We report the experimental application of distributed optical fiber sensors, based on stimulated Brillouin scattering (SBS), to the monitoring of a small-scale granular slope reconstituted in an ...instrumented flume and subjected to artificial rainfall until failure, and to the monitoring of a volcanic rock slope. The experiments demonstrate the sensors' ability to reveal the sudden increase in soil strain that foreruns the failure in a debris flow phenomenon, as well as to monitor the fractures in the tuff rocks. This study offers an important perspective on the use of distributed optical fiber sensors in the setting up of early warning systems for landslides in both rock and unconsolidated materials.
Among patients with peripheral arterial disease (PAD) the risk of mortality remains extremely high. We investigated whether arterial stiffness evaluated by aortic Pulse Wave Velocity (aPWV) and ...Augmentation index normalized for a standard heart rate of 75 bpm (Aix@75), predict cardiovascular disease (CVD) and total mortality in PAD and No-PAD patients. In 231 PAD patients (ankle-brachial index-ABI ≤ 0.9) and 167 No-PAD (ABI ≥ 0.91 < 1.3) the aPWV and Aix @75HR were evaluated using arterial tonometry and ABI values were obtained using an 8-MHz Doppler probe. The CVD and total mortality rates in relation to aPWV and Aix@75HR were analyzed using Cox regression model. During a mean follow-up of 5.4 ± 2 years 39 (16.9%) deaths occurred in PAD patients and 8 (4.8%) in No-PAD. In the population study, the age was a predictor of CVD mortality (HR = 0.143, 95% CI, 0.06-0.23; p = 0.0004) while the aPWV, was a predictor of total mortality (HR = 1.18, 95% CI, 1.07-1.30; p = 0.0008). In the PAD group, the aPWV remained associated with an increased risk for total mortality (HR = 1.14, 95% CI, 1.03-1.27; p = 0.010). An increase of aPWV may be an indicator of total mortality in PAD patients.
Cardiac involvement in Systemic Sclerosis (SSc) is increasingly recognized as a mayor cause of morbidity and mortality. The aim of present study is to investigate the early stages of cardiac ...involvement in SSc by Cardiovascular magnetic resonance (CMR), combining the non-invasive detection of myocardial inflammation and fibrosis using T2 and T1 mapping techniques and the assessment of microcirculatory impairment through perfusion response to cold pressor test (CPT).
40 SSc patients (30 females, mean age: 42.1 years) without cardiac symptoms and 10 controls underwent CMR at 1.5 T unit. CMR protocol included: native and contrast-enhanced T1 mapping, T2 mapping, T2-weighted, cineMR and late gadolinium enhancement (LGE) imaging. Microvascular function was evaluated by comparing myocardial blood flow (MBF) on perfusion imaging acquired at rest and after CPT. Native myocardial T1 and T2 relaxation times, extracellular volume fraction (ECV), T2 signal intensity ratio, biventricular volumes and LGE were assessed in each patient.
SSc patients had significantly higher mean myocardial T1 (1029±32ms vs. 985±18ms, p<0.01), ECV (30.1±4.3% vs. 26.7±2.4%, p<0.05) and T2 (50.1±2.8ms vs. 47±1.5ms, p<0.01) values compared with controls. No significant differences were found between absolute MBF values at rest and after CPT; whereas lower MBF variation after CPT was observed in SSc patients (+33 ± 14% vs. +44 ± 12%, p<0.01). MBF variation had inverse correlation with native T1 values (r: -0.32, p<0.05), but not with ECV.
Myocardial involvement in SSc at preclinical stage increases native T1, T2 and ECV values, reflecting inflammation and fibrosis, and reduces vasodilatory response to CPT, as expression of microvascular dysfunction.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background: Medullary sponge kidney (MSK) disease is a rare and neglected congenital condition typically associated with nephrocalcinosis/nephrolithiasis, urinary concentration defects, and cystic ...anomalies in the precalyceal ducts that, although sporadic in the general population, is relatively frequent in renal stone formers. The physiopathologic mechanism associated with this disease is not fully understood, and omics technologies may help address this gap. Summary: The aim of this review was to provide an overview of the current state of the application of proteomics in the study of this rare disease. In particular, we focused on the results of our recent Italian collaborative studies that, analyzing the MSK whole and extracellular vesicle urinary content by mass spectrometry, have displayed the existence of a large and multifactorial MSK-associated biological machinery and identified some main regulatory biological elements able to discriminate patients affected by this rare disorder from those with idiopathic calcium nephrolithiasis and autosomal dominant polycystic kidney disease (including laminin subunit alpha 2, ficolin 1, mannan-binding lectin serine protease 2, complement component 4-binding protein β, sphingomyelin, ephrins). Key Messages: The application of omics technologies has provided new insights into the comprehension of the physiopathology of the MSK disease and identified novel potential diagnostic biomarkers that may replace in future expensive and invasive radiological tests (including CT) and select novel therapeutic targets potentially employable, whether validated in a large cohort of patients, in the daily clinical practice.
Multiparametric magnetic resonance imaging (mpMRI) of the prostate has excellent sensitivity in detecting clinically significant prostate cancer (csPCa). Nevertheless, the clinical utility of ...negative mpMRI (nMRI) is less clear.
To assess outcomes of men with nMRI and clinical follow-up after 7 yr of activity at a reference center.
All mpMRI performed from January 2010 to May 2015 were reviewed. We selected all patients with nMRI and divided them in group A (naïve patients) and group B (previous negative biopsy). All patients without a diagnosis of PCa had a minimum follow-up of 2 yr and at least two consecutive nMRI. Patients with positive mpMRI were also identified to assess their biopsy outcomes.
A Kaplan-Meier analysis was performed to assess both any-grade PCa and csPCa diagnosis-free survival probabilities. Univariable and multivariable Cox regression models were fitted to identify predictors of csPCa diagnosis.
We identified 1545 men with nMRI, and 1255 of them satisfied the inclusion criteria; 659 belonged to group A and 596 to group B. Any-grade PCa and csPCa diagnosis-free survival probabilities after 2 yr of follow-up were 94% and 95%, respectively, in group A; in group B, they were 96%. After 48 mo of follow-up, any-grade PCa diagnosis-free survival probability was 84% in group A and 96% in group B (log rank p<0.001). Diagnosis-free survival probability for csPCa was unchanged after 48 mo of follow-up. On multivariable Cox regression analysis, increasing age (p=0.005) was an independent predictor of lower csPCa diagnosis probability, while increasing prostate-specific antigen (PSA) and PSA density (<0.001) independently predicted higher csPCa diagnosis probability. The prevalence of and positive predictive value for csPCa were 31.6% and 45.5%, respectively. Limitations include limited follow-up and the inability to calculate true csPCa prevalence in the study population.
mpMRI is highly reliable to exclude csPCa. Nevertheless, systematic biopsy should be recommended even after nMRI, especially in younger patients with high or raising PSA levels.
It is a matter of debate whether patients with negative multiparametric magnetic resonance imaging (mpMRI) of the prostate could obviate the need to perform a systematic biopsy. In this report, we looked at the outcomes of patients with negative mpMRI and midterm clinical follow-up at a reference center. We found mpMRI to be highly reliable to exclude significant prostate cancer; nonetheless, systematic biopsy must still be recommended after negative mpMRI in patients with high clinical suspicion of prostate cancer.
We evaluated the outcomes of patients with negative multiparametric magnetic resonance imaging at our reference center. Significant prostate cancer diagnosis-free survival after 48 mo of follow-up was 95% in naïve patients, but systematic biopsy should not be omitted in younger patients with high clinical suspicion.
Liver allograft steatosis is a significant risk factor for postoperative graft dysfunction and has been associated with inferior patient and graft survival, particularly in the case of moderate or ...severe macrovesicular steatosis. In recent years, the increasing incidence of obesity and fatty liver disease in the population has led to a higher proportion of steatotic liver grafts being used for transplantation, making the optimization of their preservation an urgent necessity. This review discusses the mechanisms behind the increased susceptibility of fatty livers to ischemia-reperfusion injury and provides an overview of the available strategies to improve their utilization for transplantation, with a focus on preclinical and clinical evidence supporting donor interventions, novel preservation solutions, and machine perfusion techniques.
Objectives
To evaluate accuracy and inter-observer variability using Vesical Imaging-Reporting and Data System (VI-RADS) for discrimination between non-muscle invasive bladder cancer (NMIBC) and ...muscle-invasive bladder cancer (MIBC).
Methods
Between September 2017 and July 2018, 78 patients referred for suspected bladder cancer underwent multiparametric MRI of the bladder (mpMRI) prior to transurethral resection of bladder tumor (TURBT). All mpMRI were reviewed by two radiologists, who scored each lesion according to VI-RADS. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for each VI-RADS cutoff. Receiver operating characteristics curves were used to evaluate the performance of mpMRI. The Ƙ statistics was used to estimate inter-reader agreement.
Results
Seventy-five patients were included in the final analysis, 53 with NMIBC and 22 with MIBC. Sensitivity and specificity were 91% and 89% for reader 1 and 82% and 85% for reader 2 respectively when the cutoff VI-RADS > 2 was used to define MIBC. At the same cutoff, PPV and NPV were 77% and 96% for reader 1 and 69% and 92% for reader 2. When the cutoff VI-RADS > 3 was used, sensitivity and specificity were 82% and 94% for reader 1 and 77% and 89% for reader 2. Corresponding PPV and NPV were 86% and 93% for reader 1 and 74% and 91% for reader 2. Area under curve was 0.926 and 0.873 for reader 1 and 2 respectively. Inter-reader agreement was good for the overall score (
Ƙ
= 0.731).
Conclusions
VI-RADS is accurate in differentiating MIBC from NMIBC. Inter-reader agreement is overall good.
Key Points
• Traditionally, the local staging of bladder cancer relies on transurethral resection of bladder tumor.
• However, transurethral resection of bladder tumor carries a significant risk of understaging a cancer; therefore, more accurate, faster, and non-invasive staging techniques are needed to improve outcomes.
• Multiparametric MRI has proved to be the best imaging modality for local staging; therefore, its use in suitable patients has the potential to expedite radical treatment when necessary and non-invasive diagnosis in patients with poor fitness.
Cadmium (Cd) represents a public health risk due to its non-biodegradability and long biological half-life. The main target of Cd is the kidney, where it accumulates. In the present narrative review, ...we assessed experimental and clinical data dealing with the mechanisms of kidney morphological and functional damage caused by Cd and the state of the art about possible therapeutic managements. Intriguingly, skeleton fragility related to Cd exposure has been demonstrated to be induced both by a direct Cd toxic effect on bone mineralization and by renal failure. Our team and other research groups studied the possible pathophysiological molecular pathways induced by Cd, such as lipid peroxidation, inflammation, programmed cell death, and hormonal kidney discrepancy, that, through further molecular crosstalk, trigger serious glomerular and tubular injury, leading to chronic kidney disease (CKD). Moreover, CKD is associated with the presence of dysbiosis, and the results of recent studies have confirmed the altered composition and functions of the gut microbial communities in CKD. Therefore, as recent knowledge demonstrates a strong connection between diet, food components, and CKD management, and also taking into account that gut microbiota are very sensitive to these biological factors and environmental pollutants, nutraceuticals, mainly present in foods typical of the Mediterranean diet, can be considered a safe therapeutic strategy in Cd-induced kidney damage and, accordingly, could help in the prevention and treatment of CKD.
Several evidences suggest that cancer cells have abnormal cholesterol biosynthetic pathways and prenylation of small guanosine triphosphatase proteins. Tomato lycopene has been suggested to have ...beneficial effects against certain types of cancer, including that of prostate, although the exact molecular mechanism(s) is unknown. We tested the hypothesis that lycopene may exert its antitumor effects through changes in mevalonate pathway and in Ras activation. Incubation of the Ras-activated prostatic carcinoma LNCaP cells with a 24 h lycopene treatment (2.5–10 μM) dose dependently reduced intracellular total cholesterol by decreasing 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase expression and by inactivating Ras, as evidenced by its translocation from cell membranes to cytosol. Concomitantly, lycopene reduced the Ras-dependent activation of nuclear factor-kappaB (NF-κB). Such a reduction was parallel to an inhibition of reactive oxygen species production and to a decrease in the phosphorylation ofc-jun N-terminal kinase, extracellular signal-regulated kinase 1/2 and p38. These effects were also accompanied by an arrest of cell cycle progression and by apoptosis induction, as evidenced by a decrease in cyclin D1 and phospho-AKT levels and by an increase in p21, p27 and p53 levels and in Bax:Bcl-2 ratio. The addition of mevalonate prevented the growth-inhibitory effects of lycopene as well as its increase in Ras cytoplasmatic accumulation and the subsequent changes in NF-κB. The ability of lycopene in inhibiting HMG-CoA reductase expression and cell growth and in inactivating Ras was also found in prostate PC-3, colon HCT-116 and HT-29 and lung BEN cancer cells. These findings provide a novel mechanistic insight into the growth-inhibitory effects of lycopene in cancer.
Following the development of the COVID-19 pandemic, a rigid public health strategy of reduced social contact and shelter-in-place has been adopted by the Italian Government to reduce the spread of ...the virus. In this paper, we aim at evaluating the impact that the COVID-19 pandemic, and the relative containment measures, have had on a real-life sample of patients suffering from substance use disorders (SUDs) and/or behavioral addictions.
An anonymous questionnaire was filled out by 153 addicted patients, both outpatients and residential inpatients, recruited across Italy and highly representative of the current Italian population suffering from addictions. Psychopathological burden (anxiety and depressive symptomatology, somatization, irritability, and post-traumatic symptoms), quality of life, and craving changes in daily habits were assessed.
In our sample, we found moderate rates of depression (22.9%), anxiety (30.1%), irritability (31.6%), and post-traumatic stress (5.4%) symptoms. Psychopathological burden was globally higher among residential patients. Reported levels of craving were generally low.
This study is the first attempt to collect Italian data regarding the effects of the rigid quarantine period, during the COVID-19 pandemic, on patients suffering from a SUD and/or behavioral addictions. The presence of a moderate psychopathological burden correlated to poor quality of life and low craving scores represented the main outcomes. Long-term studies, with follow-up after the end of the restrictive measures, should be considered to implement our findings.
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