Anaesthesia training designs across Europe: A survey-based study from the trainees committee of the European Society of Anaesthesiology and Intensive Care.

BACKGROUND: Anaesthesiology training programs in Europe vary in duration, content, and requirements for completion. This survey-based study conducted by the Trainees Committee of the European Society of Anaesthesiology and Intensive Care explores current anaesthesia training designs across Europe. METHODS: Between May and July 2018, we sent a 41-item online questionnaire to all National Trainee Representatives, members of the National Anaesthesiologists Societies Committee, and Council Representatives of the European Society of Anaesthesiology and Intensive Care (ESAIC) of all member countries. We cross-validated inconsistent data with different country representatives. RESULTS: Forty-three anaesthesiologists from all 39 associated ESAIC countries completed the questionnaire. Results showed considerable variability in teaching formats, frequency of teaching sessions during training, and differences in assessments made during and at the end of training. The reported duration of training was 60 months in 59% (n = 23) of participating countries, ranging from 24 months in Russia and Ukraine to 84 months in the UK. CONCLUSION: This study shows the significant differences in anaesthesiology training formats across Europe, and highlights the importance of developing standardised training programs to ensure a consistent level of training and to improve patient safety. This study provides valuable insights into European anaesthesia training, and underlines the need for further research and collaboration to improve requirements.

Bemisia tabaci MEAM1 still remains the dominant species in open field crops in Brazil

Abstract Among Bemisia tabaci species, the invasive MEAM1 and MED species are key agricultural pests for many crops. In Brazil, most part of B. tabaci population outbreaks were associated with MEAM1, which, since 1990s quickly spread across the entire country. Later in 2014, the MED was identified in Brazil, initially more restricted to greenhouses, but suddenly reaching new areas in the South and Southeast open regions. Thus, our objective was to investigate the geographical distribution of MEAM1 and MED on open field crops in Brazil. MEAM1 is still the predominant species on open field crops such as soybean, cotton, and tomato. The sequencing of a cytochrome c oxidase subunit I (COI) gene fragment revealed a single haplotype of MEAM1, suggesting the establishment of a single MEAM1 strain in the country. The haplotypes found for MEAM1 and MED are genetically related to the globally dispersed strains, Jap1 and Mch1, respectively. Continuous monitoring of B. tabaci species is crucial because landscape alterations, climatic changes, and pest management methods may shift the B. tabaci species distribution and dominance in Brazilian crop areas.

Resumo Dentre as espécies de Bemisia tabaci, as espécies invasoras MEAM1 e MED se destacam como pragas de grande importância para várias culturas. No Brasil, a maior parte dos surtos populacionais de mosca-branca são associados a presença da espécie MEAM1, que a partir 1990 se espalhou por todo o país. Por outro lado, em 2014 a espécie MED foi identificada no Brasil, inicialmente restrita a casas de vegetação, mas rapidamente se difundindo em novas áreas nas regiões Sul e Sudeste do Brasil. Assim, nosso objetivo foi investigar a distribuição geográfica das espécies MEAM1 e MED em grandes culturas no Brasil. A espécie MEAM1 continua sendo predominante nas monoculturas como algodão, soja e tomate. O sequenciamento de um fragmento do gene citocromo c oxidase subunidade I (COI) revelou a presença de um haplótipo para MEAM1, sugerindo o estabelecimento de apenas uma linhagem no país. Os haplótipos encontrados para MEAM1 e MED são geneticamente relacionados as linhagens globalmente dispersas Jap1 e Mch1, respectivamente. O monitoramento contínuo das espécies de B. tabaci é crucial pois as mudanças na paisagem, mudanças climáticas e métodos de manejo das pragas podem alterar a dominância e a distribuição dessas espécies nas áreas agrícolas do Brasil.

Bemisia tabaci MEAM1 still remains the dominant species in open field crops in Brazil / Bemisia tabaci MEAM1 ainda é a espécie dominante em cultivos a céu aberto no Brasil

Among Bemisia tabaci species, the invasive MEAM1 and MED species are key agricultural pests for many crops. In Brazil, most part of B. tabaci population outbreaks were associated with MEAM1, which, since 1990s quickly spread across the entire country. Later in 2014, the MED was identified in Brazil, initially more restricted to greenhouses, but suddenly reaching new areas in the South and Southeast open regions. Thus, our objective was to investigate the geographical distribution of MEAM1 and MED on open field crops in Brazil. MEAM1 is still the predominant species on open field crops such as soybean, cotton, and tomato. The sequencing of a cytochrome c oxidase subunit I (COI) gene fragment revealed a single haplotype of MEAM1, suggesting the establishment of a single MEAM1 strain in the country. The haplotypes found for MEAM1 and MED are genetically related to the globally dispersed strains, Jap1 and Mch1, respectively. Continuous monitoring of B. tabaci species is crucial because landscape alterations, climatic changes, and pest management methods may shift the B. tabaci species distribution and dominance in Brazilian crop areas.

Dentre as espécies de Bemisia tabaci, as espécies invasoras MEAM1 e MED se destacam como pragas de grande importância para várias culturas. No Brasil, a maior parte dos surtos populacionais de mosca-branca são associados a presença da espécie MEAM1, que a partir 1990 se espalhou por todo o país. Por outro lado, em 2014 a espécie MED foi identificada no Brasil, inicialmente restrita a casas de vegetação, mas rapidamente se difundindo em novas áreas nas regiões Sul e Sudeste do Brasil. Assim, nosso objetivo foi investigar a distribuição geográfica das espécies MEAM1 e MED em grandes culturas no Brasil. A espécie MEAM1 continua sendo predominante nas monoculturas como algodão, soja e tomate. O sequenciamento de um fragmento do gene citocromo c oxidase subunidade I (COI) revelou a presença de um haplótipo para MEAM1, sugerindo o estabelecimento de apenas uma linhagem no país. Os haplótipos encontrados para MEAM1 e MED são geneticamente relacionados as linhagens globalmente dispersas Jap1 e Mch1, respectivamente. O monitoramento contínuo das espécies de B. tabaci é crucial pois as mudanças na paisagem, mudanças climáticas e métodos de manejo das pragas podem alterar a dominância e a distribuição dessas espécies nas áreas agrícolas do Brasil.

HLA-G expression in Merkel cell carcinoma and the correlation with Merkel cell polyomavirus infection.

Merkel cell carcinoma (MCC) is a rare aggressive neuroendocrine cutaneous carcinoma with a high mortality rate. The MCC etiology is not fully understood. Merkel cell-associated polyomavirus (MCPyV) was found in MCC patients, indicating a risk factor for the tumor. Caucasian, elderly, and immunocompromised individuals are more likely to develop this tumor. HLA-G consists of a non-classical class I (Ib) HLA molecule with an immunoregulatory function and was associated with tumor escape in different types of tumors, nonetheless, never been studied in MCC. The purpose of this study was to evaluate the HLA-G expression and also to detect the MCPyV in MCC patients and correlate it with the clinical course of the disease. Forty-five MCC patients were included in a retrospective study. Formalin-fixed paraffin-embedded cutaneous skin biopsies were used by immunohistochemistry and RT-PCR to verify the HLA-G expression and MCPyV infection. HLA-G expression was found in 7 (15.6%), while the presence of MCPyV was detected in 28 (62.2%) of the studied patients. No significant association was found between HLA-G expression and MCPyV infection (p = 0.250). The presence of MCPyV was associated with areas of low sunlight exposure (p = 0.042) and the HLA-G expression with progression to death (p = 0.038). HLA-G expression was detected in MCC patients, as well as the MCPyV presence was confirmed. These markers could represent factors with a possible impact on patient survival; however, further studies with a greater number of patients are needed, to better elucidate the possible role in disease progression.

Analysis of the toxicological and pharmacokinetic profile of Kaempferol-3-O-ß-D-(6"-E-p-coumaryl) glucopyranoside - Tiliroside: in silico, in vitro and ex vivo assay / Análise do perfil toxicológico e farmacocinético de Kaempferol-3-O-ß-D- (6 "-E-p-cumaril) glucopiranosídeo - Tilirosídeo: ensaio in silico, in vitro e ex vivo

Abstract Tiliroside is a glycosidic flavonoid present in many plants species including Helicteres velutina K. Schum (Malvaceae sensu lato), commonly known in Brazil as "pitó". This molecule has been shown to have many biological activities, however no study has been carried out to investigate the toxicity of this substance. The present work aimed to evaluate the possible cellular toxicity in silico, in vitro and ex-vivo of the kaempferol-3-O-β-D-(6"-E-p-coumaroyl) glucopyranoside (tiliroside), through chemical structure analysis, toxicity assessment and predictive bioactive properties, using human samples for in vitro and ex-vivo tests. The in silico analysis suggests that tiliroside exhibited great absorption index when penetrating biological membranes. In addition, it also displayed considerable potential for cellular protection against free radicals, and anticarcinogenic, antioxidant, antineoplastic, anti-inflammatory, anti-hemorrhagic and antithrombotic activities. The assessment of the hemolytic and genotoxic effects of tiliroside showed low hemolysis rates in red blood cells and absence of cellular toxicity in the oral mucosa cells. The data obtained indicate that this molecule could be a promising therapeutic approach as a possible new drug with biotechnological potential.

Resumo O tilirosídeo é um flavonóide glicosídico presente em muitas espécies de plantas, incluindo Helicteres velutina K. Schum (Malvaceae sensu lato), conhecida no Brasil como "pitó". Esta molécula mostrou ter muitas atividades biológicas, porém nenhum estudo foi realizado para investigar a toxicidade dessa substância. O presente trabalho teve como objetivo avaliar a possível toxicidade celular in silico, in vitro e ex-vivo do kaempferol-3-O-β-D- (6 "-Ep-coumaroil) glucopiranosídeo (tilirosídeo), por meio de análises de estrutura química, toxicidade avaliação e propriedades bioativas preditivas, utilizando amostras humanas para testes in vitro e ex-vivo. A análise in silico sugere que o tilirosídeo exibe bom índice de absorção para penetrar nas membranas biológicas. Além disso, apresentou considerável potencial de proteção celular contra os radicais livres e com atividades anticarcinogênica, antioxidante, antineoplásica, antiinflamatória, anti-hemorrágica e antitrombótica. A avaliação dos efeitos hemolíticos e genotóxicos do tilirosídeo mostrou baixas taxas de hemólise nas hemácias e ausência de toxicidade em células da mucosa oral. Os dados obtidos indicam que esta molécula pode possuir uma abordagem terapêutica promissora como uma possível nova droga com potencial biotecnológico.

Analysis of the toxicological and pharmacokinetic profile of Kaempferol-3-O-β-D-(6"-E-p-coumaryl) glucopyranoside - Tiliroside: in silico, in vitro and ex vivo assay / Análise do perfil toxicológico e farmacocinético de Kaempferol-3-O-β D-(6"-E-p-cumaril) glucopiranosídeo - Tilirosídeo: ensaio in silico, in vitro e ex vivo

Tiliroside is a glycosidic flavonoid present in many plants species including Helicteres velutina K. Schum (Malvaceae sensu lato), commonly known in Brazil as "pitó". This molecule has been shown to have many biological activities, however no study has been carried out to investigate the toxicity of this substance. The present work aimed to evaluate the possible cellular toxicity in silico, in vitro and ex-vivo of the kaempferol-3-O-β-D-(6”-E-p-coumaroyl) glucopyranoside (tiliroside), through chemical structure analysis, toxicity assessment and predictive bioactive properties, using human samples for in vitro and ex-vivo tests. The in silico analysis suggests that tiliroside exhibited great absorption index when penetrating biological membranes. In addition, it also displayed considerable potential for cellular protection against free radicals, and anticarcinogenic, antioxidant, antineoplastic, anti-inflammatory, anti-hemorrhagic and antithrombotic activities. The assessment of the hemolytic and genotoxic effects of tiliroside showed low hemolysis rates in red blood cells and absence of cellular toxicity in the oral mucosa cells. The data obtained indicate that this molecule could be a promising therapeutic approach as a possible new drug with biotechnological potential.

O tilirosídeo é um flavonóide glicosídico presente em muitas espécies de plantas, incluindo Helicteres velutina K. Schum (Malvaceae sensu lato), conhecida no Brasil como “pitó”. Esta molécula mostrou ter muitas atividades biológicas, porém nenhum estudo foi realizado para investigar a toxicidade dessa substância. O presente trabalho teve como objetivo avaliar a possível toxicidade celular in silico, in vitro e ex-vivo do kaempferol-3-O-β-D- (6 ”-Ep-coumaroil) glucopiranosídeo (tilirosídeo), por meio de análises de estrutura química, toxicidade avaliação e propriedades bioativas preditivas, utilizando amostras humanas para testes in vitro e ex-vivo. A análise in silico sugere que o tilirosídeo exibe bom índice de absorção para penetrar nas membranas biológicas. Além disso, apresentou considerável potencial de proteção celular contra os radicais livres e com atividades anticarcinogênica, antioxidante, antineoplásica, antiinflamatória, anti-hemorrágica e antitrombótica. A avaliação dos efeitos hemolíticos e genotóxicos do tilirosídeo mostrou baixas taxas de hemólise nas hemácias e ausência de toxicidade em células da mucosa oral. Os dados obtidos indicam que esta molécula pode possuir uma abordagem terapêutica promissora como uma possível nova droga com potencial biotecnológico.

Analysis of the toxicological and pharmacokinetic profile of Kaempferol-3-O--D-(6-E-p-coumaryl) glucopyranoside - Tiliroside: in silico, in vitro and ex vivo assay

Abstract Tiliroside is a glycosidic flavonoid present in many plants species including Helicteres velutina K. Schum (Malvaceae sensu lato), commonly known in Brazil as pitó. This molecule has been shown to have many biological activities, however no study has been carried out to investigate the toxicity of this substance. The present work aimed to evaluate the possible cellular toxicity in silico, in vitro and ex-vivo of the kaempferol-3-O--D-(6-E-p-coumaroyl) glucopyranoside (tiliroside), through chemical structure analysis, toxicity assessment and predictive bioactive properties, using human samples for in vitro and ex-vivo tests. The in silico analysis suggests that tiliroside exhibited great absorption index when penetrating biological membranes. In addition, it also displayed considerable potential for cellular protection against free radicals, and anticarcinogenic, antioxidant, antineoplastic, anti-inflammatory, anti-hemorrhagic and antithrombotic activities. The assessment of the hemolytic and genotoxic effects of tiliroside showed low hemolysis rates in red blood cells and absence of cellular toxicity in the oral mucosa cells. The data obtained indicate that this molecule could be a promising therapeutic approach as a possible new drug with biotechnological potential.

Resumo O tilirosídeo é um flavonóide glicosídico presente em muitas espécies de plantas, incluindo Helicteres velutina K. Schum (Malvaceae sensu lato), conhecida no Brasil como pitó. Esta molécula mostrou ter muitas atividades biológicas, porém nenhum estudo foi realizado para investigar a toxicidade dessa substância. O presente trabalho teve como objetivo avaliar a possível toxicidade celular in silico, in vitro e ex-vivo do kaempferol-3-O--D- (6 -Ep-coumaroil) glucopiranosídeo (tilirosídeo), por meio de análises de estrutura química, toxicidade avaliação e propriedades bioativas preditivas, utilizando amostras humanas para testes in vitro e ex-vivo. A análise in silico sugere que o tilirosídeo exibe bom índice de absorção para penetrar nas membranas biológicas. Além disso, apresentou considerável potencial de proteção celular contra os radicais livres e com atividades anticarcinogênica, antioxidante, antineoplásica, antiinflamatória, anti-hemorrágica e antitrombótica. A avaliação dos efeitos hemolíticos e genotóxicos do tilirosídeo mostrou baixas taxas de hemólise nas hemácias e ausência de toxicidade em células da mucosa oral. Os dados obtidos indicam que esta molécula pode possuir uma abordagem terapêutica promissora como uma possível nova droga com potencial biotecnológico.

Bemisia tabaci MEAM1 still remains the dominant species in open field crops in Brazil.

Among Bemisia tabaci species, the invasive MEAM1 and MED species are key agricultural pests for many crops. In Brazil, most part of B. tabaci population outbreaks were associated with MEAM1, which, since 1990s quickly spread across the entire country. Later in 2014, the MED was identified in Brazil, initially more restricted to greenhouses, but suddenly reaching new areas in the South and Southeast open regions. Thus, our objective was to investigate the geographical distribution of MEAM1 and MED on open field crops in Brazil. MEAM1 is still the predominant species on open field crops such as soybean, cotton, and tomato. The sequencing of a cytochrome c oxidase subunit I (COI) gene fragment revealed a single haplotype of MEAM1, suggesting the establishment of a single MEAM1 strain in the country. The haplotypes found for MEAM1 and MED are genetically related to the globally dispersed strains, Jap1 and Mch1, respectively. Continuous monitoring of B. tabaci species is crucial because landscape alterations, climatic changes, and pest management methods may shift the B. tabaci species distribution and dominance in Brazilian crop areas.

HLA-G expression in Merkel cell carcinoma and the correlation with Merkel cell polyomavirus infection

Merkel cell carcinoma (MCC) is a rare aggressive neuroendocrine cutaneous carcinoma with a high mortality rate. The MCC etiology is not fully understood. Merkel cell-associated polyomavirus (MCPyV) was found in MCC patients, indicating a risk factor for the tumor. Caucasian, elderly, and immunocompromised individuals are more likely to develop this tumor. HLA-G consists of a non-classical class I (Ib) HLA molecule with an immunoregulatory function and was associated with tumor escape in different types of tumors, nonetheless, never been studied in MCC. The purpose of this study was to evaluate the HLA-G expression and also to detect the MCPyV in MCC patients and correlate it with the clinical course of the disease. Forty-five MCC patients were included in a retrospective study. Formalin-fixed paraffin-embedded cutaneous skin biopsies were used by immunohistochemistry and RT-PCR to verify the HLA-G expression and MCPyV infection. HLA-G expression was found in 7 (15.6%), while the presence of MCPyV was detected in 28 (62.2%) of the studied patients. No significant association was found between HLA-G expression and MCPyV infection (p = 0.250). The presence of MCPyV was associated with areas of low sunlight exposure (p = 0.042) and the HLA-G expression with progression to death (p = 0.038). HLA-G expression was detected in MCC patients, as well as the MCPyV presence was confirmed. These markers could represent factors with a possible impact on patient survival; however, further studies with a greater number of patients are needed, to better elucidate the possible role in disease progression.

Arte de cuidar milenar: crenças e saberes de idosos sobre a fitoterapia / Arte milenario de cuidar: creencias y saberes de los adultos mayores sobre la fitoterapia / Millennial art of caring: beliefs and knowledge of the elderly about phytotherapy

Existe uma vasta gama de terapias conhecidas no mundo e uma das principais, que faz parte de diversas culturas no mundo percorrendo a história da humanidade, é a utilização das plantas e ervas medicinais com finalidade terapêutica. No Brasil, deduz-se que as práticas de fitoterapia estejam presentes desde antes da colonização, quando os indígenas faziam o uso curativo de acordo com seus conhecimentos e suas experiências [Fragmento de texto] (AU)

In silico, in vitro, and ex vivo studies of the toxicological and pharmacological properties of the flavonoid 5,7-dihydroxy-3,8,4'-trimethoxy.

Phytochemical studies of the species Pavonia glazioviana were performed. Quercetin, kaempferol, acacetin, and trimethoxylated flavonoid compounds (which present biological activity) were isolated. We aimed to evaluate the in silico, in vitro, and ex vivo toxicity of flavonoid 5,7-dihydroxy-3,8,4'-trimethoxy (Pg-1) obtained from P. glazioviana through chemical structure analyses, toxicity assessment, and predictive bioactive properties, using human samples in in vitro tests. In silico analysis suggested that Pg-1 presents a good absorption index for penetrating biological membranes (for oral bioavailability), while also suggesting potential antimutagenic, anticarcinogenic, antioxidant, antineoplastic, anti-inflammatory, anti-hemorrhagic, and apoptosis agonist bioactivities. Assessment of hemolytic and genotoxic effects revealed low hemolysis rates in red blood cells with no cellular toxicity in oral mucosa cells. The reduced cytotoxic activity suggested the safety of the concentrations used (500-1000 µg/mL), and demonstrated the varied interactions of Pg-1 with the analyzed cells. The data obtained in the present study suggested potential therapeutic application, and the non-toxic profile indicated viability for future studies.

Progress testing as a pattern of excellence for the assessment of medical students' knowledge - concepts, history, and perspective / Teste de progresso como padrão de excelência para avaliação de conhecimento dos alunos de medicina ­ conceitos, história e perspectivas

ABSTRACT: Progress test has been created with the necessity of an assessment method aligned with problem-based learning. Although it was specifically created to overcome the limitations of traditional assessment for problem-based learning, nowadays is used by different types of curricula. In this paper, we first present the basic assumptions, history, benefit and progress test challenges. Progress test overcomes many limitations of traditional assessment, such as validity and reliability. However, the implementation of a progress test is a logistical challenge. In addition, we discuss the limitation of progress tests when used as a summative assessment, which may not always be aligned with constructivist theory. When adding feedback and methods of analysis that consider multiple testing, progress test is then aligned with constructivist theory. Finally, the use of the progress test's sub scores may lack validity because of the low number of items; thus, pass/fail decision should not be based on the sub scores, but only on general scores. (AU)

RESUMO: O teste de progresso foi criado como um método de avalição alinhado a aprendizagem baseada em problemas. Apesar do teste de progresso ser criado especificamente para superar limitações da avaliação tradicional em currículos de aprendizagem baseada em problemas, hoje em dia, ele é utilizado em diferentes tipos de currículos. Nesse artigo, primeiro, apresentamos as premissas básicas, história, benefício e desafios do teste de progresso. O teste de progresso superou muitas limitações da avaliação tradicional, como os problemas de validade e confiabilidade. No entanto, a implementação do teste de progresso apresenta grandes desafios logísticos. Ademais, discutimos as limitações do teste de progresso quando utilizada de forma somativa, sendo que nem sempre é alinhada a teoria construtivista. Quando adicionado o feedback e métodos de análises que consideram múltiplos testes, o teste de progresso então se alinha a teoria construtivista. Finalmente, o uso das subcategorias do teste de progresso pode apresentar problemas de validade por causa do baixo número de item e consequentemente, decisões de aprovar ou reprovar não poderiam ser baseadas nas subcategorias, mas apenas na categoria geral (AU)

Analysis of the toxicological and pharmacokinetic profile of Kaempferol-3-O-ß-D-(6"-E-p-coumaryl) glucopyranoside - Tiliroside: in silico, in vitro and ex vivo assay.

Tiliroside is a glycosidic flavonoid present in many plants species including Helicteres velutina K. Schum (Malvaceae sensu lato), commonly known in Brazil as "pitó". This molecule has been shown to have many biological activities, however no study has been carried out to investigate the toxicity of this substance. The present work aimed to evaluate the possible cellular toxicity in silico, in vitro and ex-vivo of the kaempferol-3-O-ß-D-(6"-E-p-coumaroyl) glucopyranoside (tiliroside), through chemical structure analysis, toxicity assessment and predictive bioactive properties, using human samples for in vitro and ex-vivo tests. The in silico analysis suggests that tiliroside exhibited great absorption index when penetrating biological membranes. In addition, it also displayed considerable potential for cellular protection against free radicals, and anticarcinogenic, antioxidant, antineoplastic, anti-inflammatory, anti-hemorrhagic and antithrombotic activities. The assessment of the hemolytic and genotoxic effects of tiliroside showed low hemolysis rates in red blood cells and absence of cellular toxicity in the oral mucosa cells. The data obtained indicate that this molecule could be a promising therapeutic approach as a possible new drug with biotechnological potential.

Modulation of inflammation by anti-TNF α mAb-dendrimer nanoparticles loaded in tyramine-modified gellan gum hydrogels in a cartilage-on-a-chip model.

Rheumatoid arthritis (RA) is an autoimmune and chronic inflammatory disease characterized by joint inflammation. Since the inflammatory condition plays an important role in the disease process, it is important to develop and test new therapeutic approaches that specifically target and treat joint inflammation. In this study, a human 3D inflammatory cartilage-on-a-chip model was established to test the therapeutic efficacy of anti-TNFα mAb-CS/PAMAM dendrimer NPs loaded-Tyramine-Gellan Gum in the treatment of inflammation. The results showed that the proposed therapeutic approach applied to the human monocyte cell line (THP-1) and human chondrogenic primary cells (hCH) cell-based inflammation system revealed an anti-inflammatory capacity that increased over 14 days. It was also possible to observe that Coll type II was highly expressed by inflamed hCH upon the culture with anti-TNF α mAb-CS/PAMAM dendrimer NPs, indicating that the hCH cells were able maintain their biological function. The developed preclinical model allowed us to provide more robust data on the potential therapeutic effect of anti-TNF α mAb-CS/PAMAM dendrimer NPs loaded-Ty-GG hydrogel in a physiologically relevant model.

Gastrointestinal Toxicity of Pelvic Radiotherapy: Are We Letting Women Down?

For all cancers there are four areas of importance: prevention, early diagnosis, optimising therapy and living with and beyond. For women diagnosed with gynaecological cancers, progress in these first three areas has been immense. However, living with and beyond has largely been ignored as a significant issue. As a group, patients treated for gynaecological cancer are more often young and more often suffer the most difficult long-term issues. Despite the growing number of long-term survivors, little has been done to ensure appropriate assessment and treatment of side-effects of cancer therapies, especially when radiotherapy has been used. For many affected patients their symptoms become part of everyday life, 'normality' is adjusted and these changes are tolerated even when severely limiting activities. Data show that even expert clinicians frequently do not appreciate the true impact of these problems and the focus of treatment and of follow-up remains fixed on 5-year survival and cancer recurrence, respectively. Many clinicians are unaware of what experts can do for toxicity and do not know where to refer their patients. However, rapid identification of patients with significant symptoms can lead to earlier diagnosis of treatable pathologies and improvement in patients' quality of life. In addition, the underlying pathophysiology of radiation-induced damage is potentially amenable to disease-modifying therapies. This review focuses on the factors that contribute to patients developing pelvic radiation disease, what can be done to mitigate the toxicity of treatment and highlights the challenges that must be addressed to reduce the gastrointestinal toxicity of pelvic radiotherapy.

Neuroanatomy and behavior in mice with a haploinsufficiency of AT-rich interactive domain 1B (ARID1B) throughout development.

BACKGROUND: One of the causal mechanisms underlying neurodevelopmental disorders (NDDs) is chromatin modification and the genes that regulate chromatin. AT-rich interactive domain 1B (ARID1B), a chromatin modifier, has been linked to autism spectrum disorder and to affect rare and inherited genetic variation in a broad set of NDDs. METHODS: A novel preclinical mouse model of Arid1b deficiency was created and validated to characterize and define neuroanatomical, behavioral and transcriptional phenotypes. Neuroanatomy was assessed ex vivo in adult animals and in vivo longitudinally from birth to adulthood. Behavioral testing was also performed throughout development and tested all aspects of motor, learning, sociability, repetitive behaviors, seizure susceptibility, and general milestones delays. RESULTS: We validated decreased Arid1b mRNA and protein in Arid1b+/- mice, with signatures of increased axonal and synaptic gene expression, decreased transcriptional regulator and RNA processing expression in adult Arid1b+/- cerebellum. During neonatal development, Arid1b+/- mice exhibited robust impairments in ultrasonic vocalizations (USVs) and metrics of developmental growth. In addition, a striking sex effect was observed neuroanatomically throughout development. Behaviorally, as adults, Arid1b+/- mice showed low motor skills in open field exploration and normal three-chambered approach. Arid1b+/- mice had learning and memory deficits in novel object recognition but not in visual discrimination and reversal touchscreen tasks. Social interactions in the male-female social dyad with USVs revealed social deficits on some but not all parameters. No repetitive behaviors were observed. Brains of adult Arid1b+/- mice had a smaller cerebellum and a larger hippocampus and corpus callosum. The corpus callosum increase seen here contrasts previous reports which highlight losses in corpus callosum volume in mice and humans. LIMITATIONS: The behavior and neuroimaging analyses were done on separate cohorts of mice, which did not allow a direct correlation between the imaging and behavioral findings, and the transcriptomic analysis was exploratory, with no validation of altered expression beyond Arid1b. CONCLUSIONS: This study represents a full validation and investigation of a novel model of Arid1b+/- haploinsufficiency throughout development and highlights the importance of examining both sexes throughout development in NDDs.

Systemic inflammatory biomarkers and somatic cell count in dairy cows with subclinical mastitis.

Systemic parameters and its relationship with Somatic Cell Count (SCC) in dairy cows were evaluated. Cows that presented subclinical mastitis (SMC; n = 16) and healthy cows (HC; n = 6) were selected and identified by the California Mastitis Test and SCC in milk. SCC results were logarithmically transformed into somatic cell score (SCS). HC presented SCS 〈 4.32 while SMC presented SCS 〉 4.32. Milk and blood samples were collected in three days: D1 (first day of sampling), D2 (48 h after D1) and D3 (7 days after D1), to determine White Blood Cells (WBC), albumin, total protein, total bilirubin and malondialdehyde (MDA). Results were expressed as mean ± standard deviation. It was considered significant at P < 0.05. The data of SCS on D1, D2 and D3 in SMC were: 6.8 ± 1.7, 6.4 ± 1.8, and 6.3 ± 2.0, respectively. In SMC the MDA (nmolL-1) were: D1 - 9.3 ± 2.6, D2 - 8.6 ± 2.4, and D3 - 11.5 ± 3.5. The MDA on D3 in SMC (11.5 ± 3.5) were increase when compared to HC (6.0 ± 1.3) (P < 0.001). No significant difference was found in WBC, TP, ALB, and TB between groups. It was observed a positive correlation between MDA-SCS (ρ = 0.4) and between WBC-SCS (ρ = 0.3) in the SMC group. It was concluded that the systemic repercussion damage in the mammary gland promoted by subclinical mastitis in dairy cows can be assessed using the MDA and WBC biomarkers.

Dietary ethanol extract of mango increases antioxidant activity of pork.

Ethanol extract of mango seeds (EEMS) are composed of several polyphenolic compounds with considerable in vitro antioxidant activity that can be used in pig feed and may contribute positively to meat quality characteristics. The aim of this study was to evaluate the effect of EEMS as a source of antioxidants in growing-finishing pig diets on meat quality, lipid stability, sulfhydryl groups non-proteinaceous (SG-NP), total phenolic compounds, total antioxidant potential and total antioxidant activity of meat after 1 and 7 days of refrigeration storage. Thirty-two (60-day-old) barrows, weighing 20.20 ±â€¯1.34 kg, were used in a randomized block design consisting of eight animals with four treatment regimens. Treatments consisted of: Control = no dietary antioxidant; butylated hydroxytoluene (BHT) = diet with 200 ppm BHT; EEMS200 = diet with 200 ppm EEMS; EEMS400 = diet with 400 ppm EEMS. At 145 days of age and average weight of 95.47 ±â€¯6.19 kg, the animals were slaughtered and loin samples were collected and frozen before for qualitative analysis and evaluation of the effect of subsequent storage for 1 or 7 days at 8 °C on lipid stability, SG-NP, phenolic compounds, total antioxidant capacity and total antioxidant activity Meat from animals fed EEMS400 diet showed lower cooking loss (P < 0.0001) and higher non-protein sulfhydryl groups, phenolic compounds and total antioxidant activity at both 1 and 7 days of storage (P < 0.0001) compared to the other treatments. Greater antioxidant capacity was observed at 1 day storage in the meat of animals that consumed EEMS regardless of concentration when compared to the control group (P < 0.01). The dietary inclusion of EEMS to pig diets is more effective at 400 ppm in improving meat quality after cooking and antioxidant parameters of pork.

Sex Hormone Depletion Augments Glucocorticoid Induction of Tau Hyperphosphorylation in Male Rat Brain.

Steroid hormones secreted by the gonads (sex steroids) and adrenal glands (glucocorticoids, GC) are known to influence brain structure and function. While levels of sex steroids wane in late adulthood, corticosteroid levels tend to rise in many individuals due to age-related impairments in their feedback on central mechanisms regulating adrenal function. These fluctuations in sex and adrenal steroid secretion may be relevant to age-related neurodegenerative disorders such as Alzheimer's disease (AD) in which hyperphosphorylation of Tau protein is a key pathological event. We here report that both, long-term GC deprivation (by adrenalectomy) and exogenous GC administration with natural or synthetic glucocorticoid receptor ligands (corticosterone and dexamethasone, respectively) induce Tau hyperphosphorylation in the hippocampus and frontocortical regions at epitopes associated with disruption of cytoskeletal and synaptic function. Interestingly, we observed that the changes in Tau induced by manipulation of the GC milieu of male rats were exacerbated by testosterone depletion (by orchiectomy). While this finding supports previous suggestions of a neuroprotective role of male sex hormones, this is the first study to address interactions between adrenal and sex steroids on Tau hyperphosphorylation and accumulation that are known to endanger neuronal function and plasticity. These results are particularly important for understanding the mechanisms that can precipitate AD because, besides being modulated by age, GC are elevated by stress, a phenomenon now established as a trigger of deficits in neural plasticity and survival, cognitive behaviour and AD-like Tau pathology.