Evaluation of trueness and precision of removable partial denture metal frameworks manufactured with digital technology and different materials.

PURPOSE: The aim of this study is to evaluate the accuracy of removable partial denture (RPD) frameworks produced using different digital protocols. MATERIALS AND METHODS: 80 frameworks for RPDs were produced using CAD-CAM technology and divided into four groups of twenty (n = 20): Group 1, Titanium frameworks manufactured by digital metal laser sintering (DMLS); Group 2, Co-Cr frameworks manufactured by DMLS; Group 3, Polyamide PA12 castable resin manufactured by multi-jet fusion (MJF); and Group 4, Metal (Co-Cr) casting by using lost-wax technique. After the digital acquisition, eight specific areas were selected in order to measure the Δ-error value at the intaglio surface of RPD. The minimum value required for point sampling density (0.4 mm) was derived from the sensitivity analysis. The obtained Δ-error mean value was used for comparisons: 1. between different manufacturing processes; 2. between different manufacturing techniques in the same area of interest (AOI); and 3. between different AOI of the same group. RESULTS: The Δ-error mean value of each group ranged between -0.002 (Ti) and 0.041 (Co-Cr) mm. The Pearson's Chi-squared test revealed significant differences considering all groups paired two by two, except for group 3 and 4. The multiple comparison test documented a significant difference for each AOI among group 1, 3, and 4. The multiple comparison test showed significant differences among almost all different AOIs of each group. CONCLUSION: All Δ-mean error values of all digital protocols for manufacturing RPD frameworks optimally fit within the clinical tolerance limit of trueness and precision.

Analysis of the trueness and precision of complete denture bases manufactured using digital and analog technologies.

PURPOSE: Digital technology has enabled improvements in the fitting accuracy of denture bases via milling techniques. The aim of this study was to evaluate the trueness and precision of digital and analog techniques for manufacturing complete dentures (CDs). MATERIALS AND METHODS: Sixty identical CDs were manufactured using different production protocols. Digital and analog technologies were compared using the reference geometric approach, and the Δ-error values of eight areas of interest (AOI) were calculated. For each AOI, a precise number of measurement points was selected according to sensitivity analyses to compare the Δ-error of trueness and precision between the original model and manufactured prosthesis. Three types of statistical analysis were performed: to calculate the intergroup cumulative difference among the three protocols, the intergroup among the AOIs, and the intragroup difference among AOIs. RESULTS: There was a statistically significant difference between the dentures made using the oversize process and injection molding process (P < .001), but no significant difference between the other two manufacturing methods (P = .1227). There was also a statistically significant difference between the dentures made using the monolithic process and the other two processes for all AOIs (P = .0061), but there was no significant difference between the other two processes (P = 1). Within each group, significant differences among the AOIs were observed. CONCLUSION: The monolithic process yielded better results, in terms of accuracy (trueness and precision), than the other groups, although all three processes led to dentures with Δ-error values well within the clinical tolerance limit.

A retrotransposon storm marks clinical phenoconversion to late-onset Alzheimer's disease.

Recent reports have suggested that the reactivation of otherwise transcriptionally silent transposable elements (TEs) might induce brain degeneration, either by dysregulating the expression of genes and pathways implicated in cognitive decline and dementia or through the induction of immune-mediated neuroinflammation resulting in the elimination of neural and glial cells. In the work we present here, we test the hypothesis that differentially expressed TEs in blood could be used as biomarkers of cognitive decline and development of AD. To this aim, we used a sample of aging subjects (age > 70) that developed late-onset Alzheimer's disease (LOAD) over a relatively short period of time (12-48 months), for which blood was available before and after their phenoconversion, and a group of cognitive stable subjects as controls. We applied our developed and validated customized pipeline that allows the identification, characterization, and quantification of the differentially expressed (DE) TEs before and after the onset of manifest LOAD, through analyses of RNA-Seq data. We compared the level of DE TEs within more than 600,000 TE-mapping RNA transcripts from 25 individuals, whose specimens we obtained before and after their phenotypic conversion (phenoconversion) to LOAD, and discovered that 1790 TE transcripts showed significant expression differences between these two timepoints (logFC ± 1.5, logCMP > 5.3, nominal p value < 0.01). These DE transcripts mapped both over- and under-expressed TE elements. Occurring before the clinical phenoconversion, this TE storm features significant increases in DE transcripts of LINEs, LTRs, and SVAs, while those for SINEs are significantly depleted. These dysregulations end with signs of manifest LOAD. This set of highly DE transcripts generates a TE transcriptional profile that accurately discriminates the before and after phenoconversion states of these subjects. Our findings suggest that a storm of DE TEs occurs before phenoconversion from normal cognition to manifest LOAD in risk individuals compared to controls, and may provide useful blood-based biomarkers for heralding such a clinical transition, also suggesting that TEs can indeed participate in the complex process of neurodegeneration.

Surgical aortic valve replacement for low-gradient aortic stenosis.

AIMS: Low-gradient aortic stenosis is a challenging entity that needs accurate preoperative evaluation. For this high-risk patient population, ad hoc predictive scores are not available and profile risk is currently revealed by the EuroSCOREs. Aims of this study are to verify the suitability of the ES II as predictor of mortality in low-gradient aortic stenosis and to analyse the role of surgery as a treatment. METHODS: From June 2013 to August 2019, 414 patients underwent surgical aortic valve replacement for low-gradient aortic stenosis. Mean age was 75.78 ±â€Š6.77 years and 190 were women. The prognostic value of Logistic EuroSCORE and EuroSCORE II were compared by receiver-operating characteristics (ROC) curve analysis. RESULTS: In-hospital, 30-day and 1-year mortality rates were respectively 3.4, 2.9 and 4.8% (14, 12 and 20 patients over 414). In-hospital mortality risk calculated by the Additive EuroSCORE was 7.2 ±â€Š2.7%, by the Logistic EuroSCORE was 9 ±â€Š5.2% and by the ES II was 4.13 ±â€Š2.56%. The prognostic values of the EuroSCORE II and of the EuroSCORE were analysed in a ROC curve analysis for the prediction of in-hospital mortality [area under the curve (AUC): 0.62 vs. 0.58], 30-day mortality (AUC: 0.63 vs. 0.64) and 1-year mortality (AUC: 0.79 vs. 0.65). Both scores did not show significant differences with the only exception of 1-year mortality, for which EuroSCORE II had a better predictive ability than the Logistic EuroSCORE (P < 0.05). CONCLUSION: In low-gradient aortic stenosis undergoing surgery, the EuroSCORE II is a strong predictor of 1-year mortality.

The effects of cerebrospinal fluid tap-test on idiopathic normal pressure hydrocephalus: an inertial sensors based assessment.

BACKGROUND: Gait disturbances are typical of persons with idiopathic normal pressure hydrocephalus (iNPH) without signs distinctive from other neurodegenerative and vascular conditions. Cerebrospinal fluid tap-test (CSF-TT) is expected to improve the motor performance of iNPH patients and is a prognostic indicator in their surgical management. This observational prospective study aims to determine which spatio-temporal gait parameter(s), measured during instrumented motor tests, and clinical scale(s) may provide a relevant contribution in the evaluation of motor performance pre vs. post CSF-TT on iNPH patients with and without important vascular encephalopathy. METHODS: Seventy-six patients (20 with an associated vascular encephalopathy) were assessed before, and 24 and 72 h after the CSF-TT by a timed up and go test (TUG) and an 18 m walking test (18 mW) instrumented using inertial sensors. Tinetti Gait, Tinetti Balance, Gait Status Scale, and Grading Scale were fulfilled before and 72 h after the CSF-TT. Stride length, cadence and total time were selected as the outcome measures. Statistical models with mixed effects were implemented to determine the relevant contribution to response variables of each quantitative gait parameter and clinical scales. RESULTS AND CONCLUSION: From baseline to 72 h post CSF-TT patients improved significantly by increasing cadence in 18 mW and TUG (on average of 1.7 and 2.4 strides/min respectively) and stride length in 18 mW (on average of 3.1 cm). A significant reduction of gait apraxia was reflected by modifications in double support duration and in coordination index. Tinetti Gait, Tinetti Balance and Gait Status Scale were able to explain part of the variability of response variables not covered by instrumental data, especially in TUG. Grading Scale revealed the highest affinity with TUG total time and cadence when considering clinical scales alone. Patients with iNPH and an associated vascular encephalopathy showed worst performances compared to pure iNPH but without statistical significance. Gait improvement following CSF-TT was comparable in the two groups. Overall these results suggest that, in order to augment CSF-TT accuracy, is key to assess the gait pattern by analyzing the main spatio-temporal parameters and set post evaluation at 72 h. TRIAL REGISTRATION: Approved by ethics committee: CE 14131 23/02/2015.

Total Lymphadenectomy and Nodes-Based Prognostic Factors in Surgical Intervention for Esophageal Adenocarcinoma.

BACKGROUND: To evaluate prognostic factors based on the number of resected lymph nodes, we considered 202 patients who underwent radical resection and "total lymphadenectomy" for esophageal adenocarcinoma according to a prospective protocol. METHODS: Fifty-eight tumors surrounded by Barrett's epithelium underwent esophagectomy and esophagogastrostomy, and 144 tumors without Barrett's epithelium underwent esophageal resection at the azygos vein level, total gastrectomy, and Roux-en-Y esophagojejunostomy. All nodes and fat tissue were resected at the following stations: chest 4L and R3, R4, R7, R8, and R9 (TNM seventh edition) and abdomen 1-12 according to the Japanese Classification of Gastric Carcinoma (1998). The nodes were counted, excluding fragments. The correlations between the number of nodes yielded and the ratio of the metastatic lymph nodes/lymph nodes yielded with pT stage, grading measurements, and cancer-specific survival (CSS) were calculated. RESULTS: A total of 6,270 nodes were yielded (interquartile range per patient, 22-38; minimum, 4 nodes; maximum, 61 nodes). In 3 of 21 (14%) stage pT1 cases, less than 10 nodes were counted, in 2 of 27 (8%) stage pT2 cases, less than 20 were counted, and in 73 of 154 (47%) stage pT3-4 cases, less than 30 nodes were counted. The lymph node yield (LNY) and T stage were not correlated (r = 0 .048; p = 0.5). The metastatic lymph nodes to lymph nodes yielded ratio was correlated with pT stage (r = 0.272; p = 0.0001), and G (r = 0.385; p = 0.0001). CSS positively correlated with pT stage (p = 0.02), G (p = 0.001), and metastatic lymph nodes/lymph nodes yielded ratio (p = 0.01) (multivariate analysis). CONCLUSIONS: The total number of lymph nodes to be removed in total and within each T stage indicated as thresholds could not be reached in up to 38.6% of patients. The metastatic lymph nodes/lymph nodes yield ratio not the total LNY, did correlate with cancer-specific survival.

MDP, a database linking drug response data to genomic information, identifies dasatinib and statins as a combinatorial strategy to inhibit YAP/TAZ in cancer cells.

Targeted anticancer therapies represent the most effective pharmacological strategies in terms of clinical responses. In this context, genetic alteration of several oncogenes represents an optimal predictor of response to targeted therapy. Integration of large-scale molecular and pharmacological data from cancer cell lines promises to be effective in the discovery of new genetic markers of drug sensitivity and of clinically relevant anticancer compounds. To define novel pharmacogenomic dependencies in cancer, we created the Mutations and Drugs Portal (MDP, http://mdp.unimore.it), a web accessible database that combines the cell-based NCI60 screening of more than 50,000 compounds with genomic data extracted from the Cancer Cell Line Encyclopedia and the NCI60 DTP projects. MDP can be queried for drugs active in cancer cell lines carrying mutations in specific cancer genes or for genetic markers associated to sensitivity or resistance to a given compound. As proof of performance, we interrogated MDP to identify both known and novel pharmacogenomics associations and unveiled an unpredicted combination of two FDA-approved compounds, namely statins and Dasatinib, as an effective strategy to potently inhibit YAP/TAZ in cancer cells.

Causes and timing of death during long-term follow-up after transcatheter aortic valve replacement.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is an effective therapeutic option for patients with severe aortic stenosis at high risk for surgery. Identification of causes of death after TAVR may help improve patient selection and outcome. METHODS: We enrolled 874 consecutive patients who underwent TAVR at 3 centers using all approved bioprostheses and different access routes. Clinical outcomes during follow-up were defined according to the Valve Academic Research Consortium 2 definitions. Causes of deaths were carefully investigated. RESULTS: Mean logistic European System for Cardiac Operative Risk Evaluation was 23.5% ± 15.3%; Society of Thoracic Surgery score, 9.0% ± 8.2%. The Corevalve (Medtronic, Minneapolis, MN) was used in 41.3%; the Edwards Sapien (Edwards Lifesciences Inc., Irvine, CA) in 57.3%. Vascular access was transfemoral in 75.7%. In-hospital mortality was 5.0%. Cumulative mortality rates at 1 to 3 years were 12.4%, 23.4%, and 31.5%, respectively. Landmark analysis showed a significantly higher incidence of cardiovascular (CV) death in the first 6 months of follow-up and a significantly higher incidence of non-CV death thereafter. At Cox regression analysis, the independent predictors of in-hospital mortality were acute kidney injury grades 2 to 3 (hazard ratio [HR] 3.41) life-threatening bleeding (HR 4.26), major bleeding (HR 4.61), and myocardial infarction (HR 3.89). The independent predictors of postdischarge mortality were chronic obstructive pulmonary disease (HR 1.48), left ventricular ejection fraction at discharge (HR 0.98), and glomerular filtration rate <30 mL/min per 1.73 m(2) (HR 1.64). CONCLUSIONS: Around a third of patients treated with TAVR in daily practice die within the first 3 years of follow-up. Early mortality is predominantly CV, whereas late mortality is mainly non-CV, and it is often due to preexisting comorbidity.

UCbase 2.0: ultraconserved sequences database (2014 update).

UCbase 2.0 (http://ucbase.unimore.it) is an update, extension and evolution of UCbase, a Web tool dedicated to the analysis of ultraconserved sequences (UCRs). UCRs are 481 sequences >200 bases sharing 100% identity among human, mouse and rat genomes. They are frequently located in genomic regions known to be involved in cancer or differentially expressed in human leukemias and carcinomas. UCbase 2.0 is a platform-independent Web resource that includes the updated version of the human genome annotation (hg19), information linking disorders to chromosomal coordinates based on the Systematized Nomenclature of Medicine classification, a query tool to search for Single Nucleotide Polymorphisms (SNPs) and a new text box to directly interrogate the database using a MySQL interface. To facilitate the interactive visual interpretation of UCR chromosomal positioning, UCbase 2.0 now includes a graph visualization interface directly linked to UCSC genome browser. Database URL: http://ucbase.unimore.it.

[Prevalence of degenerative aortic valve stenosis in the elderly: results of a large community-based epidemiological study]. / Prevalenza della stenosi aortica degenerativa negli anziani: risultati di uno studio epidemiologico di comunità

BACKGROUND: There is a paucity of epidemiological data on the prevalence of degenerative aortic stenosis (AS) after the recent demographic changes and in the present therapeutic era. We sought to assess the prevalence of AS in an elderly population of an Italian urban area and to derive an epidemiological estimate of AS prevalence on a larger scale. METHODS: Elderly people (aged 75-95 years) of a 26 000 inhabitants town were clinically screened by general practitioners and classified into four groups: (1) no signs of AS; (2) known AS; (3) suspected AS (on the basis of the presence of a systolic murmur); (4) prior aortic valve replacement (AVR). Group 2 and 3 patients underwent physical examination and transthoracic echocardiography to confirm or rule out the diagnosis of AS, and to assess main comorbidities. RESULTS: Among the eligible patients, 2203 (93.7%) had no sign of AS; 49 (2.1%) had known AS; in 74 (3.1%) there was a systolic murmur suggesting AS, and 26 (1.1%) had previous AVR because of AS. Ten patients refused further screening, therefore 113 patients underwent transthoracic echocardiography. Among them, degenerative aortic disease without stenosis was observed in 22, and 63 had confirmed AS (severe in 21). Important comorbidities were frequently diagnosed in these patients. Including patients with previous AVR, AS was confirmed in 89/2350 patients (3.8%). On a regional scale, based on the demographics of this area, we estimated a prevalence of severe AS of 2248 cases per million inhabitants. CONCLUSIONS: The prevalence of AS in a population aged 75-95 years was 3.8%, and it was not previously diagnosed in a sizable proportion. More attention for early diagnosis of AS in the elderly is warranted.

Estrogen mediated-activation of miR-191/425 cluster modulates tumorigenicity of breast cancer cells depending on estrogen receptor status.

MicroRNAs (miRNAs), single-stranded non-coding RNAs, influence myriad biological processes that can contribute to cancer. Although tumor-suppressive and oncogenic functions have been characterized for some miRNAs, the majority of microRNAs have not been investigated for their ability to promote and modulate tumorigenesis. Here, we established that the miR-191/425 cluster is transcriptionally dependent on the host gene, DALRD3, and that the hormone 17ß-estradiol (estrogen or E2) controls expression of both miR-191/425 and DALRD3. MiR-191/425 locus characterization revealed that the recruitment of estrogen receptor α (ERα) to the regulatory region of the miR-191/425-DALRD3 unit resulted in the accumulation of miR-191 and miR-425 and subsequent decrease in DALRD3 expression levels. We demonstrated that miR-191 protects ERα positive breast cancer cells from hormone starvation-induced apoptosis through the suppression of tumor-suppressor EGR1. Furthermore, enforced expression of the miR-191/425 cluster in aggressive breast cancer cells altered global gene expression profiles and enabled us to identify important tumor promoting genes, including SATB1, CCND2, and FSCN1, as targets of miR-191 and miR-425. Finally, in vitro and in vivo experiments demonstrated that miR-191 and miR-425 reduced proliferation, impaired tumorigenesis and metastasis, and increased expression of epithelial markers in aggressive breast cancer cells. Our data provide compelling evidence for the transcriptional regulation of the miR-191/425 cluster and for its context-specific biological determinants in breast cancers. Importantly, we demonstrated that the miR-191/425 cluster, by reducing the expression of an extensive network of genes, has a fundamental impact on cancer initiation and progression of breast cancer cells.