Primary prophylaxis of neutropenia in women affected by breast cancer undergoing adjuvant chemotherapy with fec 100+/- docetaxel. Comparison of efficacy and tolerability between lenograstim and pegfilgrastim

Objectives: evaluate safety and toxicity of a single injection of pegfilgrastim compared to daily administration of lenograstim in breast cancer patient undergoing adjuvant chemotherapy

Persistent intraepithelial lymphocytosis in celiac patients adhering to gluten-free diet is not abolished despite a gluten contamination elimination diet

The gluten-free diet (GFD) is the only validated treatment for celiac disease (CD), but despite strict adherence, complete mucosal recovery is rarely obtained. The aim of our study was to assess whether complete restitutio ad integrum could be achieved by adopting a restrictive diet (Gluten Contamination Elimination Diet, GCED) or may depend on time of exposure to GFD. Two cohorts of CD patients, with persisting Marsh II/Grade A lesion at duodenal biopsy after 12–18 months of GFD (early control) were identified. Patients in Cohort A were re-biopsied after a three-month GCED (GCED control) and patients in Cohort B were re-biopsied after a minimum of two years on a standard GFD subsequent to early control (late control). Ten patients in Cohort A and 19 in Cohort B completed the study protocol. There was no change in the classification of duodenal biopsies in both cohorts. The number of intraepithelial lymphocytes, TCR + (T-Cell Receptor gamma delta) T cell and eosinophils significantly decreased at GCED control (Cohort A) and at late control (Cohort B), compared to early control. Duodenal intraepithelial lymphocytosis persisting in CD patients during GFD is not eliminated by a GCED and is independent of the length of GFD. [NCT 02711696

Local structure of temperature and pH-sensitive colloidal microgels

The temperature dependence of the local intra-particle structure of colloidal microgel particles, composed of interpenetrated polymer networks, has been investigated by small-angle neutron scattering at different pH and concentrations, in the range (299÷315) K, where a volume phase transition from a swollen to a shrunken state takes place. Data are well described by a theoretical model that takes into account the presence of both interpenetrated polymer networks and cross-linkers. Two different behaviors are found across the volume phase transition. At neutral pH and T 307 K, a sharp change of the local structure from a water rich open inhomogeneous interpenetrated polymer network to a homogeneous porous solid-like structure after expelling water is observed. Differently, at acidic pH, the local structure changes almost continuously. These findings demonstrate that a fine control of the pH of the system allows to tune the sharpness of the volume-phase transition

Integrated Care for Heart Failure in Primary Care

Chronic heart failure (CHF or simply HF) is a complex clinical syndrome that involves more than 2% of the general population and over 10% of the older people. For people with reduced ventricular function (the classical HFrEF phenotype), the guideline-directed medical therapy (GDMT) (e.g., Ace-inhibitors, beta-blockers, diuretics, rehabilitation or implantable ventricular devices) demonstrated to be efficacious in reducing hospitalisations and prolonging survival. Vice-versa, the HF with preserved ejection fraction (diastolic HF or HFpEF phenotype) is a much more complex syndrome, in which co-morbidities (such as COPD, depression, anemia, and diabetes, CAD) play a significant role in the decompensation episodes

In vivo validation of the adequacy calculator for continuous renal replacement therapies

INTRODUCTION: The study was conducted to validate in vivo the Adequacy Calculator, a Microsoft Excel-based program, designed to assess the prescription and delivery of renal replacement therapy in the critical care setting. METHODS: The design was a prospective cohort study, set in two intensive care units of teaching hospitals. The participants were 30 consecutive critically ill patients with acute renal failure treated with 106 continuous renal replacement therapies (CRRT). Urea clearance computation was performed with the Adequacy Calculator (K(CALC)). Simultaneous blood and effluent urea samples were collected to measure the effectively delivered urea clearance (K(DEL)) at the beginning of each treatment and, during 73 treatments, between the 18th and 24th treatment hour. The correlation between 179 computed and 179 measured clearances was assessed. Fractional clearances for urea were calculated as spKt/V (where sp represents single pool, K is clearance, t is time, and V is urea volume of distribution) obtained from software prescription and compared with the delivered spKt/V obtained from empirical data. RESULTS: We found that the value of clearance predicted by the calculator was strongly correlated with the value obtained from computation on blood and dialysate determination (r = 0.97) during the first 24 treatment hours, regardless of the renal replacement modality used. The delivered spKt/V (1.25) was less than prescribed (1.4) from the Adequacy Calculator by 10.7%, owing to therapy downtime. CONCLUSION: The Adequacy Calculator is a simple tool for prescribing CRRT and for predicting the delivered dose. The calculator might be a helpful tool for standardizing therapy and for comparing disparate treatments, making it possible to perform large multi-centre studies on CRRT

AI technology for remote clinical assessment and monitoring

Objective: To report the clinical validation of an innovative, artificial intelligence (AI)-powered, portable and non-invasive medical device called Wound Viewer. The AI medical device uses dedicated sensors and AI algorithms to remotely collect objective and precise clinical data, including three-dimensional (3D) wound measurements, tissue composition and wound classification through the internationally recognised Wound Bed Preparation (WBP) protocol; this data can then be shared through a secure General Data Protection Regulation (GDPR)- and Health Insurance Portability and Accountability Act (HIPAA)-compliant data transfer system. This trial aims to test the reliability and precision of the AI medical device and its ability to aid health professionals in clinically evaluating wounds as efficiently remotely as at the bedside. Method: This non-randomised comparative clinical trial was conducted in the Clinica San Luca (Turin, Italy). Patients were divided into three groups: (i) patients with venous and arterial ulcers in the lower limbs; (ii) patients with diabetes and presenting with diabetic foot syndrome; and (iii) patients with pressure ulcers. Each wound was evaluated for area, depth, volume and WBP wound classification. Each patient was examined once and the results, analysed by the AI medical device, were compared against data obtained following visual evaluation by the physician and research team. The area and depth were compared with a Kruskal–Wallis one-way analysis of variations in the obtained distribution (expected p-value>0.1 for both tests). The WBP classification and tissue segmentation were analysed by directly comparing the classification obtained by the AI medical device against that of the testing physician. Results: A total of 150 patients took part in the trial. The results demonstrated that the AI medical device's AI algorithm could acquire objective clinical parameters in a completely automated manner. The AI medical device reached 97% accuracy against the WBP classification and tissue segmentation analysis compared with that performed in person by the physician. Moreover, data regarding the measurements of the wounds, as analysed through the Kruskal–Wallis technique, showed that the data distribution proved comparable with the other methods of measurement previously clinically validated in the literature (p=0.9). Conclusion: These findings indicate that remote wound assessment undertaken by physicians is as effective through the AI medical device as bedside examination, and that the device was able to assess wounds and provide a precise WBP wound classification. Furthermore, there was no need for manual data entry, thereby reducing the risk of human error while preserving high-quality clinical diagnostic data

The application of scanning near field optical imaging to the study of human sperm morphology

BackgroundThe morphology of spermatozoa is a fundamental aspect to consider in fertilization, sperm pathology, assisted reproduction and contraception. Head, neck, midpiece, principal and terminal part of flagellum are the main sperm components to investigate for identifying morphological features and related anomalies. Recently, scanning near-field optical microscopy (SNOM), which belongs to the wide family of nanoscopic techniques, has opened up new routes for the investigation of biological systems. SNOM is the only technique able to provide simultaneously highly resolved topography and optical images with a resolution beyond the diffraction limit, typical of conventional optical microscopy. This offers the advantage to obtain complementary information about cell surface and cytoplasmatic structures.ResultsIn this work human spermatozoa both healthy and with morphological anomalies are analyzed by SNOM, to demonstrate the potentiality of such approach in the visualization of sperm morphological details. The combination of SNOM topography with optical (reflection and transmission) images enables to examine typical topographic features of spermatozoa together with underlying cytoplasmic structures. Indeed the head shape and inner components as acrosome and nucleus, and the organization of mitochondria in the midpiece region are observed. Analogously for principal tract of the tail, the ridges and the columns are detected in the SNOM topography, while their internal arrangement can be observed in the corresponding SNOM optical transmission images, without requiring specific staining procedures or invasive protocols.ConclusionsSuch findings demonstrate that SNOM represents a versatile and powerful tool to describe topographical and inner structural details of spermatozoa simultaneously. This analysis could be helpful for better characterizing several morphological anomalies, often related to sperm infertility, which cannot be examined by conventional techniques all together

A Novel Functional Domain of Tab2 Involved in the Interaction with Estrogen Receptor Alpha in Breast Cancer Cells

Tab2, originally described as a component of the inflammatory pathway, has been implicated in phenomena of gene de-repression in several contexts, due to its ability to interact with the NCoR corepressor. Tab2 interacts also with steroid receptors and dismisses NCoR from antagonist-bound Estrogen and Androgen Receptors on gene regulatory regions, thus modifying their transcriptional activity and leading to pharmacological resistance in breast and prostate cancer cells. We demonstrated previously that either Tab2 knock-down, or a peptide mimicking the Estrogen Receptor alpha domain interacting with Tab2, restore the antiproliferative response to Tamoxifen in Tamoxifen-resistant breast cancer cells. In this work, we map the domain of Tab2 responsible of Estrogen Receptor alpha interaction. First, using both co-immunoprecipitation and pull-down with recombinant proteins, we found that the central part of Tab2 is primarily responsible for this interaction, and that this region also interacts with Androgen Receptor. Then, we narrowed down the essential interaction region by means of competition assays using recombinant protein pull-down. The interaction motif was finally identified as a small region adjacent to, but not overlapping, the Tab2 MEKK1 phosphorylation sites. A synthetic peptide mimicking this motif efficiently displaced Tab2 from interacting with recombinant Estrogen Receptor alpha in vitro, prompting us to test its efficacy using derivatives of the MCF7 breast carcinoma cell lines that are spontaneously resistant to Tamoxifen. Indeed, we observed that this mimic peptide, made cell-permeable by addition of the TAT minimal carrier domain, reduced the growth of Tamoxifen-resistant MCF7 cells in the presence of Tamoxifen. These data indicate a novel functional domain of the Tab2 protein with potential application in drug design