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Background: Psoriatic arthritis (PsA) develops in ~30% of patients with psoriasis. The diagnosis of PsA is challenging, and there are no reliable molecular markers in clinical use. MicroRNAs are short non‐coding regulatory RNAs, which can be actively packaged into extracellular vesicles (EVs) and secreted to the circulation. Objectives: To explore whether plasma‐derived EV microRNAs may serve as biomarkers for PsA in patients with psoriasis. Methods: Plasma samples were obtained from patients with cutaneous‐only psoriasis (PsC) and patients with psoriasis and PsA. Plasma EVs were isolated using miRCURY™ Exosome Isolation Kit. RNA sequencing was used to identify differentially expressed EV miRNAs in the discovery phase (PsC, n = 15; PsA, n = 14). In the validation phase (PsC, n = 29; PsA, n = 28), 41 selected miRNAs were analysed in plasma EVs by qPCR. The association of the identified miRNAs with PsA was assessed by logistic regression analysis. Results: RNA sequencing identified 19 plasma EV miRNAs with significantly different levels between PsA and PsC in the discovery cohort. Significantly lower levels of plasma EV let‐7b‐5p and miR‐30e‐5p in PsA vs. PsC were confirmed in the validation cohort, and their decreased levels were found to be associated with the presence of PsA. ROC analysis revealed an AUC of 0.68 (95% CI 0.53–0.83) for let‐7b‐5p and 0.69 (95% CI 0.55–0.84) for miR‐30e‐5p. Conclusions: Circulating EV microRNA levels are altered in patients with PsA as compared with PsC. Findings of this exploratory study suggest that circulating EV microRNAs may serve as biomarkers for arthritis in psoriasis patients. [ABSTRACT FROM AUTHOR]

Background Neurodegenerative diseases may extend outside the central nervous system (CNS) and involve the gastrointestinal (GI) tract. The gut would appear to be a pathological marker for neurodegeneration, as well as a site for studying the pathophysiology of neurodegeneration. In fact, both in the ENS and CNS, misfolded proteins are likely to initiate a process of neurodegeneration. For example, the very same protein aggregates can be detected both in the ENS and CNS. In both systems, misfolded proteins are likely to share common cell-to-cell diffusion mechanisms, which may occur through a parallel prion-like diffusion process. Independently from the enteric or central origin, misfolded proteins may proceed along the following steps, they: (i) form aggregates; (ii) are expressed on plasma membrane; (iii) are secreted extracellularly; (iv) are glycated to form advanced glycation end-products (AGEs); (v) are internalized through specific receptors placed on neighboring cells (RAGEs); (vi) are cleared by autophagy; and (vii) are neurotoxic. These features are common for a-synuclein (in Parkinson's disease and other synucleinopathies), β-amyloid and tau (in degenerative dementia), SOD-1 and TDP43 (in amyotrophic lateral sclerosis), and PrPsc (in prion diseases). While in some diseases these features are common to both ENS and CNS, in others this remains a working hypothesis. Purpose This review analyzes GI alterations from a pathological perspective to assess whether the enteric nervous system (ENS) mirrors the neuropathology described in the CNS. We discuss the potential mechanisms that lead to the onset and spread of neurodegeneration within the gut, from the gut to the brain, and vice versa. [ABSTRACT FROM AUTHOR]

Parkinson’s disease (PD) is a neurodegenerative disorder which leads to severe movement impairment; however, Parkinsonian patients frequently suffer from gastrointestinal (GI) problems which at present are poorly understood, scarcely investigated, and lack an effective cure. Traditionally, PD is attributed to the loss of mesencephalic dopamine-containing neurons; nonetheless, additional nuclei, such as the dorsal motor nucleus of the vagus nerve and specific central noradrenergic nuclei, are now identified as targets of PD. While the effects of PD on the somatic motor systems are well characterized, the influence on the digestive system still needs to be clarified. Recent findings demonstrate the occurrence of pathological alterations within peripheral neuronal networks in the GI tract of Parkinsonian patients. However, it remains unclear whether a real cell loss occurs, and whether this happens specifically for a subclass of autonomic neurons or if it reflects the sole loss of autonomic nerves. This review summarizes the neurochemical and morphological changes which might be responsible for impaired GI motility. Moreover, we focus on the experimental models to reproduce the altered digestive system of Parkinsonian patients since an experimental model able to mimic such features of PD is required. In the last part of the manuscript, we suggest potential therapeutic targets. [ABSTRACT FROM AUTHOR]

This study evaluated the influence of image processing of digital subtraction images on inter- and intra-examiner agreement relative to the detection of alveolar bone change on radiographs. 62 sites on digital subtraction images from standardized radiographs from patients requiring periodontal surgery were included in this study. The images were displayed as digital subtraction images, contrast enhanced subtraction images and as color-converted digital subtraction images. The images were projected in random order, analyzed by 4 interpreters and 1 of 8 possible diagnostic decisions was noted for each one of 62 sites. 2 months after the first evaluation, the slides were re-analyzed. 3 different computations (overall agreement, specific agreement and κ-value) were calculated. The results indicated that image processing of subtraction images using pseudocolor display of the density changes might improve the intra- and inter-examiner agreement. [ABSTRACT FROM AUTHOR]

The region-of-interest (ROI) in computer-assisted densitometric image analysis (CADIA) is defined by tis sized and location. This study evaluated the effects of these variables on two quantitative parameters, the change in density and the area with change in density. Pairs of radiographs for these analyses were obtained from sites with "no change" or "known loss" in Cynomolgus monkeys during a study of ligature-induced periodontitis. The size and location of the ROI had clear effects on the two CADIA parameters. To reduce these effects, a corrective procedure hypothesizing a linear relationship between the ROI size and the area with change in density was tested, while this procedure was sufficient to correct for ROI size-dependent differences among "no change" images, it was not effective in images with "known loss". In such images additional adjustments by increasing threshold levels for the registered change in density were found to reduce but not to eliminate differences between ROIs of different size and location. when densitometric radiographic analysis is used for quantitative comparison of different sites, it is primarily recommended to select ROIs of similar size and location. Application of corrective procedures should follow only after careful evaluation of their effects on sensitivity and specificity. [ABSTRACT FROM AUTHOR]

Quantitative evaluation of radiographic changes by computer-assisted densitometric image analysis (CADIA) requires exact knowledge about method errors. In the present study, density change errors were determined from pairs of films with "no change". From this distribution of error values, a series of threshold values for correction of changes due to method errors was selected. The threshold values were then applied to results from analysis of densitometric changes in sites with "known loss" or "no change" of the alveolar bone among films from cynomolgus monkeys. The density errors formed non-normal distributions with no difference in magnitudes between the absolute values expressing density decreases and density increases in the same areas. Calculation of sensitivity. specificity, type 1 and type 2 errors showed that these variables were clearly influenced by selection of different threshold values for correction of the density change errors. It is therefore recommended that threshold values be determined for each analytical system initially as well as following any equipment or computer program modification. Before selecting the threshold value for a specific radiographic analysis, the desired level of sensitivity and specificity should be evaluated. [ABSTRACT FROM AUTHOR]

A videobased computer assisted densitometric image analysis (CADIA) system to quantify alveolar bone density changes on standardized dental radiographs was tested. An algorithm was used for grey level correction of a subsequent image to the baseline image. Quantitative information regarding positive and/or negative grey level changes were obtained automatically. Comparison of the ability of CADIA to detect surgically induced bone loss with interpretation of digital subtraction images and conventional radiographic interpretation revealed that CADIA was the most sensitive of the 3 methods, followed by interpretation of digital subtraction images which was considerably more sensitive than conventional radiographic interpretation. CADIA was capable of assessing differences in alveolar bone changes due to periodontal surgery between sites exposed to ostectomy/osteoplasty and control sites and sites exposed to periodontal surgery without ostectomy/osteoplasty. Finally, CADIA was capable of assessing differences in remodeling activity over 4-6 weeks after periodontal surgery between 45 surgical sites and 45 control sites. The system offers an objective method to quantitatively follow alveolar bone density changes over time and appears to be the most sensitive of previously described radiographic interpretation techniques.

The purposes of this study were to evaluate digitized images from standardized radiographs for quantitative changes in alveolar bone density following periodontal surgical procedures, and to correlate these changes to the changes in the clinical parameters P1I, GI, PD, AL. 14 crown-lengthening procedures for restorative purposes were performed in 13 patients and 15 modified Widman flaps were performed in 15 patients, providing 61 surgical interdental test sites and 61 matching controls. Standardized radiographs were obtained immediately post-operatively, and at 1 and 6 months postsurgically. Digitized images were obtained from the radiographs by means of a video camera linked to an image processor and a computer. Quantitative information regarding density changes within windows covering the interdental alveolar crest was obtained after superimposition and grey-level correction of images to be compared. The results indicated statistically significantly more density loss 4 to 6 weeks postsurgically at test sites treated by periodontal surgical procedures compared to corresponding controls. Significant differences in the remodelling activity between the patients exposed to crown lengthening procedures for restorative purposes and the periodontitis patients in the period 1 to 6 months postsurgically were evident. CADIA assessed differences in the tissue changes in the healing phase following periodontal surgical procedures, which were not detected by the clinical variables applied.

The purpose of this study was to test the applicability of computer-assisted densitometric image analysis (CADIA) for the quantitative assessment of alveolar bone density changes in furcations of multirooted teeth. In 21 patients, standardized radiographs were obtained immediately after and at 1, 6 and 12 months after periodontal flap procedures. Digitized images were obtained by means of a video-camera combined with an image processor that was linked to a computer. Quantitative information regarding density changes within windows covering furcation areas was obtained after superimposition and grey-level correction of images to be compared. 1 month after flap reflection, significantly more density loss was obtained in test furcations exposed to periodontal surgery, compared to the density changes in control furcation exposed to scaling and root planing. At 12 months, however, significantly greater increase in density was measured in test furcations compared to the 1-month results. The radiographic data were compared to the clinical parameters. In test furcations, there was a negative correlation of r = -0.52 between the GI and the loss in density at 1 month, and a negative correlation of r = -0.61 between the loss in density at 6 months and the probing attachment level at 12 months. These results indicate that CADIA may give valuable additional diagnostic information regarding alveolar bone density changes in furcations in studies on periodontal therapy.