Fasting glucose and body mass index as predictors of activity in breast cancer patients treated with everolimus-exemestane: the EverExt study

Evidence on everolimus in breast cancer has placed hyperglycemia among the most common high grade adverse events. Anthropometrics and biomarkers of glucose metabolism were investigated in a observational study of 102 postmenopausal, HR + HER2- metastatic breast cancer patients treated with everolimus-exemestane in first and subsequent lines. Best overall response (BR) and clinical benefit rate (CBR) were assessed across subgroups defined upon fasting glucose (FG) and body mass index (BMI). Survival was estimated by Kaplan-Meier method and log-rank test. Survival predictors were tested in Cox models. Median follow up was 12.4 months (1.0-41.0). The overall cohort showed increasing levels of FG and decreasing BMI (p < 0.001). Lower FG fasting glucose at BR was more commonly associated with C/PR or SD compared with PD (p < 0.001). We also observed a somewhat higher BMI associated with better response (p = 0.052). More patients in the lowest FG category achieved clinical benefit compared to the highest (p < 0.001), while no relevant differences emerged for BMI. Fasting glucose at re-assessment was also predictive of PFS (p = 0.037), as confirmed in models including BMI and line of therapy (p = 0.049). Treatment discontinuation was significantly associated with changes in FG (p = 0.014). Further research is warranted to corroborate these findings and clarify the underlying mechanisms

Assessment of plaque morphology in alzheimer’s mouse cerebellum using three-dimensional X-ray phase-based virtual histology

Visualization and characterization of beta -amyloid deposits is a fundamental task in pre-clinical study of Alzheimer's disease (AD) to assess its evolution and monitor the efficiency of new therapeutic strategies. While the cerebellum is one of the brain areas most underestimated in the context of AD, renewed interest in cerebellar lesions has recently arisen as they may link to motor and cognitive alterations. Thus, we quantitatively investigated three-dimensional plaque morphology in the cerebellum in APP/PS1 transgenic mouse, as a model of AD. In order to obtain a complete high-resolution three-dimensional view of the investigated tissue, we exploited synchrotron X-ray phase contrast tomography (XPCT), providing virtual slices with histology-matching resolution. We found the formation of plaques elongated in shape, and with a specific orientation in space depending on the investigated region of the cerebellar cortex. Remarkably, a similar shape is observed in human cerebellum from demented patients. Our findings demonstrate the capability of XPCT in volumetric quantification, supporting the current knowledge about plaque morphology in the cerebellum and the fundamental role of the surrounding tissue in driving their evolution. A good correlation with the human neuropathology is also reported

Prohypertensive Effect of Gestational Personal Exposure to Fine Particulate Matter. Prospective Cohort Study in Non-smoking and Non-obese Pregnant Women

Exposure to fine particulate matter (PM) is a recognized risk factor for elevated blood pressure (BP) and cardiovascular disease in adults, and this prospective cohort study was undertaken to evaluate whether gestational exposure to $PM_{2.5}$ has a prohypertensive effect. We measured personal exposure to fine particulate matter ($PM_{2.5}$) by personal air monitoring in the second trimester of pregnancy among 431 women, and BP values in the third trimester were obtained from medical records of prenatal care clinics. In the general estimating equation model, the effect of $PM_{2.5}$ on BP was adjusted for relevant covariates such as maternal age, education, parity, gestational weight gain (GWG), prepregnancy BMI, environmental tobacco smoke (ETS), and blood lead level. Systolic blood pressure (SBP) increased in a linear fashion across a dosage of $PM_{2.5}$ and on average augmented by 6.1 mm Hg (95% CI, 0.6–11.6) with log unit of $PM_{2.5}$ concentration. Effects of age, maternal education, prepregnancy BMI, blood lead level, and ETS were insignificant. Women with excessive gestational weight gain (>18 kg) had higher mean SBP parameters by 5.5 mmHg (95% CI, 2.7–8.3). In contrast, multiparous women had significantly lower SBP values (coeff. = −4.2 mm Hg; 95% CI, −6.8 to −1.6). Similar analysis performed for diastolic blood pressure (DBP) has demonstrated that PM2.5 also affected DBP parameters (coeff. = 4.1; 95% CI, −0.02 to 8.2), but at the border significance level. DBP values were positively associated with the excessive GWG (coeff. = 2.3; 95% CI, 0.3–4.4) but were inversely related to parity (coeff. = −2.7; 95% CI, −4.6 to −0.73). In the observed cohort, the exposure to fine particulate matter during pregnancy was associated with increased maternal blood pressure

X‐ray microtomography and phylogenomics provide insights into the morphology and evolution of an enigmatic mesozoic insect larva

Fossils sometimes show unusual morphological features absent in living organisms, making it difficult to reconstruct both their affinity and their function. We describe here a new lacewing larva, Ankyloleon caudatus gen. et sp.n. (Neuroptera) from the Cretaceous amber of Myanmar, characterized by an abdomen unique among insects, with ‘tail-like’ terminal segments bearing a ventral pair of vesicles. Phase-contrast X-ray microtomography reveals that these structures were dense and equipped with a median duct, suggesting that they were likely pygopods used for locomotion, holding the position through adhesive secretions. Our phylogenetic analyses, combining genomic and morphological data from both living and fossil lacewings, proved critical to placing Ankyloleon gen.n. on the lacewing tree of life as an early representative of the antlion clade, Myrmeleontiformia. These results corroborate the view that derived myrmeleontiform lacewings ‘experimented’ with unusual combinations of features and specializations during their evolutionary history, some of which are now lost

Anaesthesiological implications of Kimura's disease: a case report

<p>Abstract</p> <p>Introduction</p> <p>Kimura's disease is a chronic inflammatory condition belonging to the angio-lymphatic proliferative group of disorders, usually affecting young men of Asian race, but is rare in Western countries. It is a benign but locally injurious disease, of unknown aetiology, whose classical clinical features are a tumour-like swelling, usually in the head and neck, with or without satellite lymphadenopathy, often accompanied by eosinophilia and elevated serum IgE.</p> <p>Case presentation</p> <p>We report the case of a 33-year-old Caucasian woman with an atypical localization of Kimura's disease, discussing the anaesthesiological implications and reviewing the current literature on Kimura's disease.</p> <p>Conclusions</p> <p>The diagnosis of Kimura's disease can be difficult and misleading, and anaesthesiological precautions could be ignored. Patients with this disease are often evaluated for other disorders: unnecessary diagnostic tests and investigations, or even surgery, may be avoided by just being aware of Kimura's disease.</p

University Extension facing actual symptoms in childhood and puberty: an intervention methodology proposal

El trabajo tiene como objetivo presentar el Proyecto de Extensión “Detección e intervención de problemáticas del lazo parento-filial” del Centro de Extensión a la Comunidad de la Facultad de Psicología; y sus desagregados “Detección e intervención de problemáticas del lazo parento- filial: intervención estratégica sobre embarazo adolescente” y “Detección e intervención de problemáticas del lazo parento-filial: abordaje estratégico de síntomas actuales del despertar sexual” (Prosecretaría de Políticas Sociales, UNLP: 2014 y 2015). Partimos del reconocimiento de la vulnerabilidad en los modos actuales de presentación de los padecimientos que involucran los procesos de constitución psíquica del sujeto, atendiendo al modo particular de vinculación que establece con los otros, en especial con sus otros primordiales. Esta vulnerabilidad se evidencia en manifestaciones disruptivas, dislocadas que se presentan en distintos escenarios, dando cuenta de la precarización del lazo social: violencia entre pares y familiar, maltrato, trastornos en la alimentación, problemas en el aula, en el rendimiento escolar y en la socialización, embarazos precoces, problemáticas que se profundizan en condiciones sociomateriales adversas. El proyecto propone, por lo tanto, intervenciones en la modalidad grupal y, en caso de requerirse, abordajes individuales atendiendo a la localización del malestar y en diálogo colaborativo e interdisciplinario con actores sociales e instituciones, que puedan incidir en estas temáticas. Con dicho propósito, establecemos talleres para padres y alumnos en los colegios, y dispositivos de asesoramiento técnico para los docentes y personal de salud. Esta metodología busca propiciar herramientas en los destinatarios que puedan ser multiplicadas en diversos contextos.This work presents the way in which the Extension Team belonging to the following accredited Projects: “Detection and intervention of problematic parent-child bonds” (Center of Community Extension, Faculty of Psychology: 2011-2014; UNLP: 2015) and its disaggregated “Detection and intervention of problematic parent-child bonds: strategic interventions on adolescent pregnancy” and “Detection and intervention of problematic parent-child bonds: strategic approach of current symptoms of sexual arousal” (Pro-Secretary of Social Policies, UNLP: 2014 and 2015). We start from the recognition of the vulnerability in current modes of presentation of conditions involving the processes of subjective constitution, considering the specific link that subjects establish with the others, specially the primordial others. This vulnerability is evident in disruptive dislocated presentations that appear in different scenarios, showing the precariousness of the social bond: peer violence and family abuse, eating disorders, problems in the classroom, on school performance and the socialization, early pregnancy, problems that are deepening in sociomaterial adverse conditions. The project proposes, therefore, interventions in group mode and, if required, individual approaches taking into account the different ways in which uneasiness appears, in collaborative and interdisciplinary dialogue with social actors and institutions. For this purpose, we offer workshops for parents and students in schools, and devices of technical advice for teachers and health workers. This methodology seeks to encourage tools in the target population that can be multiplied in various contextsFacultad de Psicologí

Multicentric survey on dose reduction/interruption of cancer drug therapy in 12.472 patients: Indicators of suspected adverse reactions

Antiblastic drugs have a high number of potential side-effects. Paradoxically, according to the National Network of Pharmacovigilance, the number of reported adverse reactions to these agents is proportionally lower than that registered for non antiblastic drugs. Critical phenomena such as treatment interruptions and significant dose reductions within the first two months of use may be indicators of adverse drug reactions. The aim of the present study was to increase our knowledge of pharmacovigilance to facilitate the actions taken to improve the risk-benefit profile of cancer drugs and, consequently, their safety. This retrospective observational survey was carried out on prescriptions from 1st January 2012 to 31st December 2012.Dose reductions of more than 10% during the first 90 days of therapy were considered as a surrogate indicator of an adverse reaction. Dose interruptions during the first 60 days of therapy were taken into consideration. Of the12,472 patients 1,248 underwent a dose reduction. The drugs that most often required a dose reduction were paclitaxel and oxaliplatin (17.4% and 17.3%, respectively), docetaxel (14.8%), carboplatin (15%), fluorouracil (10.7%) and, among oral medications, capecitabine (6.9%). Of the 1896 patients treated with the same drugs, 9.7% interrupted treatment. Patients required a lower dose reduction than that reported by other authors. Around 15% of cases underwent a 30% dose reduction within three months of starting therapy, indicating a possible adverse reaction. Constant monitoring of dose prescription and continuous training of medical and nursing staff are clearly needed to increase awareness of the importance of reporting adverse events.Antiblastic drugs have a high number of potential side-effects. Paradoxically, according to the National Network of Pharmacovigilance, the number of reported adverse reactions to these agents is proportionally lower than that registered for non antiblastic drugs. Critical phenomena such as treatment interruptions and significant dose reductions within the first two months of use may be indicators of adverse drug reactions. The aim of the present study was to increase our knowledge of pharmacovigilance to facilitate the actions taken to improve the risk-benefit profile of cancer drugs and, consequently, their safety. This retrospective observational survey was carried out on prescriptions from 1st January 2012 to 31st December 2012. Dose reductions of more than 10% during the first 90 days of therapy were considered as a surrogate indicator of an adverse reaction. Dose interruptions during the first 60 days of therapy were taken into consideration. Of the12,472 patients 1,248 underwent a dose reduction. The drugs that most often required a dose reduction were paclitaxel and oxaliplatin (17.4% and 17.3%, respectively), docetaxel (14.8%), carboplatin (15%), fluorouracil (10.7%) and, among oral medications, capecitabine (6.9%). Of the 1896 patients treated with the same drugs, 9.7% interrupted treatment. Patients required a lower dose reduction than that reported by other authors. Around 15% of cases underwent a 30% dose reduction within three months of starting therapy, indicating a possible adverse reaction. Constant monitoring of dose prescription and continuous training of medical and nursing staff are clearly needed to increase awareness of the importance of reporting adverse events

The PDE4 Inhibitor Tanimilast Restrains the Tissue-Damaging Properties of Human Neutrophils

: Neutrophils, the most abundant subset of leukocytes in the blood, play a pivotal role in host response against invading pathogens. However, in respiratory diseases, excessive infiltration and activation of neutrophils can lead to tissue damage. Tanimilast-international non-proprietary name of CHF6001-is a novel inhaled phosphodiesterase 4 (PDE4) inhibitor in advanced clinical development for the treatment of chronic obstructive pulmonary disease (COPD), a chronic inflammatory lung disease where neutrophilic inflammation plays a key pathological role. Human neutrophils from healthy donors were exposed to pro-inflammatory stimuli in the presence or absence of tanimilast and budesonide-a typical inhaled corticosteroid drug-to investigate the modulation of effector functions including adherence to endothelial cells, granule protein exocytosis, release of extracellular DNA traps, cytokine secretion, and cell survival. Tanimilast significantly decreased neutrophil-endothelium adhesion, degranulation, extracellular DNA traps casting, and cytokine secretion. In contrast, it promoted neutrophil survival by decreasing both spontaneous apoptosis and cell death in the presence of pro-survival factors. The present work suggests that tanimilast can alleviate the severe tissue damage caused by massive recruitment and activation of neutrophils in inflammatory diseases such as COPD