Preferential expression of the transcription coactivator HTIF1alpha gene in acute myeloid leukemia and MDS-related AML

HTIF1α, a transcription coactivator which is able to mediate RARα activity and functionally interact with PML, is encoded by a gene on chromosome 7q32–34, which is a critical region in acute myeloid leukemias (AML). With the assumption that this gene may be related to AML, we investigated the HTIF1α DNA structure and RNA expression in leukemic cells from 36 M1–M5 AML patients (28 ‘de novo’ and eight ‘secondary’ to myelodysplastic syndrome (MDS)). Abnormal HTIF1α DNA fragments were never found, whereas loss of HTIF1α DNA was observed in the patients with chromosome 7q32 deletion and translocation, and in one case without detectable chromosome 7 abnormality. HTIF1α RNA was found in acute myelocytic leukemic blasts, and was almost undetectable in normal mononuclear cells. The expression varied among the patients: higher in M1 to M3 subtypes, with the highest values in M1; low levels were constantly observed in M4 and M5 AML. In addition, HTIF1α was significantly overexpressed in MDS-related AML (MDR-AML), but not in MDS. We also found that HTIF1α expression was high in myeloid cell lines. In myeloblastic HL60 and promyelocytic NB4 cells, induced to differentiate along the monocytic–macrophage pathway by TPA or vitamin D3, HTIF1α expression decreased, whereas it was maintained at high levels on induction to granulocytic differentiation by RA or DMSO. In K562 cells, HTIF1α RNA levels did not change after hemin-induced erythroid differentiation. These results suggest that HTIF1α could play a role in myeloid differentiation, being distinctly regulated in hematopoietic lineages

a comparison of integration models for professionals with different skills in healthcare

Integration between hospital and territory has to be faced as a critical aspect in modern health systems. The evolving of health care demand in Western countries leads the debate on health care system to focus on how to meet the needs of chronic diseases. Creating gatekeeper models for admission to health care facilities presumes a high level of integration between a wide variety of professions that interact in patients' therapy processes. This paper analyzes two models of integration of professionals with different skills: Clinical commissioning groups (CCGs) in United Kingdom health care system and Case della Salute (CdS) in Italian regional health care system of Emilia Romagna. The analysis of the two models highlights critical situations, strong points, and success critical factors in the two models. In particular, the analysis will highlight how the two systems faced the necessity to integrate the different category of professionals that, during the care process of a chronic patient, have to integrate in order to guarantee the continuity of the care process and the most effective response for the patient. This study highlights the methodologies used to share competences and knowledge on which the building of a system with high professional integration is based

Differential expression of microRNA501-5p affects the aggressiveness of clear cell renal carcinoma

AbstractRenal cell carcinoma is a common neoplasia of the adult kidney that accounts for about 3% of adult malignancies. Clear cell renal carcinoma is the most frequent subtype of kidney cancer and 20–40% of patients develop metastases. The absence of appropriate biomarkers complicates diagnosis and prognosis of this disease. In this regard, small noncoding RNAs (microRNAs), which are mutated in several neoplastic diseases including kidney carcinoma, may be optimal candidates as biomarkers for diagnosis and prognosis of this kind of cancer. Here we show that patients with clear cell kidney carcinoma that express low levels of miR501-5p exhibited a good prognosis compared with patients with unchanged or high levels of this microRNA. Consistently, in kidney carcinoma cells the downregulation of miR501-5p induced an increased caspase-3 activity, p53 expression as well as decreased mTOR activation, leading to stimulation of the apoptotic pathway. Conversely, miR501-5p upregulation enhanced the activity of mTOR and promoted both cell proliferation and survival. These biological processes occurred through p53 inactivation by proteasome degradation in a mechanism involving MDM2-mediated p53 ubiquitination. Our results support a role for miR501-5p in balancing apoptosis and cell survival in clear cell renal carcinoma. In particular, the downregulation of microRNA501-5p promotes a good prognosis, while its upregulation contributes to a poor prognosis, in particular, if associated with p53 and MDM2 overexpression and mTOR activation. Thus, the expression of miR501-5p is a possible biomarker for the prognosis of clear cell renal carcinoma

Insulators for 2D nanoelectronics: the gap to bridge

Nanoelectronic devices based on 2D materials are far from delivering their full theoretical performance potential due to the lack of scalable insulators. Amorphous oxides that work well in silicon technology have ill-defined interfaces with 2D materials and numerous defects, while 2D hexagonal boron nitride does not meet required dielectric specifications. The list of suitable alternative insulators is currently very limited. Thus, a radically different mindset with respect to suitable insulators for 2D technologies may be required. We review possible solution scenarios like the creation of clean interfaces, production of native oxides from 2D semiconductors and more intensive studies on crystalline insulators

Insulators for 2D nanoelectronics: the gap to bridge

Nanoelectronic devices based on 2D materials are far from delivering their full theoretical performance potential due to the lack of scalable insulators. Amorphous oxides that work well in silicon technology have ill-defined interfaces with 2D materials and numerous defects, while 2D hexagonal boron nitride does not meet required dielectric specifications. The list of suitable alternative insulators is currently very limited. Thus, a radically different mindset with respect to suitable insulators for 2D technologies may be required. We review possible solution scenarios like the creation of clean interfaces, production of native oxides from 2D semiconductors and more intensive studies on crystalline insulators

Multipoint pacing by a left ventricular quadripolar lead improves the acute hemodynamic response to CRT compared with conventional biventricular pacing at any site

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A 3D non invasive assessment of the position of the occlusal plane

Introduction. The occlusal plane has a key-role in various dental and medical fields. Several methods have analyzed and measured the relative positions of the occlusal and facial planes; most of these investigations used 2D radiographic exams. Currently, 3D assessments may be performed overlapping CT reconstructions and digitized dental casts, but the method requires ionizing radiations, and it is not applicable in reference studies performed with healthy subjects. The efficacy of these measurements could be improved by a 3D, non invasive approach to the problem. Methods. 20 healthy subjects were selected to have their maxillary dental casts digitized by laser scanning, and their 3D facial soft tissue stereophotogrammetry acquisition merged in a single file. The digital 3D coordinates of three facial (right and left Tragus, Subnasale) and three dental landmarks (inter-incisor, tips of the mesio-vestibular cuspids of right and left first permanent molars), were obtained and exported in a 3D CAD (computed aided design) software for a geometrical analysis. The 3D orientation of the planes, referred to a Cartesian orthogonal reference system, was estimated calculating angular values between the sagittal midlines of the two planes. To evaluate the repeatability of the measurements the protocol was performed independently by two different operators. In total 120 measurements were obtained; descriptive statistics were calculated for each variable. To evaluate the method repeatability mean absolute difference between repeated measurements (MAD), technical error of measurement (REM) and Paired Student’s T tests (P<0.05) were computed. Results. In the frontal and horizontal projections, the occlusal plane resulted nearly parallel to Camper’s plane, with average inclinations of 1.5 (frontal) and 1.9 (horizontal) degrees. In the sagittal projection, the two planes had an average angle of 4.9 degrees, with the occlusal plane more anteriorly inclined than Camper’s plane. For all three projections, a fair inter-operator repeatability was found, with all MADs and TEMs slightly lower than 2 degrees. No systematic errors between repeated measurements were found (T test > 0.05). Conclusions. The current non-invasive method resulted appropriate to the aims. Camper’s and occlusal planes resulted almost parallel in the frontal and horizontal projections, while in the sagittal projection the occlusal plane was 5 degrees more anteriorly inclined than Camper’s plane

The Collaborative for the Research on Black Women and Girls

<p>Seven patients per group. **P<0.01 Mann-Whitney U test. Representative granule cell layer hippocampal sections from patients without granule cell pathology (B) or with type-2 GCP (C) exhibiting DAB-labeled ANTXR1-like immunoreactivity (LI). Omitting the primary antibody to estimate nonspecific signal yielded completely negative labeling (data not shown). Note a widespread increase in ANTXR1-LI in granule cells from patients with type-2 GCP (C).</p

Inflammatory Microenvironment in Early Non-Small Cell Lung Cancer: Exploring the Predictive Value of Radiomics

Patient prognosis is a critical consideration in the treatment decision-making process. Conventionally, patient outcome is related to tumor characteristics, the cancer spread, and the patients’ conditions. However, unexplained differences in survival time are often observed, even among patients with similar clinical and molecular tumor traits. This study investigated how inflammatory radiomic features can correlate with evidence-based biological analyses to provide translated value in assessing clinical outcomes in patients with NSCLC. We analyzed a group of 15 patients with stage I NSCLC who showed extremely different OS outcomes despite apparently harboring the same tumor characteristics. We thus analyzed the inflammatory levels in their tumor microenvironment (TME) either biologically or radiologically, focusing our attention on the NLRP3 cancer-dependent inflammasome pathway. We determined an NLRP3-dependent peritumoral inflammatory status correlated with the outcome of NSCLC patients, with markedly increased OS in those patients with a low rate of NLRP3 activation. We consistently extracted specific radiomic signatures that perfectly discriminated patients’ inflammatory levels and, therefore, their clinical outcomes. We developed and validated a radiomic model unleashing quantitative inflammatory features from CT images with an excellent performance to predict the evolution pattern of NSCLC tumors for a personalized and accelerated patient management in a non-invasive way

Guideline on carotid surgery for stroke prevention: updates from the Italian Society of Vascular and Endovascular Surgery. A trend towards personalized medicine

Background: This guideline (GL) on carotid surgery as updating of "Stroke: Italian guidelines for Prevention and Treatment" of the ISO-SPREAD Italian Stroke Organization-Group, has recently been published in the National Guideline System and shared with the Italian Society of Vascular and Endovascular Surgery (SICVE) and other Scientific Societies and Patient's Association. Methods: GRADE-SIGN version, AGREE quality of reporting checklist. Clinical questions formulated according to the PICO model. Recommendations developed based on clinical questions by a multidisciplinary experts' panel and patients' representatives. Systematic reviews performed for each PICO question. Considered judgements filled by assessing the evidence level, direction, and strength of the recommendations. Results: The panel provided indications and recommendations for appropriate, comprehensive, and individualized management of patients with carotid stenosis. Diagnostic and therapeutic processes of the best medical therapy, carotid endarterectomy (CEA), carotid stenting (CAS) according to the evidences and the judged opinions were included. Symptomatic carotid stenosis in elective and emergency, asymptomatic carotid stenosis, association with ischemic heart disease, preoperative diagnostics, types of anesthesia, monitoring in case of CEA, CEA techniques, comparison between CEA and CAS, post-surgical carotid restenosis, and medical therapy are the main topics, even with analysis of uncertainty areas for risk-benefit assessments in the individual patient (personalized medicine [PM]). Conclusions: This GL updates on the main recommendations for the most appropriate diagnostic and medical-surgical management of patients with atherosclerotic carotid artery stenosis to prevent ischemic stroke. This GL also provides useful elements for the application of PM in good clinical practice