Drug repurposing for neurodegenerative diseases.

Neurodegenerative diseases (NDDs) are neuronal problems that include the brain and spinal cord and result in loss of sensory and motor dysfunction. Common NDDs include Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), Multiple Sclerosis (MS), and Amyotrophic Lateral Sclerosis (ALS) etc. The occurrence of these diseases increases with age and is one of the challenging problems among elderly people. Though, several scientific research has demonstrated the key pathologies associated with NDDs still the underlying mechanisms and molecular details are not well understood and need to be explored and this poses a lack of effective treatments for NDDs. Several lines of evidence have shown that NDDs have a high prevalence and affect more than a billion individuals globally but still, researchers need to work forward in identifying the best therapeutic target for NDDs. Thus, several researchers are working in the directions to find potential therapeutic targets to alter the disease pathology and treat the diseases. Several steps have been taken to identify the early detection of the disease and drug repurposing for effective treatment of NDDs. Moreover, it is logical that current medications are being evaluated for their efficacy in treating such disorders; therefore, drug repurposing would be an efficient, safe, and cost-effective way in finding out better medication. In the current manuscript we discussed the utilization of drugs that have been repurposed for the treatment of AD, PD, HD, MS, and ALS.

The rotation vs translation behavior during habitual opening and closing movements of the mandible and the relationship to movement paths of condylar points.

When recording condylar movement paths with the aid of electronic measuring systems, it is often found that, especially in jaw opening and closing movements, excursive and incursive paths of movement are not congruent but run separately, independently of one another to a greater or lesser degree. The objective of the study was to investigate this phenomenon in the context of rotation vs translation behavior, also taking into consideration additional side-specific condylar movement patterns. For this purpose, the electronic movement records of habitual jaw opening of 259 participants of the associated project of the population-representative basic study SHIP 0 were evaluated. The condylar movement path (condylar tracing, ConTrac) at the arbitrary axis point, the excursion vs incursion behavior in the condylar tracing grid (ExInGrid), and the rotation vs translation behavior (RotTrans) were classified, and the translational condylar path and the maximum angle of rotation were determined metrically. Relationships between the parameters ConTrac, ExInGrid, and RotTrans were statistically analyzed using cross tabulations and Spearman's correlation coefficient. Only about 18% of ConTrac showed congruence of excursive and incursive movement path components, while 39% demonstrated noncongruent paths, and 43% showed further conspicuous features in the movement path. For the parameter ExInGrid, recognizable to highly pronounced loop formation patterns to a degree of 89% were observed in the condylar tracing grid. An average of 12.5 mm (min 2.1 mm, max 21.7 mm) was determined for the purely translational component of the condylar movement path, and 32.1 degrees (min 12 degrees, max 45 degrees) for the maximum angle of rotation. Concerning the rotation vs translation behavior, the linear basic pattern occurred at around 9%; the sigmoidal pattern at 28%; and the hysteretic, loopy or irregular pattern at 63%. The parameters RotTrans and ExInGrid showed a strong correlation, whereas the strength of the correlation for ConTrac and ExInGrid or RotTrans and ConTrac was evaluated as weak or very weak. The rotation vs translation behavior influences condylar movement paths in the positional relationship of excursive and incursive components. The visualization of several condylar movement paths in the form of a condylar tracing grid helps to capture complex rotational and translational motion components of the real condyles more effectively than the assessment of a single condylar movement path.

Occlusion of artificial teeth in complete dentures: population-based analysis.

Occlusion is a central aspect of all prosthetic restorations, including complete dentures. Within the follow-up (SHIP 1) of the regional population-based "Study of Health in Pomerania" (SHIP), a number of 3300 study participants were examined concerning the occlusion of artificial teeth in purely mucosa and non-implant-borne complete dentures. These subjects were representative of the population. Therefore, occlusal bite registrations obtained in habitual intercuspation (IP) were made and were digitally evaluated with the Greifswald Digital Analyzing System (GEDAS) software based on transparent contact areas. A total of 495 subjects wore such complete dentures, of whom 438 wore maxillary dentures (217 men, 71.3 ± 9.2 years; 221 women, 68.9 ± 9.1 years), and 278 wore mandibular dentures (141 men, 70.4 ± 8.5 years; 137 women, 70.4 ± 8.5 years). The mean number of denture teeth was 13.4 ± 0.89 in the maxilla (of which 6.8 ± 2.77 were in occlusal contact), and 13.3 ± 0.91 in the mandible (of which 6.8 ± 2.97 were in occlusal contact). In general, the premolars (maxilla: 2.8 ± 1.31; mandible: 2.6 ± 1.29 teeth) had more occlusal contact than the molars (maxilla: 2.2 ± 1.24; mandible: 2.3 ± 1.23 teeth). The differences were highly significant, with P < 0.01 in the Wilcoxon test for paired samples. Furthermore, there were distinctions between both sides, with the right side having more posterior teeth in contact than the left side (maxillary right: 2.6 ± 1.18; maxillary left: 2.5 ± 1.14; mandibular right: 2.5 ± 1.13; mandibular left: 2.4 ± 1.13), each significant for the maxilla at P = 0.022 (Wilcoxon test). Here, the number of denture teeth played a role. In dentures with exactly 14 denture teeth (maxillary: n = 301; mandibular: n = 179), there were significantly more molars than premolars in contact in the mandible (premolars: 2.4 ± 1.37; molars: 2.7 ± 1.27; P = 0.026), whereas in the maxilla the ratio of premolars to molars in contact was reversed (premolars: 2.8 ± 1.36; molars: 2.6 ± 1.25); however, the latter difference proved barely significant at just P = 0.099. Women tended to have slightly fewer contact-bearing teeth than men (posteriors in men: 5.1 ± 2.04; in women: 4.9 ± 2.03); the differences were not significant. Nor were there any significant differences between the groups < 70 years (maxillary: n = 189; mandibular: n = 101), and ≥ 70 years (maxillary: n = 249; mandibular: n = 177). The presence of dysfunction of the masticatory system was determined using the Helkimo Index (HI). A value of HI ≥ 2 was regarded as dysfunctional. The groups with and without dysfunctions differed significantly for the number of posterior teeth on the right side of the maxilla (HI ≥ 2: 2.2 ± 1.34; HI < 2: 2.6 ± 1.6; P = 0.041) in the Mann-Whitney U test. The difference in the groups according to HI was found to be slightly significant regarding the number of posteriors (HI ≥ 2: 4.5 ± 2.28; HI < 2: 5.1 ± 2.00; P = 0.063) and molars (HI ≥ 2: 1.9 ± 1.34; HI < 2: 2.3 ± 1.22; P = 0.092) with occlusal contacts. The differences for the mandibular premolars and for the maxillary left posterior teeth were not significant. CONCLUSION: With regard to masticatory system dysfunctions, it makes sense to ensure that there are molar contacts, especially in the maxilla. A tendency to "premolarize" contacts should be counteracted by appropriate measures.