Clenching the Strings of Bruxism Etiopathogenesis: Association Analyses on Genetics and Environmental Risk Factors in a Deeply Characterized Italian Cohort.

Bruxism is a worldwide oral health problem. Although there is a consensus about its multifactorial nature, its precise etiopathogenetic mechanisms are unclear. This study, taking advantage of a deeply characterized cohort of 769 individuals (aged 6-89 years) coming from Northern Italy's genetically isolated populations, aims to epidemiologically describe environmental risk factors for bruxism development and identify genes potentially involved through a Genome-Wide Association Study (GWAS) approach. Logistic mixed models adjusted for age and sex were performed to evaluate associations between bruxism and possible risk factors, e.g., anxiety, smoking, and alcohol and caffeine intake. A case-control GWAS (135 cases, 523 controls), adjusted for age, sex, and anxiety, was conducted to identify new candidate genes. The GTEx data analysis was performed to evaluate the identified gene expression in human body tissues. Statistical analyses determined anxiety as a bruxism risk factor (OR = 2.54; 95% CI: 1.20-5.38; p-value = 0.015), and GWAS highlighted three novel genes potentially associated with bruxism: NLGN1 (topSNP = rs2046718; p-value = 2.63 × 10-7), RIMBP2 (topSNP = rs571497947; p-value = 4.68 × 10-7), and LHFP (topSNP = rs2324342; p-value = 7.47 × 10-6). The GTEx data analysis showed their expression in brain tissues. Overall, this work provided a deeper understanding of bruxism etiopathogenesis with the long-term perspective of developing personalized therapeutic approaches for improving affected individuals' quality of life.

The Bittersweet Symphony of COVID-19: Associations between TAS1Rs and TAS2R38 Genetic Variations and COVID-19 Symptoms.

The innate immune system is crucial in fighting SARS-CoV-2 infection, which is responsible for coronavirus disease 2019 (COVID-19). Therefore, deepening our understanding of the underlying immune response mechanisms is fundamental for the development of novel therapeutic strategies. The role of extra-oral bitter (TAS2Rs) and sweet (TAS1Rs) taste receptors in immune response regulation has yet to be fully understood. However, a few studies have investigated the association between taste receptor genes and COVID-19 symptom severity, with controversial results. Therefore, this study aims to deepen the relationship between COVID-19 symptom presence/severity and TAS1R and TAS2R38 (TAS2Rs member) genetic variations in a cohort of 196 COVID-19 patients. Statistical analyses detected significant associations between rs307355 of the TAS1R3 gene and the following COVID-19-related symptoms: chest pain and shortness of breath. Specifically, homozygous C/C patients are exposed to an increased risk of manifesting severe forms of chest pain (OR 8.11, 95% CI 2.26-51.99) and shortness of breath (OR 4.83, 95% CI 1.71-17.32) in comparison with T/C carriers. Finally, no significant associations between the TAS2R38 haplotype and the presence/severity of COVID-19 symptoms were detected. This study, taking advantage of a clinically and genetically characterised cohort of COVID-19 patients, revealed TAS1R3 gene involvement in determining COVID-19 symptom severity independently of TAS2R38 activity, thus providing novel insights into the role of TAS1Rs in regulating the immune response to viral infections.

The Clinical Profile of Tremor in Parkinson's Disease.

Background: Tremor is one of the most troublesome manifestations of Parkinson's Disease (PD) and its response to dopaminergic medication is variable; an evidence-based framework of PD tremor is lacking yet needed to inform future investigations. Objective: To perform a comprehensive longitudinal analysis on the clinical characteristics, course and response to dopaminergic medication of tremor in de-novo PD. Methods: Three hundred ninety-seven participants were recruited in the Parkinson Progressive Markers Initiative, a prospective observational cohort study in early de-novo PD. Rest, postural and kinetic tremor scores were extracted from the Movement Disorders Society-Unified Parkinson's Disease Rating Scale. Progression from baseline to 7-year follow-up of rest, postural and kinetic tremor scores, and their response to in-clinic dopaminergic medication were analyzed through linear mixed-effects models adjusted for age, sex and disease duration at enrollment. A sensitivity analysis was conducted through subgroup and imputation analyses. Results: 382 (96.2%) participants showed tremor and 346 (87.2%) showed rest tremor in at least one assessment over 7 years. Off-state rest, postural and kinetic tremor scores increased significantly over time, coupled with a significant effect of dopaminergic medication in reducing tremor scores. However, at each assessment, tremor was unresponsive to in-clinic dopaminergic medication in at least 20% of participants for rest, 30% for postural and 38% for kinetic tremor. Conclusions: PD tremor is a troublesome manifestation, with increasing severity and variable response to medications. This analysis details the current clinical natural history of tremor in early-to-mid stage PD, outlining an evidence-based framework for future pathophysiological and interventional studies.

Odontostomatological Traits in North-Eastern Italy's Isolated Populations: An Epidemiological Cross-Sectional Study.

Malocclusions and temporomandibular disorders (TMDs) are oral health problems that are spread worldwide. To date, few studies focused on their prevalence and associated risk factors are available. This study aims to define the prevalence and distribution of odontostomatological traits and evaluate specific risk factors in isolated villages in north-eastern Italy, taking advantage of their environmental homogeneity. Nine hundred and forty-four participants aged six to eighty-nine years were enrolled. Thirty-one odontostomatological phenotypes, classified into five domains (airways, bad habits, extraoral and intraoral parameters, TMDs, and teeth), were evaluated. A descriptive statistical analysis was performed; mixed logistic models were used to test the relationships among the traits. According to the study's findings, Angle's class I was prevalent (65.3%) followed by class II malocclusion (24.3%); class III and reversed overjet were the least frequent malocclusions (10.4% and 1.8%, respectively). Temporomandibular joint (TMJ) click/noise was prevalent among TMDs (34.7%). The statistically significant (p-value < 0.05) risk factors were ankyloglossia for phonetic issues (OR 1.90) and bruxism for TMJ click/noise (OR 1.70) and pain (OR 2.20). Overall, this work provides a picture of the prevalence of malocclusions and TMDs in a large Italian sample and reveals risk factors to take into account in the development of preventive strategies and treatments.

Hands-feet wireless devices: Test-retest reliability and discriminant validity of motor measures in Parkinson's disease telemonitoring.

BACKGROUND: Telemonitoring, a branch of telemedicine, involves the use of technological tools to remotely detect clinical data and evaluate patients. Telemonitoring of patients with Parkinson's disease (PD) should be performed using reliable and discriminant motor measures. Furthermore, the method of data collection and transmission, and the type of subjects suitable for telemonitoring must be well defined. OBJECTIVE: To analyze differences in patients with PD and healthy controls (HC) with the wearable inertial device SensHands-SensFeet (SH-SF), adopting a standardized acquisition mode, to verify if motor measures provided by SH-SF have a high discriminating capacity and high intraclass correlation coefficient (ICC). METHODS: Altogether, 64 patients with mild-to-moderate PD and 50 HC performed 14 standardized motor activities for assessing bradykinesia, postural and resting tremors, and gait parameters. SH-SF inertial devices were used to acquire movements and calculate objective motor measures of movement (total: 75). For each motor task, five or more biomechanical parameters were measured twice. The results were compared between patients with PD and HC. RESULTS: Fifty-eight objective motor measures significantly differed between patients with PD and HC; among these, 32 demonstrated relevant discrimination power (Cohen's d > 0.8). The test-retest reliability was excellent in patients with PD (median ICC = 0.85 right limbs, 0.91 left limbs) and HC (median ICC = 0.78 right limbs, 0.82 left limbs). CONCLUSION: In a supervised environment, the SH-SF device provides motor measures with good results in terms of reliability and discriminant ability. The reliability of SH-SF measurements should be evaluated in an unsupervised home setting in future studies.

Cardiac troponins: are there any differences between T and I?

The most recent international guidelines recommend the measurement of cardiac troponin I (cTnI) and cardiac troponin T (cTnT) using high-sensitivity methods (hs-cTn) for the detection of myocardial injury and the differential diagnosis of acute coronary syndromes. Myocardial injury is a prerequisite for the diagnosis of acute myocardial infarction, but also a distinct entity. The 2018 Fourth Universal Definition of Myocardial Infarction states that myocardial injury is detected when at least one value above the 99th percentile upper reference limit is measured in a patient with high-sensitivity methods for cTnI or cTnT. Not infrequently, increased hs-cTnT levels are reported in patients with congenital or chronic neuromuscular diseases, while the hs-cTnI values are often in the normal range. Furthermore, some discrepancies between the results of laboratory tests for the two troponins are occasionally found in individuals apparently free of cardiac diseases, and also in patients with cardiac diseases. In this review article, authors discuss the biochemical, pathophysiological and analytical mechanisms which may cause discrepancies between hs-cTnI and hs-cTnT test results.

Objective assessment of blinking and facial expressions in Parkinson's disease using a vertical electro-oculogram and facial surface electromyography.

OBJECTIVE: Hypomimia is a common and early symptom of Parkinson's disease (PD), which reduces the ability of PD patients to manifest emotions. Currently, it is visually evaluated by the neurologist during neurological examinations for PD diagnosis, as described in task 3.2 of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Since such an evaluation is semi-quantitative and affected by inter-variability, this paper aims to measure the physiological parameters related to eye blink and facial expressions extracted from a vertical electro-oculogram (VEOG) and facial surface electromyography (fsEMG) to differentiate PD patients from healthy control subjects (HCs). APPROACH: The spontaneous eye blink rate-minute (sEBR), its maximum amplitude (BMP), and facial cutaneous muscle activity were measured in 24 PD patients and 24 HCs while the subjects looked at a visual-tester composed of three main parts: static vision, dynamic vision and reading silently. Specificity and sensitivity for each parameter were calculated. MAIN RESULTS: The VEOG and the fsEMG allowed the identification of some parameters related to eye blink and facial expressions (i.e. sEBR, BMP, frontal and peribuccal muscular activities), being able to distinguish between PD patients and HCs with high sensitivity and specificity. SIGNIFICANCE: The demonstration that the combination of parameters related to eye blink and facial expressions can discriminate (with high accuracy) between PD patients versus HCs, thus resulting in a useful tool to support the neurologist in objective assessment of hypomimia for improving PD diagnosis.

Potential Direct Costs of Adverse Drug Events and Possible Cost Savings Achievable by their Prevention in Tuscany, Italy: A Model-Based Analysis.

INTRODUCTION: Adverse drug events (ADEs) may represent an important item of expenditure for healthcare systems and their prevention could be associated with a relevant cost saving. OBJECTIVE: The objective of this study was to simulate the annual economic burden for ADEs in Tuscany (Italy) and the potential cost savings related to avoidable ADEs. METHODS: A systematic review was performed, according to the Preferred Reporting Items for Systematic review and Meta-Analysis (PRISMA) and Meta-analysis Of Observational Studies in Epidemiology (MOOSE) statements, on observational studies published from 2006 to 2016 in MEDLINE and EMBASE, focusing on direct costs of ADEs in the inpatient setting from high-income countries. The mean probability of preventable ADEs was estimated over the included studies. The mean ADE cost was calculated by means of Monte Carlo simulation. We then extrapolated the spontaneous reports of ADEs in Tuscany, Italy in 2016 from the Italian National Pharmacovigilance Network (Rete Nazionale di Farmacovigilanza), and we assumed the same costs and preventability probability for these as obtained in the systematic review. Finally, we simulated the possible costs of ADEs and preventable ADEs in Tuscany. Three sensitivity analyses were also performed to test the robustness of the results. RESULTS: Of 11,936 articles initially selected, 12 observational studies were included. The estimated mean [± standard deviation (SD)] ADE cost was €2471.46 (± €1214.13). The mean (± SD) probability of preventable ADEs was 45% (± 21). The Tuscan expenditure for ADEs was €3,406,280.63 per million inhabitants (95% confidence interval (CI) 1,732,910.44-5,079,664.61) and the potential cost saving was €1,532,760.25 per million inhabitants (95% CI 779,776.1-2,285,750.60). Sensitivity analyses confirmed the robustness of the results. CONCLUSIONS: The present simulation showed that ADEs could have a relevant economic impact on the Tuscan healthcare system. In this setting, the prevention of ADEs would result in important cost savings. These results could be likely extended to other healthcare systems.