The role of HMG-CoA reductase inhibition in endothelial dysfunction and inflammation

Statin-induced inhibition of HMG-CoA reductase reduces cholesterol production and prevents the formation of many non-steroidal isoprenoid compounds, such as farnesylpyrophosphate and geranylgeranylpyrophosphate, that act as lipid attachments for the post-translational modification of various proteins, including the G-proteins and transcription factors involved in a number of cell processes. However, the blockade of isoprenylation elicited by statin treatment also has biological effects on cell function that go beyond the decrease in cholesterol synthesis: these are the so-called “pleiotropic” effects that mainly relate to vascular function. Endothelial dysfunction is an independent predictor of cardiovascular events that correlates with inflammation markers/mediators and robust predictors of cardiovascular diseases such as increased high-sensitivity C-reactive protein levels. The results of in vivo and in vitro studies indicate that the statins have beneficial effects unrelated to cholesterol lowering, such as improving endothelial function, increasing myocardial perfusion, and enhancing the availability of nitric oxide. This review describes the pleiotropic effects of statins that may be involved in modulating/preventing endothelial dysfunction and inflammatory processes, as well as the cellular and molecular mechanisms through which they improve endothelial function

Improvement of spatial contrast sensitivity threshold after surgical reduction of intraocular pressure in unilateral high-tension glaucoma.

PUKPOSE. To measure the effect of a surgical reduction of IOP on the spatial contrast sensitivity threshold in eyes showing a considerably increased IOP but no glaucomatous visual field defect, on white-on-white computer-assisted static perimetry. METHODS. Prospective clinical trial, lasting 36 months; 10 consecutive subjects with untreated IOP ≥ 30 mm Hg in one eye and <18 mm Hg in the fellow eye, no evidence of field damage in both eyes, best corrected visual acuity ≥ 20/20 in both eyes, and scheduled for a primary trabeculectomy in the eye showing a high IOP. The spatial contrast sensitivity threshold was measured before surgery and at each follow-up visit. RESULTS. Preoperative spatial contrast sensitivity was worse in those eyes bearing a high IOP relative to the normal fellow eyes (paired samples t-test, P < 0.0005). An improvement of contrast sensitivity threshold, exceeding the 95% confidence limits of the preoperative test-retest variability, was observed at 3, 6, and 12 cyc/deg in each surgical eye at the end of follow-up. No change was observed in the fellow untreated normal eyes. The improvement correlated directly with the amount of decrease in pressure obtained by surgery. CONCLUSIONS. Eyes with no field defects on white-on-white computer-assisted static perimetry, but bearing a IOP ≥ 30 mm Hg, show a decreased spatial contrast sensitivity. A surgically obtained reduction of IOP is paralleled by an improvement of spatial contrast sensitivity

An adaptive stigmergy-based system for evaluating technological indicator dynamics in the context of smart specialization

Regional innovation is more and more considered an important enabler of welfare. It is no coincidence that the European Commission has started looking at regional peculiarities and dynamics, in order to focus Research and Innovation Strategies for Smart Specialization towards effective investment policies. In this context, this work aims to support policy makers in the analysis of innovation-relevant trends. We exploit a European database of the regional patent application to determine the dynamics of a set of technological innovation indicators. For this purpose, we design and develop a software system for assessing unfolding trends in such indicators. In contrast with conventional knowledge-based design, our approach is biologically-inspired and based on self-organization of information. This means that a functional structure, called track, appears and stays spontaneous at runtime when local dynamism in data occurs. A further prototyping of tracks allows a better distinction of the critical phenomena during unfolding events, with a better assessment of the progressing levels. The proposed mechanism works if structural parameters are correctly tuned for the given historical context. Determining such correct parameters is not a simple task since different indicators may have different dynamics. For this purpose, we adopt an adaptation mechanism based on differential evolution. The study includes the problem statement and its characterization in the literature, as well as the proposed solving approach, experimental setting and results

Detecting User’s Behavior Shift with Sensorized Shoes and Stigmergic Perceptrons

As populations become increasingly aged, health monitoring has gained increasing importance. Recent advances in engineering of sensing, processing and artificial learning, make the development of non-invasive systems able to observe changes over time possible. In this context, the Ki-Foot project aims at developing a sensorized shoe and a machine learning architecture based on computational stigmergy to detect small variations in subjects gait and to learn and detect users behaviour shift. This paper outlines the challenges in the field and summarizes the proposed approach. The machine learning architecture has been developed and publicly released after early experimentation, in order to foster its application on real environments

Rehabilitation of COVID-19 patients

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Carcinoma della prostata: prostatectomia radicale nei pazienti over 70

Prostate cancer is one of the most common male cancers in industrialized countries and it occurs mainly in men older than 50 years. In light of a rapidly ageing population it seems certain tha increasingly many septuagenarians with significant life-expectancy will present with prostate cancer to urologist. However currently there is a lack of consensus on prostate cancer and its treatment in the cohort of men ≥ 70 years of age. Although elderly men are often recommended a watchfull waiting option based on lower life expentancy and potentially slow disease progression, recent evidences indicate suggest a potential benefit of radical prostatectomy in selected older patients. The aim of this review is to illustrate the evidences demonstrating the efficacy and safety and of radical prostatectomy in patients over 70. Also, are presented the results of a small Italian study on patients aged ≥ 70 years with clinically localized prostate cancer undergoing radical prostatectomy. The results show that radical prostatectomy is a safe and effective option in elderly patients, with low incidence of complications and recovery of continence in about two-thirds of patients

Detection rate for significant cancer at confirmatory biopsy in men enrolled in Active Surveillance protocol: 20 cores vs 30 cores vs MRI/TRUS fusion prostate biopsy

Introduction: The detection rate for significant prostate cancer of extended vs saturation vs mMRI/TRUS fusion biopsy was prospectively evaluated in men enrolled in active surveillance (AS) protocol. Mterials and methods: From May 2013 to September 2016 75 men aged 66 years (median) with very low risk PCa were enrolled in an AS protocol and elegible criteria were: life expectancy greater than 10 years, cT1C, PSA below 10 ng/ml, PSA density &lt; 0.20, 2 &lt; unilateral positive biopsy cores, Gleason score (GS) equal to 6, greatest percentage of cancer (GPC) in a core &lt; 50%. All patients underwent 3.0 Tesla pelvic mpMRI before confirmatory transperineal extended (20 cores) or saturation biopsy (SPBx; 30 cores) combined with mpMRI/TRUS fusion targeted biopsy (4 cores) of suspicious lesions (PI-RADS 3-5). Results: 21/75 (28%) patients were reclassified by SPBx based on upgraded GS ≥ 7; mpMRI lesions PI-RADS 4-5 vs PI-RADS 3-5 diagnosed 9/21 (42.8%) vs 16/21 (76.2%) significant PCa with 2 false positives (6.5%). The detection rate for significant PCa was equal to 76.2% (mpMRI/TRUS fusion biopsy) vs 81% (extended) vs 100% (SPBx) (p = 0.001); mpMRI/TRUS targeted biopsy and extended biopsy missed 5/21 (23.8%) and 4/21 (19%) significant PCa which were found by SPBx (p = 0.001) being characterised by the presence of a single positive core of GS ≥ 7 with GPC &lt; 10%. Conclusions: Although mpMRI improve the diagnosis of clinically significant PCa, SPBx is provided of the best detection rate for PCa in men enrolled in AS protocols who underwent confirmatory biopsy

Differential Toll like receptor expression in cystic fibrosis patients' airways during rhinovirus infection

Objectives: Since an inappropriate and sustained activation of TLRs may contribute to a chronic inflammatory response resulting in detrimental effects in cystic fibrosis (CF) patients, we sought to examine whether HRV infection might alter the respiratory expression of TLRs according to the microbiological status of CF patients. Methods: Respiratory samples were collected from the respiratory tract of CF patients (n = 294) over a period of 12 months. In addition to the usual microbiological investigation, HRV-RNA detection and typing were performed by RT-PCR and sequencing. HRV viral load and TLRs levels were measured by RT-Real Time PCR. Results: HRV-RNA was detected in 80 out of 515 respiratory samples (15.5%) with a similar rate in all age groups (0–10 years, 11–24 years, ≥ 25 years). Patients infected with different HRV A, B and C species exhibited higher levels of TLR2, TLR4 and TLR8 as compared to HRV negative patients. Moreover, the expression level of TLR2, TLR4 and TLR8 correlated with high level of HRV viral load. HRV positive patients co-colonized by Staphylococcus aureus or Pseudomonas aeruginosa showed also enhanced amounts of TLR2 and TLR2/4-mRNAs expression respectively. In the case of presence of both bacteria, TLR2, TLR4, TLR8 and TLR9 levels are elevated in positive HRV patients. Conclusions: TLRs, especially TLR2 and TLR4, increased in HRV positive CF individuals and varies according to the presence of S. aureus, P. aeruginosa and both bacteria

A population-based study on myelodysplastic syndromes in the Lazio Region (Italy), medical miscoding and 11-year mortality follow-up. The Gruppo Romano-Laziale Mielodisplasie experience of retrospective multicentric registry

Data on Myelodysplastic Syndromes (MDS) are difficult to collect by cancer registries because of the lack of reporting and the use of different classifications of the disease. In the Lazio Region, data from patients with a confirmed diagnosis of MDS, treated by a hematology center, have been collected since 2002 by the Gruppo Romano-Laziale Mielodisplasie (GROM-L) registry, the second MDS registry existing in Italy. This study aimed at evaluating MDS medical miscoding during hospitalizations, and patients' survival. For these purposes, we selected 644 MDS patients enrolled in the GROM-L registry. This cohort was linked with two regional health information systems: the Hospital Information System (HIS) and the Mortality Information System (MIS) in the 2002-2012 period. Of the 442 patients who were hospitalized at least once during the study period, 92% had up to 12 hospitalizations. 28.5% of patients had no hospitalization episodes scored like MDS, code 238.7 of the International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM). The rate of death during a median follow-up of 46 months (range 0.9-130) was 45.5%. Acute myeloid leukemia (AML) was the first cause of mortality, interestingly a relevant portion of deaths is due to cerebro-cardiovascular events and second tumors. This study highlights that MDS diagnosis and treatment, which require considerable healthcare resources, tend to be under-documented in the HIS archive. Thus we need to improve the HIS to better identify information on MDS hospitalizations and outcome. Moreover, we underline the importance of comorbidity in MDS patients' survival