (UFU) for entering the course. It is a quali-quanti nature study, which involved the application of an online questionnaire, through the SurveyMonkey Platform, answered by 374 students from 36 master's and doctoral programs. Data analysis was carried out using the Statistical Package for Social Sciences (SPSS) and content analysis and allowed the organization of responses into four axes of analysis: a) Academic career; b) Professional qualification for insertion in the labor market and salary increase; c) Deepening knowledge / Research, d) Personal issues / Lack of options. The learning and development processes need to be understood and mediated by pedagogical actions intentionally designed and aimed at this public at the university. In addition, the reason that generates meaning for pursuing a master's or doctorate needs to be linked to the social meaning of postgraduate studies in an expanded way, aiming at training and human emancipation.

Neurological and Psychiatric Disorders in Patients with Rheumatic Heart Disease: Unveiling what is Beyond Cardiac Manifestations.

Background: Rheumatic heart disease (RHD) is the most serious manifestation of rheumatic fever, which may also affect the brain. The current study assessed the prevalence of neuropsychiatric manifestations in patients with RHD, including clinical features associated with basal ganglia motor dysfunction (BGMD). Methods: We conducted neurologic and psychiatric assessments in consecutive patients with RHD referred to a tertiary center for heart valve diseases. Echocardiography was performed to assess the pattern of valvular involvement and RHD severity. Validated questionnaires for the evaluation of cognition, depression, anxiety, and obsessive-compulsive symptoms (OCS) were applied. BGMD was clinically defined by the presence of hyperkinetic movement disorders. Results: Fifty patients with age of 43.2 ± 10.8 years, 84% female, were included. Mitral valve was affected in 47 patients (94%), and 21 of them (42%) also had aortic valve involvement. Chorea (22%), chronic tics (18%), OCS (48%), major depression (34%), generalized anxiety disorder (54%), cognitive complaints (66%), migraine (52%) and seizures (18%) were frequently reported. The factors associated with BGMD were age (p = 0.018), major depression (p = 0.013), and Yale-Brown Obsessive Compulsive (Y-BOCS) score (p = 0.011). The severity of heart disease was not associated with BGMD. Conclusions: Neuropsychiatric manifestations are frequent in RHD patients, which may persist up to three decades after acute rheumatic fever. Age, major depression and severity of OCS were independently associated with BGMD. These manifestations deserve a close attention of clinicians and researchers dealing with adult patients with RHD.

Nursing Diagnoses and Interventions in Women with Hypertensive Disorders of Pregnancy: A Scoping Review / Diagnósticos e intervenciones de enfermería en mujeres con hipertensión inducida en el embarazo: revisión de alcance / Diagnósticos e intervenções de enfermagem em mulheres com distúrbios hipertensivos da gravidez: revisão de escopo

Objective: To map the diverse scientific evidence on nursing diagnoses and interventions in women with pregnancy hypertensive disorders under Primary Health Care. Materials and method: A scoping review was conducted through nine stages in seven databases and the thesis and dissertation catalog of the Coordinating Office for Improving Higher Education Personnel. The search was performed from January to March 2021. Results: A total of 2,505 articles were retrieved, of which five were included in the final review. Nine primary diagnoses from the 2009-2011 version of NANDA-I were identified. Each diagnosis was classified according to physical, psychological, behavioral, and environmental characteristics. The interventions were related to controlling pain, anxiety, hemodynamic dysfunctions, self-esteem level, fluid replacement, patient/environment hygiene, and sleep-rest ratio. Conclusions: The nursing diagnoses and interventions presented in this study corroborate the clinical practice and aid nursing professionals' reasoning.

Objetivo: mapear las evidencias científicas acerca de los diagnósticos e intervenciones de enfermería en mujeres con hipertensión inducida en el embarazo en la atención primaria de salud. Materiales y método: scoping review en nueve etapas, en siete bases de datos y en el catálogo de tesis de la Coordinación de Perfeccionamiento de Nivel Superior de Brasil. Se realizó la búsqueda de enero a marzo de 2021. Resultados: se recopilaron 2505 artículos, de los cuales cinco se excluyeron en la revisión final. Nueve diagnósticos principales de la versión 2009-2011 de la NANDA-I. Se clasificó cada diagnóstico en cuanto a las características físicas, psicológicas, comportamentales y ambientales. Las intervenciones se relacionaron con el control del dolor, de la ansiedad, de las disfunciones hemodinámicas, del nivel de autoestima, de la reposición hídrica, de la higienización del paciente/ambiente y a la relación sueño-reposo. Conclusiones: los diagnósticos e intervenciones de enfermería presentados en el estudio corroboran la práctica clínica y auxilian en el razonamiento del profesional de enfermería.

Objetivo: mapear as evidências científicas sobre os diagnósticos e intervenções de enfermagem em mulheres com distúrbios hipertensivos da gravidez na atenção primária à saúde. Materiais e método: scoping review em nove etapas, em sete bases de dados e no catálogo de teses e dissertações da Coordenação de Aperfeiçoamento de Nível Superior. Realizou-se a busca de janeiro a março de 2021. Resultados: 2505 artigos foram recuperados, dos quais cinco foram incluídos na revisão final. Nove diagnósticos principais da versão 2009-2011 da NANDA-I. Classificou-se cada diagnóstico quanto às características físicas, psicológicas, comportamentais e ambientais. As intervenções foram relacionadas ao controle da dor, da ansiedade, das disfunções hemodinâmicas, do nível de autoestima, da reposição hídrica, da limpeza do paciente/ambiente e à relação sono-repouso. Conclusões: os diagnósticos e intervenções de enfermagem apresentados neste estudo corroboram a prática clínica e auxiliam no raciocínio do profissional de enfermagem.

Simulation of alpha particle emitted by 222Rn from natural spring water in Puebla, México.

A computational simulation of alpha-particle expansion, emitted by 222Rn naturally diluted in the water of a spring located in the state of Puebla Mexico, is presented. This simulation provided information on the volume of expansion of the alpha particles in the vicinity of the spring and thus awareness if there was a radiological risk for the users or the population that lived near to it. Before performing the simulation, several measurements were made to water samples with a dynamic measurement system. This in order to know the level of radon concentration and compare the results obtained with the levels recommended by the United States Environmental Protection Agency (US-EPA) and the World Health Organization (WHO). In addition, to know if there was a radiological risk due to the presence of gamma emitting radionuclides, complementary water analyses were carried out using gamma-ray spectrometry techniques. The simulation was developed using the scientific software of particle interaction with matter, Geant4. The different variables declared for the software parameters are presented in this document. The results of the radon measurements in the water and the computational simulation, determined that there was no radiological risk due to alpha radiation. Furthermore, the results from the gamma-ray spectrometer showed that there was no presence of other hazardous radionuclides in the water.

Subcutaneous vacuoles with suppuration and granulomas: a histological clue to atypical mycobacterial infection.

An 83-year-old woman was referred to the Dermatology department with a papular eruption on her left arm, occurring below the scar site of a malignant melanoma in situ, which had been excised 6 months previously. On physical examination, multiple, tender, violaceous papules and nodules inferior to the scar were noted, with central pustules in some of the lesions.

NR3C1 gene methylation and cortisol levels in preterm and healthy full-term infants in the first 3 months of life.

Aim: To describe NR3C1 exon-1F methylation and cortisol levels in newborns. Materials & methods: Preterm ≤1500 g and full-term infants were included. Samples were collected at birth and at days 5, 30 and 90 (or at discharge). Results: 46 preterm and 49 full-term infants were included. Methylation was stable over time in full-term infants (p = 0.3116) but decreased in preterm infants (p = 0.0241). Preterm infants had higher cortisol levels on the fifth day, while full-term infants showed increasing levels (p = 0.0177) over time. Conclusion: Hypermethylated sites in NR3C1 at birth and higher cortisol levels on day 5 suggest that prematurity, reflecting prenatal stress, affects the epigenome. Methylation decrease over time in preterm infants suggests that postnatal factors may modify the epigenome, but their role needs to be clarified.

We investigated the methylation of a gene, NR3C1 exon-1F, and cortisol levels in newborns. DNA methylation is a biochemical process that can modify gene activity. In the case of this gene, higher methylation might be associated with higher cortisol levels. We studied 46 preterm infants (born weighing 1500 g or less) and 49 full-term infants. Our results revealed that the preterm infants had hypermethylation at birth and higher cortisol levels on day 5, but decreasing methylation and stable cortisol levels over time. Meanwhile, methylation remained stable and cortisol levels increased in full-term babies with time. These unexpected results suggest that prematurity can be associated with prenatal epigenetic changes in the NR3C1 gene, but postnatal factors may induce further modifications. More research is needed to understand these findings better.

Pulmonary artery pressure response to percutaneous mitral valvuloplasty: Associated factors and clinical implications.

BACKGROUND: Pulmonary hypertension (PH) is a marker of poor outcome in mitral stenosis (MS), which improves after percutaneous mitral valvuloplasty (PMV). However, mechanical interventions for relief of valve obstruction often but not always reduce pulmonary pressures. This study aimed to assess the parameters associated with abnormal pulmonary artery pressure (PAP) response immediately after a successful PMV, and also its impact on long-term outcome. METHODS: A total of 181 patients undergoing PMV for rheumatic MS were prospectively enrolled. Invasive hemodynamic and echocardiographic measures were examined in all patients. Abnormal PAP response was defined as the mean PAP (mPAP) values unchanged at the end of the procedure. Long-term outcome was a composite endpoint of death, mitral valve replacement, repeat PMV, new onset of atrial fibrillation (AF), or stroke. RESULTS: The mean age was 44.1 ± 12.6 years, and 157 patients were women (86.7%). In the overall population, mPAP decreased from 33.4 ± 13.1 mmHg pre to 27.6 ± 9.8 mmHg post (p < 0.001). Following PMV, 52 patients (28.7%) did not have any reduction of mPAP immediately after the PMV. Multivariable analysis adjusting for baseline values of PAP and mitral valve area revealed that AF (Odds ratio [OR] 2.7, 95% [confidence interval] CI 1.3 to 6.7), maximum mitral valve leaflets displacement (OR 0.8, 95% CI 0.7 to 0.9), and post-procedural left ventricular compliance (OR 0.7, 95% CI 0.5 to 0.9) were predictors of a lack of improvement in mPAP. During a median follow-up of 4.4 years, the endpoint was reached in 56 patients (31%). The pulmonary pressure response to PMV was not an independent predictor of long-term events. CONCLUSIONS: In patients with MS undergoing PMV, pulmonary pressures may not reduce immediately after the procedure, despite adequate opening of the valve. Abnormal PAP response can be predicted from baseline clinical and valvular characteristics as well as post-procedural left ventricular compliance. The lack of any immediate reduction in mPAP is not associated with long-term adverse outcomes.

Bone formation in sinus augmentation with different xenograft particle sizes: systematic review and meta-analysis / Formação óssea em levantamento de seio maxilar com diferentes tamanhos de partículas de enxerto xenográfico: revisão sistemática e meta-análise

ABSTRACT The commercial bovine bone mineral most commonly used is available in two particle sizes and studies have demonstrated contradictory results regarding bone formation volume using small or large particles. The aim of this systematic review and meta-analysis was to compare the bone formation volume and residual bovine bone volume in sinus floor augmentation using small and large particles. The following outcome measures were assessed: bone formation volume (%) and residual bovine bone particles volume (%) assessed by histomorphometric analysis. The initial screening resulted in 236 records. After removal of duplicated articles and analysis of titles, abstracts and full texts, three articles were included in the meta-analysis. The bone formation volume and residual bovine bone volume did not differ between small and large particles, with low heterogeneity of studies. The particle size of bovine bone mineral did not influence bone formation percentage; small and large particles of bovine bone graft presented similar residual bone mineral; more randomized clinical trials should be performed to completely confirm that bovine bone mineral particle size does not affect the result of sinus floor augmentation.

RESUMO O enxerto ósseo bovino comercial mais comumente utilizado está disponível em dois tamanhos de partícula, que tem demonstrado resultados contraditórios em relação à formação óssea usando partículas pequenas ou grandes. O objetivo desta revisão sistemática e meta-análise é comparar o volume de formação óssea e o volume de enxerto residual em levantamento de seio usando partículas pequenas e grandes. Os seguintes dados foram comparados: volume de formação óssea (%) e volume residual de partículas de enxerto (%) dados por análise histomorfométrica. A seleção inicial resultou em 236 artigos. Após remoção de artigos duplicados e análise dos títulos, resumos e textos completos, três artigos foram incluídos na meta-análise. Os volumes de formação óssea e de enxerto residual não diferenciam entre os tamanhos de partícula pequeno e grande, com baixa heterogeneidade dos artigos. O tamanho de partícula de enxerto ósseo bovino não influencia o percentual de formação óssea; partículas de enxerto ósseo bovino pequenas e grandes apresentaram enxerto residual similar; mais ensaios clínicos randomizados deveriam ser realizados para confirmar que o tamanho de partícula de enxerto não afeta os resultados de levantamento de seio maxilar.

DNA damage modeled with Geant4-DNA: effects of plasmid DNA conformation and experimental conditions.

The chemical stage of the Monte Carlo track-structure (MCTS) code Geant4-DNA was extended for its use in DNA strand break (SB) simulations and compared against published experimental data. Geant4-DNA simulations were performed using pUC19 plasmids (2686 base pairs) in a buffered solution of DMSO irradiated by60Co or137Csγ-rays. A comprehensive evaluation of SSB yields was performed considering DMSO, DNA concentration, dose and plasmid supercoiling. The latter was measured using the super helix density value used in a Brownian dynamics plasmid generation algorithm. The Geant4-DNA implementation of the independent reaction times method (IRT), developed to simulate the reaction kinetics of radiochemical species, allowed to score the fraction of supercoiled, relaxed and linearized plasmid fractions as a function of the absorbed dose. The percentage of the number of SB after •OH + DNA and H• + DNA reactions, referred as SSB efficiency, obtained using MCTS were 13.77% and 0.74% respectively. This is in reasonable agreement with published values of 12% and 0.8%. The SSB yields as a function of DMSO concentration, DNA concentration and super helix density recreated the expected published experimental behaviors within 5%, one standard deviation. The dose response of SSB and DSB yields agreed with published measurements within 5%, one standard deviation. We demonstrated that the developed extension of IRT in Geant4-DNA, facilitated the reproduction of experimental conditions. Furthermore, its calculations were strongly in agreement with experimental data. These two facts will facilitate the use of this extension in future radiobiological applications, aiding the study of DNA damage mechanisms with a high level of detail.

Evaluation of the Relationships between Simple Anthropometric Measures and Bioelectrical Impedance Assessment Variables with Multivariate Linear Regression Models to Estimate Body Composition and Fat Distribution in Adults: Preliminary Results.

BACKGROUND: Overweight and obesity are conditions associated with sedentary lifestyle and accumulation of abdominal fat, determining increased mortality, favoring chronic diseases, and increasing cardiovascular risk. Although the evaluation of body composition and fat distribution are highly relevant, the high cost of the gold standard techniques limits their wide utilization. Therefore, the aim of this work was to explore the relationships between simple anthropometric measures and BIA variables using multivariate linear regression models to estimate body composition and fat distribution in adults. METHODS: In this cross-sectional study, sixty-eight adult individuals (20 males and 48 females) were subjected to bioelectrical impedance analysis (BIA), anthropometric measurements (waist circumference (WC), neck circumference (NC), mid-arm circumference (MAC)), allowing the calculation of conicity index (C-index), fat mass/fat-free mass (FM/FFM) ratios, body mass index (BMI) and body shape index (ABSI). Statistical analyzes were performed with the R program. Nonparametric Statistical tests were applied to compare the characteristics of participants of the groups (normal weight, overweight and obese). For qualitative variables, the Fisher's exact test was applied, and for quantitative variables, the paired Wilcoxon signed-rank test. To evaluate the linear association between each pair of variables, the Pearson correlation coefficient was calculated, and Multivariate linear regression models were adjusted using the stepwise variable selection method, with Akaike Information Criterion (p ≤ 0.05). RESULTS: BIA variables with the highest correlations with anthropometric measures were total body water (TBW), body fat percentage (BFP), FM, FFM and FM/FFM. The multiple linear regression analysis showed, in general, that the same variables can be estimated through simple anthropometric measures. CONCLUSIONS: The assessment of fat distribution in the body is desirable for the diagnosis and definition of obesity severity. However, the high cost of the instruments (dual energy X-ray absorptiometry, hydrostatic weighing, air displacement plethysmography, computed tomography, magnetic resonance) to assess it, favors the use of BMI in the clinical practice. Nevertheless, BMI does not represent a real fat distribution and body fat percentage. This highlights the relevance of the findings of the current study, since simple anthropometric variables can be used to estimate important BIA variables that are related to fat distribution and body composition.

Quantum Biochemical Investigation of Lys49-PLA2 from Bothrops moojeni.

Envenomation via snakebites occurs largely in areas where it is harder to access the hospital. Its mortality rate and sequelae acquired by the survivors symbolize a big challenge for antivenom therapy. In particular, the homologous phospholipase A2 (Lys49-PLA2) proteins can induce myonecrosis and are not effectively neutralized by current treatments. Thus, by taking advantage of crystallographic structures of Bothrops moojeni Lys49-PLA2 complexed with VRD (varespladib) and AIN (aspirin), a quantum biochemistry study based on the molecular fractionation with conjugate cap scheme within the density functional theory formalism is performed to unveil these complexes' detailed interaction energies. The calculations revealed that important interactions between ligands and the Lys49-PLA2 pocket could occur up to a pocket radius of r = 6.5 (5.0 Å) for VRD (AIN), with the total interaction energy of the VRD ligand being higher than that of the AIN ligand, which is well-correlated with the experimental binding affinity. Furthermore, we have identified the role played by the amino acids LYS0069, LYS0049, LEU0005, ILE0009, CYS0029, GLY0030, HIS0048, PRO0018, ALA0019, CYS0045, TYR0052, TYR0022, PRO0125*, and PHE0126* (LYS0069, LYS0049, GLY0032, LEU0002, and LEU0005) in the VRD↔Lys49-PLA2 (AIN↔Lys49-PLA2) complex. Our simulations are a valuable tool to support the big challenge for neutralizing the damages in victims of snakebites.

New ethionamide boosters and EthR2: structural and energetic analysis.

Ethionamide (ETH) is a high-profile drug for the treatment of patients with multidrug-resistant Mycobacterium tuberculosis and, in order to produce its inhibitory effects, it needs to be bioactivated by monooxygenase EthA. This process is under the control of the transcriptional repressors EthR and EthR2, so that their inhibition results in the boosting of ethionamide activation. Herein, through crystallographic data and computer simulations, we calculated the interaction binding energies of four inhibitors with improved in vitro potency, namely BDM76060 (PDB ID: 6HS1), BDM72201 (PDB ID: 6HRX), BDM76150 (PDB ID: 6HS2) and BDM72719 (PDB ID: 6HRY), in complexes with the transcriptional repressor EthR2, using density functional theory (DFT) within the molecular fractionation with conjugated caps (MFCC) approach. It was observed that these ligands share the same binding site within a 10.0 Å radius of the EthR2 protein; however, their structural particularities have a significant impact on the global energies of systems. The BDM72201 and BDM72719 components are weakly attached to the binding site, while BDM76060 and BDM76150 components produce stronger bonds, corroborating with experimental studies demonstrating that BDM76060 and BDM76150 are more successful in producing inhibitory effects. BDM76060 and BDM76150 have many functional groups that increase the contact surface with the protein and attract a more significant number of amino acid residues, being able to produce polarities that generate stronger interactions. In the current scenario of a growing number of cases of bacterial resistance, the obtained data can be used to guide clinical trials of these inhibitors and other inhibitors that act on the alternative EthR2 pathway, focusing on improving the activity of ethionamide, its effectiveness, a reduction in the treatment time and exposure to cytotoxic effects.

Large-scale Degradation of the Tocantins-Araguaia River Basin.

The Tocantins-Araguaia Basin is one of the largest river systems in South America, located entirely within Brazilian territory. In the last decades, capital-concentrating activities such as agribusiness, mining, and hydropower promoted extensive changes in land cover, hydrology, and environmental conditions. These changes are jeopardizing the basin's biodiversity and ecosystem services. Threats are escalating as poor environmental policies continue to be formulated, such as environmentally unsustainable hydropower plants, large-scale agriculture for commodity production, and aquaculture with non-native fish. If the current model persists, it will deepen the environmental crisis in the basin, compromising broad conservation goals and social development in the long term. Better policies will require thought and planning to minimize growing threats and ensure the basin's sustainability for future generations.

Factors associated with alcohol, tobacco and illicit drug use among Brazilian undergraduate students.

OBJECTIVES: to analyze the factors associated with the use of alcohol, tobacco and illicit drugs among Brazilian undergraduate students. METHODS: observational, cross-sectional study, with convenience sampling, conducted in 2014/2015, involving institutional data and a self-completed online questionnaire, analyzed using measures of frequency, central tendency/dispersion and logistic regression. RESULTS: among 126,326 students, 62.8% reported alcohol use; 11%, tobacco; and 7.5%, illicit drugs. Several academic factors-such as not residing with family (sororities [alcohol: aOR:2.38;95%CI:2.28-2.48; tobacco: AOR:2.20;95%CI:2.09-2.33; illicit drugs: AOR:2.53;95%CI:2.38-2.70]), acting in university movements (student [alcohol: AOR:1.74;95%CI:1.65-1.83; tobacco: AOR:1.97;95%CI:1.86-2.08; illicit drugs: AOR:2.43;95%CI:2.28-2.59] and religious [alcohol: AOR:0.28;95%CI:0.26-0.29; tobacco: AOR:0.23;95%CI:0.21-0.26; illicit drugs: AOR:0.18;95%CI:0.16-0.21]) and lack of discipline/study habit (alcohol: AOR:1.41;95%CI:1.37-1.45; tobacco: AOR:1.53;95%CI:1.46-1.59; illicit drugs: AOR:1.85;95%CI:1.76-1.94) - were associated with the use of the three categories of substances. CONCLUSIONS: we identified that a number of academic factors are associated with licit and illicit drug use. These findings may help in designing preventive strategies among college students.

Exploring human porphobilinogen synthase metalloprotein by quantum biochemistry and evolutionary methods.

Previous studies have shown the porphobilinogen synthase (PBGS) zinc-binding mechanism and its conservation among the living cells. However, the precise molecular interaction of zinc with the active center of the enzyme is unknown. In particular, quantum chemistry techniques within the density functional theory (DFT) framework have been the key methodology to describe metalloproteins, when one is looking for a compromise between accuracy and computational feasibility. Considering this, we used DFT-based models within the molecular fractionation with conjugate caps scheme to evaluate the binding energy features of zinc interacting with the human PBGS. Besides, phylogenetic and clustering analyses were successfully employed in extracting useful information from protein sequences to identify groups of conserved residues that build the ions-binding site. Our results also report a conservative assessment of the relevant amino acids, as well as the benchmark analysis of the calculation models used. The most relevant intermolecular interactions in Zn2+-PBGS are due to the amino acids CYS0122, CYS0124, CYS0132, ASP0169, SER0168, ARG0221, HIS0131, ASP0120, GLY0133, VAL0121, ARG0209, and ARG0174. Among these residues, we highlighted ASP0120, GLY0133, HIS0131, SER0168, and ARG0209 by co-occurring in all clusters generated by unsupervised clustering analysis. On the other hand, the triple cysteines at 2.5 Å from zinc (CYS0122, CYS0124, and CYS0132) have the highest energy attraction and are absent in the taxa Viridiplantae, Sar, Rhodophyta, and some Bacteria. Additionally, the performance of the DFT-based models shows that the processing time-dependence is more associated with the choice of the basis set than the exchange-correlation functional.

Effects of exercise training on autonomic modulation and mood symptoms in patients with obstructive sleep apnea.

We evaluated the effects of exercise training (ET) on the profile of mood states (POMS), heart rate variability, spontaneous baroreflex sensitivity (BRS), and sleep disturbance severity in patients with obstructive sleep apnea (OSA). Forty-four patients were randomized into 2 groups, 18 patients completed the untrained period and 16 patients completed the exercise training (ET). Beat-to-beat heart rate and blood pressure were simultaneously collected for 5 min at rest. Heart rate variability (RR interval) was assessed in time domain and frequency domain (FFT spectral analysis). BRS was analyzed with the sequence method, and POMS was analyzed across the 6 categories (tension, depression, hostility, vigor, fatigue, and confusion). ET consisted of 3 weekly sessions of aerobic exercise, local strengthening, and stretching exercises (72 sessions, achieved in 40±3.9 weeks). Baseline parameters were similar between groups. The comparisons between groups showed that the changes in apnea-hypopnea index, arousal index, and O2 desaturation in the exercise group were significantly greater than in the untrained group (P<0.05). The heart rate variability and BRS were significantly higher in the exercise group compared with the untrained group (P<0.05). ET increased peak oxygen uptake (P<0.05) and reduced POMS fatigue (P<0.05). A positive correlation (r=0.60, P<0.02) occurred between changes in the fatigue item and OSA severity. ET improved heart rate variability, BRS, fatigue, and sleep parameters in patients with OSA. These effects were associated with improved sleep parameters, fatigue, and cardiac autonomic modulation, with ET being a possible protective factor against the deleterious effects of hypoxia on these components in patients with OSA.

Characterization of novel human intragenic antimicrobial peptides, incorporation and release studies from ureasil-polyether hybrid matrix.

Intragenic antimicrobial peptides (IAPs) are internal sequences of proteins with physicochemical similarities to Antimicrobial Peptides (AMPs) that, once identified and synthesized as individual entities, present antimicrobial activity. Many mature proteins encoded by the genomes of virtually any organism may be regarded as inner reservoirs of IAPs, conferring them ample biotechnological potential. However, IAPs may also share shortcomings with AMPs, such as low half-life in biological media and non-specific adsorption in eukaryotic cells. The present manuscript reports a translational approach that encompasses the uncovering of two novel IAPs from human proteins as well as the first results concerning the incorporation and sustained release of one of these peptides from ureasil-polyether hybrid polymeric films. For such, the software Kamal was used to scan putative IAPs in the human proteome, and two peptides, named Hs05 and Hs06, were identified, synthesized, and tested as antimicrobials. Biophysical assays were conducted using model phospholipid vesicles and 1H NMR solution structures in phospholipid micelles were obtained for the IAP Hs05. This peptide was incorporated in a polymeric matrix composed of the ureasil/PPO-PEO-PPO triblock copolymer, and the resulting films were evaluated by atomic force microscopy and imaging mass spectrometry. The release rate of Hs05 from the polymeric matrix was assessed and the antimicrobial activity of Hs05-loaded hybrid polymeric films was evaluated against the bacterium Escherichia coli. This study represents the first steps towards the development of polymeric films enriched with IAPs obtained from the human proteome as sustained release devices for topical application.