Biomarkers in motor neuron disease: A state of the art review

Motor neuron disease can be viewed as an umbrella term describing a heterogeneous group of conditions, all of which are relentlessly progressive and ultimately fatal. The average life expectancy is 2 years, but with a broad range of months to decades. Biomarker research deepens disease understanding through exploration of pathophysiological mechanisms which, in turn, highlights targets for novel therapies. It also allows differentiation of the disease population into sub-groups, which serves two general purposes: (a) provides clinicians with information to better guide their patients in terms of disease progression, and (b) guides clinical trial design so that an intervention may be shown to be effective if population variation is controlled for. Biomarkers also have the potential to provide monitoring during clinical trials to ensure target engagement. This review highlights biomarkers that have emerged from the fields of systemic measurements including biochemistry (blood, cerebrospinal fluid, and urine analysis); imaging and electrophysiology, and gives examples of how a combinatorial approach may yield the best results. We emphasize the importance of systematic sample collection and analysis, and the need to correlate biomarker findings with detailed phenotype and genotype data

Changes in Lips, Cheeks And Tongue Pressures After Upper Incisor Protrusion in Class Ii Division 2 Malocclusion: A Prospective Study

Background The etiology of Class II division 2 (CII/2) malocclusion focuses on heredity; however lip, cheek, and tongue pressures that are associated with the environmental effect are considered to have an effect. The aim of this study was to evaluate the relation between perioral pressures and the upper incisor inclination in CII/2 malocclusion. Methods Twenty patients (8 females, 12 males; mean age 10.29 ± 0.90 years) with CII/2 malocclusion were included in the study group, and 15 patients (5 females, 10 males; mean age 10.56 ± 1.06 years) with Class I malocclusion were included. The upper incisors were protruded with a utility arch (0.016 × 0.022 in. blue elgiloy wire). Perioral pressure assessment was made with the Iowa Oral Pressure Instrument. Upper lip pressure, lower lip pressure, vertical lip pressure, left-right buccal pressures, swallowing, and maximum tongue pressures were measured. Repeated measure ANOVA was used to test the intragroup differences. Intergroup comparisons were made using two-way repeated measure ANOVA with Bonferroni correction. Relationships between the variables were analyzed using rank correlation (Spearman’s rho). The significance for all statistical tests was predetermined at p < 0.05. Results A significant change occurred in the upper lip pressure, lower lip pressure, and vertical lip pressure; however, significant difference was not found between the groups. Upper lip pressure increased significantly in both groups. In the CII/2 group, lower lip pressure increased after protrusion and decreased after retention, while vertical lip pressure decreased and then increased significantly. Left buccal pressure changes between the groups were not parallel. Right buccal pressure, swallowing, and maximum tongue pressure changes were not statistically significant. Statistically significant correlation was found between U1-NA (mm) and vertical lip pressure (r −0.467). Conclusions In the CII/2 group, upper lip pressure increased only in retention. Lower lip pressure increased and vertical lip pressure decreased after protrusion. Nevertheless, these changes did not remain stable after the retention period. The difference between groups was not statistically significant at the end of retention.PubMedWoSScopu

Europeanization, EU conditionality, and governance quality: Empirical evidence on Central and Eastern European countries

A large body of work within the Europeanization and conditionality literature has examined EU’s effect on governance quality in Central and Eastern European countries (CEECs). This article aims to contribute to existing work by addressing two questions. First, was EU’s accession conditionality conducive to better governance in CEECs or was it designed to pick up already committed reformers? Secondly, during which period was the EU more influential on governance quality in CEECs: accession or membership? To address these questions, we propose a simple model of moral hazard and adverse selection, and draw on survey-based governance quality data to test its predictions. We report that the EU has offered candidate status to countries that already had better governance quality relative to their peers before 1997. Nonetheless, EU conditionality also had some positive effects on CEEC governance during the accession period, but this effect tended to disappear during the membership period. On the basis of these findings, we argue that EU’s impact on governance quality in CEECs has to be examined in conjunction with path dependence and therefore the perceived risk of ‘backsliding’ requires more detailed analysis