The MADS-box genes SOC1 and AGL24 antagonize XAL2 functions in Arabidopsis thaliana root development.

MADS-domain transcription factors play pivotal roles in numerous developmental processes in Arabidopsis thaliana. While their involvement in flowering transition and floral development has been extensively examined, their functions in root development remain relatively unexplored. Here, we explored the function and genetic interaction of three MADS-box genes (XAL2, SOC1 and AGL24) in primary root development. By analyzing loss-of-function and overexpression lines, we found that SOC1 and AGL24, both critical components in flowering transition, redundantly act as repressors of primary root growth as the loss of function of either SOC1 or AGL24 partially recovers the primary root growth, meristem cell number, cell production rate, and the length of fully elongated cells of the short-root mutant xal2-2. Furthermore, we observed that the simultaneous overexpression of AGL24 and SOC1 leads to short-root phenotypes, affecting meristem cell number and fully elongated cell size, whereas SOC1 overexpression is sufficient to affect columella stem cell differentiation. Additionally, qPCR analyses revealed that these genes exhibit distinct modes of transcriptional regulation in roots compared to what has been previously reported for aerial tissues. We identified 100 differentially expressed genes in xal2-2 roots by RNA-seq. Moreover, our findings revealed that the expression of certain genes involved in cell differentiation, as well as stress responses, which are either upregulated or downregulated in the xal2-2 mutant, reverted to WT levels in the absence of SOC1 or AGL24.

RECAPACITA PROJECT: Impact of the New York Convention on capacity modification judgments in persons with severe mental disorders: A comparative study using mixed methodology.

In 2013, Spain aligned its capacity modification processes (CM) legislation with the UN Convention on the rights of persons with disabilities, specifically for individuals with severe mental disorders (SMD). The reforms replaced incapacity verdicts with support provision and introduced the term "CM". However, the social impact of these changes remains uncertain. The RECAPACITA project was initiated to generate knowledge on SMD and CM, and this study aims to investigate modifications in CM sentences and associated terminology. Using a qualitative-quantitative methodology, content analysis was conducted on 56 sentences from individuals with SMD. Terminology analysis utilized 19 sentences to achieve information saturation. A comparison was made between sentences prior to 2013 and those spanning 2014 to 2023, analyzing the data through ANOVA and Bonferroni tests (significance level: 0.05). The analysis revealed that psychiatric illness, its evolution, lack of self-governance, and economic management were frequently mentioned aspects in the sentences. However, no significant correlations were found. Qualitatively, mentions of self-governance were more prevalent in sentences before 2013. Conversely, after 2013, there was an increased focus on substances use, lack of insight and medical adherence, and the need for support in daily life. The term "incapable person" appeared in 100% of the sentences, indicating no differences in terminology. The study suggests that current CM sentences provide increasingly individualized information, addressing the specific support needs of individuals. To enhance future legal proceedings, incorporating neuroscience in studying SMD individuals and reconsidering terminology based on Convention guidelines is recommended.

Inkjet-printed morphogenesis of tumor-stroma interface using bi-cellular bioinks of collagen-poly(N-isopropyl acrylamide-co-methyl methacrylate) mixture.

Recent advances in biomaterials and 3D printing/culture methods enable various tissue-engineered tumor models. However, it is still challenging to achieve native tumor-like characteristics due to lower cell density than native tissues and prolonged culture duration for maturation. Here, we report a new method to create tumoroids with a mechanically active tumor-stroma interface at extremely high cell density. This method, named "inkjet-printed morphogenesis" (iPM) of the tumor-stroma interface, is based on a hypothesis that cellular contractile force can significantly remodel the cell-laden polymer matrix to form densely-packed tissue-like constructs. Thus, differential cell-derived compaction of tumor cells and cancer-associated fibroblasts (CAFs) can be used to build a mechanically active tumor-stroma interface. In this methods, two kinds of bioinks are prepared, in which tumor cells and CAFs are suspended respectively in the mixture of collagen and poly (N-isopropyl acrylamide-co-methyl methacrylate) solution. These two cellular inks are inkjet-printed in multi-line or multi-layer patterns. As a result of cell-derived compaction, the resulting structure forms tumoroids with mechanically active tumor-stroma interface at extremely high cell density. We further test our working hypothesis that the morphogenesis can be controlled by manipulating the force balance between cellular contractile force and matrix stiffness. Furthermore, this new concept of "morphogenetic printing" is demonstrated to create more complex structures beyond current 3D bioprinting techniques.

Comparison of human amniotic membrane and collagen nerve wraps around sciatic nerve reverse autografts in a rat model.

Human amniotic membrane (hAM) and collagen nerve wraps are biomaterials that have been investigated as therapies for improving outcomes of peripheral nerve regeneration; however, their efficacy has not been compared. The purpose of this study is to compare the efficacy of collagen and human amniotic membrane nerve wraps in a rodent sciatic nerve reverse autograft model. Lewis rats (n = 29) underwent sciatic nerve injury and repair in which a 10-mm gap was bridged with reverse autograft combined with either no nerve wrap (control), collagen nerve wrap or hAM nerve wrap. Behavioral analyses were performed at baseline and 4, 8 and 12 weeks. Electrophysiological studies were conducted at 8, 10 and 12 weeks. Additional outcomes assessed included gastrocnemius muscle weights, nerve adhesions, axonal regeneration and scarring at 12 weeks. Application of both collagen and hAM nerve wraps resulted in improvement of functional and histologic outcomes when compared with controls, with a greater magnitude of improvement for the experimental group treated with hAM nerve wraps. hAM-treated animals had significantly higher numbers of axons compared to control animals (p < 0.05) and significantly less perineural fibrosis than both control and collagen treated nerves (p < 0.05). The ratio of experimental to control gastrocnemius weights was significantly greater in hAM compared to control samples (p < 0.05). We conclude that hAM nerve wraps are a promising biomaterial that is effective for improving outcomes of peripheral nerve regeneration, resulting in superior nerve regeneration and functional recovery compared to collagen nerve wraps and controls.

[Dermatological emergencies. Prospective and multicentric study in Argentina]. / Urgencias dermatológicas. Estudio prospectivo y multicéntrico en Argentina.

Dermatological emergencies are a frequent reason for emergency departments consultation. In order to determine the prevalence of dermatological emergencies, to describe the kind of dermatological diseases that present as emergencies, to analyze the coincidence between the diagnoses received by the patients in those cases with a previous consultations for the same cutaneous manifestation, and to analyze the behavior according to the health system segment in which they were attended: public segment and private segment; a prospective, observational, analytical, cross-sectional and multi-center study was carried out. Two thousand eight hundred one patients were included. The prevalence of consultations for dermatological emergencies in adults was 15% in the same time period (public segment: 10.6 and private segment: 22.5%, p < 0.05). The consultation was due to an infectious disease in 35.5%, allergic in 29.6% and neoplastic in 8.6%; 0.7% of patients were hospitalized. In 31.7% of patients who had a previous consultation, a coincidence was found between the diagnoses made in 80.7% of those attended by a dermatologist, and 52.6% evaluated by non-dermatologist physician. The high prevalence of dermatological consultations and the existing differences in the probability of receiving an appropriate diagnosis according to the specialization of the intervening professional, show the importance of the presence of dermatology-trained physicians in the emergency area.

Las urgencias dermatológicas constituyen un motivo de consulta frecuente en los departamentos de urgencias. Con el objetivo de determinar la prevalencia de las consultas por urgencias dermatológicas, describir las mismas, analizar la coincidencia entre los diagnósticos recibidos por los pacientes, en los casos que realizaron dos consultas por el mismo cuadro, y analizar el comportamiento de las variables de acuerdo al subsector del sistema de salud en el cual fueron atendidos: subsector público, y subsector privado, se realizó un estudio prospectivo, observacional, analítico, de corte transversal y multicéntrico. Se incluyeron 2801 pacientes. La prevalencia de las consultas por urgencias dermatológicas en adultos fue de 15% en el mismo período horario (subsector público: 10.6% y subsector privado: 22.5%, p < 0.05). Motivó la consulta una enfermedad infecciosa en el 35.5%, alérgica en el 29.6% y neoplásica en el 8.6%. Se hospitalizó el 0.7% de los pacientes. El 31.7% de los pacientes había realizado consultas previas. En estos casos se encontró coincidencia entre los diagnósticos realizados en el 80.7% de los atendidos de forma precedente por un médico dermatólogo, y el 52.6% de los evaluados por médicos no dermatólogos. La alta prevalencia de las consultas por urgencias dermatológicas y las diferencias existentes en la probabilidad de recibir un diagnóstico apropiado de acuerdo con la especialización del profesional interviniente, muestran la importancia de la presencia de un médico con formación en dermatología en el área de urgencias.

Urgencias dermatológicas. Estudio prospectivo y multicéntrico en Argentina / Dermatological emergencies. Prospective and multicentric study in Argentina

Resumen Las urgencias dermatológicas constituyen un motivo de consulta frecuente en los departamentos de urgencias. Con el objetivo de determinar la prevalencia de las consultas por urgencias dermato lógicas, describir las mismas, analizar la coincidencia entre los diagnósticos recibidos por los pacientes, en los casos que realizaron dos consultas por el mismo cuadro, y analizar el comportamiento de las variables de acuerdo al subsector del sistema de salud en el cual fueron atendidos: subsector público, y subsector privado, se realizó un estudio prospectivo, observacional, analítico, de corte transversal y multicéntrico. Se incluyeron 2801 pacientes. La prevalencia de las consultas por urgencias dermatológicas en adultos fue de 15% en el mismo período horario (subsector público: 10.6% y subsector privado: 22.5%, p < 0.05). Motivó la consulta una enfermedad infecciosa en el 35.5%, alérgica en el 29.6% y neoplásica en el 8.6%. Se hospitalizó el 0.7% de los pacientes. El 31.7% de los pacientes había realizado consultas previas. En estos casos se encontró coincidencia entre los diagnósticos realizados en el 80.7% de los atendidos de forma precedente por un médico dermatólogo, y el 52.6% de los evaluados por médicos no dermatólogos. La alta prevalencia de las consultas por urgencias dermatológicas y las diferencias existentes en la probabilidad de recibir un diagnóstico apropiado de acuerdo con la especialización del profesional interviniente, muestran la importancia de la presencia de un médico con formación en dermatología en el área de urgencias.

Abstract Dermatological emergencies are a frequent reason for emergency departments consultation. In order to determine the prevalence of dermatological emergencies, to describe the kind of dermatological diseases that present as emergencies, to analyze the coincidence between the diagnoses received by the patients in those cases with a previous consultations for the same cutaneous manifestation, and to analyze the behavior according to the health system segment in which they were attended: public segment and private segment; a prospective, ob servational, analytical, cross-sectional and multi-center study was carried out. Two thousand eight hundred one patients were included. The prevalence of consultations for dermatological emergencies in adults was 15% in the same time period (public segment: 10.6 and private segment: 22.5%, p < 0.05). The consultation was due to an infectious disease in 35.5%, allergic in 29.6% and neoplastic in 8.6%; 0.7% of patients were hospitalized. In 31.7% of patients who had a previous consultation, a coincidence was found between the diagnoses made in 80.7% of those attended by a dermatologist, and 52.6% evaluated by non-dermatologist physician. The high prevalence of dermatological consultations and the existing differences in the probability of receiving an appropri ate diagnosis according to the specialization of the intervening professional, show the importance of the presence of dermatology-trained physicians in the emergency area.

Smartphones addiction associated with academic achievement among dental students: A cross-sectional study.

PURPOSE: The study sought to examine the association between dental students' smartphone addiction and academic achievement. METHODS: Study participants were 374 dental students from the Universidad Cooperativa de Colombia school of dentistry. Smartphone addiction was assessed using the short version of the Smartphone Addiction Scale (SAS-SV), an instrument that was validated a priori using item response theory, information function test, and confirmatory factor analysis. Students' semester grade point average (GPA) served as a measure of academic performance. The association between SAS-SV scores and GPA was tested using generalized linear modeling adjusting for covariates. RESULTS: The prevalence of smartphone addiction was low (4.8%) in this sample of dental students. Smartphone use was significantly and positively associated with GPA (b = 0.012; 95% confidence interval = 0.005-0.020; P = 0.001) while accounting for students' age and year of study. CONCLUSIONS: Smartphone usage was positively associated with dental students' academic performance. Importantly, a small number of students were identified as suffering from smartphone addiction. Future research should help clarify the mechanisms underlying this association, identify students at risk for smartphone addiction, and further elucidate the relevance of these findings in dental education.

Acute Effects of Sitting Out of Bed and Exercise on Lung Aeration and Oxygenation in Critically Ill Subjects.

BACKGROUND: Early mobilization during critical illness is safe and has beneficial effects on functional outcomes. However, its impact on pulmonary function has not been thoroughly explored. We hypothesized that a sitting position out of bed coupled with exercise could result in an improvement in oxygenation and lung aeration. METHODS: The study was conducted on a cohort of adult subjects within a week of their admission to an ICU. Subjects were transferred to a chair and undertook a 15-min session of exercise, either active or passive. Subjects in the control group were only transferred to a chair. Electrical impedance tomography, a reliable bedside technique monitoring regional lung aeration and the distribution of ventilation, was continuously performed, and blood gases were assessed at baseline and 20 min post-exercise. RESULTS: The cohort included 40 subjects, 17 of whom were mechanically ventilated and 23 spontaneously breathing. The control group for each modality consisted of 5 mechanically ventilated or 5 spontaneously breathing subjects. Mild hypoxemia was present in 45% of the spontaneously breathing cohort, whereas the mechanically ventilated subjects demonstrated moderate (50%) or severe (12%) hypoxemia. Compared with the control group, early mobilization induced a significant increase in lung aeration. In mechanically ventilated subjects, lung aeration increased, especially in the anterior lung regions (mean impedance [95% CI]: T1 (baseline in bed) = 1,265 [691-1,839]; T2 (chair sitting) = 2,003 [1,042-2,963]; T3 (exercise) = 1,619 [810 2,427]; T4 (post exercise in chair) = 2,320 [1,186-3,455]). In spontaneously breathing subjects, lung aeration increased mainly in the posterior lung regions (mean impedance [95% CI]: T1 = 380 [124-637]; T2 = 655 [226-1,084]; T3 = 621 [335-906]; T4 = 600 [340-860]). [Formula: see text] increased, especially in subjects with lower [Formula: see text] at baseline (< 200) (133 ± 31 to 158 ± 48, P = .041). CONCLUSIONS: For critically ill subjects, a sitting position and exercise increased lung aeration and were associated with an improvement in [Formula: see text] in the more severely hypoxemic subjects.

Partial acquisition of stemness properties in tumorspheres obtained from interleukin-8-treated MCF-7 cells.

The interleukin-8 is an important regulator of the tumor microenvironment, promoting the epithelial-mesenchymal transition and the acquisition of stem-like cell properties in cancer cells. The tumorsphere-formation assay has been used for the identification of cancer stem cell. Interleukin-8 induces the formation of larger tumorspheres in Michigan Cancer Foundation-7 (MCF-7) cells, suggesting cancer stem cell enrichment. In this work, we aimed to study the phenotypic and functional characteristics of the cells present within the tumorspheres of MCF-7 cells previously treated with interleukin-8. MCF-7 cells treated for 5 days or not with this cytokine were further cultivated in ultralow attachment plates for another 5 days to allow tumorspheres formation. We showed that the enhanced sphere formation by MCF-7 cells was not a consequence of higher cell proliferation by interleukin-8 stimulation. Despite maintaining an epithelial-mesenchymal transition phenotype with the presence of epithelial and mesenchymal markers, basic stemness properties were impaired in tumorspheres and in those treated with interleukin-8, while others were increased. Self-renewal capacity was increased in interleukin-8-treated cells only in the first generation of tumorspheres but was not sustained in consecutive assays. Accordingly, self-renewal and reprogramming gene expression, differentiation capacity to adipocytes, and clonogenicity were also impaired. We showed also that tumorspheres were enriched in differentiated luminal cells (EpCAM+/CD49f-). Nevertheless, cells were more quiescent and maintain a partial epithelial-mesenchymal transition, consistent with their increased resistance to Paclitaxel and Doxorubicin. They also presented higher migration and interleukin-8-directed invasion. Therefore, the breast cancer cell line MCF-7, having a low stemness index, might partially acquire some stem-like cell attributes after interleukin-8 stimulation, increasing its aggressiveness.

El mercurio como contaminante y factor de riesgo para la salud humana / Mercury as a pollutant and risk factor for human health / Mercúrio como poluente e fator de risco para a saúde humana

Resumen El mercurio (Hg) es considerado en la actualidad un contaminante a nivel mundial, que además impacta de manera negativa sobre la salud de las personas que están expuestas a este. Dentro de sus efectos más graves se encuentran afectaciones a nivel del sistema nervioso, por lo cual se considera un problema de salud pública que requiere la atención adecuada. El mercurio puede entrar al cuerpo a través de la ingesta, inhalación y absorción, por lo cual las poblaciones expuestas a actividades como la minería en pequeña escala representa un factor de riesgo importante sobre el cual se deben establecer estrategias para la mitigación de la exposición al mercurio. Teniendo en cuenta lo anterior, este artículo de revisión presenta los avances y tendencias significativas reportadas por bibliografía indexada, tanto a nivel nacional como latinoamericano e internacional. Las evidencias son claras: la intervención de estrategias de mayor escala es urgente para controlar la contaminación por mercurio de las fuentes de abastecimiento de agua y alimentos y prevenir afectaciones graves a la salud de los seres humanos.

Abstract Mercury (Hg) is currently considered a global pollutant, which also has a negative impact on the health of people who are exposed to it. Among its most serious effects are affectations at the level of the nervous system, which is why it is considered a public health problem that requires adequate attention. Mercury can enter the body through ingestion, inhalation and absorption, which is why populations exposed to activities such as small-scale mining represent an important risk factor on which strategies must be established to mitigate mercury exposure. Taking the foregoing into account, this review article presents the progress and trends of 50 articles consulted from different indexed journals, both nationally and at the Latin American and international level. The evidence is clear: the intervention of larger-scale strategies is urgent to control mercury contamination of food and water supplies and prevent serious damage to human health.

Resumo O mercúrio (Hg) é atualmente considerado um poluente global, que também tem um impacto negativo na saúde das pessoas que estão expostas a este. Entre seus efeitos de maior gravedade estão as afecções do sistema nervoso, por isso é considerado um problema de saúde pública que requer atenção adequada. O mercúrio pode entrar no corpo através da ingestão, inalação e absorção, razão pela qual populações expostas a atividades como a mineração em pequena escala representam um importante fator de risco sobre o qual estratégias devem ser estabelecidas para mitigar a exposição ao mercúrio. Tendo em conta o exposto, este artigo de revisão apresenta os avanços e tendências significativas relatadas pela bibliografia indexada, tanto no âmbito nacional, quanto latino-americano e internacional. A evidência é clara: a intervenção de estratégias em larga escala é urgente para controlar a contaminação por mercúrio das fontes de abastecimento de água e alimentos e prevenir sérios danos à saúde humana.

Validez de contenido del cuestionario de juego patológico SOGS en el ámbito forense colombiano / The Validity of the SOGS Pathological Gambling Survey's Content in the Colombian Forensic Field / Validade de conteúdo do questionário de jogo patológico SOGS no campo forense colombiano

Resumen Tradicionalmente se ha distinguido el juego como pasatiempo (play) del juego con apuestas (gambling). El juego con apuestas ha facilitado la aparición de conductas problemáticas como el juego patológico, conocido como ludopatía. En Colombia la Ley 1554 de 2012 en el artículo 7° parágrafo I, menciona la importancia de definir guías y protocolos de atención y evaluación de la ludopatía. No obstante, en el contexto colombiano son escasos los estudios que evalúen y atiendan esta problemática. El presente estudio, tuvo como objetivo establecer la validez de contenido del instrumento South Oaks Gambling Screen (SOGS) ampliamente utilizado en el ámbito de la psicología forense. La metodología consistió, en primer lugar, en una etapa de adaptación y ajustes al instrumento, y posteriormente, una etapa de juicio de expertos mediante el método Delphi. Entre los principales resultados del estudio se encuentran: la adaptación de los criterios diagnósticos del cuestionario del DSM-III-R al DSM-5, la adaptación al lenguaje colombiano que permite establecer una mayor comprensión del cuestionario y la incorporación de aspectos relacionados con el juego y las apuestas en línea. El producto de este estudio constituye un instrumento viable para su utilización en el ámbito jurídico y forense, mediante el criterio probatorio del artículo 226 del Código General del Proceso.

Abstract Traditionally, "play" has been distinguished as a hobby within "gambling". Gambling has facilitated the appearance of problematic conducts, such as pathological gambling, also known as compulsive gambling. In Colombia, Law 1554/2020, in article 7, paragraph 1, mentions the importance of defining attention and assessment guides and protocols for compulsive gambling. However, there are few studies in the Colombian context that assess and attend to this issue. This study's objective was to establish the validity of the South Oaks Gambling Screen (SOGS) instrument's content, which is widely used in the field of forensic psychology. The methodology first consisted of a stage adapting to and adjusting the instruments and then a stage of expert judgment through the Delphi method. The study's main results includes: adapting the survey's diagnostic criteria from DSM-III-R to DSM-5, adapting it to Colombian Spanish, which ensures better understanding of the survey and incorporating aspects related to online gambling and betting. This study's product comprises an instrument that may be used in legal and forensic fields through the standard of proof in article 226 of the General Procedural Code.

Resumo Tradicionalmente, tem sido distinguido o jogo como um passatempo (play) do jogo com apostas (gambling). O jogo com apostas facilitou o aparecimento de comportamentos problemáticos, como o jogo patológico, conhecido como jogo compulsivo. Na Colômbia, a Lei 1554 de 2012 em seu artigo 7, parágrafo I, menciona a importância de definir diretrizes e protocolos para o atendimento e avaliação do jogo patológico. Porém, no contexto colombiano, existem poucos estudos que avaliem e abordem esse problema. O presente estudo teve como objetivo estabelecer a validade de conteúdo do instrumento South Oaks Gambling Screen (SOGS) amplamente utilizado na área da psicologia forense. A metodologia consistiu, em primeiro lugar, em uma etapa de adaptação e ajustes do instrumento e, posteriormente, em uma etapa de julgamento de especialistas através método Delphi. Entre os principais resultados do estudo estão: a adaptação dos critérios de diagnóstico do questionário DSM-III-R ao DSM-5, a adaptação à língua colombiana que permite uma maior compreensão do questionário e a incorporação de aspectos relacionados com o jogo e as apostas online. O produto deste estudo constitui um instrumento viável para sua utilização no campo jurídico e forense, através do critério probatório do artigo 226 do Código Geral do Processo.

Subtype-specific characterization of breast cancer invasion using a microfluidic tumor platform.

Understanding progression of breast cancers to invasive ductal carcinoma (IDC) can significantly improve breast cancer treatments. However, it is still difficult to identify genetic signatures and the role of tumor microenvironment to distinguish pathological stages of pre-invasive lesion and IDC. Presence of multiple subtypes of breast cancers makes the assessment more challenging. In this study, an in-vitro microfluidic assay was developed to quantitatively assess the subtype-specific invasion potential of breast cancers. The developed assay is a microfluidic platform in which a ductal structure of epithelial cancer cells is surrounded with a three-dimensional (3D) collagen matrix. In the developed platform, two triple negative cancer subtypes (MDA-MB-231 and SUM-159PT) invaded into the surrounding matrix but the luminal A subtype, MCF-7, did not. Among invasive subtypes, SUM-159PT cells showed significantly higher invasion and degradation of the surrounding matrix than MDA-MB-231. Interestingly, the cells cultured on the platform expressed higher levels of CD24 than in their conventional 2D cultures. This microfluidic platform may be a useful tool to characterize and predict invasive potential of breast cancer subtypes or patient-derived cells.

MADS-Box Genes Are Key Components of Genetic Regulatory Networks Involved in Abiotic Stress and Plastic Developmental Responses in Plants.

Plants, as sessile organisms, adapt to different stressful conditions, such as drought, salinity, extreme temperatures, and nutrient deficiency, via plastic developmental and growth responses. Depending on the intensity and the developmental phase in which it is imposed, a stress condition may lead to a broad range of responses at the morphological, physiological, biochemical, and molecular levels. Transcription factors are key components of regulatory networks that integrate environmental cues and concert responses at the cellular level, including those that imply a stressful condition. Despite the fact that several studies have started to identify various members of the MADS-box gene family as important molecular components involved in different types of stress responses, we still lack an integrated view of their role in these processes. In this review, we analyze the function and regulation of MADS-box gene family members in response to drought, salt, cold, heat, and oxidative stress conditions in different developmental processes of several plants. In addition, we suggest that MADS-box genes are key components of gene regulatory networks involved in plant responses to stress and plant developmental plasticity in response to seasonal changes in environmental conditions.

Genomic Analysis of Colombian Leishmania panamensis strains with different level of virulence.

The establishment of Leishmania infection in mammalian hosts and the subsequent manifestation of clinical symptoms require internalization into macrophages, immune evasion and parasite survival and replication. Although many of the genes involved in these processes have been described, the genetic and genomic variability associated to differences in virulence is largely unknown. Here we present the genomic variation of four Leishmania (Viannia) panamensis strains exhibiting different levels of virulence in BALB/c mice and its application to predict novel genes related to virulence. De novo DNA sequencing and assembly of the most virulent strain allowed comparative genomics analysis with sequenced L. (Viannia) panamensis and L. (Viannia) braziliensis strains, and showed important variations at intra and interspecific levels. Moreover, the mutation detection and a CNV search revealed both base and structural genomic variation within the species. Interestingly, we found differences in the copy number and protein diversity of some genes previously related to virulence. Several machine-learning approaches were applied to combine previous knowledge with features derived from genomic variation and predict a curated set of 66 novel genes related to virulence. These genes can be prioritized for validation experiments and could potentially become promising drug and immune targets for the development of novel prophylactic and therapeutic interventions.

Composición, estructura trófica y patrón de actividad de murciélagos de sotobosque en la Reserva Forestal Bitaco / Composition, trophic structure and activity patterns of the understory bats of the bitaco forest reserve

ABSTRACT The present study describes composition and trophic structure, and assesses the effect of environmental temperature and rainfall on the pattern of nocturnal activity of understory bats in an Andean forest, in the first half of the night. Seven sampling events were conducted, lasting six nights each one. Ten mist nets were used to capture bats, which were checked every hour between 18:00 and 00:00 hours. Bat species, sex and capture time were registered. In addition, environmental temperature and rainfall were also recorded during sampling. The bat assemblage of the understory of the study area was represented mostly by frugivore species, within this guild there was a lower richness of nomadic than sedentary species. For the first half of the night, bat activity peaked between 18:00 and 19:00 hours and declined to a minimum level between 22:00 and 23:00 hours. The most accurate model to explain variation in bat captures included only the effect of air temperature, which positively affected the number of captures. In conclusion, for the sampled period the activity of the bat assemblage in the study area was not related to rainfall and exhibited a slight but significant relationship with air temperature.

RESUMEN En el presente trabajo se describe la composición y estructura trófica, y se evalúa el efecto de la temperatura ambiental y la precipitación sobre el patrón de actividad nocturna de los murciélagos de sotobosque que habitan que un bosque Andino, para la primera mitad de la noche. Para esto se realizaron siete campañas de muestreo, con una duración de seis noches cada una, en las que se utilizaron diez redes de niebla que operaron entre las 18:00 y 00:00 horas, siendo revisadas cada hora. Además, se registró la temperatura ambiental y la precipitación durante los eventos de muestreo. El ensamblaje de murciélagos de sotobosque del área de estudio estuvo representado principalmente por especies frugívoras, y dentro de este gremio, se registró una menor riqueza de especies nómadas que sedentarias. La actividad de los murciélagos, para la primera mitad de la noche, fue máxima entre las 18:00 y 19:00 horas, disminuyendo hasta alcanzar una actividad mínima entre las 22:00 y 23:00 horas. El modelo más adecuado para explicar la variación en las capturas de murciélagos incluyó sólo el efecto de la temperatura ambiental, la cual afectó positivamente el número de capturas. En conclusión, para el periodo evaluado, la actividad del ensamble de murciélagos de sotobosque en el área de estudio no se relacionó con la precipitación y exhibió relación leve pero significativa con la temperatura ambiental.

Randomized Trial of Dexamethasone Versus Prednisone for Children with Acute Asthma Exacerbations.

OBJECTIVE: To determine whether 2 doses of dexamethasone is as effective as 5 days of prednisolone/prednisone therapy in improving symptoms and quality of life of children with asthma exacerbations admitted to the emergency department (ED). STUDY DESIGN: We conducted a randomized, noninferiority trial including patients aged 1-14 years who presented to the ED with acute asthma to compare the efficacy of 2 doses of dexamethasone (0.6 mg/kg/dose, experimental treatment) vs a 5-day course of prednisolone/prednisone (1.5 mg/kg/d, followed by 1 mg/kg/d on days 2-5, conventional treatment). Two follow-up telephone interviews were completed at 7 and 15 days. The primary outcome measures were the percentage of patients with asthma symptoms and quality of life at day 7. Secondary outcomes were unscheduled returns, admissions, adherence, and vomiting. RESULTS: During the study period, 710 children who met the inclusion criteria were invited to participate and 590 agreed. Primary outcome data were available in 557 patients. At day 7, experimental and conventional groups did not show differences related to persistence of symptoms (56.6%, 95% CI 50.6-62.6 vs 58.3%, 95% CI 52.3-64.2, respectively), quality of life score (80.0 vs 77.7, not significant [ns]), admission rate (23.9% vs 21.7%, ns), unscheduled ED return visits (4.6% vs 3.3%, ns), and vomiting (2.1% vs 4.4%, ns). Adherence was greater in the dexamethasone group (99.3% vs 96.0%, P < .05). CONCLUSION: Two doses of dexamethasone may be an effective alternative to a 5-day course of prednisone/prednisolone for asthma exacerbations, as measured by persistence of symptoms and quality of life at day 7. CLINICAL TRIAL REGISTRATION: clinicaltrialsregister.eu: 2013-003145-42.

Disulfide cross-linked multimers of TDP-43 and spinal motoneuron loss in a TDP-43A315T ALS/FTD mouse model.

Tar DNA binding protein 43 (TDP-43) is the principal component of ubiquitinated protein inclusions present in nervous tissue of most cases of both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Previous studies described a TDP-43A315T transgenic mouse model that develops progressive motor dysfunction in the absence of protein aggregation or significant motoneuron loss, questioning its validity to study ALS. Here we have further characterized the course of the disease in TDP-43A315T mice using a battery of tests and biochemical approaches. We confirmed that TDP-43 mutant mice develop impaired motor performance, accompanied by progressive body weight loss. Significant differences were observed in life span between genders, where females survived longer than males. Histopathological analysis of the spinal cord demonstrated a significant motoneurons loss, accompanied by axonal degeneration, astrogliosis and microglial activation. Importantly, histopathological alterations observed in TDP-43 mutant mice were similar to some characteristic changes observed in mutant SOD1 mice. Unexpectedly, we identified the presence of different species of disulfide-dependent TDP-43 aggregates in cortex and spinal cord tissue. Overall, this study indicates that TDP-43A315T transgenic mice develop key features resembling key aspects of ALS, highlighting its relevance to study disease pathogenesis.

Electrocardiographic Changes After Suicidal Digoxin Intoxication in a Healthy Woman.

BACKGROUND: Suicidal digoxin intoxication is a rare clinical entity. Clinical suspicious remains of paramount importance as adequate interpretation of the electrocardiographic changes enable to readily initiate treatment. METHOD: We describe a case of suicidal attempt after massive digoxin intake that was satisfactory managed with conservative management strategy that involved a close clinical surveillance of the evolving electrocardiographic changes and digoxin serum levels.

Consumo de sustancias psicoactivas antes y después del ingreso a prisión en catorce centros carcelarios de Colombia / Consumption of psychoactive substances before and after admission to prison in fourteen prisons in Colombia

Objetivo: describir la frecuencia del consumo de sustancias psicoactivas y las sustancias consumidas antes y después del ingreso a prisión, en personas recluidas en 14 establecimientos penitenciarios y carcelarios adscritos a la Dirección Regional Oriente del Instituto Nacional Penitenciario y Carcelario de Colombia (INPEC). Método: la muestra de este estudio estuvo constituida por 323 internos (hombres n = 303, mujeres n = 20), a quienes se les administró el cuestionario "Vigilancia Epidemiológica del Uso y Abuso de Sustancias Psicoactivas" (VESPA). Resultados: existe una reducción del consumo de drogas estadísticamente significativa, por sustancia, tras el ingreso a prisión, y solo los barbitúricos y la heroína dejan de consumirse en su totalidad. Conclusiones:el consumo de sustancias ilícitas sigue la tendencia mundial y nacional, lo cual debe preocupar a las instituciones competentes, puesto que los efectos del uso y abuso de sustancias psicoactivas constituyen un factor de riesgo que impiden cumplir con la finalidad resocializadora que persigue la pena privativa de la libertad

Objective: to describe the frequency of psychoactive substances and substances used before and after being admitted to prison, inmates in 14 prisons and detention facilities assigned to the Regional East Directorate of the Colombian National Institute Penitentiary and Prisons (INPEC). Methods: The study sample was made up of 323 inmates (men n = 303, women n = 20) who were administered the questionnaire "Epidemiological Monitoring of Use and Substance Abuse" (VESPA). Results: there is a statistically significant reduction of use, per drug, after being admitted to prison; quitting barbiturates and heroin consumption in its entirety. Conclusions: The use of illicit substances follows the global and national trend; which should concern the competent institutions, since the effects of the use and abuse of psychoactive substances constitute a risk factor preventing the re-socializing objective of deprivation of liberty

PPARγ Agonists as an Anti-Inflammatory Treatment Inhibiting Rotavirus Infection of Small Intestinal Villi.

Rotavirus infection has been reported to induce an inflammatory response in the host cell accompanied by the increased expression or activation of some cellular molecules including ROS, NF-κB, and COX-2. PPARγ stimulation and N-acetylcysteine (NAC) treatment have been found to interfere with viral infections including rotavirus infection. Small intestinal villi isolated from in vivo infected mice with rotavirus ECwt were analyzed for the percentage of ECwt-infected cells, the presence of rotavirus antigens, and infectious virion yield following treatment with pioglitazone. Isolated villi were also infected in vitro and treated with PPARγ agonists (PGZ, TZD, RGZ, DHA, and ALA), all-trans retinoic acid (ATRA), and NAC. After treatments, the expression of cellular proteins including PPARγ, NF-κB, PDI, Hsc70, and COX-2 was analyzed using immunochemistry, ELISA, immunofluorescence, and Western blotting. The results showed that rotavirus infection led to an increased accumulation of the cellular proteins studied and ROS. The virus infection-induced accumulation of the cellular proteins studied and ROS was reduced upon pioglitazone treatment, causing also a concomitant reduction of the infectious virion yield. We hypothesized that rotavirus infection is benefiting from the induction of a host cell proinflammatory response and that the interference of the inflammatory pathways involved leads to decreased infection.