Multifunctional mats by antimicrobial nanoparticles decoration for bioinspired smart wound dressing solutions.

Developing advanced materials for wound dressings is a very challenging, yet unaddressed task. These systems are supposed to act as temporary skin substitutes, performing multiple functions, including fluid absorption and antimicrobial action, supporting cell proliferation and migration in order to promote the skin regeneration process. Following a global bioinspired approach, in this study, we developed a multifunctional textile for wound dressing applications. Biodegradable polyhydroxybutyrate/poly-3-caprolactone (PHB/PCL) mats were fabricated by electrospinning to mimic the extracellular matrix (ECM), thus providing structural and biochemical support to tissue regeneration. Furthermore, inspired by nature's strategy which exploits melanin as an effective weapon against pathogens infection, PHB/PCL mats were modified with hybrid Melanin-TiO2 nanostructures. These were combined to PHB/PCL mats following two different strategies: in-situ incorporation during electrospinning process, alternately ex-post coating by electrospraying onto obtained mats. All samples revealed huge water uptake and poor cytotoxicity towards HaCat eukaryotic cells. Melanin-TiO2 coating conferred PHB/PCL mats significant antimicrobial activity towards both Gram(+) and Gram(-) strains, marked hydrophilic properties as well as bioactivity which is expected to promote materials-cells interaction. This study is going to provide a novel paradigm for the design of active wound dressings for regenerative medicine.

Nose-pharyngeal swabs as a screening test for SARS-CoV-2 infection in patients with scheduled elective surgery: the experience of the Hygiene Service of the Local Health Authority Roma 1.

ABSTRACT: The COVID-19 (COrona Virus Disease 2019), due to the SARS-COV-2 (Severe Acute Respiratory Syndrome Corona Virus 2) has been an unprecedented global challenge for the healthcare systems (1).

Characterisation of EFV12 a bio-active small peptide produced by the human intestinal isolate Lactobacillus gasseri SF1109.

EFV12 is a small bioactive peptide produced by Lactobacillus gasseri SF1109, a human intestinal isolate with probiotic features. In this study, EFV12 antimicrobial and anti-inflammatory properties are characterised. In particular, we propose a possible mechanism of action for EFV12 involving bacterial membranes targeting. Moreover, we show that this small peptide is able to bind lipopolysaccharides (LPS) and to counteract its inflammatory insult preventing LPS action on Toll-like receptor 4, thus interfering with extracellular signal-regulated kinase, p38 and Jun N-terminal kinase, mitogen-activated protein kinases signalling pathways. Altogether these observations suggest that the bioactive peptide EFV12 is a good candidate to promote L. gasseri induced gut homeostasis and counteracting intestinal pathogens.

New records of Batrachochytrium dendrobatidis in the state of Bahia, Brazil: histological analysis in anuran amphibian collections.

Infection caused by the fungus Batrachochytrium dendrobatidis (Bd) produces chytridiomycosis, a disease considered one of the main causes of amphibian population declines in the world. In Brazil, Bd has been recorded in several regions, but mainly in the Atlantic Forest biome. This study aimed to investigate the occurrence of Bd in amphibian species in Bahia State to test the hypothesis that Bd is widespread in other Brazilian biomes. Using histological analysis, we evaluated the skin of 190 anurans of 85 species preserved in herpetological collections. Based on these analyses, the distribution of Bd was extended approximately 400 km to the west, 150 km to the north and 105 km to the east in the state of Bahia. Of the 190 specimens analyzed, Bd infection was diagnosed in 16 individuals, from 14 species, with the earliest record from a specimen collected in 1996 in the Caatinga biome. We identified Bd in 13 adult specimens, including 2 individuals showing suggestive signs of the disease (loss of skin pigmentation). In tadpoles, we recorded fungal structures in the oral region and on the epidermis adjacent to the rows of teeth. The results of this study corroborate the prediction that Bd is widespread in the Atlantic Forest biome, and suggest that it is widespread in the other biomes of the state (Cerrado and Caatinga, at least since 1996). Conservation efforts should involve long-term studies aimed at providing information on the dynamics of the infection, its relationship with its host and its effect on amphibian populations.

Akkermansia muciniphila: key player in metabolic and gastrointestinal disorders.

OBJECTIVE: Gut microbiota has a key role in host metabolic regulation and immune response, and its dysbiosis represents one of the main causes of gastrointestinal diseases. In this scenario, Akkermansia muciniphila is a crucial player in keeping the integrity of the gastrointestinal tract. MATERIALS AND METHODS: This review focuses on the correlation between gut microbiota and intestinal homeostasis, primarily exploring A. muciniphila and its involvement in the development of metabolic disorders and gastrointestinal diseases. RESULTS: Akkermansia muciniphila belongs to the Verrucomicrobia phylum, and it colonizes the mucus layer in the gastrointestinal tract, representing 1 to 4% of the fecal microbiota. It stimulates mucosal microbial networks, and it improves intestinal barrier function, providing crucial host immunological responses. Several studies have demonstrated the possible involvement of A. muciniphila in the development of intestinal and metabolic disorders. Indeed, adipose and glucose metabolisms are influenced by A. muciniphila, and its levels inversely correlate to inflammatory conditions, such as inflammatory bowel disease, obesity, and diabetes. Conversely, its therapeutic administration decreases their development. CONCLUSIONS: A. muciniphila exerts a key role in the maintenance of intestinal health and in host metabolic modulation. Future studies could open new horizons towards its potential therapeutic applications in gastrointestinal and extra-intestinal diseases.

Comparison of cheeses from goats fed 7 forages based on a new health index.

This study proposed the General Health Index of Cheese (GHIC) as an indicator for the presence of health-promoting compounds in cheese and compared the antioxidant capacity and phenolic and fatty acid contents of cheeses from goats consuming 7 forage species. Ninety-one homogeneous Red Syrian goats were randomly assigned to 1 of 7 feeding treatments (Festuca arundinacea, Hordeum vulgare, Triticosecale, Pisum sativum, Trifolium alexandrinum, Vicia sativa, and Vicia faba minor). The housed goat groups received the scheduled forage ad libitum. Forage species affected the antioxidant capacity, the phenolic and fatty acid contents, the Health Promoting Index, and the GHIC. Trifolium alexandrinum, Triticosecale, and Hordeum vulgare showed a clear advantage in terms of beneficial fatty acids content in goat cheese. Cheese from the Triticosecale group also showed a high antioxidant capacity value even if its polyphenol content was intermediate compared with others. Trifolium alexandrinum and Triticosecale had the highest value of the new index GHIC. This comparison suggests that there are important differences in fatty acid profile and polyphenol content among cheeses from goats fed grasses and legumes commonly used in the Mediterranean area. In this first approach, GHIC index, which combines the positive components found in cheese, seems to be a useful tool to provide an indication concerning the general health value of the product.

Attenuation of negative effects of senescence in human skin using an extract from Sphingomonas hydrophobicum: development of new skin care solution.

OBJECTIVE: Intrinsic skin ageing is mainly caused by cellular senescence. p16 and p21 are two important tumour suppressor proteins that play essential roles during cell proliferation and ageing through regulating the expression of several genes. Moreover, physical changes between the ages of 55 and 60 years affect one's physical and disrupt self-esteem. The cosmetics industry has focused on bioactive substances derived from natural products such as plants, mushrooms and marine algae to counteract the deleterious effect on skin senescence. Besides these products, compounds produced by bacteria may decelerate individual senescence. METHODS: In order to evaluate the potential benefits of bacteria extract over skin ageing, we investigated whether a Sphingomonas hydrophobicum (SH) extract is able to protect our skin against senescence mechanisms. We used an ageing full-thickness skin equivalent model, which was treated or not with the bacteria extract in a systemic way for 42 days. p21 and p16 and senescence-associated galactosidase activity were used to detect cellular senescence with immunohistology. Using a psychobiological approach, we evaluated in vivo the effect of SH extract on self-esteem, isotropy and suppleness. RESULTS: Sphingomonas extract significantly suppressed senescence associated with ß-galactosidase activation. It also significantly inhibited the expression of cell cycle inhibitors (p21 and p16). At the same time, the bacteria extract has a significant positive impact on the issue by increasing the expression of versican and fibrillin-1. Significant improvements of self-esteem were reported after 56 days of SH extract application. These psychological benefits were accompanied by a significant improvement in skin suppleness and isotropy. CONCLUSION: Sphingomonas extract delays intrinsic skin ageing process by inhibiting cellular senescence, and has also the capability to restructure the skin. These beneficial physiological effects induced by SH extract have a positive influence on self-esteem. Because skin ageing causes emotional distress, SH extract can serve as an anti-ageing cosmeceutical agent and help to build a better psychological health, and help individuals to assume ageing.

OBJECTIF: Le vieillissement intrinsèque de la peau est principalement causé par la sénescence cellulaire. p16 et p21 sont deux importantes protéines suppressives de tumeurs qui jouent un rôle essentiel dans la prolifération et le vieillissement cellulaire en régulant l'expression de plusieurs gènes. De plus, les changements physiques survenant entre 55 et 60 ans affectent le physique et perturbent l'estime de soi. L'industrie cosmétique s'est concentrée sur les substances bioactives dérivées de produits naturels tels que les plantes, les champignons et les algues marines pour contrer les effets délétères sur la sénescence de la peau. En plus de ces produits, les composés produits par les bactéries peuvent ralentir la sénescence individuelle. MÉTHODES: Afin d'évaluer les bénéfices potentiels de l'extrait de bactérie sur le vieillissement cutané, nous avons étudié si un extrait de Sphingomonas hydrophobicum (SH) est capable de protéger notre peau des mécanismes de sénescence. Nous avons utilisé un modèle équivalent de peau vieillissante de pleine épaisseur, qui a été traitée ou non avec l'extrait de bactérie de façon systémique pendant 42 jours. p21 et p16, et l'activité galactosidase associée à la sénescence ont été utilisés pour détecter la sénescence cellulaire par immunohistologie. En utilisant une approche psychobiologique, nous avons évalué in vivo l'effet de l'extrait de SH sur l'estime de soi, l'isotropie et la souplesse. RÉSULTATS: L'extrait de Sphingomonas a considérablement supprimé la sénescence associée à l'activation de ß-galactosidase. Il a également inhibé de manière significative l'expression des inhibiteurs du cycle cellulaire (p21 et p16). En même temps, l'extrait de bactérie a un impact positif significatif sur le problème en augmentant l'expression du versican et de la fibrilline-1. Des améliorations significatives de l'estime de soi ont été rapportées après 56 jours d'application de l'extrait de SH. Ces bienfaits psychologiques s'accompagnaient d'une amélioration significative de la souplesse et de l'isotropie de la peau. CONCLUSION: L'extrait de Sphingomonas retarde le processus de vieillissement intrinsèque de la peau en inhibant la sénescence cellulaire et a également la capacité de restructurer la peau. Ces effets physiologiques bénéfiques induits par l'extrait de SH ont une influence positive sur l'estime de soi. Parce que le vieillissement de la peau provoque une détresse émotionnelle, l'extrait de SH peut servir d'agent cosméceutique anti-âge et aider à construire une meilleure santé psychologique, ainsi qu'aider les individus à assumer le vieillissement.

Imidazoline Receptor Agonists for Managing Hypertension May Hold Promise for Treatment of Intracerebral Hemorrhage.

Intracerebral hemorrhage (ICH), which accounts for 10% of all strokes, leads to higher morbidity and mortality compared with other stroke subtypes. Hypertension has been recognized as a major risk factor for ICH. Current antihypertensive options have not been fully effective for either prevention of ICH or ameliorating its complications. Therefore, attempts should be made to use novel antihypertensive medications for more effective management of blood pressure (BP) in the acute phase of ICH. Imidazoline receptor (IR) agonists can potentially be effective agents for BP control with the adjunctive ability to attenuate post-ICH brain injury. IR agonists render neuroprotective effects including inhibition of inflammatory reactions, apoptotic cell death, excitotoxicity, and brain edema. Given these properties, the present review aims to focus on the application of IR agonists for managing BP in ICH patients.

Novel Way to Search for Light Dark Matter in Lepton Beam-Dump Experiments.

A novel mechanism to produce and detect light dark matter in experiments making use of GeV electrons (and positrons) impinging on a thick target (beam dump) is proposed. The positron-rich environment produced by the electromagnetic shower allows us to produce an A^{'} via nonresonant (e^{+}+e^{-}→γ+A^{'}) and resonant (e^{+}+e^{-}→A^{'}) annihilation on atomic electrons. The latter mechanism, for some selected kinematics, results in a larger sensitivity with respect to limits derived by the commonly used A^{'}-strahlung. This idea, applied to beam-dump experiments and active beam-dump experiments, pushes down the current limits by an order of magnitude.

Trabectedin in Ovarian Cancer: is it now a Standard of Care?

In patients with recurrent ovarian cancer, the choice of second-line therapy is complex. Several factors have to be considered, such as platinum-free interval (PFI), residual toxicity from the previous treatments, BRCA1/2 gene mutation status. Trebectedin is a minor groove DNA binder derived from a marine organism that has shown efficacy in different settings in ovarian cancer therapy. It has been approved in the treatment of partially platinum sensitive (PPS) (PFI between 6 and 12 months) relapsed ovarian cancer according to the statistically significant progression-free survival (7.3 versus 5.8 months) and overall survival (22.2 versus 18.9 months) benefit compared with single-agent pegylated liposomal doxorubicin (PLD) in the OVA 301 phase III trial. This drug has been shown to prolong the time to first subsequent treatment and improve the efficacy of further platinum-based chemotherapy. The role of trabectedin/PLD followed by platinum combination compared with the reverse sequence in PPS is actually in evaluation in the INOVATYON phase III study, which will clarify the best sequence to be adopted in this setting. Trabectedin has been shown to be active in patient carriers of BRCA mutations, probably for its mechanism of action directly affecting DNA and it is actually tested as a single agent in some phase III trials in BRCA mutated and BRCAness ovarian cancer patients. Trabectedin is also active on the immune system. There is, therefore, the rational for new trials of a combination with immune checkpoint inhibitors.

Quality-of-life analysis of the MITO-8, MaNGO, BGOG-Ov1, AGO-Ovar2.16, ENGOT-Ov1, GCIG study comparing platinum-based versus non-platinum-based chemotherapy in patients with partially platinum-sensitive recurrent ovarian cancer.

Background: MITO-8 showed that prolonging platinum-free interval by introducing non-platinum-based chemotherapy (NPBC) does not improve prognosis of patients with partially platinum-sensitive recurrent ovarian cancer. Quality of life (QoL) was a secondary outcome. Patients and methods: Ovarian cancer patients recurring or progressing 6-12 months after previous platinum-based chemotherapy (PBC) were randomized to receive PBC or NPBC as first treatment. QoL was assessed at baseline, third and sixth cycles, with the EORTC C-30 and OV-28 questionnaires. Mean changes and best response were analysed. Progression-free survival, response rate, and toxicity are also reported for proper interpretation of data. All analyses were based on intention-to-treat. Results: Out of the 215 patients, 151 (70.2%) completed baseline questionnaire, balanced between the arms; thereafter, missing rate was higher in the NPBC arm. At mean change analysis, C30 scores were prevalently worse in the NPBC than PBC arm, statistical significance being attained for emotional functioning, global health status/QoL, fatigue, and dyspnoea (effect sizes ranging from 0.30 to 0.51). Conversely, as for OV28 scale, the other chemotherapy side-effects item was significantly worse with PBC at three and six cycles, with a larger effect size (0.70 and 0.54, respectively). At best response analysis, improvement of emotional functioning and pain and worsening of peripheral neuropathy and other chemotherapy side-effects were significantly more frequent in the PBC arm. Progression-free survival (median 9 versus 5 months, P = 0.001) and objective response rate (51.6% versus 19.4%, P = 0.0001) were significantly better with PBC. Allergy, blood cell count, alopecia, nausea, musculoskeletal, and neurological side-effects were more frequent and severe with PBC; hand-foot skin reaction, rash/desquamation, mucositis, and vascular events were more frequent with NPBC. Conclusion: MITO-8 QoL analysis shows that deterioration of some functioning and symptom scales is lower with PBC, with improvement of emotional functioning and pain, despite worsening of toxicity-related items. ClinicalTrials.gov: NCT00657878.

Women's satisfaction with mammography and predictors of participation in an organized breast cancer screening program: Perspectives of a Local Health Unit in Rome.

OBJECTIVES: The aims of the study were to evaluate satisfaction with the mammography service of the Local Health Unit RMA (Rome, Lazio Region) among women who have attended the program and to identify the predictors of participation. STUDY DESIGN: Cross-sectional study. METHODS: A telephone-based questionnaire was administered to women eligible for mammography screening. The respondents were randomly selected and interviewed by the health center staff. RESULTS: A total of 502 women were interviewed, of which 264 (52.6%) have attended the screening program at least once. The attendees received the invitation letter more often than the non-attendees (88.3% vs 77.7%; P = 0.002), were more willing to participate (85.6% vs 69.3%; P = 0.001), they considered the letter very clear (15% vs 10.8%; P = 0.003), and information obtained through the hotline appropriate (64.7% vs 56.7%; P = 0.002). Overall satisfaction was high. Critical issues were lack of response from the hotline staff, medium-long waiting time for the results and further examinations. Age >61 years (odds ratio [OR] = 2.747; 95% confidence interval [CI] = 1.842-4.096), receiving the invitation letter (OR = 2.539; 95% CI = 1.519-4.242), and intention to participate (OR = 3.086; 95% CI = 1.938-4.915) were significantly associated with participation in the screening program. CONCLUSIONS: Women's satisfaction with mammography is an important aspect of service utilization. Implementation of strategies to reduce waiting time, increase operating hours, and improve the invitation procedure and the hotline service could enhance satisfaction and attendance rate.

Can the Local Health Unit staff serve as role model for positive health behaviours? Results from an observational study in Italy.

BACKGROUND: Lifestyles as well as health behaviors and attitudes are a matter of personal health and a public health concern for healthcare providers. The aims of the study were to examine lifestyles and health behaviors - i.e., smoking habit, diet, predisposition to undergo for cancer screening tests among the staff of a Local Health Unit in Rome and the prevalence of some of the major preventable chronic degenerative pathologies associated to lifestyles. METHODS: The survey was carried out through the administration of a questionnaire. Descriptive and univariate analyses were performed and binary logistic regression models were used to identify possible associations with an unhealthy lifestyles. Hosmer-Lemeshow test was performed. The level of significance was set at p ≤ 0.05. RESULTS: 355 employees entered the study (87,8%); 43.4% resulted in overweight/obesity and 36.6% is a current smoker. Those with a high degree of studies had an higher odds to be smokers (for low education OR=0.76; 95% CI:0,61-0.94) and healthcare workers were less likely to follow an unhealthy diet than administrative staff (OR=0.52; 95% CI: 0.29-0.91). CONCLUSION: Despite the Local Health Unit employees have, in the specific context of their workplace, an important role in promoting healthy lifestyles, in our survey they show unhealthy habits and lifestyles.

Rendimiento diagnóstico de la histerosalpingografía por resonancia magnética: resultados iniciales / Diagnostic performance of magnetic resonance hysterosalpingography: initial results Abstract

Objetivo: Determinar el rendimiento diagnóstico de la histerosalpingografía por resonancia magnética (HSG-RM), utilizando la laparoscopia como método de referencia. Materiales y métodos: Se incluyeron 22 pacientes. A todas se les realizó una HSG-RM con un resonador 1.5 Tesla y luego una laparoscopia con cromotubación. Dos radiólogos examinaron las RM, determinando la permeabilidad tubaria por consenso. Se realizaron análisis descriptivos y de rendimiento diagnóstico. Resultados: La HSG-RM tuvo una tasa de éxito del 91%. La duración del estudio fue 49ą15 minutos, el volumen inyectado 26 ą 16 cm³ y la escala de dolor 30ą 19 de 100. La sensibilidad y especificidad de la HSG-RM fueron del 100% para la prueba de Cotte global y a la izquierda, y del 25% y 93,3% para la prueba de Cotte a la derecha, respectivamente. Hubo 2 complicaciones menores y ninguna importante. Discusión: Nuestros resultados iniciales demostraron una alta sensibilidad y especificidad. Si bien otros estudios analizaron la capacidad de la HSG-RM para evaluar la permeabilidad tubaria con buenos resultados, el uso de un patrón de referencia defectuoso dejaba margen para una duda razonable, impidiendo una recomendación basada en pruebas sólidas. Sin embargo, al cotejar nuestros resultados con los publicados, observamos un alto grado de concordancia en tanto el derrame positivo se diagnostica correctamente con una especificidad de 100% o con un porcentaje cercano a esta cifra. Conclusión: La HSG-MR es una alternativa factible y segura de la HSG convencional o virtual, la histerosonografía y la cromotubación.

Objective: To determine the diagnostic performance of magnetic resonance hysterosalpingography (MRHSG) using laparoscopic chromotubation as a method of reference. Materials and methods: Twenty-two patients were included. The MRHSG was performed in a 1.5 Tesla MR scanner. Afterwards, patients underwent laparoscopic chromotubation. MR images were examined by two trained radiologists, and tubal patency was determined by consensus. A descriptive analysis was carried out, as well as an analysis of the diagnostic performance. Results: MRHSG had a 91% success rate. Exam duration of the examination was 49ą15min, with an injected volume 26ą 16cc, and pain scale 30ą 19 out of 100. Sensitivity and specificity of MRHSG was 100% for global and left Cotte, and 25% and 93.3% for right Cotte, respectively. Only 2 minor and no major complications were observed. Discussion: The initial results of MRHSG have shown high sensitivity and specificity. Even though other studies have analysed the potential of MRHSG with good results, the use of a flawed reference standard left a margin for a reasonable doubt as regards its true potential, thus preventing a solid evidence based recommendation. Nevertheless, if our results are compared to those published, a high level of agreement is observed in that positive spillage is correctly diagnosed with specificities near or at 100%. Conclusion: MRHSG is a feasible and safe alternative to conventional or virtual HSG, ultrasound-hysterography and chromotubation.

Cisplatin can be safely administered to ovarian cancer patients with hypersensitivity to carboplatin.

OBJECTIVE: Hypersensitivity reactions (HSR) are frequently reported in patients rechallenged with carboplatin for recurrent ovarian cancer (ROC) and represent a critical issue, since discontinuation of the platinum-based therapy could affect prognosis. Several strategies to allow platinum rechallenge have been described, with controversial outcomes. The aim of this study is to illustrate a 10-year experience with cisplatin in patients with a previous HSR to carboplatin or at risk for allergy. METHODS: A retrospective review of all patients with platinum sensitive ROC retreated with carboplatin was performed between January 2007 and May 2016 at the Istituto Nazionale Tumori, Fondazione "G. Pascale", Naples. RESULTS: Among 183 patients, 49 (26.8%) presented HSR to carboplatin, mainly during second line therapy. Mean number of cycles before HSR was 8 (range 3-17). G2, G3 and G4 reaction were detected in 83%, 15% and 2% of patients, respectively. In a multivariate analysis including age, hystotype, BRCA status, previous known HSR, and combination drug administered, only the type of carboplatin-based doublet used as 2nd line therapy was found to significantly affect HSR development, with a protective effect of PLD (pegylated liposomal doxorubicin) (p = 0.014, OR = 0.027). Thirty seven patients (77%) with a previous HSR to carboplatin were rechallenged with cisplatin. Treatment was generally well tolerated. 5 patients (13.1%) experienced mild HSR to cisplatin, successfully managed in all cases. 14 patients were treated with cisplatin even without a carboplatin-related HSR due to other allergies. Among these, only one developed HSR (7.1%). CONCLUSIONS: Cisplatin rechallenge is a feasible approach in patients experiencing HSR to carboplatin to maintain the beneficial effect of platinum while reducing hypersensitivity-related risks.

Investigation of the

This Letter reports a study of the highly debated ^{10}Li structure through the d(^{9}Li,p)^{10}Li one-neutron transfer reaction at 100 MeV. The ^{10}Li energy spectrum is measured up to 4.6 MeV and angular distributions corresponding to different excitation energy regions are reported for the first time. The comparison between data and theoretical predictions, including pairing correlation effects, shows the existence of a p_{1/2} resonance at 0.45±0.03 MeV excitation energy, while no evidence for a significant s-wave contribution close to the threshold energy is observed. Moreover, two high-lying structures are populated at 1.5 and 2.9 MeV. The corresponding angular distributions suggest a significant s_{1/2} partial-wave contribution for the 1.5 MeV structure and a mixing of configurations at higher energy, with the d_{5/2} partial-wave contributing the most to the cross section.

TAp63 suppresses mammary tumorigenesis through regulation of the Hippo pathway.

Mechanisms regulating the transition of mammary epithelial cells (MECs) to mammary stem cells (MaSCs) and to tumor-initiating cells (TICs) have not been entirely elucidated. The p53 family member, p63, is critical for mammary gland development and contains transactivation domain isoforms, which have tumor-suppressive activities, and the ΔN isoforms, which act as oncogenes. In the clinic, p63 is often used as a diagnostic marker, and further analysis of the function of TAp63 in the mammary gland is critical for improved diagnosis and patient care. Loss of TAp63 in mice leads to the formation of aggressive metastatic mammary adenocarcinoma at 9-16 months of age. Here we show that TAp63 is crucial for the transition of mammary cancer cells to TICs. When TAp63 is lost, MECs express embryonic and MaSC signatures and activate the Hippo pathway. These data indicate a crucial role for TAp63 in mammary TICs and provide a mechanism for its role as a tumor- and metastasis-suppressor in breast cancer.

Cuestionario de evaluación de factores psicosociales (cefap): estructura y propiedades psicométricas / Questionnaire for the evaluation of psychosocial factors (cefap): structure and psychometric properties

A una muestra de 873 trabajadores de organizaciones públicas de Argentina, se ha administrado el Cuestionario de Evaluación de Factores Psicosociales (CEFAP) que incluye once dimensiones, con una serie de ítems con formato tipo Likert organizados de acuerdo con un modelo teórico según el cual éstos cubrirían el espectro de factores psicosociales que contextualizan el trabajo. Todos los factores mostraron una alta consistencia interna, con valores α de Cronbach comprendidos entre .49 (Relación salud-trabajo) y .92 (Apoyo Social y Estima). Además, el cuestionario cuenta con un apartado donde se relevan variables sociolaborales. Los resultados indican que el CEFAP reproduce fielmente la estructura del modelo teórico propuesto ampliando lo presentado por otros instrumentos de evaluación.

The Questionnaire for the Evaluation of Psychosocial Factors (CEFAP) was administered to a sample of 873 employees of public organizations of Argentina. The questionnaire includes eleven dimensions, with a series of items Likert-formatted organized according to a theoretical model that states that these would cover the spectrum of psychosocial factors that contextualize the working activity. All factors showed high internal consistency with Cronbach α values ranging from .49 (Health-work relationship) and .92 (Social Support and Esteem). In addition, the questionnaire has a section where occupational variables are collected. The results indicate that the CEFAP faithfully reproduces the structure of the proposed theoretical model, expanding what was presented by other assessment tools.

Prospective phase II trial of trabectedin in BRCA-mutated and/or BRCAness phenotype recurrent ovarian cancer patients: the MITO 15 trial.

BACKGROUND: Current evidence suggest that trabectedin is particularly effective in cells lacking functional homologous recombination repair mechanisms. A prospective phase II trial was designed to evaluate the activity of trabectedin in the treatment of recurrent ovarian cancer patients presenting BRCA mutation and/or BRCAness phenotype. PATIENTS AND METHODS: A total of 100 patients with recurrent BRCA-mutated ovarian cancer and/or BRCAness phenotype (≥2 previous responses to platinum) were treated with trabectedin 1.3 mg/mq i.v. q 3 weeks. The activity of the drug with respect to BRCA mutational status and to a series of polymorphisms [single-nucleotide polymorphisms (SNPs)] involved in DNA gene repair was analyzed. RESULTS: Ninety-four were evaluable for response; in the whole population, 4 complete and 33 partial responses were registered for an overall response rate (ORR) of 39.4. In the platinum-resistant (PR) and -sensitive (PS) population, an ORR of 31.2% and 47.8%, and an overall clinical benefit of 54.2% and 73.9%, respectively, were registered. In the whole series, the median progression-free survival (PFS) was 18 weeks and the median overall survival (OS) was 72 weeks; PS patients showed a more favorable PFS and OS compared with PR patients. BRCA gene mutational status was available in 69 patients. There was no difference in ORR, PFS and OS according to BRCA 1-2 status nor any association between SNPs of genes involved in DNA repair and NER machinery and response to trabectedin was reported. CONCLUSIONS: Our data prospectively confirmed that the signature of 'repeated platinum sensitivity' identifies patients highly responsive to trabectedin. In this setting, the activity of trabectedin seems comparable to what could be obtained using platinum compounds and the drug may represent a valuable alternative option in patients who present contraindication to receive platinum. EUDRACT NUMBER: 2011-001298-17.

Monomeric C-reactive protein--a key molecule driving development of Alzheimer's disease associated with brain ischaemia?

Alzheimer's disease (AD) increases dramatically in patients with ischaemic stroke. Monomeric C-reactive protein (mCRP) appears in the ECM of ischaemic tissue after stroke, associating with microvasculature, neurons and AD-plaques, Aß, also, being able to dissociate native-CRP into inflammatory, mCRP in vivo. Here, mCRP injected into the hippocampal region of mice was retained within the retrosplenial tract of the dorsal 3rd ventrical and surrounding major vessels. Mice developed behavioural/cognitive deficits within 1 month, concomitant with mCRP staining within abnormal looking neurons expressing p-tau and in beta-amyloid 1-42-plaque positive regions. mCRP co-localised with CD105 in microvessels suggesting angiogenesis. Phospho-arrays/Western blotting identified signalling activation in endothelial cells and neurons through p-IRS-1, p-Tau and p-ERK1/2-which was blocked following pre-incubation with mCRP-antibody. mCRP increased vascular monolayer permeability and gap junctions, increased NCAM expression and produced haemorrhagic angiogenesis in mouse matrigel implants. mCRP induced tau244-372 aggregation and assembly in vitro. IHC study of human AD/stroke patients revealed co-localization of mCRP with Aß plaques, tau-like fibrils and IRS-1/P-Tau positive neurons and high mCRP-levels spreading from infarcted core regions matched reduced expression of Aß/Tau. mCRP may be responsible for promoting dementia after ischaemia and mCRP clearance could inform therapeutic avenues to reduce the risk of future dementia.