Relation between high-sensitivity troponin I serum levels and myocardial ischemia in patients with suspected chronic coronary syndrome: The reset-MI study.

BACKGROUND: Previous studies showed that exercise may increase cardiac troponin serum levels; whether the occurrence of myocardial ischemia influences the changes of exercise-induced troponin raise, however, remains debatable. METHODS: We prospectively enrolled consecutive patients undergoing for the first time an elective stress myocardial perfusion scintigraphy (MPS) because of clinical suspicion of obstructive coronary artery disease (CAD). Patients were divided into 3 groups based on the evidence and degree of stress-induced myocardial ischemia at MPS: 1) group 1, no myocardial ischemia (≤4 %); 2) group 2, mild myocardial ischemia (5-10 %); 3) group 3, moderate-to-severe myocardial ischemia (≥10 %). High-sensitivity cardiac troponin I (cTnI) was measured immediately before (T0) and 1 hour (T1) and 4 h (T2) after the stress test. RESULTS: One hundred-seven patients (71 males; age 65.6 ± 9.4 years) were enrolled in the study. Serum hs-cTnI concentrations (logarithmic values) significantly increased after MPS, compared to baseline, in the whole population, from 1.47±1.26 ng/L at T0, to 1.68±1.12 ng/L at T1 (p<0.001) and 2.15±1.02 ng/L at T2 (p<0.001 vs. both T0 and T1). The increase in hs-cTnI did not significantly differ between the 3 groups (p = 0.44). The heart rate achieved during the test was the strongest determinant of cTnI increase (p < 0.001) after the stress test. CONCLUSIONS: In patients with suspected CAD, stress MPS induces an increase of cTnI that is independent of the induction and extension/severity of myocardial ischemia and is mainly related to myocardial work, as indicated by the heart rate achieved during the test.

Comparative Analysis of Antimicrobial Antibodies between Mild and Severe COVID-19.

Patients with 2019 coronavirus disease (COVID-19) exhibit a broad spectrum of clinical presentations. A person's antimicrobial antibody profile, as partially shaped by past infection or vaccination, can reflect the immune system health that is critical to control and resolve the infection. We performed an explorative immunoproteomics study using microbial protein arrays displaying 318 full-length antigens from 77 viruses and 3 bacteria. We compared antimicrobial antibody profiles between 135 patients with mild COVID-19 disease and 215 patients with severe disease in 3 independent cohorts from Mexico and Italy. Severe disease patients were older with higher prevalence of comorbidities. We confirmed that severe disease patients elicited a stronger anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) response. We showed that antibodies against HCoV-229E and HcoV-NL63 but not against HcoV-HKU1 and HcoV-OC43 were also higher in those who had severe disease. We revealed that for a set of IgG and IgA antibodies targeting coronaviruses, herpesviruses, and other respiratory viruses, a subgroup of patients with the highest reactivity levels had a greater incidence of severe disease compared to those with mild disease across all three cohorts. On the contrary, fewer antibodies showed consistent greater prevalence in mild disease in all 3 cohorts. IMPORTANCE The clinical presentations of COVID-19 range from asymptomatic to critical illness that may lead to intensive care or even death. The health of the immune system, as partially shaped by past infections or vaccinations, is critical to control and resolve the infection. Using an innovative protein array platform, we surveyed antibodies against hundreds of full-length microbial antigens from 80 different viruses and bacteria in COVID-19 patients from different geographic regions with mild or severe disease. We not only confirmed the association of severe COVID-19 disease with higher reactivity of antibody responses to SARS-CoV-2 but also uncovered known and novel associations with antibody responses against herpesviruses and other respiratory viruses. Our study represents a significant step forward in understanding the factors contributing to COVID-19 disease severity. We also demonstrate the power of comprehensive antimicrobial antibody profiling in deciphering risk factors for severe COVID-19. We anticipate that our approach will have broad applications in infectious diseases.

CSF neuron-specific enolase as a biomarker of neurovascular conflict severity in drug-resistant trigeminal neuralgia: a prospective study in patients submitted to microvascular decompression.

BACKGROUND: Although neurovascular conflict (NVC) is the most widely accepted cause of trigeminal neuralgia (TN), few articles have analyzed molecular and biochemical mechanisms underlying TN. In the present study, we dosed neuron-specific enolase (NSE) on serum and CSF samples of 20 patients submitted to microvascular decompression (MVD) and correlated these findings with the type of NVC. METHODS: Blood samples were obtained preoperatively and 48 h after MVD. CSF from trigeminal cistern was intraoperatively obtained. NSE levels were measured using the Diasorin kit (LIAISON®NSE). NVC was classified as "contact" or "trigeminal nerve distortion/indentation" or "trigeminal root atrophy" based on MRI and intraoperative findings. Clinical outcome was measured by acute pain relief (APR) and Barrow Neurological Institute (BNI) scale at last available follow-up (FU; 6.40 ± 5.38 months). RESULTS: APR was obtained in all patients. A statistically significant BNI reduction was obtained at latest FU (p < 0.0001). Serum NSE levels significantly decreased following MVD (from 12.15 ± 3.02 ng/mL to 8.95 ± 2.83 ng/mL, p = 0.001). The mean CSF NSE value was 48.94 ng/mL, and the mean CSF/serum NSE rate was 4.18 with a strong correlation between these two variables (p = 0.0008). CSF NSE level in "trigeminal root atrophy" group was significantly higher compared to "contact" (p = 0.0045) and "distortion/indentation" (p = 0.010) groups. CONCLUSION: NSE levels seem to be related to the etiopathology and severity of NVC. A significant reduction of serum NSE levels could be related to the resolution of the NVC and clinical TN improvement.

Sinonasal Biomarkers Defining Type 2-High and Type 2-Low Inflammation in Chronic Rhinosinusitis with Nasal Polyps.

The complex pathophysiology of chronic rhinosinusitis with nasal polyps (CRSwNP) generates a spectrum of phenotypes with a wide variety of inflammatory states. We enrolled 44 very-likely-to-be type 2 CRSwNP patients in order to evaluate the load of inflammation and to analyze human interleukins in nasal secretion. Clinical data were collected to evaluate the severity of the disease. High levels of IL-5, IL-4, IL-6, and IL-33 were detected in all type 2 CRSwNP patients. By analyzing type 2 cytokine profiles and local eosinophil count, we identified two coherent clusters: the first was characterized by high levels of IL-4, IL-5, IL-6, and a high-grade eosinophil count (type 2-high); the second had lower levels of cytokines and poor or absent eosinophilic inflammation (type-2 low). IL-5 levels were significantly higher within the type 2 cytokine and it was the most reliable biomarker for differentiating the two clusters. In type 2-high inflammatory profile clinical scores, the mean number of previous surgeries and need for systemic corticosteroids were significantly higher compared to type 2-low. Our research demonstrated the potential role of type 2 biomarkers, and in particular, of IL-5 in identifying patients with a more severe phenotype based on a high inflammatory load.

Calprotectin in nasal secretion: a new biomarker of non-type 2 inflammation in CRSwNP.

Objective: We analysed calprotectin in sinonasal secretions of different chronic rhinosinusitis with nasal polyps (CRSwNP) endotypes to assess its role as a biomarker of non-type 2 inflammation. Methods: We included primary diffuse CRSwNP patients (n = 41) and three different control groups [non-allergic rhinitis (NAR) (n = 13), non-allergic eosinophilic syndrome (NARES) (n = 10) and healthy subjects (n = 12)]. Calprotectin levels were detected in nasal secretions using a chemiluminescent immunoassay (CLIA). Results: Calprotectin levels in nasal secretions were significantly higher in all non-type 2 endotypes of CRSwNP compared to healthy controls (p < 0.05). In contrast, in type-2 CRSwNP calprotectin was significantly lower compared to controls (p < 0.05). A significant correlation between calprotectin levels and neutrophilic count/HPF was found in CRSwNP (p < 0.01). Clinically, mean levels of calprotectin and neutrophilia were significantly higher in patients who previously underwent 3 or more endoscopic sinus surgeries (p < 0.05). Conclusions: Calprotectin in nasal secretions may be a biomarker of non-type 2 inflammation. Low levels of calprotectin are indicative of a type-2 immune response in both CRSwNP and non-allergic rhinitis. We observed that calprotectin levels significantly increased based on the number of previous surgeries.

The Relationship between ACE, ACTN3 and MCT1 Genetic Polymorphisms and Athletic Performance in Elite Rugby Union Players: A Preliminary Study.

Athletic performance is influenced by many factors such as the environment, diet, training and endurance or speed in physical effort and by genetic predisposition. Just a few studies have analyzed the impact of genotypes on physical performance in rugby. The aim of this study was to verify the modulation of genetic influence on rugby-specific physical performance. Twenty-seven elite rugby union players were involved in the study during the in-season phase. Molecular genotyping was performed for: angiotensin-converting enzyme (ACE rs4646994), alfa-actinin-3 (ACTN3 rs1815739) and monocarboxylate transporter 1 (MCT1 rs1049434) and their variants. Lean mass index (from skinfolds), lower-limb explosive power (countermovement jump), agility (505), speed (20 m), maximal aerobic power (Yo-yo intermittent recovery test level 1) and repeated sprint ability (12 × 20 m) were evaluated. In our rugby union players ACE and ACTN3 variants did not show any influence on athletic performance. MCT1 analysis showed that TT-variant players had the highest peak vertical power (p = 0.037) while the ones with the AA genotype were the fastest in both agility and sprint tests (p = 0.006 and p = 0.012, respectively). Considering the T-dominant model, the AA genotype remains the fastest in both tests (agility: p = 0.013, speed: p = 0.017). Only the MCT1 rs1049434 A allele seems to be advantageous for elite rugby union players, particularly when power and speed are required.

Genetics and Sport Injuries: New Perspectives for Athletic Excellence in an Italian Court of Rugby Union Players.

Several genes are involved in sport performance, especially in injuries incidence. The aim of this study was to investigate the association of ACE, ACTN3, COL1A1, and MCT1 genotypes and injuries in rugby players in order to find a genotype/phenotype correlation and provide useful information improving athletic performance. One-hundred male professional and semiprofessional rugby players were selected. Analysis was performed genotyping the genes ACE, ACTN3, COL1A1, and MCT1 as candidate gene of interest involved in athletic performance. A control group of non-athletic Italian male participants was analyzed to compare the results. We found statistical significance of MCT1 rs1049434 AA for total injuries (χ2 = 0.115; p = 0.003) and bone injuries (χ2 = 0.603; p = 0.007) in the rugby athlete population. No statistical significance was found between injury incidence and ACE, ACTN3, COL1A1 genotypes. The MCT1 AA genotype is associated with the incidence of total and bone injuries in the rugby player population. Although environmental factors such as lifestyle, diet, training, and stress can influence athletic performance, our data demonstrated the importance of genetic study in sport aimed at developing personalized training and achieving the best possible athletic excellence.

The role of biomarkers in drug-resistant trigeminal neuralgia: a prospective study in patients submitted to surgical treatment.

BACKGROUND: Molecular mechanisms underlying trigeminal neuralgia (TN) have been poorly understood. Recently, different biomarkers have been studied in several chronic neuropathic diseases or in neuronal damage, but their role in TN has not yet been investigated. Here, we firstly analyzed the serum levels of the neuron-specific enolase (NSE) (as an index of neuronal tissue damage) in TN patients submitted to surgical treatment. Different cytokines and interleukins related to inflammation were also studied. METHODS: Blood samples from 40 patients were prospectively collected preoperatively and after the surgical procedure, namely microvascular decompression (MVD) and percutaneous balloon compression (PBC). Serum levels of uric acid, NSE, ferritin, CRP, IL-2R, and IL-6 were studied. The acute pain relief (APR) and the pre- and postoperative BNI were used to evaluate the clinical outcome. RESULTS: Overall, we obtained an APR in 87.5% of patients and a significant reduction of BNI after surgery (p < 0.0001). We observed a significant reduction of postoperative NSE values in the group of patients undergoing MVD (p = 0.0055) and a significant increase of postoperative NSE values in patients undergoing PBC (p < 0.05). Furthermore, in the group of patients undergoing MVD, we found a significant postoperative increase of CRP (p < 0.0001), ferritin (p = 0.001), and IL-6 (p = 0.01) values. The only patient who did not respond to MVD had NSE levels unchanged. CONCLUSION: Our results suggest the hypothesis that TN would be related to the neural damage instead of the systemic inflammatory status and indicate NSE as a possible biomarker of response in patients submitted to MVD.

Analytical Performance Evaluation of a New Calcitonin Assay.

BACKGROUND: The use of efficient laboratory calcitonin (CT) testing is required for optimal management of medullary thyroid carcinoma. Several pitfalls are related to the calcitonin laboratory assays and a careful evaluation is needed. We report the analytical performances of the new Siemens ADVIA-Centaur-CALCT (CT-XPT) assay and its comparison with our standard method DiaSorin-Calcitonin-II-Gen (CT-LIA) assay. METHODS: Analytical performance of the CT-XPT-assay, limit of blank (LOB), limit of detection (LOD), and limit of quantification (LOQ), were determined. We also evaluated the in vitro stability of the sample, together with the linearity and percentage recovery. RESULTS: The CT-XPT-assay showed a better detection limit than the CT-LIA assay, with lower values of LOB (0.86 pg/mL vs 1.00 pg/mL) and LOQ (1.65 pg/mL vs 3.00 pg/mL). Both values were in agreement with those reported by the manufacturer. Within- and between-run precision demonstrated a good concordance of results. Regarding the in vitro stability of CT, the low CT concentration sera showed a much greater decrease in CT levels compared to the high concentration sera. Correlation studies showed a good correlation between the two methods (Kappa Cohen coefficent, KC: 0.68, agreement % for male: 89.58%; KC: 0.63; agreement % for female: 88.33%). CONCLUSIONS: Our findings showed a good correlation between the CT-LIA and CT-XPT methods. Moreover, we demonstrated that the analytical performance of the CT-XPT assay, together with its technical specifications, could represent major features of the CT-XPT method. Collectively, the technical evaluation and the analytical results described in the presented paper highlight that the novel CT-XPT is a valid method for CT testing in a clinical diagnostic setting.

Health care-associated infections: Controlled delivery of cationic antiseptics from polymeric excipients.

Nowadays, the treatment of health care-associated infections represents a serious issue, due to the increasing number of bacterial strains resistant to traditional antibiotics. The use of antiseptics like quaternary ammonium salts and biguanides is a viable alternative to face these life-threatening infections. However, their inherent toxicity as well as the necessity of providing a sustained release to avoid the formation of pathogen biofilms are compelling obstacles towards their assessment in the hospitals. Within this framework, the role of polymeric drug delivery systems is fundamental to overcome the aforementioned problems. Biocompatibility, biodegradability and excipient-drug interactions are crucial properties determining the efficacy of the formulation. In this work, we provide an in-depth analysis of the polymer drug delivery systems that have been developed or are under development for the sustained release of positively charged antiseptics, highlighting the crucial characteristics that allowed to achieve the most relevant therapeutic effects. We reported and compared natural occurring polymers and synthetic carriers to show their pros and cons and applicability in the treatment of health care-associated infections. Then, the discussion is focused on a particularly relevant class of materials adopted for the scope, represented by polyesters, which gave rise, due to their biodegradability, to the field of resorbable drug delivery devices. Finally, a specific analysis on the effect of the polymer functionalization over the formulation performances for the different types of polymeric carriers is presented.

Special-needs patients in pediatric dentistry: Progeroid syndrome. A case of dental management and oral rehabilitation.

This report presents a case of an eightyear- old girl affected by a progeroid syndrome of unclear genetic origins. The patient's dental history included oligodontia, premature deciduous exfoliation and roots abnormalities. She was treated with comprehensive oral rehabilitation using dentures. Oral health instructions were given during the whole treatment and follow- up period. The goal of improving the masticatory function and the esthetic was achieved, allowing the patient to increase her social abilities and self-confidence.

Modelling and testing of a wave energy converter based on dielectric elastomer generators.

This paper introduces the analysis and design of a wave energy converter (WEC) that is equipped with a novel kind of electrostatic power take-off system, known as dielectric elastomer generator (DEG). We propose a modelling approach which relies on the combination of nonlinear potential-flow hydrodynamics and electro-hyperelastic theory. Such a model makes it possible to predict the system response in operational conditions, and thus it is employed to design and evaluate a DEG-based WEC that features an effective dynamic response. The model is validated through the design and test of a small-scale prototype, whose dynamics is tuned with waves at tank-scale using a set of scaling rules for the DEG dimensions introduced here in order to comply with Froude similarity laws. Wave-tank tests are conducted in regular and irregular waves with a functional DEG system that is controlled using a realistic prediction-free strategy. Remarkable average performance in realistically scaled sea states has been recorded during experiments, with peaks of power output of up to 3.8 W, corresponding to hundreds of kilowatts at full-scale. The obtained results demonstrated the concrete possibility of designing DEG-based WEC devices that are conceived for large-scale electrical energy production.

Fabrication and Test of an Inflated Circular Diaphragm Dielectric Elastomer Generator Based on PDMS Rubber Composite.

This paper introduces a fabrication method and the experimental characterization of a soft polymeric energy converter manufactured using a combination of dielectric and conductive polydimethylsiloxane elastomers. The presented system is an inflated circular diaphragm dielectric elastomer generator; i.e., a deformable electrostatic transducer that converts the mechanical work done by a time-varying pressure into electricity. A prototype of the system is realized on the basis of a simple fabrication procedure that makes use of commercially available silicone dielectric elastomer films and custom-prepared deformable conductive electrodes. A test-bench is developed and employed to estimate the energy conversion performance. Remarkable results are obtained, such as an amount of energy converted per cycle of up to 0.3 J, converted power of up to 0.15 W, energy per unit of employed elastomer mass of up to 173 J/kg, and fraction of the input mechanical work converted into electricity of 30%.

Evaluation of a Novel Cone Beam Computed Tomography Scanner for Bone Density Examinations in Preoperative 3D Reconstructions and Correlation with Primary Implant Stability.

BACKGROUND: Bone density examination (BDE) using preoperative cone beam computed tomography (CBCT) might be used to predict primary implant stability in implant patients. PURPOSE: The aim of the study was to validate a novel CBCT scanner in vitro with regard to BDE in preoperative scans and to analyze the in vivo correlation of CBCT scan results with primary implant stability measurements. MATERIALS AND METHODS: A CBCT scanner was validated in vitro with regard to spatial uniformity and linearity of CT numbers (Hounsfield units, HU) by using a series of phantoms and plastic and hydroxyapatite specimens of various densities. Forty-nine patients (27 female and 22 male, mean age 55.6 ± 9.8) were scanned prior to and 1 to 6 months after the placement of 155 dental implants of different lengths and diameters. Mean and peak insertion torque (IT) in Ncm were registered during implant placement. Resonance frequency analysis (RFA) measurements in ISQ units were performed after placement. The second scan was used to export and superimpose the exact positions of bone and implants into the first scan. Virtual probes with the same length as the actual implant were automatically placed at the implant sites, and mean HU values were measured in a 1 mm-wide circular corridor from the tip of the threads and out. RESULTS: The in vitro validation showed high uniformity and linearity of CT numbers (HU). The clinical study showed significant correlations between bone density and ISQ, mean IT, and peak IT, respectively. CONCLUSIONS: The WhiteFox CBCT scanner measures bone density with high accuracy. There is a correlation between bone density and primary implant stability as assessed with IT and RFA measurements. The findings suggest that BDE may be used as an additional feature in treatment-planning software to estimate primary stability at predetermined implant sites.