Corrigendum: Evaluation of PIK3CA mutations in advanced ER+/HER2-breast cancer in Portugal - U-PIK Project.

[This corrects the article DOI: 10.3389/fmolb.2023.1082915.].

Enterotoxigenic profiles and submerged and interface biofilms in Bacillus cereus group isolates from foods / Perfiles enterotoxigénicos y biopelículas de superficie y sumergidas en aislados del grupo Bacillus cereus de alimentos

Abstract Biofilm formation by Bacillus cereus strains is now recognized as a systematic contaminaron mechanism in foods; the aim of this study was to evaluate the production of submerged and interface biofilms in strains of B. cereus group in different materials, the effect of dex-trose, motility, the presence of genes related to biofilms and the enterotoxigenic profile of the strains. We determine biofilm production by safranin assay, motility on semi-solid medium, toxin gene profiling and genes related to biofilm production by PCR in B. cereus group iso-lated from food. In this study, we observe strains used a higher production of biofilms in PVC; in the BHI broth, no submerged biofilms were found compared to phenol red broth and phenol red broth supplemented with dextrose; no strains with the ces gene were found, the enterotoxin profile was the most common the profile that includes genes for the three enterotoxins. We observed a different distribution of tasA and sipW with the origin of isolation of the strain, being more frequent in the strains isolated from eggshell. The production and type of biofilms are differential according to the type of material and culture medium used.

Resumen La formación de biopelículas por cepas de Bacillus cereus es reconocida como un mecanismo de contaminación sistemática en alimentos; el objetivo del estudio fue evaluar la producción de biopelículas sumergidas y de superficie en cepas del grupo de Bacillus cereus en diferentes materiales, el efecto de la dextrosa, la motilidad, la presencia de genes relacionados a biopelículas y el perfil enterotoxigénico de las cepas. Determinamos la producción de biopelículas por el ensayo de safranina, motilidad en medio sólido, perfil enterotoxigénico y genes relacionados a producción de biopelículas por PCR en aislados del grupo de Bacillus cereus de alimentos. En este estudio, observamos en las cepas utilizadas una alta producción de biopelículas en PVC; en caldo BHI, no se encontraron biopelículas sumergidas en comparación con el caldo rojo de fenol y caldo rojo de fenol suplementando con dextrosa; no se encontraron cepas con el gen ces, el perfil de enterotoxinas más común fue el perfil que incluía los genes de las tres enterotoxinas, también observamos una distribución diferente de tasA y sipW con relación al origen de la cepa, siendo más frecuente estos genes en las cepas aisladas de huevos. La producción y el tipo de biopelículas es diferente de acuerdo con el tipo de material y el medio de cultivo utilizado.

Comparison of the Efficiency of Different Eradication Treatments to Minimize the Impacts Caused by the Invasive Tunicate Styela plicata in Mussel Aquaculture.

In 2017, aquaculture producers of the Albufeira lagoon, Portugal, reported an invasion of tunicates that was disrupting mussel production, particularly the tunicate Styela plicata (Lesueur, 1823). A totally effective eradication method still does not exist, particularly for S. plicata, and the effects of the eradication treatments on bivalves' performance are also poorly understood. Our study examined the effectiveness of eradication treatments using three laboratory trials and five treatments (air exposure, freshwater immersion, sodium hypochlorite, hypersaline solution and acetic acid) for S. plicata, as well as their effects on survival and growth of blue mussel Mytilus edulis Linnaeus, 1758. While air exposure and freshwater immersion caused a 27% mortality rate in S. plicata, the acetic acid treatment was the most effective in eliminating this species (>90% mortality). However, a 33-40% mortality rate was registered in mussels. Both species were not affected by the hypersaline treatment in the last trial, but the sodium hypochlorite treatment led to a 57% mortality rate in mussels. Differences in mussels' growth rates were not detected. These trials represent a step forward in responding to the needs of aquaculture producers. However, further studies are needed to investigate the susceptibility of tunicates to treatments according to sexual maturation, as well as to ensure minimum mussel mortality in the most effective treatments, and to better understand the effects on mussel physiological performance in the long-term.

Enterotoxigenic profiles and submerged and interface biofilms in Bacillus cereus group isolates from foods.

Biofilm formation by Bacillus cereus strains is now recognized as a systematic contamination mechanism in foods; the aim of this study was to evaluate the production of submerged and interface biofilms in strains of B. cereus group in different materials, the effect of dextrose, motility, the presence of genes related to biofilms and the enterotoxigenic profile of the strains. We determine biofilm production by safranin assay, motility on semi-solid medium, toxin gene profiling and genes related to biofilm production by PCR in B. cereus group isolated from food. In this study, we observe strains used a higher production of biofilms in PVC; in the BHI broth, no submerged biofilms were found compared to phenol red broth and phenol red broth supplemented with dextrose; no strains with the ces gene were found, the enterotoxin profile was the most common the profile that includes genes for the three enterotoxins. We observed a different distribution of tasA and sipW with the origin of isolation of the strain, being more frequent in the strains isolated from eggshell. The production and type of biofilms are differential according to the type of material and culture medium used.

Evaluation of PIK3CA mutations in advanced ER+/HER2-breast cancer in Portugal - U-PIK Project.

Background: Around 40% of ER+/HER2-breast carcinomas (BC) present mutations in the PIK3CA gene. Assessment of PIK3CA mutational status is required to identify patients eligible for treatment with PI3Kα inhibitors, with alpelisib currently the only approved tyrosine kinase inhibitor in this setting. U-PIK project aimed to conduct a ring trial to validate and implement the PIK3CA mutation testing in several Portuguese centers, decentralizing it and optimizing its quality at national level. Methods: Eight Tester centers selected two samples of patients with advanced ER+/HER2- BC and generated eight replicates of each (n = 16). PIK3CA mutational status was assessed in two rounds. Six centers used the cobas® PIK3CA mutation test, and two used PCR and Sanger sequencing. In parallel, two reference centers (IPATIMUP and the Portuguese Institute of Oncology [IPO]-Porto) performed PIK3CA mutation testing by NGS in the two rounds. The quality of molecular reports describing the results was also assessed. Testing results and molecular reports were received and analyzed by U-PIK coordinators: IPATIMUP, IPO-Porto, and IPO-Lisboa. Results: Overall, five centers achieved a concordance rate with NGS results (allele frequency [AF] ≥5%) of 100%, one of 94%, one of 93%, and one of 87.5%, considering the overall performance in the two testing rounds. NGS reassessment of discrepancies in the results of the methods used by the Tester centers and the reference centers identified one probable false positive and two mutations with low AF (1-3%, at the analytical sensitivity threshold), interpreted as subclonal variants with heterogeneous representation in the tissue sections processed by the respective centers. The analysis of molecular reports revealed the need to implement the use of appropriate sequence variant nomenclature with the identification of reference sequences (HGVS-nomenclature) and to state the tumor cell content in each sample. Conclusion: The concordance rates between the method used by each tester center and NGS validate the use of the PIK3CA mutational status test performed at these centers in clinical practice in patients with advanced ER+/HER2- BC.

Desafios no atendimento a mulheres vítimas de violência de gênero na universidade / Challenges in assisting women victims of gender violence at the university / Retos en la atención a mujeres víctimas de violencia de género en la universidad

INTRODUÇÃO: A violência de gênero é um problema de saúde pública que atinge majoritariamente as mulheres, prejudicando sua saúde mental e física. Esse tipo de violência encontra espaço também no campo universitário, fazendo com que as mulheres envolvidas tenham seu desempenho acadêmico e profissional afetado. Para combater esse fenômeno, é necessário atuação conjunta que envolva diversos setores e a qualificação de profissionais que mobilizem novos saberes voltados para a emancipação da mulher. OBJETIVO: O presente estudo buscou investigar a atuação de técnicos administrativos de uma universidade federal junto a vítimas de violência de gênero, identificando os desafios e dificuldades vivenciados por esses profissionais. MÉTODO: Foram entrevistados 8 técnicos(as) administrativos(as) utilizando um roteiro semiestruturado elaborado pela pesquisadora. Os dados foram analisados qualitativamente a partir da análise temática. RESULTADOS: Os resultados indicaram conhecimento sobre a violência de gênero, ferramentas e técnicas eficientes para promover um modelo de atenção integral e conhecimento da rede de atendimento. Evidenciaram-se dificuldades relacionadas a questões estruturais, como a falta de políticas e medidas de enfrentamento e desarticulação das ações. CONCLUSÃO: A pesquisa realizada demonstrou a falta de estratégias de enfrentamento para lidar com questões de violência de gênero dentro do contexto universitário e contribui no sentido de proporcionar maior reflexão acerca do funcionamento do atendimento a tais vítimas.

INTRODUCTION: Gender violence is a public health problem that mostly affects women, harming their mental and physical health. This type of violence also finds space in the university field, causing the women involved to have their academic and professional performance affected. To combat this phenomenon, it is necessary to act together, involving different sectors and the qualification of professionals who mobilize new knowledge aimed at the emancipation of women. OBJECTIVE: The present study sought to investigate the performance of administrative technicians from a federal university with victims of gender violence, identifying the challenges and difficulties experienced by these professionals. METHOD: Eight administrative technicians were interviewed using a semi-structured script prepared by the researcher. Data were analyzed qualitatively using thematic analysis. RESULTS: The results indicated knowledge about gender violence, efficient tools and techniques to promote a comprehensive care model and knowledge of the care network. Difficulties related to structural issues were evident, such as the lack of policies and measures to confront and disarticulate actions. CONCLUSION: The research demonstrated the lack of coping strategies to deal with issues of gender violence within the university context and contributes to providing greater reflection on the functioning of care for such victims.

INTRODUCCIÓN: La violencia de género es un problema de salud pública que afecta principalmente a las mujeres, perjudicando su salud mental y física. Este tipo de violencia también encuentra espacio en el ámbito universitario, provocando que las mujeres involucradas vean afectado su desempeño académico y profesional. Para combatir este fenómeno se necesita una acción conjunta, involucrando a diferentes sectores y la cualificación de profesionales que movilicen nuevos conocimientos encaminados a la emancipación de la mujer. OBJETIVO: Este estudio buscó investigar la actuación de técnicos administrativos de una universidad federal con víctimas de violencia de género, identificando los desafíos y dificultades experimentados por estos profesionales. MÉTODO: Ocho técnicos administrativos fueron entrevistados mediante guión semiestructurado elaborado por la investigadora. Los datos fueron analizados cualitativamente mediante análisis temático. RESULTADOS: Los resultados indicaron conocimiento sobre violencia de género, herramientas y técnicas eficientes para promover un modelo de atención integral y conocimiento de la red de atención. Se evidenciaron dificultades relacionadas con cuestiones estructurales, como la falta de políticas y medidas para enfrentar y desarticular acciones. CONCLUSIÓN: La investigación realizada demostró la falta de estrategias de enfrentamiento para abordar problemáticas de violencia de género en el contexto universitario y contribuye a brindar una mayor reflexión sobre el funcionamiento de la atención a estas víctimas.

Genetic diversity of enterotoxigenic Bacillus cereus strains in coriander in southwestern Mexico.

Background: Coriander, like other leafy green vegetables, is available all year round and is commonly consumed raw in Mexico as in other countries in the preparation of street or homemade food. Bacillus cereus (B. cereus) is a microorganism that can reach coriander because it is usually found in the soil and in some regions the vegetables are irrigated with polluted water. Therefore, the aim of this study was to determinate the presence of B. cereus in coriander used for human consumption in southwestern Mexico and determine the toxigenic profile, biofilm production, genes associated with the production of biofilms, sporulation rates, enzymatic profile, psychotropic properties, and genetic diversity of B. cereus. Methods: Fresh coriander samples were collected from several vegetable retailers in different markets, microbiological analysis was performed. Molecular identification, genes related to the production of biofilm, and toxin gene profiling of B. cereus isolates were determined by PCR. The biofilm formation was measured by performing a crystal violet assay. The genetic diversity of B. cereus strains was determined by PCR of repetitive elements using oligonucleotide (GTG) 5. Results: We found a frequency of B. cereus in vegetables was 20% (13/65). In this study, no strains with genes for the HBL toxin were found. In the case of genes related to biofilms, the frequency was low for sipW [5.8%, (1/17)] and tasA [11.7%, (2/17)]. B. cereus strains produce a low amount of biofilm with sporulation rates around 80%. As for genetic diversity, we observed that strains isolated from the same market, but different vegetable retailers are grouped into clusters. In the coriander marketed in southwestern Mexico, were found B. cereus strains with genes associated with the production of diarrheal toxins. Together, these results show actual information about the state of art of B. cereus strains circulating in the southwestern of Mexico.

Antioxidant and Anti-inflammatory Extracts From Sea Cucumbers and Tunicates Induce a Pro-osteogenic Effect in Zebrafish Larvae.

Bone metabolic disorders such as osteoporosis are characterized by the loss of mineral from the bone tissue leading to its structural weakening and increased susceptibility to fractures. A growing body of evidence suggests that inflammation and oxidative stress play an important role in the pathophysiological processes involved in the rise of these conditions. As the currently available therapeutic strategies are often characterized by toxic effects associated with their long-term use, natural antioxidants and anti-inflammatory compounds such as polyphenols promise to be a valuable alternative for the prevention and treatment of these disorders. In this scope, the marine environment is becoming an important source of bioactive compounds with potential pharmacological applications. Here, we explored the bioactive potential of three species of holothurians (Echinodermata) and four species of tunicates (Chordata) as sources of antioxidant and anti-inflammatory compounds with a particular focus on polyphenolic substances. Hydroethanolic and aqueous extracts were obtained from animals' biomass and screened for their content of polyphenols and their antioxidant and anti-inflammatory properties. Hydroethanolic fractions of three species of tunicates displayed high polyphenolic content associated with strong antioxidant potential and anti-inflammatory activity. Extracts were thereafter tested for their capacity to promote bone formation and mineralization by applying an assay that uses the developing operculum of zebrafish (Danio rerio) to assess the osteogenic activity of compounds. The same three hydroethanolic fractions from tunicates were characterized by a strong in vivo osteogenic activity, which positively correlated with their anti-inflammatory potential as measured by COX-2 inhibition. This study highlights the therapeutic potential of polyphenol-rich hydroethanolic extracts obtained from three species of tunicates as a substrate for the development of novel drugs for the treatment of bone disorders correlated to oxidative stress and inflammatory processes.

Redes de apoio à mulher em situação de violência durante a pandemia de Covid-19 / Support networks for women in situations of violence during the Covid-19 pandemic / Redes de apoyo a mujeres en situación de violencia durante la pandemia de Covid-19

A adoção de medidas de distanciamento social decorrentes da pandemia de covid-19 agravou o fenômeno da violência contra as mulheres, especialmente a praticada por parceiros íntimos (VPI). O presente artigo tem por objetivo analisar a VPI em contexto de pandemia e descrever iniciativas de proteção à mulher em situação de VPI. A partir da análise sobre a VPI, suas consequências e formas de enfrentamento, foram descritas ações tanto das redes formais quanto das redes informais de apoio à mulher. Por meio de buscas no Google e nas redes sociais, foram levantadas as seguintes estratégias de combate à VPI: a capacitação dos profissionais de saúde para identificação de sinais de violência e o desenvolvimento de aplicativos, projetos e campanhas de conscientização, incentivo à denúncia e acolhimento das vítimas. É notória a necessidade das redes de apoio para a prevenção da VPI e de pesquisas futuras que avaliem as potencialidades dessas estratégias.

The adoption of social distance measures resulting from the covid-19 pandemic has aggravated the phenomenon of violence against women, especially that practiced by an intimate partner (IPV). This article aims to reflect on IPV in a pandemic context and describe existing initiatives to protect women in a situation of IPV. Based on the analysis of IPV, its consequences and coping strategies, actions were described both from formal and informal networks to support women. Searches on Google and social media raised the following strategies for combating IPV: the training of health professionals to identify signs of violence and the development of apps, projects and awareness-raising campaigns, to report violence and welcome victims in a pandemic context. There is a clear need for support networks to prevent the IPV and for future research to assess the potential of these strategies.

La adopción de medidas de distancia social derivadas de la pandemia de covid-19 ha agravado el fenómeno de la violencia contra las mujeres, especialmente la practicada por parejas (VPM). Este artículo tiene como objetivo analizar la VPM en contexto de pandemia y describir iniciativas para proteger a las mujeres en esa situación. A partir del análisis de la VPM, sus consecuencias y formas de afrontamiento, se describieron acciones tanto de las redes formales como informales de apoyo a las mujeres. A través de búsquedas en Google y redes sociales, se plantean las siguientes estrategias para combatir la VPM: la capacitación de profesionales de la salud para identificación de señales de violencia y el desarrollo de aplicaciones, proyectos y campañas de sensibilización, incentivo a la denuncia y acogida de las víctimas. Las redes de apoyo resultan esenciales para la prevención de VPM. Futuras investigaciones podrán evaluar el potencial de estas estrategias.

BR-BCSC Signature: The Cancer Stem Cell Profile Enriched in Brain Metastases that Predicts a Worse Prognosis in Lymph Node-Positive Breast Cancer.

Brain metastases remain an unmet clinical need in breast oncology, being frequently found in HER2-overexpressing and triple-negative carcinomas. These tumors were reported to be highly cancer stem-like cell-enriched, suggesting that brain metastases probably arise by the seeding of cancer cells with stem features. Accordingly, we found that brain-tropic breast cancer cells show increased stem cell activity and tumorigenic capacity in the chick embryo choriallantoic membrane when compared to the parental cell line. These observations were supported by a significant increase in their stem cell frequency and by the enrichment for the breast cancer stem cell (BCSC) phenotype CD44+CD24-/low. Based on this data, the expression of BCSC markers (CD44, CD49f, P-cadherin, EpCAM, and ALDH1) was determined and found to be significantly enriched in breast cancer brain metastases when compared to primary tumors. Therefore, a brain (BR)-BCSC signature was defined (3-5 BCSC markers), which showed to be associated with decreased brain metastases-free and overall survival. Interestingly, this signature significantly predicted a worse prognosis in lymph node-positive patients, acting as an independent prognostic factor. Thus, an enrichment of a BCSC signature was found in brain metastases, which can be used as a new prognostic factor in clinically challenging breast cancer patients.

Biofilm Production by Enterotoxigenic Strains of Bacillus cereus in Different Materials and under Different Environmental Conditions.

Foodborne illnesses, such as infections or food poisoning, can be caused by bacterial biofilms present in food matrices or machinery. The production of biofilms by several strains of Bacillus cereus on different materials under different culture conditions was determined, as well as the relationship of biofilms with motility, in addition to the enterotoxigenic profile and candidate genes that participate in the production of biofilms. Biofilm production of B. cereus strains was determined on five materials: glass, polystyrene, polyethylene, polyvinylchloride (PVC), PVC/glass; in three culture media: Phenol red broth, tryptic soy broth, and brain heart infusion broth; in two different temperatures (37 °C and 25 °C), and in two different oxygen conditions (oxygen and CO2 tension). Furthermore, the strains were molecularly characterized by end-point polymerase chain reaction. Motility was determined on semi-solid agar. The B. cereus strains in this study were mainly characterized as enterotoxigenic strains; statistically significant differences were found in the PVC material and biofilm production. Motility was positively associated with the production of biofilm in glass/PVC. The sipW and tasA genes were found in two strains. The results of this study are important in the food industry because the strains carry at least one enterotoxin gene and produce biofilms on different materials.

360 Health Analysis (H360) - A Proposal for an Integrated Vision of Breast Cancer in Portugal.

H360 aims to provide a comprehensive picture of breast cancer management in Portugal by retrieving real-world data from 10 Portuguese hospitals and deriving a snapshot from the medical interpretation of evidence-based data to patient perspective on the quality and effectiveness of medical care provided. This article reviews evidence on breast cancer clinical practice and quality of care and disease management in Portugal. A review of evidence on breast cancer clinical practice and quality of care over the last 10 years was performed in PubMed using the query "Organization and Administration"[Mesh] AND "breast cancer"[All Fields] NOT "Review" [ptyp]. National cancer initiatives relevant for quality of care and national and international guidelines and consensus were analyzed. Retrieved results showed that breast cancer incidence is still increasing, including in Portugal. Studies investigating disease outcomes seek to derive improvements to clinical practice and better financial resource allocation. Setting performance measures (KPIs) in institutions treating cancer is not a reality in Portugal yet, but has potential to leverage the quality of clinical performance. A multidisciplinary approach within one health structure is also desirable. More investment in clinical (including academic) research is key to optimize the quality of care. Implementation of clinical practice guidelines (largely based on ESMO guidelines in Portugal) is crucial to improve patient outcomes. Not less importantly, quality of life is a treatment goal on its own in breast cancer care. Breast cancer remains a health challenge and a multidimensional, 360-degree appraisal, beyond the exclusively clinical perspective, may provide new insights towards an optimal patient-centered approach.

Prevalencia de cepas del grupo de Bacillus cereus productoras de biopelicula en helados comercializados en México / Prevalence of strains of the Bacillus cereus group biofilm producers in ice cream in Mexico

El helado es un vehículo para la transmisión de patógenos como Bacillus cereus. Por lo cual, se determinó la frecuencia de cepas del grupo Bacillus cereus en helados, perfil enterotoxigénico, psicrofilia y producción de biopelícula. Un total de 230 muestras de seis marcas de helado de producción y distribución nacional fueron colectadas en México. El análisis microbiológico incluyó aislamiento en agar manitol yema de huevo. Las cepas se identificaron molecularmente a partir de la amplificación del gen de la topoisomerasa (gyrB) y el perfil enterotoxigénico por la amplificación de regiones conservadas de los operones nheABC y hblABD y del gen cytK. Además, se determinó la producción de biopelícula en vidrio y policloruro de vinilo. La frecuencia de contaminación por cepas del grupo B. cereus fue de 3,6%, se encontró una cepa positiva para nheABC y cinco para cytK, el 87,5% de las cepas generó biopelícula en vidrio y todas en policloruro de vinilo, dos cepas fueron psicrofilicas. En conclusión, en el helado distribuido en México, se encontró una baja contaminación por cepas del grupo B. cereus con alta producción de biopelícula; sin embargo, no se debe subestimar el potencial enterotoxigénico de estas cepas

Ice cream is a medium for microbial growth due to its nutritional value and neutral pH. Therefore, the frequency of strains of the Bacillus cereus group in ice cream was determined, the enterotoxigenic profile, psychrophilic strains and biofilm production. A total of 230 samples of six brands of ice cream produced and distributed nationwide were collected in Mexico. The microbiological analysis was a cold pre-enrichment and isolation of the microorganism in egg yolk agar. The strains were identified molecularly from the amplification of the topoisomerase gene (gyrB) and the enterotoxigenic profile by the amplification of conserved regions of the nheABC and hblABD operons and of the cytK gene. In addition, the production of biofilm in glass and polyvinyl chloride and psychophilia was determined. The frequency of contamination by strains of the B. cereus group was 3.6%, a positive strain was found for nheABC and five for cytK, 87.5% of the strains generated biofilm in glass and all in polyvinyl chloride, two strains were psychrophilic. In the ice cream distributed in Mexico, a low contamination by strain of the B. cereus group was found, however, the enterotoxigenic potential of the strains should not be underestimated

[Ultrasound Assessment of Ventilator-induced Diaphragmatic Dysfunction in Paediatrics]. / Avaliação Ecográfica da Disfunção Diafragmática Induzida pelo Ventilador em Idade Pediátrica.

INTRODUCTION: Invasive mechanical ventilation contributes to ventilator-induced diaphragmatic dysfunction, delaying extubation and increasing mortality in adults. Despite the possibility of having a higher impact in paediatrics, this dysfunction is not routinely monitored. Diaphragm ultrasound has been proposed as a safe and non-invasive technique for this purpose. The aim of this study was to describe the evolution of diaphragmatic morphology and functional measurements by ultrasound in ventilated children. MATERIAL AND METHODS: Prospective exploratory study. Children admitted to Paediatric Intensive Care Unit requiring mechanical ventilation > 48 hours were included. The diaphragmatic thickness, excursion and the thickening fraction were assessed by ultrasound. RESULTS: Seventeen cases were included, with a median age of 42 months. Ten were male, seven had comorbidities and three in seventeen had malnutrition at admission. The median time under mechanical ventilation was seven days. The median of the initial and minimum diaphragmatic thickness was 2.3 mm and 1.9 mm, respectively, with a median decrease in thickness of 13% under pressure-regulated volume control. Diaphragmatic atrophy was observed in 14/17 cases. Differences in the median thickness variation were found between patients with sepsis and without (0.70 vs 0.25 mm; p = 0.019). During pressure support ventilation there was a tendency to increase diaphragmatic thickness and excursion. Extubation failure occurred for diaphragmatic thickening fraction ≤ 35%. DISCUSSION: Under pressure-regulated volume control there was a tendency for a decrease in diaphragmatic thickness. In the pre-extubation stage under pressure support, there was a tendency for it to increase. These results suggest that, by titrating ventilation using physiological levels of inspiratory effort, we can reduce the diaphragmatic morphological changes associated with ventilation. CONCLUSION: The early recognition of diaphragmatic changes may encourage a targeted approach, namely titration of ventilation, in order to reduce ventilator-induced diaphragmatic dysfunction and its clinical repercussions.

Introdução: A ventilação mecânica invasiva condiciona disfunção diafragmática, atrasando a extubação e aumentando a mortalidade em adultos. Em pediatria, apesar de eventualmente mais relevante, essa disfunção não é sistematicamente avaliada. A ecografia diafragmática tem sido proposta como uma técnica não invasiva e segura para esse fim. O objetivo deste estudo foi descrever a evolução dos índices ecográficos de morfologia e função diafragmáticas em crianças ventiladas. Material e Métodos: Estudo exploratório, prospetivo. Foram incluídas crianças admitidas num Serviço de Cuidados Intensivos Pediátricos sob ventilação mecânica invasiva > 48 horas e realizadas medições ecográficas de espessura, excursão e fração de espessamento diafragmáticas. Resultados: Foram incluídos 17 casos. Mediana de idades: 42 meses. Eram do género masculino 10/17, tinham comorbilidades 7/17 e manifestavam desnutrição na admissão 3/17 casos. Mediana do tempo sob ventilação invasiva: sete dias. Medianas das espessuras diafragmáticas inicial e mínima: 2,3 e 1,9 mm, respetivamente, tendo-se observado uma diminuição mediana da espessura de 13% sob volume controlado regulado por pressão. Observou-se atrofia diafragmática em 14/17 casos. Verificaram-se diferenças na mediana da variação da espessura entre os grupos com e sem sépsis (0,70 vs 0,25 mm; p = 0,019). Durante a ventilação em pressão de suporte, observou-se uma tendência para aumento da espessura e excursão diafragmáticas. Ocorreu falência de extubação parafração de espessamento ≤ 35%. Discussão: Sob volume controlado regulado por pressão verificou-se tendência para diminuição da espessura diafragmática. Sob pressão de suporte, verificou-se uma tendência para o seu aumento. Estes resultados sugerem que, titulando a ventilação, podemos reduzir as alterações morfológicas diafragmáticas associadas à ventilação. Conclusão: O reconhecimento precoce de alterações diafragmáticas poderá fomentar uma abordagem dirigida, de forma a limitar a disfunção diafragmática induzida pelo ventilador e suas repercussões.

Clinical and translational pharmacology of drugs for the prevention and treatment of bone metastases and cancer-induced bone loss.

Bone disease is a frequent event in cancer patients, both due to cancer spread to bone and to cancer therapies. Bone is the organ most frequently affected by metastatic disease when considering the two most frequent cancers in the Western world (breast and prostate cancers). Bone metastases can have a substantial detrimental effect on patients' quality of life, as well as significant morbidity due to complications collectively known as skeletal-related events (SREs), which include hypercalcaemia, pathological fractures, spinal cord compression, and need of radiotherapy or surgery to the bone. These have been successfully mitigated with the development of bone-targeted agents (BTAs; bisphosphonates and denosumab), focused on inhibiting osteoclast activity. The potential direct antitumour effect of bisphosphonates, as well as the impact of osteoclast inhibition with subsequent decrease in bone metabolism, have also propelled investigation on the role of BTAs in preventing cancer relapse in bone. In this review, the authors aimed to discuss the role of BTAs in the treatment and prevention of bone metastases, as well as their potential value in preventing cancer treatment-induced bone loss (CTIBL). The review will focus on breast and prostate cancers, with the aim of providing the most relevant clinical data emerging from bench to bedside translational research in the field of cancer-induced bone disease.

Methicillin-Resistant Staphylococcus aureus (MRSA) in Artisanal Cheeses in México.

Milk and dairy foods have frequently been implicated in staphylococcal food poisoning, and contaminated raw milk is often involved. The aim of the study was to determine the occurrence of methicillin-resistant Staphylococcus aureus (MRSA) in raw cow milk cheese produced in Mexico. A total of 78 unpasteurized cow milk cheese samples were screened for S. aureus. The isolates were identified as S. aureus based on morphology, Gram stain, catalase test, coagulase test, and mannitol salt agar fermentation. Isolates were subjected to biotyping, the methicillin resistance was analyzed using the disk diffusion, and the Staphylococcus enterotoxin A (SEA) production was examined by a dot-blot analysis. From a total of 78 samples of unpasteurized cheeses analyzed in this study, 44 cheeses were positive for S. aureus; however, a differential contamination between the different types of cheeses was observed, with high risk of contamination in adobero cheese (12, 95% CI 1.75 to 94.20; p=0.002). In this study, the frequency of methicillin-resistant Staphylococcus aureus (MRSA) was 18.1% (8/44) and of enterotoxin A producers was 18.1% (8/44). When classified by biotypes, MRSA only belongs to the human ecovar biotype (2/8, 25%) and the D biotype (4/8, 50%). S. aureus producers of enterotoxin A were distributed in specific nonhost biotypes.

P-cadherin: a useful biomarker for axillary-based breast cancer decisions in the clinical practice.

Axillary lymph node metastases represent the most powerful breast cancer prognostic factor, dictating disease staging and clinical therapeutic decisions. Nonetheless, breast cancer patients with positive lymph nodes still exhibit a heterogeneous behavior regarding disease progression. Stem-like subpopulations of cancer cells show high migratory and metastatic capacity, thus we hypothesize that breast cancer stem cell markers evaluation in metastasized lymph nodes could provide a more accurate prediction of patient's prognosis. Therefore, the expression profile of P-cadherin, CD44, and CD49f, which have been already associated to stem cell properties in breast cancer, has been evaluated by immunohistochemistry in a series of 135 primary tumors and matched axillary lymph node metastases from 135 breast cancer patients. Taking in consideration the expression of the stem cell markers only in axillary nodes, P-cadherin was the only biomarker significantly associated with poor disease-free and overall patient's survival. Moreover, although a concordant expression between primary tumors and matched lymph nodes has been found in the majority of the cases, a small but significant percentage displayed divergent expression (18.2-26.2%). Remarkably, although CD44 and CD49f changes between primary tumors and lymph node metastasis did not impact survival, the cases that were positive for P-cadherin in lymph node metastases being negative in the primary tumor, presented the worst disease-free and overall survival of the whole series. Accordingly, negative cases for this marker in the lymph nodes with positive expression in the matched breast carcinoma demonstrated a better prognosis, which overlapped with tumors that were negative in both sites. P-cadherin and CD49f gain of expression was mainly found in triple-negative carcinomas. Our results indicate for the first time that the evaluation of P-cadherin expression in lymph node metastases is an important predictor of disease outcome, being a putative valuable marker for axillary-based breast cancer decisions in the clinical practice.

Metronomic chemotherapy for advanced breast cancer patients.

Metronomic chemotherapy refers to the minimum biologically effective dose of a chemotherapy agent given as a continuous dosing regimen with no prolonged drug-free breaks that leads to antitumor activity. This schedule seems to have not only a direct cytotoxicity on cancer cells but also an effect on the tumor microenvironment by inhibiting tumor angiogenesis and modulating immune response. Metronomic chemotherapy was widely investigated in patients with breast cancer. The results of these studies showed that this strategy is not only effective but has a low toxicity profile too, proposing as a promising strategy for breast cancer patients. In this review we summarize the results of Phase II and III studies evaluating metronomic therapy in metastatic breast cancer.

Sobreexpresión de C-MET en carcinoma de vesícula y del tracto biliar: prevalencia y correlación clínico-molecular / Overexpression of C-MET in gallbladder and biliary tract carcinoma: prevalence and clinical-molecular correlation

El objetivo fue determinar la sobreexpresión de c-MET en pacientes con cáncer biliar y analizar asociaciones con parámetros clínicos. Este es un estudio descriptivo, longitudinal, retrospectivo y prospectivo. Se determinó la sobreexpresión por inmunohistoquímica en 58 pacientes con resultados: positivo fuerte, positivo débil y negativo. Se construyeron curvas de supervivencia global con el método de KaplanMeier en todos los pacientes y en subgrupos según estadío, género, origen tumoral y grado de diferenciación histológica. La diferencia en supervivencia global entre subgrupos se analizó por el método log-rank. La asociación entre sobreexpresión y grado de diferenciación se estudió por el método chi cuadrado. Las pruebas estadísticas se realizaron a dos colas con un valor de p 0.05. Veintinueve muestras (50%) fueron negativas, 24 (41%) positivas débiles y 5 (9%) positivas fuertes. La mediana de supervivencia fue 18.2, 11.3 y 11.7 meses en pacientes con sobreexpresión negativa, positiva débil y positiva fuerte, respectivamente. Sin embargo, la diferencia en supervivencia global entre pacientes c-MET negativos y positivos (fuerte y débil) no alcanzó significancia estadística (p 0.068). En los subgrupos los resultados fueron similares. La sobreexpresión se asoció al grado de diferenciación (p 0.015), mostrando una relación inversa; y no se correlacionó con tasa de respuesta a la quimioterapia y tiempo a la progresión. La sobreexpresión de c-MET es frecuente en cáncer biliar, se asocia al grado de diferenciación tumoral y podría tener valor pronóstico. Si la vía c-MET es importante, los fármacos inhibidores tendrían impacto en la supervivencia global (AU)

The objective was to determine the overexpression of c-MET in patients with biliary cancer and to analyze associations with clinical parameters. This is a descriptive, longitudinal, retrospective and prospective study. Overexpression was obtained by immunohistochemistry in 58 patients, with the following results: strong positive, weak positive and negative. Overall survival curves were constructed using the Kaplan-Meier method in all patients and in subgroups according to stage, gender, tumor origin and grade of histological differentiation. The difference in overall survival between groups was analyzed by the log-rank test. The association between overexpression and grade of differentiation was studied using the chisquare method. Statistical tests were two-tailed with a p value 0.05. Twenty nine samples (50%) were negative, 24 (41%) weak positive and 5 (9%) strong positive. Median survival was 18.2, 11.3 and 11.7 months in patients with negative, weak positive and strong positive overexpression, respectively. However, the difference in overall survival between negative and positive (strong and weak together) c-MET patients did not reach statistical significance (p 0.068). In the subgroup analyses the results were similar. Overexpression correlated with tumor grade (p 0.015), showing an inverse association; and was not associated neither with chemotherapy response rate nor with time to progression. Overexpression of c-MET is common in biliary cancer, is associated with grade of tumor differentiation and could have prognostic value. If the c-MET pathway is important, the inhibitory drugs would have an impact on overall survival (AU)