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CRC cells evolve a variety of strategies to limit or circumvent apoptosis cell death. RNA binding proteins (RBPs) regulate many of the molecular mechanisms that underlie the development of cancer. The insulin-like growth factor II mRNA-binding proteins (IMP) family are oncofoetal RBPs, consisting of IMP1, IMP2 and IMP3, which have an important role in RNA metabolism. IMP3 is highly expressed in colorectal cancer (CRC) tissue, where its expression often correlates with poor prognosis. However, the role of IMP3 in CRC is not fully understood. IMP3 expression was analysed using a public database and by Western blotting and immunohistochemistry in human colon samples derived from patients with sporadic CRC and healthy subjects. To address whether IMP3 controls cancer cell survival, we analysed cell death pathways in in vitro and in vivo experiments after IMP3 downregulation by siRNA or an antisense oligonucleotide. IMP3 was highly expressed in CRC samples compared to normal control tissues. The knockdown of IMP3 enhanced a caspase-independent cell death in CRC cell lines. Furthermore, the treatment of CRC cells with IMP3 siRNA did not alter the expression of GSDMD, GPX-4 and the activated form of RIP3, three key molecules that govern pyroptosis, ferroptosis and necroptosis, respectively. Abrogation of IMP3 in CRC significantly reduced Bcl-2 and Bcl-xL mRNA and was associated with an altered mitochondrial membrane potential that allowed the nuclear migration of the apoptosis-inducing factor (AIF). Moreover, specific immunoprecipitation experiments on CRC human cell lines indicated that IMP3 binds Bcl-2 and Bcl-xL mRNA, suggesting that IMP3 acts as a regulator of the intrinsic apoptotic pathway through the surveillance of anti-apoptotic Bcl mRNA metabolism. Finally, we showed that IMP3 block inhibited the growth of CRC cell lines in vivo after transplantation into immunodeficient mice. Altogether, these data support a novel role for IMP3 in controlling the intrinsic caspase-independent apoptotic pathway in CRC.

Background and Purpose The aim of this study was to describe the variations in the speech range profile (SRP) of patients affected by cognitive decline. Methods We collected the data of patients managed for suspected voice and speech disorders, and suspected cognitive impairment. Patients underwent an Ear Nose and Throat evaluation and Mini-Mental State Examination (MMSE). To obtain SRP, we asked the patients to read 18 sentences twice, at their most comfortable pitch and loudness as they would do in daily conversation, and recorded their voice on to computer software. Results The study included 61 patients. The relationship between the MMSE score and SRP parameters was established. Increased severity of the MMSE score resulted in a statistically significant reduction in the average values of the semitones to the phonetogram, and the medium and maximum sound pressure levels (p

As novel drug treatments for diabetes have shown favorable cardiovascular effects, interest has mounted with regard to their possible vascular actions, particularly in relation to visceral adipose tissue perfusion and remodeling in obesity. The present study tested the vasorelaxing effect of the SGLT2 (sodium-glucose transporter type 2) inhibitor canagliflozin in arteries from visceral adipose tissue of either nonobese or obese humans and investigated the underlying mechanisms. Also, the vasorelaxing effect of canagliflozin and the GLP-1 (glucagon-like peptide 1) agonist liraglutide were compared in arteries from obese patients. To these purposes, small arteries (116–734 μm) isolated from visceral adipose tissue were studied ex vivo in a wire myograph. Canagliflozin elicited a higher concentration-dependent vasorelaxation in arterioles from obese than nonobese individuals ( P =0.02). The vasorelaxing response to canagliflozin was not modified ( P =0.93) by inhibition of nitric oxide synthase (L-NAME) or prostacyclin (indomethacin), or by H 2 O 2 scavenging (catalase); also, canagliflozin-induced relaxation was similar ( P =0.23) in endothelium-intact or -denuded arteries precontracted with high potassium concentration, thereby excluding an involvement of endothelium-derived hyperpolarizing factors. The vasorelaxing response to canagliflozin was similar to that elicited by the Na + /H + exchanger 1 inhibitor BIX ( P =0.67), but greater than that to the Na + /Ca ++ exchanger inhibitor SEA 0400 ( P =0.001), hinting a role of Na + /H + exchanger inhibition in canagliflozin-induced relaxation. In arterioles from obese patients, the vasorelaxing response to canagliflozin was greater than that to liraglutide ( P =0.004). These findings demonstrate that canagliflozin induces endothelium-independent vasorelaxation in arterioles from human visceral adipose tissue, thereby suggesting that SGLT2 inhibition might favorably impact the processes linking visceral adipose burden to vascular disease in obesity.

As inadequate perfusion has emerged as a key determinant of adipose tissue dysfunction in obesity, interest has grown regarding possible pharmacological interventions to prevent this process. Mirabegron has proved to improve insulin sensitivity and glucose homeostasis in obese humans via stimulation of βSmall arteries (116-734 μm) isolated from visceral adipose tissue were studied ex vivo in a wire myograph. After vessels had been contracted, changes in vascular tone in response to mirabegron were determined under different conditions.Mirabegron did not elicit vasorelaxation in vessels contracted with U46619 or high-KMirabegron induces endothelium-independent vasorelaxation in arteries from visceral adipose tissue, likely through antagonism of α

Flavonoids are interesting molecules synthetized by plants. They can be found abundantly in seeds and fruits, determining the color, flavor, and other organoleptic characteristics, as well as contributing to important nutritional aspects. Beyond these characteristics, due to their biochemical properties and characteristics, they can be considered bioactive compounds. Several interesting studies have demonstrated their biological activity in different cellular and physiological processes in high-order organisms including humans. The flavonoid molecular structure confers the capability of reacting with and neutralizing reactive oxygen species (ROS), behaving as scavengers in all processes generating this class of molecules, such as UV irradiation, a process widely present in plant physiology. Importantly, the recent scientific literature has demonstrated that flavonoids, in human physiology, are active compounds acting not only as scavengers but also with the important role of counteracting the inflammation process. Among the wide variety of flavonoid molecules, significant results have been shown by investigating the role of the flavones luteolin and luteolin-7-O-glucoside (LUT-7G). For these compounds, experimental results demonstrated an interesting anti-inflammatory action, both in vitro and in vivo, in the interaction with JAK/STAT3, NF-κB, and other pathways described in this review. We also describe the effects in metabolic pathways connected with inflammation, such as cellular glycolysis, diabetes, lipid peroxidation, and effects in cancer cells. Moreover, the inhibition of inflammatory pathway in endothelial tissue, as well as the NLRP3 inflammasome assembly, demonstrates a key role in the progression of such phenomena. Since these micronutrient molecules can be obtained from food, their biochemical properties open new perspectives with respect to the long-term health status of healthy individuals, as well as their use as a coadjutant treatment in specific diseases.

Indeterminate solitary pulmonary nodules (SPNs), measuring up to 3 cm in diameter, are incidental radiological findings. The ever-growing use of modern imaging has increased their detection. The majority of those nodules are benign; however, the possibility of diagnosing early-stage lung cancer still stands. Guidelines for the management of SPNs have never been validated in prospective comparative studies. Positron emission tomography (PET) is a useful tool to provide functional information on SPNs. However, overall sensitivity and specificity of PET in detecting malignant SPNs of at least 10 mm in diameter are about 90% and false-negative results are reported. The development of video-assisted thoracic surgery has provided minimally invasive diagnosis and treatment of SPNs. In our series, 105 patients underwent surgery based on combined increased 18F-labelled 2-fluoro-2-deoxy-d-glucose (FDG) uptake on PET computed tomography and radiological features (morphology and density) without prior histological confirmation. We detected 26 false negatives (24.8%) and only nine false positives (8.57%). Therefore, our minimally invasive surgical approach prevented 25% of patients with lung cancer from a delayed treatment versus only 9% undergoing “overtreatment”. In our monocentric cohort, patients with SPNs with large diameter, irregular outline, no calcifications, central location, increased FDG uptake and/or subsolid aspect benefited from a primary surgical resection., There is much debate on the best management of solitary pulmonary nodules. Even if they are mostly benign, they may represent an early-stage lung cancer. Minimally invasive surgical removal is probably the best approach to this insidious disease. http://ow.ly/wMKz30nemjR

Background: The relationship between nasal functions and middle ear surgery is still under debate. Nasal obstruction is considered as a negative prognostic factor in middle ear surgery. This is based on the theory that it may cause Eustachian tube dysfunction (ETD) by leading to reduced ventilation of the middle ear, as found in several patients with nasal septal deviation, chronic rhinitis and nasal polyps. Objectives: To assess how the subjective feeling of nasal function, evaluated by a preoperative questionnaire, may be predictive of surgical outcome and/or risk of failure in middle ear surgery. Methods: We prospectively evaluated data of patients undergoing middle ear surgery for chronic otitis media with and without cholesteatoma. All patients completed the SNOT-22 and ETDQ-7 questionnaires. They underwent surgery for their pathology, as appropriate. Results: The SNOT-22 score was higher in patients with retraction pocket and in patients whose retraction pockets recurred after surgery (p < 0.05). Patients with higher score at SNOT-22 questionnaire, were more likely to show recurrence of atelectasis aftersurgery. Conclusions: The SNOT-22 questionnaire, administrered before surgical procedure, can help in the identification of patients who are at risk of failure in the post-operative period, as well as ETDQ-7.

Flavonoids display a broad range of structures and are responsible for the major organoleptic characteristics of plant-derived foods and beverages. Recent data showed their activity, and in particular of luteolin-7-O-glucoside (LUT-7G), in reduction of oxidative stress and inflammatory mechanisms in different physiological systems. In this paper, we tried to elucidate how LUT-7G could exert both antioxidant and anti-inflammatory effects in endothelial cells cultured in vitro. Here, we showed that LUT-7G is able to inhibit the STAT3 pathway, to have an antiproliferative action, and an important antioxidant property in HUVEC cells. These properties are exerted by the flavone in endothelial through the transcriptional repression of a number of inflammatory cytokines and their receptors, and by the inhibition of ROS generation. ROS and STAT3 activation has been correlated with the production of oxysterols and other hydroxylated fatty acids, and they have been recognized important as players of atherogenesis and cardiocirculatory system diseases. The analysis of the general production pathway of these hydroxylated species, showed a strong decrease of cholesterol hydroxylated species such as 7-alpha-hydroxicholesterol, 7-beta-hydroxicholesterol by the treatment with LUT-7G. This confirms the anti-inflammatory properties of LUT-7G also in the endothelial district, showing for the first time the molecular pathway that verify previous postulated cardiovascular benefits of this flavone.

Purpose: This study aims to understand the factors contributing to the severity of oropharyngeal dysphagia and its persistence in the sub-acute phase of stroke. Methods: We retrospectively collected the data of all the patients suffering from a stroke in the last year. The severity of stroke was reported according to the NIHSS score. All the patients were evaluated with the Dysphagia Risk Score and with a FEES. We classified the Dysphagia Risk Score and FEES results using the PAS score and ASHA-NOMS levels. The data were analysed statistically with ANOVA test, Student’s t test and Pearson’s correlation coefficient. Results: A series of 54 patients were evaluated. The ANOVA test did not find any difference in the mean score of Dysphagia Risk Score, PAS and ASHA-NOMS when compared with the brain area of stroke. An NIHSS at hospital admission (stroke unit) of more than 12 was predictive of ASHA-NOMS score 1–4 after 60days (p < 0.05). A PAS score between 6 and 8 at first FEES evaluation was predictive of poor (1–4) ASHA-NOMS score after 60days (p < 0.01). A moderate positive linear correlation was found between NIHSS score and both PAS (r 0.65) and Dysphagia Risk Score (r 0.50); a moderate negative linear correlation was recorded between NIHSS and ASHA-NOMS (r − 0.66) scores. Conclusion: In the sub-acute phase of stroke, the predictive factors of persistent dysphagia are not linked to the damaged neuroanatomical region and others factors such as NIHSS value and high PAS score seem more useful.

Metabolic diseases are chronic disorders correlated to a greater risk of cardiovascular event and death. Recently, many data have sustained the biological link between microvascular dysfunction, oxidative stress, vascular inflammation, and metabolic diseases. The determination of new and specific blood biomarkers of vascular inflammation associated with obesity-related metabolic syndrome (MetS) and diabetes such as lipoprotein-associated phospholipase A2 (Lp-PLA2) could be useful to identify subject with high risk of cardiovascular events. Lp-PLA2 participates by a crucial role in microvascular dysfunction and oxidative stress showing positive association with metabolic disorders. In this review, we will argue the evolving role of Lp-PLA2 in predicting cardiovascular events in metabolic disease patients.

Malignant pleural effusion is diagnostically challenging in presence of negative cytology. The assessment of tumor markers in serum has become a standard tool in cancer diagnosis, while pleural fluid sampling has not met universal consensus. The evaluation of a panel of markers both in serum and pleural fluid may be crucial to improve the diagnostic accuracy. Using a machine learning-based approach, we provide a mathematical formula capable to express the complex relation existing among the expressed markers in serum and pleural effusion and the presence of lung cancer. The formula indicates CEA and CYFRA21-1 in pleural fluid as the best diagnostic markers, with 97% accuracy, 98% sensitivity, 95% specificity, 96% area under curve, 98% positive predictive value, and 92% MCC (Matthews correlation coefficient).

Background: Ataxia-telangiectasia (AT) is a rare hereditary genetic disease caused by one of more than 500 mutations in the ataxia-telangiectasia mutated gene (ATM). AT is characterized by cerebellar ataxia, telangiectasia of blood vessels, immunodeficiency with frequent lung infections, susceptibility to cancer, and sensitivity to ionizing radiation. A correct immunophenotyping of lymphocytes is necessary to identify the cause of the immunodeficiency. Methods: We evaluated a patient (female, 15 years) with AT by estimation of antibody titers, characterization of peripheral B- and T-cell subsets and investigation of proliferation response of B- and T-cells undergoing specific stimulation with PHA, CD3/CD28, and R848/CD40L. A healthy volunteer was used as a control. Results: The patient showed a heterozygous mutation in the ATM gene (c.5932G>T[p.E1978X]/c.7788+3A>G). Interestingly, despite a very low level of class-switched memory B-cells normal levels of serum immunoglobulins and antibody titers to viral and bacterial antigens could be observed. Furthermore, the analysis revealed an increase in total numbers of T-cells, caused by an extraordinarily high amount of γ/δ T-cells (CD3+CD4–CD8) (>75% of T-cells). Remaining CD4+/CD8+T-cells were decreased, naïve cells and recent thymic emigrants (RTEs) were strongly deficient. Subsequently, the proliferation activity of T-cells was strongly impaired, in contrast to normal B-cell proliferation both compared to the healthy control. Conclusions: Initial lymphocyte immunophenotyping suggested a defect in T- and B-cell differentiation, but normal humoral antibody titers and B-cell proliferation were inconsistent with this suspicion. Therefore, the results revealed an underlying T-cell defect and low levels of class-switched B-cells results from the lacking assistance from T-cells.

Purpose To evaluate the prevalence of oropharyngeal dysphagia in elderly patients suffering from minimal or mild cognitive decline. Patients and methods We retrospectively collected the data of patients suffering from mild cognitive impairment or mild dementia and were undergoing management for suspected oropharyngeal dysphagia, in our department. All our patients were subjected to Mini Mental State Examination test, MD Anderson dysphagia inventory and caregiver mealtime and dysphagia questionnaire. We performed a mealtime observation study and endoscopic evaluation of swallowing in all our patients. Following evaluation, we then analysed the data statistically. Results Out of 708 patients who visited us for cognitive decline and suspected oropharyngeal dysphagia in the last two years, 52 patients were confirming to the inclusion criteria of this study. Classification of oropharyngeal dysphagia patients according to ASHA-NOMS scale showed that 32.7% of patients presented with grade 4 of dysphagia followed by another 32.7% with grade 5 and 30.8% presented with grade 6. Only 3.8% of our patients were considered normal (grade 7 of ASHA-NOMS scale). MD Anderson dysphagia inventory could collected swallowing alterations in only 23.1% of the cases. The caregiver mealtime and dysphagia questionnaire showed acceptable caregivers patient management in 53.8% of patients. Conclusion Our study underscores the fact that oropharyngeal dysphagia is present in many cases of mild cognitive decline. While patients understate their swallowing problems, the caregivers are not competent enough to manage this situation in a great percentage of cases. Only a mealtime observation by a speech-language pathologist along with FEES is able to identify the true prevalence of the condition.

Background: Malignant pleural effusion (MPE) is diagnostically challenging in presence of negative cytology. The assessment of tumor markers in serum has become a standard tool in cancer diagnosis while pleural fluid sampling has not met universal consensus. The evaluation of a panel of markers both in serum and pleural fluid may be crucial to improve the diagnostic accuracy. Aims: Identify best expressed markers in serum and pleural effusion of lung cancer patients by a Machine Learning-based approach and a mathematical formula to retrieve their link with cancer. Methods: Carcinoembryonic antigen (CEA), Carbohydrate Antigen 125 (Ca 125), Carbohydrate Antigen 19.9 (Ca 19.9), Cytokeratin fragment 21-1 (CYFRA 21.1) and Neuron-specific Enolase (NSE) were assessed by chemiluminescence and immunofluorescence assay in serum and pleural fluid from 168 patients (124 malignant, 44 non-malignant). Video assisted thoracoscopic biopsy obviated pathology. Receiver operating curves (ROC) analysis selected markers. Genetic programming algorithm mined the link between the expression of markers in MPE and pathological outcome. Relationship was expressed by a mathematical formula. Results: CEA and CYFRA 21-1 in pleural fluid achieved the best diagnostic accuracy (92%). Machine Learning-based approach indicated that combination of CEA and CYFRA 21-1 in MPE reached a 97% sensitivity, 93% specificity, 95 % area under curve (AUC), 98% positive predictive value (PPV), and 90% MCC (Matthews correlation coefficient). Conclusions: The proposed formula indicates CEA and CYFRA 21-1 as the most efficient tumor markers in the diagnosis of cytologically negative lung cancer associated MPE.

Introduction: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a marker of vascular inflammation associated with coronary heart disease and stroke. We evaluated analytical performance of the PLAC® Activity Test on Siemens Dimension Vista® 1500 analyzer and measured Lp-PLA2 activity in Italian adults to establish reference intervals (RIs) and evaluate correlation with circulating lipids and age. Materials and methods: The evaluation protocol consisted of precision, linearity, sensitivity, method comparison, substrate depletion (“hook”) effect and interference assessment. Inhibitor (Darapladib) effect was also evaluated. Lp-PLA2 activity was measured in 250 healthy donors (123 males, 127 females, aged 18-70 years). Central 95% RIs were established using nonparametric statistics. Results: Intra-assay and inter-assay precision showed CVs of 0.6% - 1.4% and 0.9% - 2.0%, respectively. Linearity replicates showed R2 > 0.98. Limit of quantitation was 5.8 U/L (CV = 9.4%). Bland Altman plot showed bias - 0.9, 95% limits of agreement -6.5 - 4.72. Passing-Bablok regression showed excellent correlation (Slope = 1.02, 95% CI: 1.01 to 1.03; Intercept = - 1.86, 95% CI: - 3.08 to - 1.26; R2 = 0.999). No “hook effect” was observed at Lp-PLA2 activities ≤ 1000 U/L. Average Lp-PLA2 activity in 250 healthy donors was 182 ± 44 U/L (mean ± SD). Males showed statistically significant higher activities than females (P < 0.001). RIs were 107 - 265 U/L for males and 84 - 225 U/L for females. Moderate significant correlation (r = 0.29, P < 0.001) was found between Lp-PLA2 activity and total cholesterol. Conclusions: The PLAC® Activity Test shows very good performance characteristics on Dimension Vista® 1500.

A method for structural health monitoring of cable-stayed bridges based on the dynamic distributed sensing of bridge deck strains is introduced in this article. The objective is to detect the location and the magnitude of the cables that have totally or partially lost their tensile load-carrying capacities. Dynamic sensing provides a realistic approach for condition assessment of the bridge under operational conditions. A Brillouin scattering optical time domain analysis (BOTDA) fiber-optic sensor was used to monitor the distributed strain in the deck of a scaled model cable-stayed bridge in the laboratory. The formulations developed in the present study take advantage of the dynamic distributed sensing capability of the BOTDA in amplitude transfer (AT) mode for the establishment of a relationship between the redistribution of deck strains and the tension loss in the individual cables of cable-stayed bridges. The experimental program involved single cable and multicable damage scenarios. The appli...

Objective: Primary objective of this study was to find a statistical link between the most worldwide comorbidities affecting the elderly population (hypertension, diabetes, osteoarthrosis, osteoporosis and depression) and recurrent episodes of BPPV. Secondary objective was defining possible "groups of risk" for people suffering recurrent positional vertigo related to the presence of a well documented comorbidity. Methods: This was an observational, cross-sectional, multicenter, spontaneous, non-pharmacological study. The data of 1092 patients suffering BPPV evaluated in 11 different Departments of Otolaryngology, Otoneurology and Neurology, referring Centers for positional vertigo evaluation, were retrospectively collected. Results: Regarding evaluated comorbidities (hypertension, diabetes, osteoarthrosis, osteoporosis and depression), data analysis showed the presence of at least one comorbid disorder in 216 subjects (19.8%) and 2 or more in 408 subjects (37.4%). Moreover there was a statistical significant difference between the number of comorbidities and the number of recurrences, otherwise said as comorbidity disorders increased the number of relapses increased too. Conclusion: The presence of a systemic disease may worsen the status of the posterior labyrinth causing a more frequent otolith detachment. This condition increases the risk for patients suffering BPPV to have recurrent episodes, even if correctly managed by repositioning maneuvers. The combination of two or more of aforementioned comorbidities further increases the risk of relapsing BPPV, worsened by the presence of osteoporosis. On the basis of this results it was possible to define "groups of risk" useful for predicting BPPV recurrence in patients with one or more comorbidity. © 2013.

Metabolic diseases are chronic disorders correlated to a greater risk of cardiovascular event and death. Recently, many data have sustained the biological link between microvascular dysfunction, oxidative stress, vascular inflammation, and metabolic diseases. The determination of new and specific blood biomarkers of vascular inflammation associated with obesity-related metabolic syndrome (MetS) and diabetes such as lipoprotein-associated phospholipase A2 (Lp-PLA2) could be useful to identify subject with high risk of cardiovascular events. Lp-PLA2 participates by a crucial role in microvascular dysfunction and oxidative stress showing positive association with metabolic disorders. In this review, we will argue the evolving role of Lp-PLA2 in predicting cardiovascular events in metabolic disease patients.

Objective: The aim of the present study was to verify the efficacy and the safety of intratympanic dexamethasone to treat sudden sensorineural hearing loss as salvage therapy. Materials and methods: A prospective study was conducted on patients affected by idiopathic sudden hearing loss who were treated before with some systemic therapy, but without recovery of the hearing The patients able to undergo the study, but who refused salvage treatment were considered as control group. A solution of Dexamethasone 4 mg/ml was then injected through the posterior–inferior quadrant filling completely the middle ear. The follow-up in the following 6 months included an audiogram every month. Results: The number of patients treated with salvage therapy was 36. The patients who refused treatment were further 10. The salvage treatment was done with a mean delay of 24.3 days from the onset of symptoms. Mean hearing threshold after the onset of sudden hearing loss at PTA was 66.5 dB. After the failed treatment the mean PTA was 59.6 dB. The mean PTA after the intratympanic steroid administration was 46.8 dB, with a mean improvement of 12.8 dB. No hearing change was noted in the 10 patients who refused salvage therapy. The patients that assumed systemic steroid as first therapy showed a better PTA threshold after the salvage intratympanic treatment (p

Benign paroxysmal positional vertigo (BPPV) represents the most common cause of peripheral vertigo. The treatment of this apparently intractable disease is actually a physical treatment: performing manoeuvres on the patient to restore the normal condition of the inner ear. However, the following information will help readers who are unfamiliar with BPPV to improve their knowledge of the condition.

During the service life of structures, breathing-fatigue cracks may occur in structural members due to dynamic loadings acting on them. These fatigue cracks, if undetected, might lead to a catastrophic failure of the whole structural system. Although a number of approaches have been proposed to detect breathing-fatigue cracks, some of them appear rather sophisticated or expensive (requiring complicated equipment), and others suffer from a lack of sensitivity. In this study, a simple and efficient approach to detecting breathing-fatigue cracks is developed based on dynamic characteristics of breathing cracks. First, considering that breathing cracks introduce bilinearity into structures, a simple system identification method for bilinear systems is proposed by taking best advantage of dynamic characteristics of bilinear systems. This method transfers nonlinear system identification into linear system identification by dividing impulse or free-vibration responses into different parts corresponding to each stiffness region according to the stiffness interface. In this way, the natural frequency of each region can be identified using any modal identification approach applicable to linear systems. Second, the procedure for identifying the existence of breathing fatigue cracks and quantifying the cracks qualitatively is proposed by looking for the difference in the identified natural frequency between regions. Third, through introducing Hilbert transform, the proposed procedure is extended to identify fatigue cracks in piecewise-nonlinear systems. The proposed system identification method and crack detection procedure have been successfully validated by numerical simulations and experimental tests.

The architectural heritage in the world represents a fundamental resource and a sign of the national cultural background. Its maintenance and preservation require a balance between the structural safety needs and the respect for their architectural and cultural value. Structural health monitoring (SHM) is increasingly emerging as a unique tool to achieve such a balance, through a proper combination of traditional and innovative techniques. This paper presents some recent experiences of SHM applied to the historical heritage in Italy, discussing relevant tools and reporting some of the most significant case studies. © 2016, Springer-Verlag Berlin Heidelberg.

Metatypical Basal Cell Carcinoma, also known as Basosquamous Carcinoma is a subtype of Basal Cell Carcinoma. It is similar to Basal Cell Carcinoma for the gross aspect and regional recurrences, but it has the capacity to spread and develop metastasis. This terrible characteristic endangers the life of the patient if it is not readily recognized by the physicians. Herein we present a report of two patients affected by BSC originating in the nasal region and external ear that after a series of devastating local recurrences metastasized to the lung and bones in one case. The true incidence of Basoquamous Carcinoma may be higher, with underreporting arising because of rarity of diagnosis and lack of awareness on the part of clinicians. Our experience suggests that a deep biopsy is often necessary to discover a BSC that appears as BCC but with local aggressive features. © 2012 Polish Otorhinolaryngology - Head and Neck Surgery Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

during the review process; therefore more attention and space was given to the historical background of the device and to the equations describing its behavior. A steel hysteretic device using the same principle was tested and evaluated at the laboratory of the University at Buffalo (of second author), and experimental results indicated that it is a useful and reliable solution for energy dissipation. The steel hysteretic damper is never criticized in the paper; the criticism is directed to the global retrofi t solution which also uses the device. If any statement in the paper raised an ambiguous interpretation, this was not the intent of the authors. The paper by Antonacci et al. (2001) explains the

Nonlinear phenomena are widely encountered in practical applications. The presence of nonlinearity makes a system exhibit different dynamic behaviours from its linear counterpart. A typical example is that free-vibration frequencies of nonlinear systems are amplitude-dependent, resulting in the variation of free-vibration frequencies with time. Therefore, Fourier spectrum which has been widely used in linear systems cannot completely represent dynamic characteristics of nonlinear systems. On the contrary, the time-varying trend of instantaneous frequencies and vibration amplitudes can completely capture dynamic characteristics of nonlinear systems. In this study, a general system identification method based on curving-fitting the time-varying trend of instantaneous frequencies and amplitudes is proposed for nonlinear systems. Herein Hilbert transform is employed to extract instantaneous frequencies and amplitudes from the measured responses. By taking the relationships between instantaneous vibration characteristics and structural physical parameters as regression models, structural physical parameters can be estimated by a least-squares estimation or an optimization method. The combination of the instantaneous information in time domain and frequency domain leads to high accuracy of identification results. The determination of model structure of nonlinearities is solved by assuming a generalized model which involves as many types of nonlinearities as possible. The proposed method has been demonstrated by numerical simulations.

Structural health monitoring (SHM) is a relatively new paradigm for civil infrastructure stakeholders including operators, consultants and contractors which has in the last two decades witnessed an acceleration of academic and applied research in related areas such as sensing technology, system identification, data mining and condition assessment. SHM has a wide range of applications including, but not limited to, diagnostic and prognostic capabilities. However, when it comes to practical applications, stakeholders usually need answers to basic and pragmatic questions about in-service performance, maintenance and management of a structure which the technological advances are slow to address. Typical among the mismatch of expectation and capability is the topic of vibration-based monitoring (VBM), which is a subset of SHM. On the one hand there is abundant reporting of exercises using vibration data to locate damage in highly controlled laboratory conditions or in numerical simulations, while the real test of a reliable and cost effective technology is operation on a commercial basis. Such commercial applications are hard to identify, with the vast majority of implementations dealing with data collection and checking against parameter limits. In addition there persists an unhelpful association between VBM and ‘damage detection’ among some civil infrastructure stakeholders in UK and North America, due to unsuccessful transfer of technology from the laboratory to the field, and this has resulted in unhealthy industry scepticism which hinders acceptance of successful technologies. Hence the purpose of this paper is showcase successful VBM applications and to make the case that VBM does provide valuable information in real world applications when used appropriately and without unrealistic expectations.

Objective The purpose of this study was to evaluate the presence and eventually to study the features of spontaneous nystagmus (Ny) in our patients with diagnosis of benign paroxysmal positional vertigo (BPPV). Patients and methods We retrospectively reviewed the clinical records of patients who presented with vertigo spells and were managed at our tertiary care referral center. Patients with only idiopathic BPPV presenting with typical vertigo spells and positioning Ny characteristic of the disease were included in this study. To investigate the positioning Ny, we studied the patients in the sitting position, during the head shaking test, and during the Dix-Hallpike test and the McClure-Pagnini test (Ny provoked by rotation of the head in a supine patient). Ny responses in all patients were observed using infrared videoscopy. Results We managed 412 patients affected by BPPV. Of the 412 patients, 292 (70.87%) were diagnosed to be having posterior canal-BPPV and 110 (26.99%) patients had horizontal canal-BPPV (HC-BPPV). The remaining 10 patients (2.44%) were identified to have anterior canal-BPPV. Spontaneous Ny in sitting position was observed, by infrared videoscopy, only in the patients affected by HC-BPPV. Conclusion Spontaneous Ny in BPPV can be observed with infrared videoscopy in patients affected by HC-BPPV. The origin of this Ny is most likely due to a natural inclination of horizontal semicircular canal with respect to the horizontal plane. This Ny stops after flexion of the head in neutral position, and for this reason, it should be considered as a seemingly spontaneous Ny. This Ny, in our experience, is observed in most HC-BPPV patients but does not indicate the need for a different management protocol or any different prognostic value of HC-BPPV.

The 2009 L’Aquila, Italy earthquake highlighted the seismic vulnerability of historic masonry building structures due to improper “strengthening” retrofit work that has been done in the last 50 years. Italian seismic standards recommend the use of traditional reinforcement techniques such as replacing the original wooden roof structure with new reinforced concrete (RC) or steel elements, inserting RC tie-beams in the masonry and new RC floors, and using RC jacketing on the shear walls. The L’Aquila earthquake revealed the numerous limitations of these interventions, because they led to increased seismic forces (due to greater additional weight) and to deformation incompatibilities of the incorporated elements with the existing masonry walls. This paper provides a discussion of technical issues pertaining to the seismic retrofit of the Santa Maria di Collemaggio Basilica and in particular, the limitations of the last (2000) retrofit intervention. Considerable damage was caused to the church because of questionable actions and incorrect and improper technical choices.

A scaled model of a two-span masonry arch bridge has been built in order to investigate the effect of the central pile settlement due to riverbank erosion. The bridge model has been equipped with different Non Destructive Testing (NDT) instruments and subjected to incremental settlement of the pier. The evolution of the pier scour has been investigated experimentally by means of a hydraulic model and reproduced accordingly. The numerical interpretation of damage, carried out by finite element analyses, has been compared with the results of the Acoustic Emissions (AE) monitoring. Several ultrasonic emissions have been detected and main damage source areas have been localized.

This study attempts to develop a wavelet-based method, which not only localizes multiple damage sites but also provides information on when damage occurs. By performing wavelet transform of free vibration responses of structures in the damaged state, a residual wavelet force (RWF) is defined. The damage locations and the moments when damage occurs are easily determined simultaneously by the ridges in the RWF. A damage location indicator, DLIRWF, is also presented. The degrees-of-freedom that have large magnitudes in DLIRWF are associated with the potential damage members within the structure. Furthermore, the natural excitation technique is introduced to generalize the proposed method to the cases of ambient vibration. The proposed method has been demonstrated by numerical simulations of a 20-story shear building and a 5-story, 1-bay×2-bay steel-frame structure.

Objectives Our protocol to manage the intralabyrinthine schwannoma (ILS). Methods Retrospective chart review of 7 consecutive patients managed for ILS. Results Five patients underwent surgical removal of the lesions and none experienced significant complications or recurrent disease. One patient refused surgical treatment and was closely followed by serial MRI scans with no signs of tumor growth. One patient is presently managed conservatively due to a good hearing. Conclusions Diagnosis of ILS is based on high resolution MRI scans and should be included in the differential diagnosis of patients investigated for cochleovestibular symptoms. Treatment modality of ILS is controversial and depends patients’ age, severity of vertigo and hearing loss. In the authors’ experience surgery is indicated in all cases with invalidating vertigo and in the young patients with severe hearing loss. Conservative strategy is advised in older patients and in cases with preserved good hearing and no invalidating vertigo. These patients must be followed up using high resolution MRI because of the risk of tumor growth into the internal auditory canal. While tumors with exclusive involvement of the inner ear may be removed by means of a completely extradural approach, tumor growth with involvement of the internal auditory canal dictates the necessity of opening the dura exposing the patients to the potential risks associated with the procedure.

Objective: The objective of this study was to examine the usefulness of intraoperative cochlear nerve monitoring (ICNM) in the preservation of normal and social hearing in vestibular schwannoma (VS) removal. Methods: A retrospective chart review was conducted. Of 1315 patients operated for VS between June 1988 and December 2005, 150 patients were subjected to hearing preservation surgery. Among these, 99 patients with preoperative normal and social hearing (class A and B in the modified Sanna classification) and with a small tumor Results: The hearing preservation rate was 26.7% in cases operated with ICNM and 20.8% in cases without ICNM. The difference did not reach statistical significance (p = 0.79). In subgroup analyses, the ICNM did not prove to contribute to the significantly higher hearing preservation rate. Conclusions: ICNM did not increase the ratio of patients with postoperative normal and social hearing in VS surgery.

Purpose The objective of this study was to assess the usefulness of low-dose intratympanic gentamicin administration in patients with Meniere's disease (MD). Materials and Methods We carried out a retrospective review of the charts of 55 patients with definite MD in accordance with the AAO-HNS (American Academy of Otolaryngology–Head and Neck Surgery) Diagnostic Scale who were treated at Gruppo Otologico (Piacenza, Rome, Italy). The treatment protocol consisted of 3 intratympanic injections of gentamicin at a 12-hour interval between each administration. Results Results were resumed in accordance with AAO-HNS criteria and showed complete control of vertigo spells in 60% (class A), good control in 16% (class B), moderate control in 4% (class C), poor control in 16% (class D), and no control in 4% (class E) of the patients. Audiological assessment showed unchanged thresholds in 61%, improvement in 22%, and worsening in 17% of the cases. Conclusion Administration of gentamicin is a good alternative to medical and surgical procedures in the treatment of intractable MD. One-day treatment allows for adequate control of vertigo attacks without compromising hearing and quality of life and with reduced costs.

The reduced-order model of a time-invariant linear dynamical system, excited by a force of an impulsive type, may be readily obtained using the Ho-Kalman minimal-realization algorithm [1]. The method is based upon a particular factorization of the Hankel matrix in the Markovian representation of the discrete-time process. For stochastic systems, the applicability of the theory has been demonstrated by Akaike [2] on the assumption that the excitation is a zero-mean white noise of a gaussian type. Some of the most widely known output-only identification methods, such as Eigensystem Realization Algorithm (ERA), Canonical Variate Analysis (CVA), and Balanced Realization (BR)) are based upon the above-mentioned work, with the aid of a robust factorization technique, such as Singular-Value Decomposition (SVD). Notwithstanding the growing popularity of the above methods, some aspects of their applicability are not yet understood. Two points are of particular interest: the first regards the applicability of the theory in highly damped systems; and the second regards its applicability to systems driven by excitations different from the one hypothesized. The aim of the present work is to define a reliable test on the hypotheses. Some numerical and experimental results are presented.

Architectural heritage is a resource and a fundamental part of the cultural European background; it also causes concern, due to the huge investment needed to maintain it, or even to repair it after environmental injuries. The Author is general coordinator of an Italian National research project aimed to formulate new guidelines for structural health monitoring and survey of historical and monumental structures. The Project programme traces a general strategy to build maintenance related monitoring procedures, to face the problems of data uncertainties, to propose robust approaches. This paper shows the general path traced for that project, just now at its start-up phase, but the main attention is addressed to the robust approaches to dynamic testing and model updating.

Malugnant pleural effusions (MPE s) are common and important cause of cancer related mortality and morbility.Tumor markers analysis has been proposed as less invasive alternative for diagnosis. In this multi-centri study we have enrolled 102 patients from three university hospitals. The best AUC value in pleural samples was detected for CA72,Cyfra 21.1,CEA

In recent years, tuned liquid dampers (TLD) have proved a successful control strategy for reducing structural vibrations. The present study focuses on the frustum-conical TLD as an alternative to the traditional cylindrical tank. If compared to the cylindrical reservoir, the cone-shaped TLD allows calibrating its natural frequency through varying liquid depth, which makes it suitable for a semi-active implementation, and attains the same level of performance with a fewer mass, at least for small fluid oscillations. A linear model is presented which can interpret TLD’s behaviour for small excitations. For larger amplitudes, strong nonlinearities occur and the linear model is no longer predictive. Consequently, for a frustum-cone TLD subjected to harmonic excitations, a tuned mass damper (TMD) analogy is established where TMD parameters vary with the excitation amplitude.

The C.A.S.E. project was a large engineering realisation, designed and built in very short time in L'Aquila after the strong earthquake of April 2009, to supply long-term provisional houses for people having lost their homes during the seismic event. Three-storey houses were built on about 180 reinforced concrete plates supported by concrete or steel columns and base seismic isolators (about 7000 curved surface sliding devices). The Court of L'Aquila opened a preliminary investigation to ascertain the consistency of complaints about the quality of the isolating devices with respect to the contractual agreement and the technical norms. The author of the present paper was in charge of the technical aspects of such preliminary investigation. A report on the project and execution of the technical investigation is subject of this contribution.

Background Through a review of three cases, the etiopathogenetic, clinical-diagnostic, and therapeutic aspects of ectopic thyroid tissue are herein discussed to highlight the main presentations of this polymorphous disease. Case presentations The first case involved an ectopic thyroid gland in the lingual area in a 45-year-old Caucasian woman who presented with dysphagia and midline swelling at the base of the tongue. The second case involved a 22-year-old Caucasian woman with a submandibular mass comprising ectopic thyroid tissue. The third case involved a 33-year-old Caucasian man with a typical thyroglossal duct cyst characterized by the presence of thyroid tissue upon histological analysis. Conclusion Surgery seems to be the most appropriate treatment for patients with ectopic thyroid tissue showing clinical signs of upper airway obstruction or when the lesion shows signs of infection or malignant degeneration. When a site of ectopic thyroid tissue is the only such site in the body, removal of this tissue will usually lead to hypothyroidism that requires medical thyroid hormone replacement.

Background Hyperhomocysteinemia (hHcy) is a risk factor in the progression of chronic kidney disease (CKD). In type 2 diabetes (T2D), hHcy is strongly associated with increased risk of cardiovascular disease. Vitamin B12 and folic acid supplementation have been reported to lower homocysteine (tHcy) levels, but no data on plasma tHcy, cysteine (Cys), folate and vitamin B12 levels in T2D-CKD patients are reported.

Hyperhomocysteinemia (hHcy) is a risk factor in the progression of chronic kidney disease (CKD). In type 2 diabetes (T2D), hHcy is strongly associated with increased risk of cardiovascular disease. Vitamin B12 and folic acid supplementation have been reported to lower homocysteine (tHcy) levels, but no data on plasma tHcy, cysteine (Cys), folate and vitamin B12 levels in T2D-CKD patients are reported.tHcy and Cys levels were analyzed in 178 T2D-CKD patients by high performance liquid chromatography (HPLC) with fluorescence detection. In addition, we determined folate and vitamin B12 levels using a chemiluminescence method.tHcy and Cys levels were increased in T2D patients, and this rise positively correlated with the CKD stage (P0.001). Folate levels were comparable to controls at various CKD stages, whereas vitamin B12 levels were lower, except at stage IV. We did not find any correlation between B-vitamins and levels of tHcy and Cys, regardless of the CKD stage.This is the first study reporting tHcy, Cys and B-vitamins status in T2D-CKD patients. Although limited to our cohort of 178 patients, our findings could be helpful in clarifying the conflicting literature regarding B-vitamins supplementation. Further studies are necessary before any Hcy-lowering therapy can be safely established in T2D-CKD subjects.

Background Dyslipidemia and abnormal phospholipid metabolism are frequent in uremic patients and increase their risk of cardiovascular disease (CVD): ω-3 polyunsaturated fatty acids (PUFAs) may reduce this risk in the general population. In this study we compared the plasma and erythrocyte cell membrane composition of PUFAs in a group of Caucasian hemodialysis (HD) patients and in a control group of healthy subjects and evaluated the erythrocyte/cell membrane fatty acid ratio as a marker of the dietary intake of phospholipids. The relationship between ω-3 and ω-6 fatty acids and the possible differences in PUFAs concentrations were also investigated. Methods and results After obtaining a fully informed consent, a total of ninety-nine HD patients and 160 non uremic control subjects from “Tor Vergata” University Hospital were enrolled into the study. None of them took antioxidant drugs or dietary supplements for at least 90 days prior to the observation. Blood samples were analysed by gas-chromatographic coupled to a mass spectrometric detector. The daily intake of total calories, proteins, lipids and carbohydrates is significantly lower in HD patients than in controls (p

Accurate finite element models are needed in many applications of Civil Engineering. Non-structural elements (NSEs) often interfere with the main structure, altering its stiffness and modal signature. Neglecting such interaction, although a common practice in design, may lead to unreliable predictions of the structural dynamic response and to biased interpretations of experimental vibrational tests. In the literature, the role of NSEs in vibration-based finite element model calibration is well documented for NSEs working “in parallel” with the main structure (e.g. masonry infills in buildings, pavements or railings in bridges) but remains essentially unexplored for NSEs working “in series” with the main structure (e.g. non-structural appendages like suspended ceilings, piping systems, storage tanks and antennas, but also partitions and facades in their out-of-plane modes). Through the analysis of numerical and experimental case studies, this paper shows that “in series” NSEs accidentally resonating with some structural mode may deeply contaminate the overall modal behaviour and severely invalidate model calibration, unless their role is properly addressed while performing experimental modal analysis and structural modelling. Two alternative calibration strategies are finally discussed which prove effective in the presence of resonant NSEs, based on, respectively, excluding/including the NSEs from/into the model structure.

More than 23,000 structures, located in over 30 countries, have been so far protected by passive anti-seismic (AS) systems, mainly by the seismic isolation (SI) and energy dissipation (ED) ones. The use of such systems is going on increasing everywhere, although its extent is strongly influenced by earthquake lessons and the features of the design rules used. As to the latter, SI is considered as an additional safety measure (with consequent significant additional construction costs) in some countries (Japan, USA, etc.), while, in others (including Italy), the codes allow to partly take into account the reduction of the seismic forces acting on the superstructure that is induced by SI. Applications of the AS systems have been made to both new and existing civil and industrial structures of all kinds. The latter include some high risk (HR) plants (nuclear reactors and chemical installations). The applications in a civil context already include not only strategic and public structures, but also residential buildings and even many small private houses. In Italy, the use of the AS systems has become more and more popular especially after the 2009 Abruzzo earthquake (nowadays more than 400 Italian buildings are seismically isolated). Based on the information provided by the authors at the ASSISi 13th World Conference, held in Sendai (Japan) in September 2013, and on more recent data, the paper summarizes the state-of-the-art of the development and application of the AS systems and devices at worldwide level, by devoting particular attention to SI of buildings in Italy, in the context of recent seismic events. Moreover, it outlines the benefits of the aforesaid systems for ensuring the indispensable absolute integrity of strategic and public structures, as, primarily, schools, hospitals and HR plants, but also (for an adequate protection of cultural heritage) museums. Finally, based on Italian experience, it provides some remarks on costs of SI, stresses the conditions for the correct use of this technique and mentions some recent initiatives of the Italian Parliament to ensure such a correct use and to widely extend such an use to the HR chemical plants too (for which only very few applications already exist in Italy).

This paper focuses on the dynamic behaviour of Mirandola City Hall (a XV century Renaissance Palace) that was severely damaged during May 2012 Emilia earthquake in Northern Italy. Experimental investigations have been carried out on this monumental building. Firstly, detailed investigations have been carried out to identify the identification of the geometry of the main constructional parts as well as the mechanical features of the constituting materials of the palace. Then, Ambient Vibration Tests (AVT) have been applied, for the detection of the main dynamic features. Three output-only identification methods have been compared: (i) the Frequency Domain Decomposition, (ii) the Random Decrement (RD) and the (iii) Eigensystem Realization Algorithm (ERA). The modal parameters of the Palace were difficult to be identified due to the severe structural damage; however the two bending modes in the perpendicular directions were identified. The comparison of the three experimental techniques showed a good agreement confirming the reliability of the three identification methods.

Summary Heterotopic brain tissue is a rare is congenital anomaly, it may present at any age but it is frequently in infancy. This anomaly can occur most frequently in nasal region, although rests elsewhere in the digestive tract, in facial tissue or in lungs have been reported. Heterotopic brain tissue has been defined as a mass composed of mature brain tissue, outside the cranial cavity or spinal canal. We present a 9 years old girl with history of left chronic otitis and nasal obstruction caused by heterotopic brain tissue in pterygopalatine fossa.