Implementation of a quality management system according to ISO 9001:2015 standards in an Angiology Unit: an Italian experience.

Background: The International Standardization Organization operates the world's most widely recognized quality management system standard, the ISO 9001:2015. In the healthcare sector, the adoption of this standard within an organization helps to improve the overall performance and provides a foundation for development and continuous progress. Our study aims to describe the implementation process of a quality management system according to the ISO 9001:2015 standards in an Angiology Unit of an Italian Univer-sity hospital. Methods: The project was structured in 5 operational phases, which were carried out during a time frame of 14 months (March 2018-May 2019) and entailed several improvement actions associated with quality and safety outputs such as clinical management, clinical practice, safety, and patient-centeredness. Results: Implementation of the quality management system led to the improvement of many aspects of the processes performed in the Angiology Unit, both in the outpatient and day hospital setting. Overall, the project positively impacted on systems for patient safety, particularly in communication and data transmis-sion, and clinical leadership. Conclusions: The implementation of the ISO 9001 certification is a process that apparently may seem ex-pensive in terms of resources used, commitment, work, comparison, but it leads to substantial and always progressive improvements in the offer of Services to the user, safety both for the users and for the healthcare personnel involved, in addition to the care processes that translate into significant benefits in terms of quality of care for patients, as well as management savings for the organization.

Genetic and evolutionary perspectives on genogroup III, genotype 2 bovine noroviruses.

Bovine noroviruses are enteric pathogens that are detected in stool samples from cattle. Five genogroups are currently described in the genus Norovirus (family Caliciviridae), and within the genogroups, sequences are further divided into genotypes according to genetic homology and phylogenetic relationships. In this study, stool specimens from Belgian cattle were screened by RT-PCR. All of the sequences that were detected were phylogenetically related to genogroup III genotype 2 bovine noroviruses, confirming their higher prevalence in comparison with strains from genotype 1. When other sequences from around the world were introduced, phylogenetic inferences allowed neither the determination of phylogenetic lineages over time nor the deduction of topotypes for genotype 2 bovine noroviruses. Three complete genotype 2 bovine norovirus sequences were also compared genetically (Newbury2/1976 /UK, Dumfries/1994/UK and B309/2003/BE). Interestingly, the genetic divergence of the complete genomes of these three strains was relatively low, but a region of the N-terminal protein encoded by ORF1, the hypervariable region of the capsid gene encoded by ORF2, and a region of the minor structural protein encoded by ORF3 seem to be the most exposed to genetic evolution. Bayesian inference also showed that genetic evolution of genogroup III, genotype 2 bovine noroviruses over a 30-year period seemed to be lower than that already reported for noroviruses from the genotypes 3 and 4 in genogroup II.

Complete genome sequence of a novel bovine norovirus: evidence for slow genetic evolution in genogroup III genotype 2 noroviruses.

A new genogroup III genotype 2 bovine norovirus, B309/2003/BE, was entirely sequenced and genetically compared to the original Newbury2/1976/UK strain and to Dumfries/1994/UK, detected in 1976 and 1994, respectively. Interestingly, except in well-defined coding regions (N-terminal protein, 3A-like protease, hypervariable region of the capsid protein, and C-terminal part of the minor structural protein), very low genetic differences were noted between the entire genomes of these three strains along a 30-year-long period. It allowed some hypotheses of hotspots of genetic evolution through a low genetic evolution background in genotype 2 genogroup III bovine noroviruses.

Metal chelates anchored to poly-L-peptides and linear D,L-α-peptides with promising nanotechnological applications.

Regular configurationally alternating amino acid sequences generate cyclic and linear helical peptides with a local ß-conformation able to self-assemble in nanowires and nanoscaffolds directed and stabilized by hydrogen bonds. The possibility of modulating the chemical profile of the various amino acid residues containing reactive side chains means that peptides could be flexible templates for creating various building blocks. A method for the design of molecules with potential spintronic properties is described. Peptides containing lysine residues, the side chains of which are bridged through the formation of metal chelates via Schiff bases, could provide stable molecular channels. When metal chelates with high electron spin states are used, their coupling could generate materials that are interesting due to their magnetic properties as well as for the patterning of nanometric lattices driven by their orientation under a magnetic field. With this aim, three alternating D- and L-lysine-containing octapeptides are synthesized and the formation of their bis(pyridoxalaldimine) copper(II) chelate derivatives is shown by absorption and circular dichroism spectroscopies.

Regulation of sodium/iodide symporter and lactoperoxidase expression in four human breast cancer cell lines.

BACKGROUND: Agents capable of increasing radioiodine concentration by stimulating the sodium/iodide symporter (NIS) expression have been extensively investigated for the treatment of certain well-differentiated breast cancers. AIM: In this study, we analyzed the regulation of the NIS and lactoperoxidase (LPO) gene expression in 4 different human breast cancer cell lines, representative of different histotypes of breast cancer. METHODS: MCF-7, T-47D, MDA-MB231, and HCC-1937 (the latter carrying the BRCA-1 mutation) were exposed to different stimulators and the levels of NIS and LPO mRNA measured by a quantitative RT-PCR. RESULTS: All-trans-Retinoic Acid (RA), Dexamethasone (DEX), Trichostatin A (TSA), and Sodium Butyrate (NaB) induced the expression of NIS mRNA in MCF-7 and T-47D cell lines, whereas HCC-1937 and MBA-MB231 were slightly responsive only to the histone-deacetylase inhibitors TSA and NaB. Minor stimulatory effects were detected on LPO mRNA in MCF-7 and T-47D treated with TSA and NaB or RA only in MCF-7, while no effect was detectable in the other two cell lines. CONCLUSIONS: These data indicate that retinoic acid, alone or in combination with DEX, as well as HDAC-inhibitors are very promising agents for a radioiodine- based therapy in a large spectrum of breast cancers, including neoplasms from both basal and ductal cells, especially for the well-differentiated estrogen-dependent tumors. Other molecules or other drug combinations should be tested to extend the same strategy to the less differentiated and more aggressive tumor cells, including those carrying the BRCA mutation.

Notch signaling is involved in expression of thyrocyte differentiation markers and is down-regulated in thyroid tumors.

CONTEXT: Notch genes encode receptors for a signaling pathway that regulates cell growth and differentiation in various contexts, but the role of Notch signaling in thyroid follicular cells has never been fully published. OBJECTIVE: The objective of the study was to characterize the expression of Notch pathway components in thyroid follicular cells and Notch signaling activities in normal and transformed thyrocytes. DESIGN/SETTING AND PATIENTS: Expression of Notch pathway components and key markers of thyrocyte differentiation was analyzed in murine and human thyroid tissues (normal and tumoral) by quantitative RT-PCR and immunohistochemistry. The effects of Notch overexpression in human thyroid cancer cells and FTRL-5 cells were explored with analysis of gene expression, proliferation assays, and experiments involving transfection of a luciferase reporter construct containing human NIS promoter regions. RESULTS: Notch receptors are expressed during the development of murine thyrocytes, and their expression levels parallel those of thyroid differentiation markers. Notch signaling characterized also normal adult thyrocytes and is regulated by TSH. Notch pathway components are variably expressed in human normal thyroid tissue and thyroid tumors, but expression levels are clearly reduced in undifferentiated tumors. Overexpression of Notch-1 in thyroid cancer cells restores differentiation, reduces cell growth rates, and stimulates NIS expression via a direct action on the NIS promoter. CONCLUSION: Notch signaling is involved in the determination of thyroid cell fate and is a direct regulator of thyroid-specific gene expression. Its deregulation may contribute to the loss of differentiation associated with thyroid tumorigenesis.

Animal noroviruses.

Among enteric caliciviruses, noroviruses belong to the genus Norovirus, one of the four accepted genera in the family Caliciviridae. These single-stranded, positive-sense RNA viruses are highly variable both genetically and antigenically. Several animal enteric caliciviruses that are morphologically indistinguishable and genetically closely related to human noroviruses have been identified. The first bovine enteric noroviruses were described in Great Britain and are known as Newbury Agent 2. At least three genetic clusters of porcine noroviruses join together within genogroup II noroviruses. Human noroviruses are the most important cause of acute gastroenteritis illness in people of all ages. In the USA, they are associated with approximately 30-50% of all food-borne outbreaks. Until now, noroviruses have not been associated with gastroenteritis outbreaks in immunocompetent animals. Neither bovine nor porcine noroviruses can replicate in cell culture, although human norovirus can grow in a complex 3D culture system. However, the recently discovered murine noroviruses can replicate in cell culture and are therefore used as model viruses to study human noroviruses. This review focusses on virus classification, virion structure, pathogenesis, epidemiology, immune response and diagnosis of animal noroviruses in comparison with human noroviruses. The classification of animal enteric caliciviruses within the Norovirus genus raises the question of whether transmission from an animal reservoir to humans could occur. Answering this question is important in determining the risk of cross-species infections affecting the epidemiology and evolution of these viruses and so complicating the control of human norovirus infections.

BRAF mutations in papillary thyroid carcinomas inhibit genes involved in iodine metabolism.

CONTEXT: BRAF mutations are common in papillary thyroid carcinomas (PTCs). By affecting the expression of genes critically related to the development and differentiation of thyroid cancer, they may influence the prognosis of these tumors. OBJECTIVE: Our objective was to characterize the expression of thyroid-specific genes associated with BRAF mutation in PTCs. DESIGN/SETTING AND PATIENTS: We examined the expression of key markers of thyrocyte differentiation in 56 PTCs with BRAF mutations (BRAF-mut) and 37 with wild-type BRAF (BRAF-wt). Eight samples of normal thyroid tissue were analyzed as controls. Quantitative PCR was used to measure mRNA levels for the sodium/iodide symporter (NIS), apical iodide transporter (AIT-B), thyroglobulin (Tg), thyroperoxidase (TPO), TSH receptor (TSH-R), the transcription factor PAX8, and glucose transporter type 1 (Glut1). NIS protein expression and localization was also analyzed by immunohistochemistry. RESULTS: mRNA levels for all thyroid-specific genes were reduced in all PTCs vs. normal thyroid tissues. NIS, AIT-B, Tg, and TPO expression was significantly lower in BRAF-mut tumors than in the BRAF-wt group. Glut-1 transcript levels were increased in all PTCs, and additional increases were noted in BRAF-mut tumors. In both tumor subsets, the NIS protein that was expressed was abnormally retained in the cytoplasm. CONCLUSION: BRAF V600E mutation in PTCs is associated with reduced expression of key genes involved in iodine metabolism. This effect may alter the effectiveness of diagnostic and/or therapeutic use of radioiodine in BRAF-mut PTCs.

Dual role of DNA intrinsic curvature and flexibility in determining nucleosome stability.

A statistical mechanistic approach to evaluate the sequence-dependent thermodynamic stability of nucleosomes is proposed. The model is based on the calculation of the DNA intrinsic curvature, obtained by integrating the nucleotide step deviations from the canonical B-DNA structure, and on the evaluation of the first order elastic distortion energy to reach the nucleosomal superstructure. Literature data on the free energy of nucleosome formation as obtained by competitive nucleosome reconstitution of a significant pool of different DNA sequences were compared with the theoretical results, and a satisfactorily good correlation was found. A striking result of the comparison is the emergence of two opposite roles of the DNA intrinsic curvature and flexibility in determining nucleosome stability. Finally, the obtained results suggest that the curvature-dependent DNA hydration should play a relevant role in the sequence-dependent nucleosome stability.

Theoretical prediction of the gel electrophoretic retardation changes due to point mutations in a tract of SV40 DNA.

The changes of gel electrophoretic retardation due to single base substitutions in a 173 bp fragment of Sv40 DNA were predicted by using a theoretical model based on conformational energy calculations. As described in previous papers, this model allows successful prediction of the gel electrophoretic retardation of synthetic as well as natural DNAs reported in literature. The experimental retardations related to 195 point-mutated DNAs were reproduced with a standard deviation of 0.05 comparable with the experimental one of 0.04. This result, which represents a very critical test for the proposed model, indicates that DNA superstructures can be satisfactorily predicted on the simple physical basis of the integration of the nearest-neighbour perturbations in the dinucleotide steps. Thus, cooperative effects appear, in the majority of cases investigated, to play a second order role.

Channel structures in synthetic polypeptides with alternating configurations. Conformational analysis of poly(DL-proline).

Theoretical conformational analysis of L,D alternating sequences of poly alpha-amino acids is reported in connection with the ability of naturally occurring peptide and depsipeptide having alternating configurations to increase selectively the ion permeability across membranes. The most stable structures of poly(DL-proline), of which the conformational variability is practically limited to the choice between cis and trans conformations of the peptide bonds, were characterized. The all-trans conformation results in a flat helical structure possessing the main features for acting as an ion channel across membranes as actually found experimentally. Random cis-trans conformational sequences provide an alternative mechanism of ion transport intermediate between the ion channel and the ion carrier.

From the sequence to the superstructural properties of DNAs.

A theoretical model for predicting intrinsic and induced DNA superstructures as well as their thermodynamic properties is presented. Intrinsic sequence-dependent superstructures are evaluated by integrating local deviations from the canonical B-DNA of the different dinucleotide steps. Induced superstructures are obtained by adopting the principle of minimum deformation free energy, evaluated in the Fourier space, in the framework of first-order elasticity. Finally dinucleotide stacking energies and melting temperatures are considered to account for local flexibility. In fact the two scales are strongly correlated. The model works very satisfactorily in predicting the sequence-dependent effects on the DNA experimental behavior, such as the gel electrophoresis retardation, the writhe transitions in topologically constrained domains, the thermodynamic constants of circularization reactions as well as the nucleosome thermodynamic stability constants.

A theoretical model of DNA curvature.

Distortions from the uniform idealized B-DNA structure are investigated in terms of differential interactions between adjacent nucleotide pairs on the basis of conformational energy calculations. A theoretical model of DNA curvature is proposed based on the evaluation of the curvature vector defined in the complex plane and the corresponding variance. The model appears to contain the basic physical features for translating the deterministic fluctuations of DNA sequences in superstructure elements. It allows the quantitative reproduction of all the available gel electrophoresis experiments on both periodical polynucleotides and tracts of DNAs as well as the theoretical prediction of the sequence dependent DNA writhing in good agreement with the experimental data. The general pattern of agreement between the theoretical and experimental data and the biological significance of the results obtained allow an extensive application of the model for the screening of DNA regions which are possible candidates for protein recognition.

Poly(DL-proline), a synthetic polypeptide behaving as an ion channel across bilayer membranes.

The synthesis and characterization of poly(DL-proline) are reported in relation with its predicted property of forming ion channels across membranes. The analysis of the conductance induced in synthetic bilayer membranes doped with poly(DL-proline) shows ionic permeoselectivity and the characteristic time course of fluctuations of ion channels, according to the similarity with the active structure of gramicidin A in membranes during the ion passage. An alternative mechanism of ion transport across bilayer membranes is also advanced.

Localized management of sinus floor with simultaneous implant placement: a clinical report.

Localized management of sinus floor (LMSF) achieves implant placement and sinus lifting simultaneously. LMSF is a further application of the principles of the edentulous ridge expansion (ERE) technique. It comprises the dissection of a partial-thickness flap, the buccal expansion of the residual alveolar bone, and the fracture and elevation of the sinus floor with simultaneous implant placement. Three hundred three patients were treated with 499 implants placed using the LMSF between April 1988 and December 1993. The selected patients, who showed no signs of sinus pathology, exhibited insufficient vertical alveolar bone dimensions for the placement of dental implants with the traditional technique. The minimal residual alveolar bone height was between 5 and 7 mm. Based on the criteria established by Albrektsson and his coworkers in 1986, the success rate of the 499 implants placed with the LMSF was 97.5%.

The edentulous ridge expansion technique: a five-year study.

This study presents the clinical results of a surgical technique that expands a narrow ridge when its orofacial width precludes the placement of dental implants. In 170 people, 329 implants were placed in sites needing ridge enlargement using the endentulous ridge expansion procedure. This technique involves a partial-thickness flap, crestal and vertical intraosseous incisions into the ridge, and buccal displacement of the buccal cortical plate, including a portion of the underiying spongiosa. Implants were placed in the expanded ridge and allowed to heal for 4 to 5 months. When indicated, the implants were exposed during a second-stage surgery to allow visualization of the implant site. Occlusal loading was applied during the following 3 to 5 months by provisional prostheses. The final phase was the placement of the permanent prostheses. The results yielded a success rate of 98.8%.

Bone regeneration in the edentulous ridge expansion technique: histologic and ultrastructural study of 20 clinical cases.

The edentulous ridge expansion (ERE) technique is a partial-thickness flap procedure for implant surgery that was developed in 1986. The ERE technique permits the use of osseointegrated implants at sites whose minimal orofacial dimensions are insufficient for traditional implant surgery. The present work is a histologic and ultrastructural study of hard tissue repair modalities at edentulous sites that were treated with the ERE technique in 20 humans. Biopsies were obtained from the tissue regenerating within the surgically created bone gap between the mobile buccal and nonmobile lingual or palatal bone-periosteum plates ("bone flaps") on days 40, 90, 120, 150, and 480 (day 0 = day of implant insertion). The results suggest that osteoblasts differentiate from preexisting mesenchymal cells located on the original fissure walls, with consequent deposition of new bone in the surgically created intrabony defect.

Endorectal magnetic resonance imaging in the preoperative staging of rectal tumors.

A proper preoperative staging of rectal tumors is important for correct treatment planning. We included in our study 23 patients with rectal carcinoma in order to evaluate the diagnostic accuracy of endorectal MRI. This technique enabled us to show neoplasms as a hyperintense lesion as compared to the muscolaris. To better delineate the renal dimensions of the neoplasms and reduce chemical shift artifact we performed T2 weighted TSE sequences with and without fat suppression. The diagnostic accuracy in the evaluation of T and N factors as compared to surgery was respectively 78.2% and 78.9%. The major problem has been a slight tendency to overstage parietal infiltration and lymphnodal involvement. Endorectal MRI allows us to obtain an excellent anatomic detail of the three rectal wall layers and a very high spatial resolution which might make this technique the examination of choice in the evaluation of rectal carcinoma.

Peripheral arterial embolism. Report of hospitalized cases.

OBJECTIVE: We analyzed the frequency of peripheral embolisms, the underlying heart disease,triggering factors, the sites of the emboli, and evolution of the patients. METHODS: We analyzed 29 cases of peripheral arterial embolism out of a total of 20,211 hospitalizations in a cardiology center in the city of São Paulo. The age was 51.89+/-18.66 years, and 15 were males. RESULTS: Embolism in the right lower limb occurred in 18 patients (62.0%),in the left lower 11(37.9%) and right upper 3 (10.3%) limbs, and in the left arm (1). Four patients had embolism in two limbs. The heart disease, mitral valvar heart disease (9 patients - 31.0%); infective endocarditis (7- 24.1%); dilated cardiomyopathy (6 - 20.6%); ischemic coronary heart disease (6 patients - 20.6%); and one patient with cor pulmonale. Atrial fibrillation was observed in 20 patients (68.9%), chronic in 12 patients (41.3% ) and acute in 8 (27. 5%). All patients with mitral valvar heart disease had atrial fibrillation, chronic in 8 patients (88.8%); patients with cardiomyopathy and coronary heart disease, 4 in each group had atrial fibrillation, acute in 60% of the patients. Patients with infective endocarditis, 3 had staphylococcus and 2 Gram-negative bacteria. In the follow-up, 2 patients (6.8%) required limbs amputation, and 5 (17.2%) died due to embolism. CONCLUSION: Most of the time, embolism does not cause permanent complications. Our data highlight the importance of anticoagulation for patients acute atrial fibrillation in myocardial dysfunction and for patients with chronic atrial fibrillation in cases of mitral valvar heart disease to prevent peripheral embolism.

Do cardiologists at a university hospital adopt the guidelines for the treatment of heart failure?

OBJECTIVE: To verify whether the guidelines for the treatment of heart failure have been adopted at a university hospital. The guidelines recommend the following: use of angiotensin-converting enzyme inhibitors for all patients with systolic ventricular dysfunction, use of digitalis and diuretics for symptomatic patients, use of beta-blockers for patients in functional classes II or III, use of spironolactone for patients in functional classes III or IV. METHODS: We analyzed the prescriptions of 199 patients. All these patients had ejection fraction (EF)