In Vivo Tracking and 3D Mapping of Cell Death in Regeneration and Cancer Using Trypan Blue.

Tracking cell death in vivo can enable a better understanding of the biological mechanisms underlying tissue homeostasis and disease. Unfortunately, existing cell death labeling methods lack compatibility with in vivo applications or suffer from low sensitivity, poor tissue penetration, and limited temporal resolution. Here, we fluorescently labeled dead cells in vivo with Trypan Blue (TBlue) to detect single scattered dead cells or to generate whole-mount three-dimensional maps of large areas of necrotic tissue during organ regeneration. TBlue effectively marked different types of cell death, including necrosis induced by CCl4 intoxication in the liver, necrosis caused by ischemia-reperfusion in the skin, and apoptosis triggered by BAX overexpression in hepatocytes. Moreover, due to its short circulating lifespan in blood, TBlue labeling allowed in vivo "pulse and chase" tracking of two temporally spaced populations of dying hepatocytes in regenerating mouse livers. Additionally, upon treatment with cisplatin, TBlue labeled dead cancer cells in livers with cholangiocarcinoma and dead thymocytes due to chemotherapy-induced toxicity, showcasing its utility in assessing anticancer therapies in preclinical models. Thus, TBlue is a sensitive and selective cell death marker for in vivo applications, facilitating the understanding of the fundamental role of cell death in normal biological processes and its implications in disease.

Tumor-Suppressive Cross-Linking of Anti-T. cruzi Antibodies in Acute Lymphoblastic Leukemia.

Parasites have been associated with possible anticancer activity, including Trypanosoma cruzi, which has been linked to inhibiting the growth of solid tumors. To better understand this antitumor effect, we investigated the association of anti-T. cruzi antibodies with B cells of the acute lymphoblastic leukemia (ALL) SUPB15 cell line. The antibodies were generated in rabbits. IgGs were purified by affinity chromatography. Two procedures (flow cytometry (CF) and Western blot(WB)) were employed to recognize anti-T. cruzi antibodies on SUPB15 cells. We also used CF to determine whether the anti-T. cruzi antibodies could suppress SUPB15 cells. The anti-T. cruzi antibodies recognized 35.5% of the surface antigens of SUPB15. The complement-dependent cytotoxicity (CDC) results demonstrate the cross-suppression of anti-T. cruzi antibodies on up to 8.4% of SUPB15 cells. For the WB analysis, a band at 100 kDa with high intensity was sequenced using mass spectrometry, identifying the protein as nucleolin. This protein may play a role in the antitumor effect on T. cruzi. The anti-T. cruzi antibodies represent promising polyclonal antibodies that have the effect of tumor-suppressive cross-linking on cancer cells, which should be further investigated.

Rock n' Seeds: A database of seed functional traits and germination experiments from Brazilian rock outcrop vegetation.

Advancing functional ecology depends fundamentally on the availability of data on reproductive traits, including those from tropical plants, which have been historically underrepresented in global trait databases. Although some valuable databases have been created recently, they are mainly restricted to temperate areas and vegetative traits such as leaf and wood traits. Here, we present Rock n' Seeds, a database of seed functional traits and germination experiments from Brazilian rock outcrop vegetation, recognized as outstanding centers of diversity and endemism. Data were compiled through a systematic literature search, resulting in 103 publications from which seed functional traits were extracted. The database includes information on 16 functional traits for 383 taxa from 148 genera, 50 families, and 25 orders. These 16 traits include two dispersal, six production, four morphological, two biophysical, and two germination traits-the major axes of the seed ecological spectrum. The database also provides raw data for 48 germination experiments, for a total of 10,187 records for 281 taxa. Germination experiments in the database assessed the effect of a wide range of abiotic and biotic factors on germination and different dormancy-breaking treatments. Notably, 8255 of these records include daily germination counts. This input will facilitate synthesizing germination data and using this database for a myriad of ecological questions. Given the variety of seed traits and the extensive germination information made available by this database, we expect it to be a valuable resource advancing comparative functional ecology and guiding seed-based restoration and biodiversity conservation in tropical megadiverse ecosystems. There are no copyright restrictions on the data; please cite this paper when using the current data in publications; also the authors would appreciate notification of how the data are used in publications.

O avanço da ecologia funcional depende fundamentalmente da disponibilidade de dados sobre traços reprodutivos, incluindo dados de plantas tropicais, que têm sido historicamente subrepresentados em bancos de dados de traços funcionais globais. Embora alguns bancos de dados valiosos tenham sido criados recentemente, eles são restritos principalmente a áreas temperadas e a traços vegetativos, como traços de folhas e madeira. Neste artigo apresentamos Rock n' Seeds, um banco de dados de traços funcionais de sementes e experimentos de germinação de vegetações associadas a afloramentos rochosos do Brasil, os quais são reconhecidos como centros notáveis de diversidade e endemismo. Os dados foram compilados através de uma revisão sistemática na literatura, resultando em 103 publicações das quais foram extraídos os traços funcionais das sementes. O banco de dados inclui informações de 16 traços funcionais para 383 taxa de 148 gêneros, 50 famílias e 25 ordens. Estes dezesseis traços incluem dois traços de dispersão, seis de produção, quatro morfológicos, dois biofísicos e dois germinativos; os eixos principais do espectro ecológico da semente. O banco de dados também fornece os dados brutos para 48 experimentos de germinação para um total de 10.187 registros para 281 taxa. Os experimentos de germinação no banco de dados avaliaram o efeito de uma ampla gama de fatores abióticos e bióticos sobre a germinação e diferentes tratamentos de quebra de dormência. Particularmente, 8.255 desses registros incluem a contagem diária da germinação. Estas informações facilitarão a síntese de dados de germinação e a utilização deste banco de dados para uma grande variedade de questões ecológicas. Dada a variedade de traços das sementes e as amplas informações sobre germinação disponibilizadas por este banco de dados, esperamos que ele seja um recurso valioso para o avanço da ecologia funcional comparativa e para orientar a restauração baseada em sementes e a conservação da biodiversidade em ecossistemas tropicais megadiversos. Não há restrições de direitos autorais sobre os dados; favor citar este artigo ao utilizar os dados nas publicações e os autores agradeceriam uma notificação de como os dados são utilizados nas publicações.

El avance de la ecología funcional depende fundamentalmente de la disponibilidad de datos sobre rasgos reproductivos-incluyendo los de las plantas tropicales-los cuales han estado poco representados en las bases de datos globales de rasgos. Aunque recientemente se han creado algunas bases de datos valiosas, estas se encuentran restringidas principalmente a las zonas templadas y a los rasgos vegetativos, como los de las hojas y la madera. En este artículo presentamos Rock n' Seeds, una base de datos de rasgos funcionales de semillas y experimentos de germinación de la vegetación asociada a afloramientos rocosos de Brasil, los cuales son destacados centros de diversidad y endemismo. Los datos se recopilaron mediante una búsqueda bibliográfica sistemática, que dio como resultado 103 publicaciones de las que se extrajeron los rasgos funcionales de las semillas. La base de datos incluye información de dieciséis rasgos funcionales para 383 taxones de 148 géneros, 50 familias y 25 órdenes. Estos rasgos incluyen dos rasgos de dispersión, seis de producción, cuatro morfológicos, dos biofísicos y dos de germinación; siendo estos los principales ejes del espectro ecológico de las semillas. La base de datos también proporciona los datos brutos de 48 experimentos de germinación, para un total de 10.187 registros de 281 taxones. Dichos experimentos de germinación evaluaron el efecto de una amplia gama de factores abióticos y bióticos sobre la germinación y de diferentes tratamientos para romper la dormancia. En particular, 8.255 de estos registros cuentan con conteos diarios de germinación. Esto facilitará la síntesis de los datos de germinación y el uso de esta base de datos para una gran diversidad de preguntas ecológicas. Dada la variedad de rasgos de las semillas y la amplia información sobre germinación que ofrece esta base de datos, esperamos que sea un recurso valioso para el avance de la ecología funcional comparativa y para orientar la restauración basada en semillas y la conservación de la biodiversidad en ecosistemas tropicales megadiversos. No hay restricciones de derechos de autor sobre los datos; se solicita citar este documento cuando se utilicen los datos en publicaciones y los autores agradecerán ser notificados sobre cómo se utilizan los datos en las publicaciones.

Trypanosoma cruzi Antigenic Proteins Shared with Acute Lymphoblastic Leukemia and Neuroblastoma.

Background. Research studies indicate that immunization with protein extracts of Trypanosoma cruzi, the protozoan parasite that causes Chagas disease, prevents the appearance of tumors in 60% of mice injected with the murine lung carcinoma tumor line. The molecular basis of this process is unknown, although the presence of specific antigens in tumor cells and on the surface of T. cruzi suggests an antiparasitic immune response, with an effective cross-reaction against cancer cells, hence the importance to identify the antigens involved and determine their potential as target cells in anticancer therapy. Aim. This study aimed to determine the presence of antigenic proteins of T. cruzi shared with acute lymphoblastic leukemia and neuroblastoma cells. Material and methods. To achieve this, polyclonal antibodies against T. cruzi were developed in rabbits, and reactivity was determined with protein extracts of acute lymphoblastic leukemia cells and neuroblastoma. The immunodetection of five different strains of T. cruzi against anti-T. cruzi polyclonal antibodies was also performed. Conclusion. The study allows the knowledge of the immunological interactions between cancer and parasites to be expanded and, therefore, contributes to the design of more and better projects that improve the therapeutic strategies applied in oncology.

Biologic Agents in Crohn's Patients Reduce CD4+ T Cells Activation and Are Inversely Related to Treg Cells.

Crohn's disease (CD) is a chronic inflammatory disease with a complex interface of broad factors. There are two main treatments for Chron's disease: biological therapy and nonbiological therapy. Biological agent therapy (e.g., anti-TNF) is the most frequently prescribed treatment; however, it is not universally accessible. In fact, in Brazil, many patients are only given the option of receiving nonbiological therapy. This approach prolongs the subsequent clinical relapse; however, this procedure could be implicated in the immune response and enhance disease severity. Our purpose was to assess the effects of different treatments on CD4+ T cells in a cohort of patients with Crohn's disease compared with healthy individuals. To examine the immune status in a Brazilian cohort, we analyzed CD4+ T cells, activation status, cytokine production, and Treg cells in blood of Crohn's patients. Patients that underwent biological therapy can recover the percentage of CD4+CD73+ T cells, decrease the CD4+ T cell activation/effector functions, and maintain the peripheral percentage of regulatory T cells. These results show that anti-TNF agents can improve CD4+ T cell subsets, thereby inducing Crohn's patients to relapse and remission rates.

Record-breaking wildfires in the world's largest continuous tropical wetland: Integrative fire management is urgently needed for both biodiversity and humans.

In the Brazilian Pantanal, wildfire occurrence has increased, reaching record highs of over 40,000 km2 in 2020. Smoke from wildfires worsened the situation of isolated, as well as urban communities, already under an increasing toll of COVID-19. Here we review the impacts and the possible causes of the 2020 mega-fires and recommend improvements for public policies and fire management in this wetland. We calculated the amount of area burnt annually since 2003 and describe patterns in precipitation and water level measurements of the Paraguay River. Our analyses revealed that the 2020 wildfires were historically unprecedented, as 43% of the area (over 17,200 km2) had not been burnt previously in the last two decades. The extent of area affected in 2020 represents a 376% increase compared to the annual average of the area burnt annually in the last two decades, double than the value in 2019. Potential factors responsible for this increase are (i) severe drought decreased water levels, (ii) the fire corridor was located in the Paraguay River flood zone, (iii) constraints on firefighters, (iv) insufficient fire prevention strategy and agency budget reductions, and (v) recent landscape changes. Climate and land use change will further increase the frequency of these extreme events. To make fire management more efficient and cost-effective, we recommend the implementation of an Integrated Fire Management program in the Pantanal. Stakeholders should use existing traditional, local ecological, and scientific knowledge to form a collective strategy with clear, achievable, measurable goals, considering the socio-ecological context. Permanent fire brigades, including indigenous members, should conduct year-round fire management. Communities should cooperate to create a collaborative network for wildfire prevention, the location and characteristics (including flammability) of infrastructures should be (re)planned in fire-prone environments considering and managing fire-catalysed transitions, and depending on the severity of wildfires. The 2020 wildfires were tackled in an ad-hoc fashion and prioritisation of areas for urgent financial investment, management, protection, and restoration is necessary to prevent this catastrophe from happening again.

Erratum: Gestational gigantomastia

Introduction: Gigantomastia is a disease of unknown etiology, which can occur in two different situations: gestational and non-gestational phases. The gestational type is a rare complication that affects 1:28,000 to 1:100,000 pregnancies and is usually bilateral. It consists of a diffuse, massive breast increase during pregnancy. In a normal pregnancy, the breasts double in size without sequelae; however, in this disease, the breast tissue may experience a 10 to 20-fold increase. The treatment varies from drug therapy to plastic surgery (mammaplasty) and radical surgery (mastectomy). Objectives: To report a case of gestational gigantomastia, its treatment approach, and outcome. Methods: Data from this study were obtained from a multidisciplinary clinical experience, image records, and literature search. Case Report: An 18-year-old patient, admitted to the mastology department of Hospital Guilherme Álvaro, in Santos, Southeastern Brazil, was diagnosed with gigantomastia in her 23rd week of pregnancy. The exacerbated breast growth during the gestational period caused pain and functional impairment to the patient. Bilateral mastectomy was performed at 27 weeks of pregnancy due to the worsening of her pulmonary condition, leading to the risk of maternal and fetal death. Macroscopic anatomopathological examination revealed breasts with a total weight of 27 kg, lobular hyperplasia, pronounced stromal hyperplasia, and necrosis of the breast parenchyma. She stayed in the intensive care unit during the postoperative period with good progression. The patient had a normal delivery at 38 weeks of gestation with a live fetus. Discussion: The ideal management for gestational gigantomastia is not clear. The treatment includes surgeries (reduction mammaplasty and total mastectomy with or without reconstruction), medications, or a combination of both. In the current case, the treatment chosen was mastectomy during pregnancy due to respiratory distress and the risk of sepsis by ischemic tissue necrosis. During the surgical procedure, there was a risk of hemodynamic instability, given the large volume of breast removed, representing 40% of the total weight of the patient. Conclusion: Gestational gigantomastia is an exceptionally rare condition, and the literature has few reports on the subject. The therapeutic management depends on factors intrinsic to the patient, so each case requires individualization. The therapeutic decision aims at the best prognosis, taking into account possible complications and a reduction in maternal and fetal morbidity.

Co-infection of Dengue, Zika and Chikungunya in a group of pregnant women from Tuxtla Gutiérrez, Chiapas: Preliminary data. 2019.

INTRODUCTION: Dengue, Zika and Chikungunya are RNA Arboviruses present in some areas of Mexico, mainly in the endemic state of Chiapas that is characterized by presence of the vector that transmit them and an ecology that favors high transmission. According to the national epidemiological surveillance system, Dengue has intensified since 2018 and outbreaks continue in various states while for Zika and Chikungunya a decrease in cases has been reported in recent years. The main objective of this study was to determine the incidence of Dengue, Zika and Chikungunya infections during pregnancy in the state of Chiapas. PRINCIPAL FINDINGS: The presence of previous and current infections and coinfections diagnosed by molecular (RT-PCR) and immunological (ELISA for IgG determination) techniques indicates a wide circulation of viruses in asymptomatic people, specifically in pregnant women showing that silent infections in dry season contributes to the preservation of viruses. CONCLUSIONS: From 136 studied samples, 27.7% tested positive for DENV, 8% for ZIKV and 24.1% for CHIKV by RTPCR and the values of IgG in sera show that 83.9% were positive for IgG antibodies against DENV, 65% against ZIKV and 59.1% against CHIKV. Results demonstrated presence of ZIKV and CHIKV, not detected by the epidemiological surveillance system, so the importance of establishing proactive epidemiological systems more strict, especially because these infections in pregnant women can cause severe health problems for newborn children.

A Two-Way Road: Antagonistic Interaction Between Dual-Species Biofilms Formed by Candida albicans/Candida parapsilosis and Trichophyton rubrum.

Dermatomycoses include superficial fungal infections of the skin and its appendages. Trichophyton rubrum, Candida albicans, and Candida parapsilosis are some of the most prevalent species that cause dermatomycoses. Several studies show a variable predominance of Candida spp. in relation to dermatophytes, especially in onychomycosis and the possibility of isolating both from the same site. The ability of dermatophytes to form biofilms recently been explored and there is currently no evidence on the involvement of these filamentous fungi in multi-species biofilms. Thus, this study aims to investigate the probable dual-species interaction between T. rubrum and C. albicans and T. rubrum and C. parapsilosis biofilms, considering variable formation conditions, as well as the susceptibility of these dual-species biofilms against terbinafine and efinaconazole. Three conditions of formation of dual-species biofilms were tested: (a) the suspensions of T. rubrum and Candida albicans or C. parapsilosis placed together; (b) suspensions of C. albicans and C. parapsilosis added the pre-adhesion of T. rubrum biofilms; (c) after the maturation of T. rubrum sessile cells. In the first and second conditions, the quantification of metabolic activities, biomass, and polysaccharide materials of mixed biofilms tended to resemble Candida monospecies biofilms. In the third condition, the profiles were modified after the addition of Candida, suggesting that T. rubrum biofilms served as substrate for the development of Candida biofilms. Scanning electron microscopy showed Candida predominance, however, numerous blastoconidia were noted, most evident in the conditions under which Candida was added after the pre-adhesion and maturation of T. rubrum biofilms. Despite the predominance of Candida, the presence of T. rubrum appears to inhibit C. albicans filamentation and C. parapsilosis development, confirming an antagonistic interaction. Fungal burden assays performed when the biofilms were formed together confirmed Candida predominance, as well as susceptibility to antifungals. Further studies will be needed to identify the components of the Candida and T. rubrum biofilm supernatants responsible for inhibiting dermatophyte growth and C. albicans filamentation.

Nucleário, cardboard, or manual crowning: which maintenance technique is most cost-effective in tree seedling survival establishment?

In ecological restoration, one of the main challenges is to develop new methods, techniques, and incentives that both favour and reduce maintenance costs in restoration projects. Besides, post-planting maintenance is often neglected hampering seedling survival over time owing to alien grasses, which compete strongly with native plants for resources. To solve these issues, recently, an innovative technology called Nucleário has been developed in Brazil. Aiming to hinder alien competition filters, the Nucleário also attempts to condition a better microenvironment, reducing drought stress through the water storage tank, decreasing temperatures, which facilitates the survival and growth of seedlings in areas under restoration. Another method used to decrease alien grasses, which is inexpensive, is seedling crowning using cardboard lowing maintenance needs in restored areas. Cardboard has similar functions to Nucleário, such as protecting soil against loss of water and nutrients and reducing competition with invasive exotic grasses. Therefore, comparing them also with traditional manual weeding (i.e., clean-weeded crown by hoe), we aimed to verify which technique is most cost-efficient for seedling crown maintenance of Dipteryx alata Vog., which is an indigenous tree species with high economic value owing to its nuts. We tested three techniques in areas under restoration in the Cerrado, in the Environmental Protection Area "Córrego Guariroba" located in Campo Grande, Mato Grosso do Sul, Brazil. We monitored seedlings submitted to the three methods in the wet and the dry periods for biotic (competition with exotic grasses, herbivory, and growth) and abiotic (moisture and soil temperature) indicators. We observed that the Nucleário was the treatment that maintained the highest soil moisture, resulting in a larger canopy area. However, these effects do not reflect increases in the survival rate, diameter, and height of the seedlings. None of the treatments was effective in reducing herbivory. Nucleário was the most effective treatment in reducing the competition of seedlings with invasive grasses. Cardboard presented an implementation value 21.5 times lower than Nucleário and 1.2 times than manual crowning. Given the high purchase price, the Nucleário's cost-benefit ratio was very high compared to the crowning of cardboard and the manual weeding, which discourages us from recommending it for this species with high survival rates. Its project can be revised to decrease herbivory rates, as well as its efficiency tested in the short and long term in different ecosystems and species, particularly species susceptible to water stress.

Antibacterial activity of salvia officinalis L. against periodontopathogens: An in vitro study.

Being aware of the remarkable antimicrobial potential of S. officinalis L., we aimed to evaluate the antimicrobial activity of the S. officinalis dichloromethane crude extract (SOD), dichloromethane-soluble fractions (SODH and SODD), SODD subfractions (SODD1 and SODD2), and pure substances (manool, salvigenin, and viridiflorol) against periodontopathogens. This bioassay-guided study comprises five antimicrobial tests-determination of the Minimum Inhibitory Concentration (MIC), determination of the Minimum Bactericidal Concentration (MBC), determination of the antibiofilm activity, construction of the Time-kill curve (determination of Bactericidal Kinetics), and determination of the Fractional Inhibitory Concentration Index-on six clinical bacterial isolates and three standard bacterial strains involved in periodontal disease. SOD has moderate activity against most of the tested bacteria, whereas SODD1, SODH1, SODH3, and manool afford the lowest results. The Porphyromonas gingivalis (ATTC and clinical isolate) biofilm is considerably resistant to all the samples. In association with chlorhexidine gluconate, only SODH1 exerts additive action against P. gingivalis (clinical isolate). Therefore, SODH1 and manool are promising antibacterial agents and may provide therapeutic solutions for periodontal infections.

Decreased Enteric Bacterial Composition and Diversity in South American Crohn's Disease Vary With the Choice of Treatment Strategy and Time Since Diagnosis.

BACKGROUND AND AIMS: The symptomology of Crohn's disease [CD], a chronic inflammatory disease of the digestive tract, correlates poorly with clinical, endoscopic or immunological assessments of disease severity. The prevalence of CD in South America is rising, reflecting changes in socio-economic stability. Many treatment options are available to CD patients, including biological agents and corticosteroids, each of which offers variable efficacy attributed to host genetics and environmental factors associated with alterations in the gut microbiota. METHODS: Based on 16S rRNA gene sequencing and taxonomic differences, we compared the faecal microbial population of Brazilian patients with CD treated with corticosteroid or anti-tumour necrosis factor [anti-TNF] immunotherapy. Faecal calprotectin and plasma sCD14 levels were quantified as markers for local and systemic inflammation, respectively. RESULTS: Anti-TNF treatment led to an increased relative abundance of Proteobacteria and a decreased level of Bacteroidetes. In contrast, corticoid treatment was associated with an increase in the relative abundance of Actinobacteria, which has been linked to inflammation in CD. Disruption of the faecal microbiota was related to decreased bacterial diversity and composition. Moreover, the choice of clinical regimen and time since diagnosis modulate the character of the resulting dysbiosis. CONCLUSIONS: Enteric microbial populations in CD patients who have been treated are modulated by disease pathogenesis, local inflammatory microenvironment and treatment strategy. The dysbiosis that remains after anti-TNF treatment due to decreased bacterial diversity and composition abates restoration of the microbiota to a healthy state, suggesting that the identification and development of new clinical treatments for CD must include their capacity to normalize the gut microbiota.

[Frequency and determinants of the delay in the diagnosis of cancer in children, in Argentina]. / Frecuencia y determinantes del retraso en el diagnóstico de cáncer infantil en Argentina.

In Argentina, mortality from childhood cancer is higher than in more developed countries, with late diagnosis being one of the possible causes. Our objective was to determine the frequency of barriers to diagnosis faced by families assisted by a Non-Governmental Organization, and some associated demographic, institutional and medical factors. A retrospective observational and quantitative analysis of the diagnosis pathway of children with cancer assisted by the N.D. Flexer Foundation, Argentina, between 1/1/2011 and 12/31/2015 was carried out. The primary outcome was the presence of barriers to diagnosis. It was considered that there was a barrier when there were consultations without diagnostic suspicion, family delay, institutional delay, self-derivation and/or more than 30 days between the onset of symptoms and diagnosis. The frequency of barriers within each category was contrasted by the y2 test. A multivariate logistic regression was used to examine its association with relevant variables. Among the 1818 families included, 63.5% faced delays/ barriers to diagnosis. Negative modulators were diagnosis at age younger than 1-year, renal tumor and first attention at a public hospital of the City of Buenos Aires or a provincial capital hospital (all p < 0.0001). Positive modulators were the diagnosis of bone tumor (p = 0.009) and first attention at a primary healthcare center (p< 0.0001) or private doctor's office (p = 0.001). The main non-biological factor associated with the possibility of facing barriers to diagnosis was the type of first contact-health institution.

En Argentina, la mortalidad por cáncer infantil es mayor que en países más desarrollados, siendo el diagnóstico tardío una de las posibles causas. Nuestro objetivo fue determinar la frecuencia de obstáculos al diagnóstico enfrentados por las familias de niños con cáncer asistidas por un Organismo No Gubernamental, y algunos factores demográficos, institucionales y médicos asociados. Se realizó un análisis retrospectivo observacional y cuantitativo del recorrido diagnóstico de los niños con cáncer asistidos por la Fundación N.D. Flexer, Argentina, entre el 1/1/2011 y el 31/12/2015. El resultado primario fue la presencia de obstáculos para acceder al diagnóstico. Se consideró que existió un obstáculo cuando tuvieron lugar consultas no orientativas, demora familiar, demora institucional, autoderivación y/o más de 30 días entre la aparición de síntomas y el diagnóstico. La frecuencia dentro de cada categoría se contrastó mediante la prueba de y2. La influencia de distintas variables se evaluó mediante una regresión logística multivariada. De 1818 familias incluidas, 63.5% enfrentaron algún tipo de obstáculos. Resultaron moduladores negativos el diagnóstico antes del año, de tumor renal y la concurrencia a un hospital público de la Ciudad de Buenos Aires o de capital provincial como centro de primer contacto (todos p < 0.0001). Resultaron moduladores positivos el diagnóstico de tumor óseo (p = 0.009) y los centros de atención primaria (p < 0.0001) y consultorios particulares (p = 0.001) como centros de primer contacto. El principal factor no biológico asociado a la frecuencia de obstáculos al diagnóstico de cáncer infantil fue el tipo de centro de primer contacto.

Evaluation of the Effectiveness of the Fun FRIENDS Program / Avaliação da Eficácia do Programa Amigos Divertidos (fun FRIENDS) / Evaluación de la Eficacia del Programa Amigos Divertidos (fun FRIENDS)

Abstract Anxiety and depression are the main complaints related to mental health in childhood and constitute a public health problem. In Brazil, there are few studies that describe evidence-based early intervention actions for these psychopathologies. Considering the problems related to anxiety and depression in childhood and their relative stability in development, health promotion and prevention actions are justified. One of the evidence-based programs directed toward health promotion and prevention of anxiety and depression in childhood is the FRIENDS Program (Fun FRIENDS). Therefore, this study sought to evaluate the effectiveness of the FRIENDS program regarding the reduction in symptoms of anxiety and depression and increase in socioemotional skills, in a city of Paraná state. A total of 25 children, aged from 5 to 7, and their caregivers participated. The CBCL (Child Behavior Checklist), SDQ (Strengths and Difficulties Questionnaire) and SCAS (Spence Children's Anesthesia Scale) were used as the evaluation instruments. The results demonstrated increases in socioemotional skills and reductions in anxiety and depression symptoms. Thus, it was concluded that there is evidence that supports the effectiveness of the program for the Brazilian population.

Resumo A ansiedade e a depressão são as maiores queixas encontradas em relação à saúde mental na infância, sendo um problema de saúde pública. No Brasil, poucos são os estudos que descrevem ações, baseadas em evidência, para intervenções precoces quanto a essas psicopatologias. Frente as problemáticas relacionadas à ansiedade e depressão na infância, e sua relativa estabilidade no desenvolvimento, justificam-se as ações de promoção e prevenção de saúde. Um dos programas, baseados em evidências, que visam a promoção de saúde e prevenção de ansiedade e depressão na infância é o Método FRIENDS (Amigos Divertidos/Fun FRIENDS). Nesse contexto, esta pesquisa buscou avaliar a eficácia do programa Amigos Divertidos quanto a diminuição de sintomas de ansiedade e depressão e aumento de habilidades socioemocionais, em uma cidade do interior do Paraná. Participaram 25 crianças, com idade entre cinco a sete anos, e seus cuidadores. Como instrumentos de avaliação, utilizou-se os instrumentos CBCL (Child Behavior Check List), SDQ (Strengths and Difficulties Questionnaire) e SCAS (Spence Children's Anxiety Scale). Os resultados demonstraram aumentos das habilidades socioemocionais e redução de sintomas de ansiedade e depressão. Com isso, conclui-se que há evidências que apoiam a eficácia do programa para a população brasileira.

Resumen La ansiedad y la depresión son las mayores quejas en relación en relación a la salud mental en la infancia, sendo uno problema de la salud pública. En Brasil, pocos son los estudios que describen acciones basados en evidencia, para intervenciones temprano cuanto a esas psicopatologias. Frente a las problemáticas relacionadas a la ansiedad y depresión en la infancia, y su relativa estabilidad en el desenvolvimiento, justificanse las acciones de promoción y prevención de la salud. Uno de los programas basados en evidencias que visan la promoción y la prevención de ansiedad y depresión en la infancia es lo Método FRIENDS (Amigos Divertidos/Fun FRIENDS). Nese contexto, esta pesquisa buscou valuar la eficacia del programa Amigos Divertidos en una ciudad del interior del Paraná. Participaran 25 niños, con edad entre los cinco y siete años, y sus cuidadores. Como instrumiento de avalación, utilizouse los instrumientos (Child Behavior Check List), SDQ (Strengths and Difficulties Qustionnaire) y SCAS (Spence Children's Anxiety Scale). Los resultados demonstraran aumento de las habilidades socioemocionales y reducción de los sintomas de la ansiedad y depresión. Con eso, concluise que hay evidencias que apoyan la eficacia del programa a la población brasileña.

Frecuencia y determinantes del retraso en el diagnóstico de cáncer infantil en Argentina / Frequency and determinants of the delay in the diagnosis of cancer in children, in Argentina

En Argentina, la mortalidad por cáncer infantil es mayor que en países más desarrollados, siendo el diagnóstico tardío una de las posibles causas. Nuestro objetivo fue determinar la frecuencia de obstáculos al diagnóstico enfrentados por las familias de niños con cáncer asistidas por un Organismo No Gubernamental, y algunos factores demográficos, institucionales y médicos asociados. Se realizó un análisis retrospectivo observacional y cuantitativo del recorrido diagnóstico de los niños con cáncer asistidos por la Fundación N.D. Flexer, Argentina, entre el 1/1/2011 y el 31/12/2015. El resultado primario fue la presencia de obstáculos para acceder al diagnóstico. Se consideró que existió un obstáculo cuando tuvieron lugar consultas no orientativas, demora familiar, demora institucional, autoderivación y/o más de 30 días entre la aparición de síntomas y el diagnóstico. La frecuencia dentro de cada categoría se contrastó mediante la prueba de χ2. La influencia de distintas variables se evaluó mediante una regresión logística multivariada. De 1818 familias incluidas, 63.5% enfrentaron algún tipo de obstáculos. Resultaron moduladores negativos el diagnóstico antes del año, de tumor renal y la concurrencia a un hospital público de la Ciudad de Buenos Aires o de capital provincial como centro de primer contacto (todos p < 0.0001). Resultaron moduladores positivos el diagnóstico de tumor óseo (p = 0.009) y los centros de atención primaria (p < 0.0001) y consultorios particulares (p = 0.001) como centros de primer contacto. El principal factor no biológico asociado a la frecuencia de obstáculos al diagnóstico de cáncer infantil fue el tipo de centro de primer contacto.

In Argentina, mortality from childhood cancer is higher than in more developed countries, with late diagnosis being one of the possible causes. Our objective was to determine the frequency of barriers to diagnosis faced by families assisted by a Non-Governmental Organization, and some associated demographic, institutional and medical factors. A retrospective observational and quantitative analysis of the diagnosis pathway of children with cancer assisted by the N.D. Flexer Foundation, Argentina, between 1/1/2011 and 12/31/2015 was carried out. The primary outcome was the presence of barriers to diagnosis. It was considered that there was a barrier when there were consultations without diagnostic suspicion, family delay, institutional delay, self-derivation and/ or more than 30 days between the onset of symptoms and diagnosis. The frequency of barriers within each category was contrasted by the χ2 test. A multivariate logistic regression was used to examine its association with relevant variables. Among the 1818 families included, 63.5% faced delays/ barriers to diagnosis. Negative modulators were diagnosis at age younger than 1-year, renal tumor and first attention at a public hospital of the City of Buenos Aires or a provincial capital hospital (all p < 0.0001). Positive modulators were the diagnosis of bone tumor (p = 0.009) and first attention at a primary healthcare center (p< 0.0001) or private doctor's office (p= 0.001). The main non-biological factor associated with the possibility of facing barriers to diagnosis was the type of first contact-health institution.

Which spatial arrangement of green manure is able to reduce herbivory and invasion of exotic grasses in native species?

The practice of using green manure for ecological restoration has grown so significantly that there is a shortage of seeds for purchase on the market. Nonetheless, there is very little literature available demonstrating the effects and benefits commonly cited for green manure for addressing important environmental filters, such as herbivory and invasive grasses. Our objective is to determine which spatial sowing arrangement including green manure promotes the lowest rates of herbivory on native species and decreases cover by invasive grasses in ecological restoration. We experimentally tested three sowing configurations of green manure intercropping with native species: T1 the lowest herbivoy rate for both native and green manure, mixture of native and green manure species in the same row, T2, alternating rows of green manure and native species, and T3, rows of native species intercropped with a 2 m wide strip of green manure. We found that (1) green manure species experience greater damage from herbivory than do native species, with average values ranging from 1.8 times higher values in green manure than natives in T1, 2.9 times in T2, and 2.7 times in T3 (when sown in rows and in broader strips, green manure and native species attract more herbivorous insects than if they were sown together [muvuca]); and (2) when green manure and native species are planted mixed in the same row they produce greater soil cover, and thus limit invasion by undesired species. The use of green manure has been identified as an alternative method for overcoming the environmental filters of herbivory and invasive grasses in restoration areas. Considering the demand for information that supports the use of green manure for purposes of ecological restoration, the novel results of the present study fill a void and should prove to be of great interest to researchers and practitioners. In addition, the presented results provide information on efficient and low-cost restoration techniques that are necessary for the activity to gain scale, enabling countries to meet the large restoration targets.

Injection of mRNA isolated from trophozoites of Giardia intestinalis induces expression of three types of chloride currents in Xenopus laevis oocytes.

Giardia lamblia is one of the most important worldwide causes of intestinal infections, yet little is known about its cellular physiology, especially the diversity of ionic channels that this parasite expresses. In this work, we show that injection of mRNA isolated from trophozoites of Giardia, into Xenopus laevis oocytes, induces expression of three types of chloride currents (here referred to as ICl-G1, ICl-G2, and ICl-G3), which have different biophysical and pharmacological properties. ICl-G1 currents show inward rectification and voltage dependence are enhanced by hypotonicity, show a selectivity sequence of (I > Br > Cl > F), and are inhibited by NPPB, DIDS, SITS, 9AC, DPC, and Zinc. These findings suggest that ICl-G1 is the result of expression of chloride channels related to ClC2. ICl-G2 currents show outward rectification and are dependent of intracellular calcium, its selectivity sequence is (Cl > Br > I > F) and are inhibited by NPPB, DIDS, SITS, 9AC, DPC, niflumic acid, tannic acid, and benzbromarone. These findings suggest that they are produced by calcium dependent chloride channels (CaCC). The third type of currents (ICl-G3) appears only after a hypoosmotic challenge, and has similar properties to those described for ICl-swell, such as outward rectification, instant activation, and slow inactivation at large depolarizing voltages. They were blocked by NPPB, DIDS, 9AC, NIf, DCPIB, and tamoxifen. Our results indicate that Giardia intestinalis has at least three types of anion conductances.

Molecular Modelling of Potential Candidates for the Treatment of Depression.

A lot of research initiatives in the last decades have been focused on the search of new strategies to treat depression. However, despite the availability of various antidepressants, current treatment is still far from ideal. Unwanted side effects, modest response rates and the slow onset of action are the main shortcomings. As a strategy to improve symptomatic relief and response rates, the dual modulation of the serotonin transporter and the histamine H3 receptor by a single chemical entity has been proposed in the literature. Accordingly, this work aims to elucidate key structural features responsible for the dual inhibitory activity of the hexahydro-pyrrolo-isoquinoline derivatives. For this purpose, two approaches were employed, four-dimensional quantitative structure-activity relationship (4D-QSAR) and molecular docking. The 4D-QSAR models for both receptors allowed the identification of the pharmacophore groups critical for the modelled biological activity, whereas the binding mode of this class of compounds to the human serotonin transporter was assessed by molecular docking. The findings can be applicable to design new antidepressants.