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To determine the difference in force metrics measured by the laryngeal force sensor for various suspension microlaryngoscopy (SML) procedures and their perioperative narcotic requirements.Prospective observational study.Academic tertiary center.The laryngeal force sensoris a force sensor designed for SML procedures. Prospectively enrolled patients had dynamic recordings of maximum force, average force, suspension time, and total impulse. Procedures were grouped into excision of striking zone lesions, nonstriking zone lesions, endoscopic cancer surgery with margin control, and airway dilation. Narcotic administration in the intraoperative period and postanesthesia care unit was also recorded and converted into IV morphine equivalents. Surgeons were blinded to the force recordings during surgery to prevent operator bias.In total, 110 patients completed the study. There was no significant difference in average force across different procedures, however, a significant difference was seen for maximum force (P = 0.025), suspension time (P0.001), and total impulse (P = 0.002). The highest values were seen for endoscopic cancer surgeries with margin control with a mean maximum force of 49.4 lbf (95%CI, 37.1-61.7), mean suspension time of 60.2 minutes (95%CI, 40.5-79.9), and mean total impulse of 31.3 ton*s (95%CI, 15.2-47.3). A significant difference (P0.01) in perioperative narcotic requirements was also seen, with endoscopic cancer surgery cases having the highest requirements at 27.6 mg of ME (95%CI, 16.1-39.2 mg).Significant differences in force metrics exist between various SML procedures. Endoscopic cancer surgery is associated with higher force metrics and perioperative narcotic requirements.

Objective Deep extubation refers to endotracheal extubation performed while a patient is deeply anesthetized and without airway reflexes. After deep extubation, patients are sent to the post-anesthesia care unit (PACU) to recover, an area with notably different management and staffing than the operating room (OR). One of the most frequent and concerning complications to occur in the PACU is hypoxemia. As such, this study seeks to evaluate the incidence of desaturation, defined by SpO2 Results Following deep extubation, 4.3% of patients (13/300) experienced desaturation in the PACU. Every episode was notably minor, with patients reverting to normal saturation levels within a minute. Of the 26 case factors assessed, 24 had no significant association desaturation in the PACU, including the amount of time spent in the PACU. History of asthma was the only statistically significant factor found to be positively associated with desaturation. We find that PACU desaturation episodes following deep extubation are rare. Our findings suggest that deep extubation is a viable and safe option for patients without significant respiratory tract pathology.

Objective It is often unclear which patients presenting with a ruptured abdominal aortic aneurysm (rAAA) are likely to survive after surgery. The Harborview Medical Center (HMC), Dutch Aneurysm Score (DAS), and Vascular Study Group of New England (VSGNE) risk scores have been recent attempts at predicting mortality in this setting. We compared the prognostic value of these scoring systems for patients at our institution with rAAA. Methods A retrospective chart review was performed for all patients who received surgery at our institution for rAAA between January 1, 2011, and November 27, 2019. The χ2, Fisher's exact, and t-tests were used to screen preoperative variables against in-hospital mortality. HMC, DAS, and VSGNE scores were calculated for each patient and tested against in-hospital mortality. Logistic regression and receiver operating characteristic curves were used to assess performance of each scoring system. Results Sixty-four patients were identified during the study period. Fifteen patients were excluded because 4 patients chose comfort care and an additional 11 patients were missing key variables. The final cohort for analysis included 49 patients who underwent surgery, including 33 patients receiving endovascular repair and 16 patients receiving open repair. The in-hospital mortality was 37% (24% for endovascular repair vs 63% for open repair). Individual variables associated with in-hospital mortality were lowest preoperative systolic blood pressure (P = .036), creatinine greater than 2.0 mg/dL (P = .020), first recorded intraoperative pH (P = .007), and use of suprarenal aortic control (P = .025), and preoperative cardiac arrest approached significance (P = .051). Plots of the HMC and VSGNE scores vs in-hospital mortality rate produced linear relationships (R2 = 0.97 and R2 = 0.93, respectively), in which a higher score was associated with a greater likelihood of mortality. On logistic regression analysis using HMC score components, creatinine greater than 2.0 mg/dL produced a significant association with in-hospital mortality (odds ratio, 12.3; 95% confidence interval [CI], 1.1-131.7). Similar analysis using VSGNE components produced a significant association between suprarenal aortic control and in-hospital mortality (odds ratio, 5.5; 95% CI, 1.2-25.5). receiver operating characteristic curves produced an area under the curve of 0.74 (95% CI, 0.60-0.88), 0.73 (95% CI, 0.58-0.87), and 0.67 (95% CI, 0.51-0.83) for the HMC, VSGNE, and DAS, respectively. Conclusions The HMC, VSGNE, and DAS scores performed similarly and adequately predicted in-hospital mortality after rAAA. The HMC score holds the added benefit of using preoperative variables, setting it apart as a valid prognostic indicator in the preoperative setting.

The study evaluated the dynamics of macrophages and polymorphonuclear leukocytes milk-secreted by Mediterranean Buffaloes (MBs). Sixty quarter-milk-samples were collected and divided into three groups (n = 20 units each one): clinical mastitis (CM), subclinical mastitis (SCM), and intramammary infection (IMI). The control group consisted of an additional 20 healthy quarters. Their health status was assessed by clinical examination, quantitative somatic cell count (QSCC) and bacteriological milk culture. Finally, a differential somatic cell count (DSCC) was performed on all the milk samples. The mean percentage of macrophages, both in CM- and SCM-quarters, showed a significant difference as compared with the healthy-ones. Significant differences were also detected comparing the mean percentages of polymorphonuclear leukocytes between CM- and healthy-quarters, SCM and healthy, IMI and healthy. The QSCC revealed a weak-significant-negative-correlation with the quantitation of macrophages (r = −0.388), and a moderate-significant-positive-correlation with the polymorphonuclear leukocytes (r = 0.477). Macrophages and polymorphonuclear leukocytes showed a weak-significant-negative-correlation between them (r = −0.247). The interpretation of macrophages and polymorphonuclear leukocytes dynamics in milk provided beneficial information regarding the clinical status of the quarters enrolled. Future studies exploring the potential use of DSCC to improve udder health represent an interesting perspective in these ruminants.

Objectives To identify the predictive value on time to onset of heart failure (HF) or cardiac death of clinical, radiographic, and echocardiographic variables, as well as cardiac biomarkers N-terminal pro brain natriuretic peptide (NT-proBNP) and cardiac troponin I in dogs with preclinical myxomatous mitral valve disease (MMVD). Animals One hundred sixty-eight dogs with preclinical MMVD and left atrium to aortic root ratio ≥1.6 (LA:Ao) and normalized left ventricular end-diastolic diameter ≥1.7 were included. Methods Prospective, randomized, multicenter, single-blinded, placebo-controlled study. Clinical, radiographic, echocardiographic variables and plasma cardiac biomarkers concentrations were compared at different time points. Using receiving operating curves analysis, best cutoff for selected variables was identified and the risk to develop the study endpoint at six-month intervals was calculated. Results Left atrial to aortic root ratio >2.1 (hazard ratio [HR] 3.2, 95% confidence interval [95% CI] 1.9–5.6), normalized left ventricular end-diastolic diameter > 1.9 (HR: 6.3; 95% CI: 3.3–11.8), early transmitral peak velocity (E peak) > 1 m/sec (HR: 3.9; 95% CI: 2.3–6.7), and NT-proBNP > 1500 ρmol/L (HR: 5.7; 95% CI: 3.3–9.5) were associated with increased risk of HF or cardiac death. The best fit model to predict the risk to reach the endpoint was represented by the plasma NT-proBNP concentrations adjusted for LA:Ao and E peak. Conclusions Logistic and survival models including echocardiographic variables and NT-proBNP can be used to identify dogs with preclinical MMVD at higher risk to develop HF or cardiac death.

Obesity is an important health issue in dogs since it influences a plethora of associated pathologies, including dermatological disorders. Considering the scarcity of information in pets, this work aimed to evaluate the localization and expression of adiponectin (ADIPOQ) and its two receptors (ADIPOR1 and ADIPOR2) in the skin of 10 obese dogs, compared with serum ADIPOQ level. Through immunohistochemistry, ADIPOQ and ADIPOR2 were observed in the adipose tissue, sweat and sebaceous glands, endothelium, and some connective cells. Both receptors were observed in the epidermis and the hair follicles, other than in the sweat and sebaceous glands. Real-time PCR evidenced that the ADIPOQ and ADIPOR2 transcripts were expressed 5.4-fold (p &lt, 0.01) and 2.3-fold less (p &lt, 0.01), respectively, in obese than in normal weight dogs, while ADIPOR1 expression did not change. Obese dogs showed lower serum ADIPOQ levels than the normal weight group. Accordingly, ADIPOQ and ADIPOR2 expression in the skin appear negatively correlated with obesity in the same way as the serum ADIPOQ level. These findings evidence that ADIPOQ system changes in the skin of obese dogs and suggest that the ADIPOQ effect on the skin is at least in part regulated by the reduced expression of ADIPOR2.

Surface enhanced laser desorption/ionization-time of flight (SELDI-TOF) mass spectrometry is a variant of the matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry. It is used in many cases especially for the analysis of protein profiling and for preliminary screening of biomarkers in complex samples. Unfortunately, these analyses are time consuming and protein identification is generally strictly limited. SELDI-TOF analysis of mass spectra (SELYMATRA) is a web application (WA) developed to reduce these limitations by (i) automating the identification processes and (ii) introducing the possibility to predict proteins in complex mixtures from cells and tissues. The WA architectural pattern is the model-view-controller, commonly used in software development. The WA compares the mass value between two mass spectra (sample vs. control) to extract differences, and, according to the set parameters, it queries a local database to predict most likely proteins based on their masses and different expression amplification. The WA was validated in a cellular model overexpressing a tagged NURR1 receptor, being able to recognize the tagged protein in the profiling of transformed cells. A help page, including a description of parameters for WA use, is available on the website.

Liquid biopsy has emerged as a minimally invasive alternative to tumor tissue analysis for the management of lung cancer patients, especially for epidermal growth factor receptor (EGFR) oncogene addicted tumor. In these patients, despite the clear benefits of tyrosine kinase inhibitors therapy, the development of acquired resistance and progressive disease is inevitable in most cases and liquid biopsy is important for molecular characterization at resistance and, being non-invasive, may be useful for disease monitoring. In this review, the authors will focus on the applications of liquid biopsy in EGFR-mutated non small cells lung cancer at diagnosis, during treatment and at progression, describing available data and possible future scenarios.

This article analyzes practices of attraction of foreign investments, studying their perspective of territorial competitiveness. The analysis of investment attraction practices is assessed for the impact on the territory, from a territorial enhancement perspective. The perspective of corporate and property management and its complementarity with the needs of territorial competitiveness in a global competitive scenario is analyzed. The methodology follows what has been proposed by the literature for the implementation of corporate strategies, adapting methods and models to the context.

Hospital cost analysis (HCA) becomes a key topic and forefront of politics, social welfare and medical discourse. HCA includes a wide range of expenses; yet the foremost attention relates to the money expense in which hospital managers would like to draw a figure of incomes in the past and future. Based on the HCA results, they can develop many plans for improving hospital’s service quality and investing in potential healthcare services in order to deliver better services with lower costs. Machine learning methods are often opted for prediction in HCA. In this paper, we propose a new method for HCA that uses genetic algorithm (GA) and artificial neural network (ANN). Operators of GA are used to boost up calculation to get optimal weights in the forward propagation of ANN. Experiments on a real database of Hanoi Medical University Hospital (HMUH) including calculus of kidney and ureter inpatients show that the new method achieves better accuracy than the relevant ones including linear regression, K-nearest neighbors (KNN), ANN and deep learning. The mean squared error of the proposed model gets the lowest value (0.00360), compared to those of deep learning, KNN and linear regression which are 0.00901, 0.01205 and 0.01718 respectively.

We present the theoretical analysis and the numerical simulations of a polarization-independent coherent receiver for binary intensity-modulated (IM) signals. The receiver is designed for access networks or data centers and is DSP-free. It is based on a 3 × 3 symmetric coupler with phase-diversity detection. To achieve polarization independence, the receiver conveniently exploits the third input of the 3 × 3 coupler, which was previously left unused. We first introduce the scheme of the receiver and derive the analytical expressions for the final output signal, which is produced by analog processing. We then confirm the approach by numerical simulations. These are used to assess the practical potential and indicate the possible limitations. We finally discuss the role of the key parameters that must be considered in upgrading to higher bit rates and the extension to other modulation formats.

Some of the different aspects of the DSP enabled receivers in access networks will be addressed in this article. A revision of the main topics which may impact DSP design will be discussed through application examples. Modulation formats, KK receivers, and coherent receivers are analyzed at light of the DSP enabled receivers’ impact. Also, relevant are FEC and burst mode which are debated at the light of PON requirements. Simplified analog coherent receivers are presented as a use case to serve as simplification path for non-DSP high performance receivers. On the other end, aiming at discussing current PON limits, an ultra dense wavelength division multiplexing (UDWDM) use case is also presented where several advanced topics like pulse shaping, high density, and simplified DSP operations are considered.

// Carminia Maria Della Corte 1 , Umberto Malapelle 2 , Elena Vigliar 2 , Francesco Pepe 2 , Giancarlo Troncone 2 , Vincenza Ciaramella 1 , Teresa Troiani 1 , Erika Martinelli 1 , Valentina Belli 1 , Fortunato Ciardiello 1 , Floriana Morgillo 1 1 Oncologia Medica, Dipartimento Medico-Chirurgico di Internistica Clinica e Sperimentale “F. Magrassi e A. Lanzara,” Universita degli studi della Campania “Luigi Vanvitelli”, Naples, Italy 2 Dipartimento di Sanita Pubblica, Universita degli Studi di Napoli Federico II, Naples, Italy Correspondence to: Floriana Morgillo, email: florianamorgillo@yahoo.com Keywords: EGFR inhibitors, lung cancer, cell signalling, hedgehog, EMT Received: January 13, 2017 Accepted: February 08, 2017 Published: February 18, 2017 ABSTRACT Purpose: The aim of this work was to investigate the efficacy of sequential treatment with first-, second- and third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors and the mechanisms of acquired resistance occurring during the sequential use of these inhibitors. Experimental design: We developed an in vivo model of acquired resistance to EGFR-inhibitors by treating nude mice xenografted with HCC827, a human non-small-cell lung cancer (NSCLC) cell line harboring EGFR activating mutation, with a sequence of first-generation EGFR tyrosine kinase inhibitors (EGFR-TKIs) (erlotinib and gefitinib), of second-generation EGFR-TKI (afatinib) plus/minus the anti-EGFR monoclonal antibody cetuximab, and of third-generation EGFR-TKI (osimertinib). Results: HCC827-derived xenografts and with acquired resistance to EGFR-inhibitors were sensitive to the sequential use of first-, second- and third-generation EGFR-TKIs. Continuous EGFR inhibition of first-generation resistant tumors by sequential treatment with afatinib plus/minus cetuximab, followed by osimertinib, represented an effective therapeutic strategy in this model. Whereas T790M resistance mutation was not detected, a major mechanism of acquired resistance was the activation of components of the Hedgehog (Hh) pathway. This phenomenon was accompanied by epithelial-to-mesenchymal transition. Cell lines established in vitro from gefitinib-, or afatinib- or osimertinib-resistant tumors showed metastatic properties and maintained EGFR-TKIs resistance in vitro , that was reverted by the combined blockade of Hh, with the selective SMO inhibitor sonidegib, and EGFR. Conclusions: EGFR -mutant NSCLC can benefit from continuous treatment with EGFR-inhibitors, indepenently from mechanisms of resistance. In a complex and heterogenous scenario, Hh showed an important role in mediating resistance to EGFR-inhibitors through the induction of mesenchymal properties.

Cystic echinococcosis (CE) is a severe zoonosis, caused by the larval stage of the tapeworm Echinococcus granulosus. This helminth infection is of increasing public health and socio-economic concern due to the considerable morbidity rates that cause economic losses both in the public health sector and in the livestock industry. Control programmes against E. granulosus are considered long-term actions which require an integrated approach and high expenditure of time and financial resources. Since 2010, an integrated approach to control CE has been implemented in a highly endemic area of continental southern Italy (Campania region). Innovative procedures and tools have been developed and exploited during the control programme based on the following strategies: i) active and passive surveillance in livestock (using geospatial tools for georeferencing), ii) diagnosis in dogs (using the FLOTAC techniques and molecular analysis), iii) targeted treatment of farm dogs (using purpose-built confinement cages), iv) early diagnosis in livestock (by ultrasonography), v) surveillance in humans (through hospital discharge records analysis), vi) monitoring the food chain (analysing raw vegetables), vii) outreach activities to the general public (through dissemination material, e.g. brochures, gadgets, videos, virtual reality). Over eight years, the integrated approach and the new strategies developed have resulted in a noteworthy reduction of the parasite infection rates in livestock (e.g. up to 30 % in sheep). The results obtained so far highlight that using a one health multidisciplinary and multi-institution effort is of pivotal importance in preparing CE control programmes at regional level and could be extended to other endemic Mediterranean areas.

Background Mastitis is one of the most costly diseases in Mediterranean buffalo (MB). At present, just a few specific antibiotics registered for this dairy specie have been synthetized. Efficacy of an antibiotic dry buffalo therapy (aDBT) against Staphylococcus aureus (S. aureus) mastitis, based on intra-quarter administration of 600 mg of benzathine cloxacillin, have been evaluated for the first time. Eighty MB’s quarters received a drying-off therapy (aDBT-group) and 80 were left untreated (no-aDBT-group). They were sampled at drying-off (pre-treatment) and at the resumption of milking [Fresh calver mastitis rate, dry period new mastitis rate, dry period cure rate, and persistent mastitis rate were calculated for clinical monitoring. Overall proportion of positive quarters/animals, quarters affected by mastitis or intramammary infections (IMI), effects on somatic cell count (SCC) and milk yield were also assessed. Results An inter-group difference (aDBT vs. no-aDBT) was recorded for all the indexes considered. An intra-group (drying-off vs. S. aureus was observed. Regarding the subclinical ones, a higher intra-group difference was observed in aDBT than no-aDBT group, while an inter-group difference was recorded at second sampling. No protective effect was observed against IMI. SCC showed an inter-group difference at second sampling, while none difference was instead detected for milk yield. Conclusions The effects against S. aureus mastitis of benzathine cloxacillin administration at drying-off were assessed for the first time in MB. Its use shows encouraging results in reducing the proportion of mastitis and positive animals at the resumption of the lactation.

Aquaporins (AQPs) are a family of thirteen membrane proteins that play an essential role in the transport of fluids across the cell plasma membrane. Recently, the expression of AQPs in different ocular tissues and their involvement in the pathophysiology of eye diseases, have garnered attention. Considering that literature on AQP expression in the lacrimal glands and their secretion is scarce, we aimed to characterise AQP1 expression in the tears of healthy dogs using two tear collection methods (Schirmer tear strips (STS) and ophthalmic sponges (OS)). Fifteen healthy dogs, free of ophthalmic diseases, were included in the study. Tear collection was performed by using STS in one eye and OS in the other. After the extraction of proteins from the tears, the expression of AQP1 was analysed by Western blotting. AQP1 was expressed as a band of 28 kDa. In addition, differences were observed in the expression of AQP1 and in the correlation between tear volume and protein concentration, in tears collected by the two different methods. Our results suggest that AQP1 has a specific role in tear secretion, further research is required to assess its particular role in the function of the ocular surface in eye physiology and pathology.

Introduction: Efficacy of renin-angiotensin-aldosterone system (RAAS) blockade using angiotensin-converting enzyme inhibitors (ACEi) in dogs with preclinical myxomatous mitral valve disease (MMVD) is controversial. Hypothesis: Administration of spironolactone (2-4 mg q 24 h) and benazepril (0.25-0.5 mg q 24 h) in dogs with preclinical MMVD, not receiving any other cardiac medications, delays the onset of heart failure (HF) and cardiac-related death. Moreover, it reduces the progression of the disease as indicated by echocardiographic parameters and level of cardiac biomarkers N-terminal pro brain natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI). Animals: 184 dogs with pre-clinical MMVD and left atrium-to-aortic root ratio (LA:Ao) >= 1.6 and normalized left ventricular end-diastolic diameter (LVEDDn) >= 1.7. Methods: This is a prospective, randomized, multicenter, single-blinded, placebo-controlled study. Primary outcome variable was time-to-onset of first occurrence of HF or cardiac death. Secondary end points included effect of treatment on progression of the disease based on echocardiographic and radiographic parameters, as well as variations of NT-proBNP and cTnI concentrations. Results: The median time to primary end point was 902 days (95% confidence interval (CI) 682-not available) for the treatment group and 1139 days (95% CI 732-NA) for the control group (p = 0.45). Vertebral heart score (p = 0.05), LA:Ao (p < 0.001), LVEDDn (p < 0.001), trans-mitral E peak velocity (p = 0.011), and NT-proBNP (p = 0.037) were lower at the end of study in the treatment group. Conclusions: This study failed in demonstrating that combined administration of spironolactone and benazepril delays onset of HF in dogs with preclinical MMVD. However, such treatment induces beneficial effects on cardiac remodeling and these results could be of clinical relevance. (C) 2020 The Authors. Published by Elsevier B.V.

One of the most frequent cause of hypercalcemia is primary hyperparathyroidism, which can lead to systemic involvement and life-threatening conditions. We described a rare case of a parathyroid adenoma rupture with consequent bleeding and respiratory airway compression. An 84-year-old man presented to the emergency department complaining neck swelling and related dysphagia. A computer tomography of the neck revealed an extensive left lateral hematoma, and a neck ultrasonography evidenced a hemorrhagic parathyroid adenoma, later confirmed by a 99 mTc-MIBI scintigraphy. To date only 40 cases of ruptured parathyroid adenomas have been described in literature, however due to the possibility of massive bleeding and compression of the airways this diagnosis should always be ruled out. The rupture of a parathyroid adenoma is a rare, but possibly life-threatening event due to airways compression and hemodynamic instability. Testing for hypercalcemia and hyperparathyroidism is mandatory to obtain a correct diagnosis.

Background We evaluated safety and immunogenicity of the first mRNA vaccines against potentially pandemic avian H10N8 and H7N9 influenza viruses. Methods Two randomized, placebo-controlled, double-blind, phase 1 clinical trials enrolled participants between December 2015 and August 2017 at single centers in Germany (H10N8) and USA (H7N9). Healthy adults (ages 18–64 years for H10N8 study; 18–49 years for H7N9 study) participated. Participants received vaccine or placebo in a 2-dose vaccination series 3 weeks apart. H10N8 intramuscular (IM) dose levels of 25, 50, 75, 100, and 400 µg and intradermal dose levels of 25 and 50 µg were evaluated. H7N9 IM 10-, 25-, and 50-µg dose levels were evaluated; 2-dose series 6 months apart was also evaluated. Primary endpoints were safety (adverse events) and tolerability. Secondary immunogenicity outcomes included humoral (hemagglutination inhibition [HAI], microneutralization [MN] assays) and cell-mediated responses (ELISPOT assay). Results H10N8 and H7N9 mRNA IM vaccines demonstrated favorable safety and reactogenicity profiles. No vaccine-related serious adverse event was reported. For H10N8 (N = 201), 100-µg IM dose induced HAI titers ≥ 1:40 in 100% and MN titers ≥ 1:20 in 87.0% of participants. The 25-µg intradermal dose induced HAI titers > 1:40 in 64.7% of participants compared to 34.5% of participants receiving the IM dose. For H7N9 (N = 156), IM doses of 10, 25, and 50 µg achieved HAI titers ≥ 1:40 in 36.0%, 96.3%, and 89.7% of participants, respectively. MN titers ≥ 1:20 were achieved by 100% in the 10- and 25-µg groups and 96.6% in the 50-µg group. Seroconversion rates were 78.3% (HAI) and 87.0% (MN) for H10N8 (100 µg IM) and 96.3% (HAI) and 100% (MN) in H7N9 (50 µg). Significant cell-mediated responses were not detected in either study. Conclusions The first mRNA vaccines against H10N8 and H7N9 influenza viruses were well tolerated and elicited robust humoral immune responses. ClinicalTrials.gov NCT03076385 and NCT03345043 .

mRNA vaccines have the potential to tackle many unmet medical needs that are unable to be addressed with conventional vaccine technologies. A potent and well-tolerated delivery technology is integral to fully realizing the potential of mRNA vaccines. Pre-clinical and clinical studies have demonstrated that mRNA delivered intramuscularly (IM) with first-generation lipid nanoparticles (LNPs) generates robust immune responses. Despite progress made over the past several years, there remains significant opportunity for improvement, as the most advanced LNPs were designed for intravenous (IV) delivery of siRNA to the liver. Here, we screened a panel of proprietary biodegradable ionizable lipids for both expression and immunogenicity in a rodent model when administered IM. A subset of compounds was selected and further evaluated for tolerability, immunogenicity, and expression in rodents and non-human primates (NHPs). A lead formulation was identified that yielded a robust immune response with improved tolerability. More importantly for vaccines, increased innate immune stimulation driven by LNPs does not equate to increased immunogenicity, illustrating that mRNA vaccine tolerability can be improved without affecting potency., Graphical Abstract

The laryngeal force sensor (LFS) provides real-time force data for suspension microlaryngoscopy. This study investigates whether active use of the LFS can prevent the development of complications.Prospective controlled trial.Academic tertiary center.The LFS and custom software were developed to track intraoperative force metrics. A consecutive series of 100 patients had force data collected with operating surgeons blinded to intraoperative readings. The subsequent 100 patients had surgeons actively use the LFS monitoring system. Patients were prospectively enrolled, completing pre- and postoperative surveys to assess the development of tongue pain, paresthesia, paresis, dysgeusia, or dysphagia.On univariate analysis, the active monitoring group had lower total impulse (Maximum force is predictive of the development postoperative complications. Active monitoring with the LFS is able to mitigate these forces and prevent postoperative complications.2.

Cities, urban areas and neighbourhoods are complex ecosystems in which built environment and human activities interact and influence each other. In this chapter we try to analyse these interactions through the use of a simplified framework in two dimensions: the built environment, which measures the quality of tangible “hard” assets such as buildings, infrastructure and public areas, and the socio-economic environment, which measures the quality of intangible “soft” assets such as the vitality of the local community, opportunities for people and quality of life in general. “Distressed” areas are characterised by low quality on both dimensions; “Stressed” areas have a vital socio-economic environment but an inadequate built environment; “Aseptic” areas, on the contrary, have high performing buildings and infrastructures but are not able to create a vibrant local community; finally, “Ideal” areas represent the utopia of a place characterised by high quality on both dimensions. The positioning of cities, urban areas or neighbourhoods in these four categories is dynamic in the sense that virtuous urban regeneration programmes can transform Stressed areas into Ideal areas and, vice versa, lack of vision, poor governance or unexpected disruptive events can trigger the degradation of Ideal urban areas. The fundamental point we want to make here is that those who develop the territory must necessarily work on both the “hard” and “soft” dimensions with the same commitment. Creating a high-quality built environment is not enough and is just one of the necessary ingredients; to be successful, urban regeneration initiatives must also create conditions for attracting people and support social and economic activities. The built environment, both individual buildings and urban areas, can be considered not only as a “place” but also as a fundamental “tool” to promote sustainable socio-economic progress and environmental protection. With this approach the scope of activity for a real estate developer expands immensely and with it the need to develop innovative business models and additional skills.

Environmental time series are often affected by missing data, namely data unavailability at certain time points. In this paper, it is presented an Iterated Prediction and Imputation algorithm, that makes possible time series prediction in presence of missing data. The algorithm uses Dynamics Reconstruction and Machine Learning methods for estimating the model order and the skeleton of time series, respectively. Experimental validation of the algorithm on an environmental time series with missing data, expressing the concentration of Ozone in a European site, shows an average percentage prediction error of \(0.45\%\) on the test set.

Market positioning, identification of target customers and definition of value propositions are crucial decisions for success. In general terms, these decisions must be based on a systematic and objective analysis of a developer’s skills and the strengths of the context, and aimed at identifying market segments where it is possible to gain competitive advantage by leveraging these skills and strengths. At a strategic level it is possible either to enter an existing market with an innovative product, serve unmet demand or create new demand with disruptive solutions. At the base of all this, however, there must be a deep knowledge of target customers and key stakeholders, which can be acquired through traditional methods and with big data analytical tools enhanced by artificial intelligence. In order to guarantee competitiveness over time, it is necessary to provide for a continuous review of value propositions as the context changes. The creation of strong brands both for the developer and for the specific project contributes positively to the attraction of talents, access to financial resources, speed of access to the target markets and in general to the success of the initiatives.

Opportunities to create value exist at all stages of a real estate development process. In the initial product “Conception” phase—in which vision, strategy and market positioning are defined—value is created by focusing on “outputs” in terms of concrete benefits for customers and stakeholders. In the “Production” phase, value can be created by adopting an integrated industrial approach, increasing productivity, quality and safety. Finally, in the “Got-To-Market” post-development operational phase, value can be created by considering the real estate product as an integral part of a complex value proposition that has the ambition to foster the progress of the socio-economic ecosystem of reference. We have also identified four “tactics” that can be adopted to pursue value creation. First, to pursue product optimization and flexibility through an iterative process of prototyping, verification and revision. Second, to forge consensus and create strategic alliances with complementary partners of value. Third, to simultaneously pursue the enhancement of the three “Cs”: Container, Content and Context. Finally, to seek opportunities in areas of market discontinuity where there are clear supply and demand differentials.

Social distancing measures during the lockdown have had a negative impact on chronic pain patients’ function. Research, however, has only focused on the early stages of the first lockdowns. The aim of this study was to improve the understanding of the effects of COVID-19 social distancing measures on individuals with chronic pain living in Spain during the late stages of the lockdown. A group of 361 adults with pain participated in this study. They responded to an online survey and provided information on sociodemographic issues, pain, fatigue, perceived health, and quality of life. The data showed that most participants suffered moderate to severe pain and interferences with pain treatment and an increase in pain intensity during the lockdown. Most participants also informed us that fatigue had worsened during the lockdown (62%). Importantly, females with lower monthly family income and lower education have been found to be associated with greater levels of pain and fatigue. Despite this, participants perceived themselves as having good health and good quality of life. The findings from this study can be used to inform policy and specific responses for future COVID-19 waves and future pandemics where social distancing measures must be implemented. Fundação para a Ciência e Tecnologia - FCT info:eu-repo/semantics/publishedVersion

Change is no longer an exceptional event, let alone an episode affecting a specific sector at a given time. Change is everywhere and has become a constant in social and economic lives. While it is difficult to predict the future and identify, “at first glance”, the right answers to the new problems we are facing, it is also true that change brings with it as many opportunities, which are also widespread. The challenge for real estate operators, therefore, is to recognise these scenarios and develop the mindset and abilities needed to identify and seize the opportunities that will arise. To take full advantage of these opportunities, it is necessary to experiment, accept failures, challenge beliefs and consolidated business models, rather than trying to avoid the consequences of change while remaining anchored to the logic of the past. The real estate sector, like many other traditional industrial sectors, is based on well-established business models based on basic principles, logics and beliefs that have remained substantially unchanged over the past decades. In this scenario, operators have focused on improving the efficiency and productivity of the supply chains and the quality of the products and services offered. Today, and increasingly so in the future, operators will have to commit themselves to fostering innovation both of their business models and of their products and services in order to remain competitive and not be excluded from the market. In fact, the ability to innovate is, and will be, the main source of differentiation and the main driver of business competitiveness. How can we recognise and drive good innovation? In this chapter we explore some of the fundamental principles and try to understand the opportunities for the urban regeneration and real estate development sector. First and foremost, innovation can happen everywhere, from day-to-day operational tasks to the overall business model of an organisation. Second, innovation requires experimentation, openness, flexibility and ambition. Third, good innovation puts people at the centre and strives to deliver tangible benefits. Fourth, intercepting and adopting good innovation can be hard and technology can facilitate the process. Finally, urban areas can be a fertile ground for innovation, and innovation can be an extraordinary driver of sustainable social and economic progress for local communities.

We report C-band 100 Gb/s transmission (4 × 28 Gb/s) up to 6.5 km of standard single mode fiber exploiting an InP monolithically integrated WDM transmitter made by an array of four directly modulated DFB lasers on a 100 GHz spaced grid having a 3-dB bandwidth in excess of 20 GHz. To overcome the conventional chirp related chromatic dispersion limitation, we use the compact integrated transmitter in combination with a simplified DSP-free coherent detection scheme suitable for low cost, low power applications.

What are the deep-rooted motivations, aspirations and objectives that drive real estate developers to undertake a new initiative? What are their challenges and ambitions? Starting from these reflections, we propose a simplified framework in seven STEPs with the aim of providing a simple but useful “tool” for those who intend to undertake an urban regeneration or real estate development project, regardless of its nature and geographical location. The first three STEPS are aimed respectively at identifying the strengths and competitive advantages of the local context and the project (the solid “fundamentals” of the Offer); understanding customers’ and stakeholders’ needs and expectation (the potential Demand); and identifying real opportunities to create value by matching Offer and Demand. Based on the outcome of these first activities, STEP 4 involves creating a simple, clear but achievable vision (and its concrete purposes). To make the vision real, STEP 5 requires deciding strategic market positioning and high-level objectives for the initiative: what are the markets of choice? Who are the target customers and key stakeholders in these markets? What is the competitive landscape? Once these have been identified, the next STEP focuses on delineating benefits and competitive advantages offered to individual customers and stakeholders (the value propositions). Finally, STEP 7 is devoted to creating the “Executive Strategic Plan”, an operational document that includes all key actions and decisions needed to implement the initiative.

Aim of this work is to implement an environment object detection system for a marine drone. A Deep Learning based model for object detection is embedded on ARGO drone equipped with geophysical sensors and several on-board cameras. The marine drone, developed at iMTG laboratory in partnership with NEPTUN-IA laboratory, was designed to obtain high-resolution mapping of nearshore-to-foreshore sectors and equipped with a system able to detect and identify Ground Control Point (GCP) in real time. A Deep Neural Network is embedded on a Raspberry PI platform and it is adopted for developing the object detection module. Real experiments and comparisons are conducted for identifying GCP among the roughness and vegetation present in the seabed.

Heart failure (HF) is characterized by a high prevalence and hospitalization rate with considerable health and social impact; the knowledge of its epidemiological features remains the mainstay to assess adequacy of the health care needs. The aim of this study was to evaluate the prevalence of HF in Internal Medicine Units of the Campania region (Italy) and patients’ characteristics. We recruited all patients with HF admitted between April 1 and June 30, 2014, in 23 Units of Internal Medicine: 975 patients (19.5% of 5000 admissions), 518 women and 457 men, mean age 76.9±9.9 (range 34-100) with 741 (76%) older than 70 years. The mean age was higher in women than men; 35.8% of patients had atrial fibrillation, with higher prevalence in women than in men. Coronary artery disease represented the leading etiology while prevalence of non-ischemic heart failure was higher in women. New York Heart Association class was indicated in 926 patients. Left ventricular ejection fraction (LVEF) was measured in 503 patients; 18.4% of patients had a severely reduced LVEF40%. At least one hospital admission in the previous 12 months was registered in 39.6% of patients. One, two and more than two relevant comorbidities were present in 8.6%, 24.7% and 64.8% of patients, respectively. Arterial hypertension and coronary artery disease were more frequent in female. In conclusion, advanced age and clinical complexity were the main characteristics of HF patients hospitalized in the Internal Medicine Units in Campania. Gender differences also emerged from the analysis of demographic parameters and etiopathogenetic features. Some diagnostic and therapeutic aspects not in line with that recommended by the most recent HF international guidelines were registered.

Introduction: Osimertinib showed great clinical efficacy for activated-EGFR NCLC patient treatment. The aim of this work was to test the efficacy of a complete EGFR-inhibition by osimertinib plus the monoclonal antibody cetuximab or the MEK1/2-inhibitor selumetinib in EGFR-mutated NCLC in vivo models. Methods: We evaluated combinations of osimertinib plus selumetinib/cetuximab in HCC827 (E746-A759del/T790M-), H1975 (L858R/T790M+), and PC9-T790M (E746-A759del /T790M+) xenografts in second-line therapy after the development of resistance to osimertinib, and in first-line therapy, and we explored mechanisms of resistance to these treatments. Results: The addition of selumetinib or cetuximab to osimertinib in second-line therapy reverted the sensibility to osimertinib in the majority of mice, with a response rate (RR) of 50% to 80%, and a median progression-free survival (mPFS) of first- plus second-line of therapy of 28 weeks. The early use of combinations in first-line therapy increased the RR to 90%, with an mPFS not reached in all combination arms in the three xenografts models, with a statistically significant superiority (p < 0.005) as compared to osimertinib, achieving in first-line therapy an mPFS time of 17 to 18 weeks. Moreover, in ex vivo primary cell cultures obtained from osimertinib plus selumetinib-resistant tumors, we found Hedgehog pathway activation and we showed that therapy with an SMO inhibitor plus osimertinib and selumetinib inhibited proliferation and migratory and invasive properties of resistant cells. Conclusions: We showed that a dual vertical EGFR blockade with osimertinib plus selumetinib/cetuximab is a novel effective therapeutic option in EGFR-mutated NCLC and that hedgehog pathway activation and its interplay with MAPK is involved in resistance to these combination treatments.

Introduction In the era of precision medicine, research studies are aiming to design patient-tailored treatment strategies. In this work, we present a clinical case of a patient with non-small cell lung cancer (NSCLC) accompanied by a translational study with the intent to assess the correspondence of drug sensitivity in ex vivo spheroidal tumour cultures and peripheral blood biomarkers with clinical outcome. Methods Primary tumour tissue, patient-derived tumour spheroids, peripheral blood mononuclear cells and circulating DNA were analysed to assess drug sensitivity and immunological profiling, and all these data were correlated with clinical and radiological evaluations. Results Immunohistochemistry, immunofluorescence, next generation sequencing analysis and T-lymphocyte receptor repertoire assay results showed elevated concordance among primary tumour tissue, ex vivo three-dimensional tumour spheroid specimen and circulating DNA. Cisplatin-based chemotherapy and anti-programmed death 1 drug sensitivity assessed in spheroidal cultures were strictly consistent with patient clinical response to adjuvant chemotherapy and first-line immune therapy. Conclusion These results revealed that ex vivo drug sensitivity testing in three-dimensional spheroidal culture can reproduce clinical response to chemotherapy and immunotherapy, with the potential to use those culture models to predict patients‘ outcome from anticancer treatments and, therefore, the feasibility to select individualised therapy.

Background Anti-PD-1/PD-L1 drugs are effective as monotherapy in a proportion of NSCLC patients and there is a strong rationale for combining them with targeted therapy. Inhibition of MAPK pathway may have pleiotropic effects on the microenvironment. This work investigates the efficacy of combining MEK and PD-L1 inhibition in pre-clinical and ex-vivo NSCLC models. Methods We studied the effects of MEK inhibitors (MEK-I) on PD-L1 and MCH-I protein expression and cytokine production in vitro in NSCLC cell lines and in PBMCs from healthy donors and NSCLC patients, the efficacy of combining MEK-I with anti-PD-L1 antibody in ex-vivo human spheroid cultures obtained from fresh biopsies from NSCLC patients in terms of cell growth arrest, cytokine production and T-cell activation by flow cytometry. Results MEK-I modulates in–vitro the immune micro-environment through a transcriptionally decrease of PD-L1 expression, enhance of MHC-I expression on tumor cells, increase of the production of several cytokines, like IFNγ, IL-6, IL-1β and TNFα. These effects trigger a more permissive anti-tumor immune reaction, recruiting immune cells to the tumor sites. We confirmed these data on ex-vivo human spheroids, showing a synergism of MEK and PD-L1 inhibition as result of both direct cancer cell toxicity of MEK-I and its immune-stimulatory effect on cytokine secretion profile of cancer cells and PBMCs with the induction of the ones that sustain an immune-reactive and inflammatory micro-environment. Conclusions Our work shows the biological rationale for combining immunotherapy with MEK-I in a reproducible ex-vivo 3D-culture model, useful to predict sensitivity of patients to such therapies. Electronic supplementary material The online version of this article (10.1186/s13046-019-1257-1) contains supplementary material, which is available to authorized users.

One hundred and twenty dogs were enrolled to value the effect of loading condition changes on left ventricular volumes before and 24-hours after the patent ductus arteriosus (PDA) occlusion by Amplatzer Canine Duct Occluder (ACDO) using standard echocardiography. The animals were divided in pure breed (n. 94) and mixed breed (n. 26); subsequently, the pure breed dogs were divided on the basis of the size of the breed of belonging in 3 groups (small size n. 36; medium size n. 8; large size n. 50). Moreover, the animals were divided in three classes based on their age: until 6 months; 6-12 months; over 12 months. A significant reduction of all the examined parameters (left ventricle internal diameter at end-diastole-LVIDd; left ventricle internal diameter at end-systole-LVIDs; end-diastolic volume-EDV; end-systolic volume-ESV; end-diastolic volume index-EDVI; end-systolic volume index-ESVI; fractional shortening-FS) was observed after ductal closure. Twenty-four hours after the closure, the evaluation of the relative percentage difference (RPD) of the echocardiographic parameters showed a significant reduction, higher in small size breed than in large size breed dogs. No significant difference related to breed size was observed only for RPD_FS variable. A significant interaction effect, between breed size and age classes, was observed only for RPD_EDVI (F = 3.39; p = 0.039). Until six months of age there was no significant difference in RPD_EDVI reduction, but over 6 months a significant reduction between small size and large size breed dogs at 24-hours from the occlusion was observed. In conclusion, our data seem to indicate that small breed dogs show a greater tolerance to congenital volume overload than large breed dogs, and this finding could be justify a delay of PDA closure in order to simplify the interventional procedure.

Background: Endotracheal extubation is the most crucial step during emergence from general anesthesia. In the vast majority of cases, this is carried out when patients are awake with return of airway reflexes. Alternatively, extubations can also be accomplished while patients are deeply anesthetized, a technique known as “deep extubation”, in order to provide a “smooth” emergence from anesthesia. This smooth emergence is particularly important for procedures that require maintenance of stable levels of intraocular and intracranial pressures, such as in neurologic, ophthalmic, and head-and-neck surgery [1]. Reluctance to performing deep extubation in adults, even in appropriate circumstances, is common and likely derives both from concerns for potential respiratory complications [2] and limited research supporting its safety. It is in this context that we designed our prospective study to understand the factors that contribute to the success or failure of deep extubation in adults. Methods: In this prospective observational study, 300 patients, age ≥ 18, American Society of Anesthesiologists Physical Status (ASA PS) Classification I - III, who underwent head-and-neck and ocular surgeries. Patients’ demographic, comorbidity, airway assessment, O2 saturation, end tidal CO2 levels, time to exit OR, time to eye opening, and respiratory complications after deep extubation in the OR were analyzed. Results: Forty (13%) out of 300 patients had at least one complication in the OR, as defined by persistent coughing, desaturation SpO2 < 90% for longer than 10s, laryngospasm, stridor, bronchospasm and reintubation. When comparing the complication group to the no complication group, the patients in the complication group had significantly higher BMI (30 vs 26), lower O2 saturation pre and post extubation, and longer time from end of surgery to out of OR (pConclusions: The complication rate during deep extubation in adults was low and all easily reversible. And patient factors and extubation conditions may influence probability of success in deep extubation.

Background Frailty has gained prominence as a predictor of postoperative outcomes across a number of surgical specialties, vascular surgery included. The role of frailty is less defined in the acute surgical setting. We assessed the prognostic value of frailty for patients undergoing surgery for a ruptured abdominal aortic aneurysm (rAAA). Methods A single-institution retrospective chart review of all patients undergoing surgical intervention for rAAA between January 1, 2011 and November 27, 2019 was performed. Frailty was assessed for each patient using the modified frailty index (mFI), a validated frailty metric based on the Canadian Study of Health and Aging. Frailty was defined as an mFI ≥0.27. The performance of the mFI was compared to that of the Vascular Study Group of New England (VSGNE) rAAA mortality risk score. Chi square, Fisher's exact, and t tests, were used to evaluate for associations between frailty and in-hospital outcomes. Univariate and multivariate logistic regression were used to obtain odds ratios for in-hospital mortality. A receiver operating characteristic (ROC) curve was generated to compare the predictive value of the mFI and VSGNE score for in-hospital mortality. Results Sixty patients were identified during the study period with an in-hospital mortality rate of 37%. Twenty-one patients were deemed frail by mFI metric and included all patients with known myocardial infarction, stroke with a neurologic deficit or dependent functional status, however the mortality rate did not differ significantly based on frailty status (33% nonfrail vs. 43% frail, P= 0.47). Frailty status was not significantly different for patients with acute kidney injury (10% nonfrail vs. 10% frail), prolonged intubation (13% vs. 5%), abdominal compartment syndrome (8% vs. 10%), and Type I or Type III endoleak (8% vs. 19%). On multivariate analysis controlling for systolic blood pressure 2.0 mg/dl, the mFI produced an adjusted odds ratio (aOR) of 0.7 (95% confidence interval [CI]: 0.2–3.0). The ROC curve for the mFI produced an area under the curve (AUC) of 0.55 (P= 0.55) for in-hospital mortality while that of the VSGNE score produced an AUC of 0.69 (P= 0.02). Conclusions The mFI did not significantly predict in-hospital outcomes after rAAA in this cohort. This suggests that the baseline health status of a patient with rAAA may play a less significant role in their postoperative prognosis than their acuity on presentation.

Here we present the experimental characterization of 1 Mbit/s optical wireless communication system by simulating an intra-CubeSat environment where we exploit the reflections to transmit in the 2U CubeSat. The optical system uses infrared-LEDs, silicon-Avalanche photodiode, digital optical power meter and optical attenuators.

Motivation The cost of drug development has dramatically increased in the last decades, with the number new drugs approved per billion US dollars spent on R&D halving every year or less. The selection and prioritization of targets is one the most influential decisions in drug discovery. Here we present a Gaussian Process model for the prioritization of drug targets cast as a problem of learning with only positive and unlabeled examples. Results Since the absence of negative samples does not allow standard methods for automatic selection of hyperparameters, we propose a novel approach for hyperparameter selection of the kernel in One Class Gaussian Processes. We compare our methods with state-of-the-art approaches on benchmark datasets and then show its application to druggability prediction of oncology drugs. Our score reaches an AUC 0.90 on a set of clinical trial targets starting from a small training set of 102 validated oncology targets. Our score recovers the majority of known drug targets and can be used to identify novel set of proteins as drug target candidates. Availability and implementation The matrix of features for each protein is available at: https://bit.ly/3iLgZTa. Source code implemented in Python is freely available for download at https://github.com/AntonioDeFalco/Adaptive-OCGP. Supplementary information Supplementary data are available at Bioinformatics online.

For handling human-machine interactions, in this last years, many efforts have been devoted to Brain-Computer Interface (BCI). Electroencephalogram (EEG) electrodes enhance the convenience and wearability of BCI. Unfortunately, the noise induced by sampling reduces the signal quality compared to that of electrodes. In this paper a methodology for EEG waves compression and noise reduction is introduced. The approach is based on a non-linear Principal Component Analysis Neural Network for compression and decompression (reconstruction) of the data. Experiments are made on a corpus containing the activation strength of the fourteen electrodes of an EEG headset for eye state prediction. The experimental results highlight that the technique permits to obtain an higher rate of classification accuracy w.r.t. the use of row data.

We present the exploratory approach of Project FOCS (Free Space Optical communications for Space), which aims at proposing and demonstrating new applications of Visible Light Communications (VLC) for satellites. The first selected application scenario that will be investigated deals with transmission of Gbit/s signals on very small satellites, e.g. CubeSats. The second selected research line will be about low-bit-rate communication between satellites over > 100 m distances.

ObjectivesSomatosensory amplification (SA) has been described as an important feature of somatoform disorders, and an “amplifying somatic style” has been reported as a negative connotation of body perception. As widespread pain (WSP) in fibromyalgia (FM) is due to a central sensitization (CS) rather than organic alterations, there has been discussion as to whether FM is equivalent to or distinct from somatization disorder (SD). Assuming SD and FM are two distinct entities, an increase in somatic amplification should be expected only in subjects who have SD, regardless of the type of pain they experience. Purpose of the study was to explore the magnitude of SA in FM, and whether this depends on the association with SD.MethodsFM (n=159) other forms of chronic pain (OCP, n=582), psychiatric (Psy, n=53) and healthy (H, n=55) subjects were investigated using the Somatosensory Amplification Scale (SSAS), Illness Behavior Questionnaire, (IBQ), Italian Pain Questionnaire (IPQ), and Cold Pressor Test (CPT) in a retrospective observational study.ResultsFM subjects displayed higher SSAS scores than the other groups. High SSAS score was associated with FM (OR=8.39; 95%CI: 5.43–12.46) but not OCP. Although FM has the highest prevalence of SD (x2=14.07; p=.007), high SSAS scores were associated with SD in OCP but not in FM.ConclusionsUnlike in OCP, in FM high SSAS scores were independent of the presence of SD. From a biopsychosocial perspective, SSAS may be a factor associated with the onset of FM.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease associated with elevated prevalence of comorbidities, especially metabolic and cardiovascular diseases. We used a tool called Heart Rate Variability (HRV) in order to assess the correlation between HS and alterations of the sympathetic-vagal equilibrium in the autonomic cardiovascular regulation system. We found increased sympathetic activity, associated with a higher risk of cardiovascular disease. HS, according to our results, is an independent cardiovascular risk factor.