Anti-phospholipid-antibodies in patients with relapsing polychondritis

Relapsing polychondritis (RP) is an extremly rare multisystemic disease thought to be of autoimmune origin. In order to assess if RP is associated with anti-phospholipid antibodies (aPL), clinical data and sera of 21 patients with RP were collected in a multicentre study. Concentration of anti-cardiolipin antibodies (aCL) (IgG-, IgM-and IgA-isotypes), anti-phosphatidylserine-antibodies (aPS) (IgG-and IgM-isotypes) and anti-β-2-glycoprotein I-antibodies (aβ2 GPI) were measured by ELISA. In eight patients aCL were found to be elevated. One patient had elevated aPS. No patient had elevated aβ2 GPI. No patient had clinical signs and symptoms of a aPL syndrome. Interestingly, the two RP patients with the highest aPL had concomitant systemic lupus erythematosus (SLE). Therefore the presence of elevated aPL in RP is probably more closely related to an associated SLE than to RP itself. There is no convincing evidence that aPL are associated with RP

Accuracy of periodontitis diagnosis obtained using multiple molecular biomarkers in oral fluids: A systematic review and meta‐analysis

Aim To determine the accuracy of biomarker combinations in gingival crevicular fluid (GCF) and saliva through meta-analysis to diagnose periodontitis in systemically healthy subjects. Methods Studies on combining two or more biomarkers providing a binary classification table, sensitivity/specificity values or group sizes in subjects diagnosed with periodontitis were included. The search was performed in August 2022 through PUBMED, EMBASE, Cochrane, LILACS, SCOPUS and Web of Science. The methodological quality of the articles selected was evaluated using the QUADAS-2 checklist. Hierarchical summary receiver operating characteristic modelling was employed to perform the meta-analyses (CRD42020175021). Results Twenty-one combinations in GCF and 47 in saliva were evaluated. Meta-analyses were possible for six salivary combinations (median sensitivity/specificity values): IL-6 with MMP-8 (86.2%/80.5%); IL-1β with IL-6 (83.0%/83.7%); IL-1β with MMP-8 (82.7%/80.8%); MIP-1α with MMP-8 (71.0%/75.6%); IL-1β, IL-6 and MMP-8 (81.8%/84.3%); and IL-1β, IL-6, MIP-1α and MMP-8 (76.6%/79.7%). Conclusions Two-biomarker combinations in oral fluids show high diagnostic accuracy for periodontitis, which is not substantially improved by incorporating more biomarkers. In saliva, the dual combinations of IL-1β, IL-6 and MMP-8 have an excellent ability to detect periodontitis and a good capacity to detect non-periodontitis. Because of the limited number of biomarker combinations evaluated, further research is required to corroborate these observationsThis study was funded by the Instituto de Salud Carlos III (ISCIII) through the project PI21/00588 and co-funded by the European UnionS

Can we identify individuals with an ALPL variant in adults with persistent hypophosphatasaemia?

Hypophosphatasia (HPP) is an inborn error of metabolism characterized by low levels of serum alkaline phosphatase (ALP). Scarce evidence exists about features that should signal the potential association between hypophosphatasaemia and HPP in adults. The aim of this study is to estimate the prevalence of ALPL variants in subjects with persistent hypophosphatasaemia and determine the associated clinical and laboratory features. For this cross-sectional study, laboratory records of 386,353 subjects were screened by measurement of ALP activity. A total of 85 (0.18%) subjects with persistent hypophosphatasaemia (≥2 serum alkaline phosphatase-ALP-measurements ≤35 IU/L and none > 45 IU/L) were included (secondary causes previously discarded). ALPL genetic testing and a systematized questionnaire to retrieve demographic, clinical and laboratory data were performed. Descriptive analysis and logistic regression models were employed to identify the clinical and laboratory characteristics associated with ALPL variants. Results: Forty subjects (47%) had a variant(s) in ALPL. With regard to clinical characteristics, the presence of an ALPL variant was significantly associated only with musculoskeletal pain (OR: 7.6; 95% IC: 1.9-30.9). Nevertheless, a trend to present more dental abnormalities (OR: 3.6; 95% IC: 0.9-13.4) was observed. Metatarsal stress fractures were also more frequent (4 vs 0; p < 0.05) in this group. Regarding laboratory features, median ALP levels were lower in subjects with ALPL variants (26 vs 29 IU/L; p < 0.005). Interestingly, the threshold of ALP levels < 25 IU/L showed a specificity, positive predictive value and positive likelihood ratio of 97.8, 94.4% and 19.8 to detect a positive ALPL test, respectively. Conclusions: In subjects with persistent hypophosphatasaemia -secondary causes excluded- one out of two presented ALPL variants. Musculoskeletal pain and ALP levels < 25 IU/L are associated with this variant(s). In this scenario, ALP levels < 25 IU/L seem to be very useful to identify individuals with the presence of an ALPL variantGenetic testing was supported by a grant from Alexion Pharmaceuticals Inc., which had no role in the study design or data analysi

Self-Similar Interpolation in Quantum Mechanics

An approach is developed for constructing simple analytical formulae accurately approximating solutions to eigenvalue problems of quantum mechanics. This approach is based on self-similar approximation theory. In order to derive interpolation formulae valid in the whole range of parameters of considered physical quantities, the self-similar renormalization procedure is complimented here by boundary conditions which define control functions guaranteeing correct asymptotic behaviour in the vicinity of boundary points. To emphasize the generality of the approach, it is illustrated by different problems that are typical for quantum mechanics, such as anharmonic oscillators, double-well potentials, and quasiresonance models with quasistationary states. In addition, the nonlinear Schr\"odinger equation is considered, for which both eigenvalues and wave functions are constructed.Comment: 1 file, 30 pages, RevTex, no figure

Accuracy of single molecular biomarkers in gingival crevicular fluid for the diagnosis of periodontitis: A systematic review and meta-analysis

This is the peer reviewed version of the following article: Arias‐Bujanda, N, Regueira‐Iglesias, A, Balsa‐Castro, C, Nibali, L, Donos, N, Tomás, I. Accuracy of single molecular biomarkers in gingival crevicular fluid for the diagnosis of periodontitis: A systematic review and meta‐analysis. J Clin Periodontol. 2019; 46: 1166– 1182. https://doi.org/10.1111/jcpe.13188, which has been published in final form at https://doi.org/10.1111/jcpe.13188. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived VersionsAbstract Aim To analyse, by means of a meta‐analytical approach, the diagnostic accuracy of molecular biomarkers in gingival crevicular fluid (GCF) for the detection of periodontitis in systemically healthy subjects. Material and Methods Studies on GCF molecular biomarkers providing a binary classification table (or sensitivity and specificity values and group sample sizes) in individuals with clinically diagnosed periodontitis were considered eligible. The search was performed using six electronic databases. The methodological quality of studies was assessed through the tool Quality Assessment of Diagnostic Studies. Meta‐analyses were performed using the Hierarchical Summary Receiver Operating Characteristic, which adjusts classification data using random effects logistic regression. Results The included papers identified 36 potential biomarkers for the detection of periodontitis and for four of them meta‐analyses were performed. The median sensitivity and specificity were for MMP8, 76.7% and 92.0%; for elastase, 74.6% and 81.1%; for cathepsin, 72.8% and 67.3%, respectively. The worst estimates of sensitivity and specificity were for trypsin (71.3% and 66.1%, respectively). Conclusions MMP8 showed good sensitivity and excellent specificity, which resulted in this biomarker being clinically the most useful or effective for the diagnosis of periodontitis in systemically healthy subjects, regardless of smoking conditionInstituto de Salud Carlos III FEDER. Grant Number: ISCIII/PI17/01722 Consellería de Cultura, Educación e Ordenación Universitaria da Xunta de Galicia. Grant Numbers: ED431B 2017/029, ED481A‐201

Role of Mitochondrial Complex IV in Age-Dependent Obesity

Aging is associated with progressive white adipose tissue (WAT) enlargement initiated early in life, but the molecular mechanisms involved remain unknown. Here we show that mitochondrial complex IV (CIV) activity and assembly are already repressed in white adipocytes of middle-aged mice and involve a HIF1A-dependent decline of essential CIV components such as COX5B. At the molecular level, HIF1A binds to the Cox5b proximal promoter and represses its expression. Silencing of Cox5b decreased fatty acid oxidation and promoted intracellular lipid accumulation. Moreover, local in vivo Cox5b silencing in WAT of young mice increased the size of adipocytes, whereas restoration of COX5B expression in aging mice counteracted adipocyte enlargement. An age-dependent reduction in COX5B gene expression was also found in human visceral adipose tissue. Collectively, our findings establish a pivotal role for CIV dysfunction in progressive white adipocyte enlargement during aging, which can be restored to alleviate age-dependent WAT expansion

Hybrid optimization method with general switching strategy for parameter estimation

This article is available from: http://www.biomedcentral.com/1752-0509/2/26[Background] Modeling and simulation of cellular signaling and metabolic pathways as networks of biochemical reactions yields sets of non-linear ordinary differential equations. These models usually depend on several parameters and initial conditions. If these parameters are unknown, results from simulation studies can be misleading. Such a scenario can be avoided by fitting the model to experimental data before analyzing the system. This involves parameter estimation which is usually performed by minimizing a cost function which quantifies the difference between model predictions and measurements. Mathematically, this is formulated as a non-linear optimization problem which often results to be multi-modal (non-convex), rendering local optimization methods detrimental.[Results] In this work we propose a new hybrid global method, based on the combination of an evolutionary search strategy with a local multiple-shooting approach, which offers a reliable and efficient alternative for the solution of large scale parameter estimation problems.[Conclusion] The presented new hybrid strategy offers two main advantages over previous approaches: First, it is equipped with a switching strategy which allows the systematic determination of the transition from the local to global search. This avoids computationally expensive tests in advance. Second, using multiple-shooting as the local search procedure reduces the multi-modality of the non-linear optimization problem significantly. Because multiple-shooting avoids possible spurious solutions in the vicinity of the global optimum it often outperforms the frequently used initial value approach (single-shooting). Thereby, the use of multiple-shooting yields an enhanced robustness of the hybrid approach.This work was supported by the European Community as part of the FP6 COSBICS Project (STREP FP6-512060), the German Federal Ministry of Education and Research, BMBF-project FRISYS (grant 0313921) and Xunta de Galicia (PGIDIT05PXIC40201PM).Peer reviewe

Зависимость свойств толстопленочных терморезисторов от состава базовой шпинели

Изменением соотношения компонентов шпинели Cu1-x-yCo2yMn2-yO4 получены толстопленочные терморезисторы с удельным объемным электросопротивлением 1,5-33 Омм и тепловой константой В25/85 2980-3690 К

Acceptability and feasibility of a virtual community of practice to primary care professionals regarding patient empowerment: A qualitative pilot study

Background: Virtual communities of practice (vCoPs) facilitate online learning via the exchange of experiences and knowledge between interested participants. Compared to other communities, vCoPs need to overcome technological structures and specific barriers. Our objective was to pilot the acceptability and feasibility of a vCoP aimed at improving the attitudes of primary care professionals to the empowerment of patients with chronic conditions. Methods: We used a qualitative approach based on 2 focus groups: one composed of 6 general practitioners and the other of 6 practice nurses. Discussion guidelines on the topics to be investigated were provided to the moderator. Sessions were audio-recorded and transcribed verbatim. Thematic analysis was performed using the ATLAS-ti software. Results: The available operating systems and browsers and the lack of suitable spaces and time were reported as the main difficulties with the vCoP. The vCoP was perceived to be a flexible learning mode that provided up-to-date resources applicable to routine practice and offered a space for the exchange of experiences and approaches. Conclusions: The results from this pilot study show that the vCoP was considered useful for learning how to empower patients. However, while vCoPs have the potential to facilitate learning and as shown create professional awareness regarding patient empowerment, attention needs to be paid to technological and access issues and the time demands on professionals. We collected relevant inputs to improve the features, content and educational methods to be included in further vCoP implementation. Trial registration: ClinicalTrials.gov, NCT02757781. Registered on 25 April 2016.This study was financed by Instituto de Salud Carlos III and Cofinanced by Fondo Europeo de Desarrollo Regional (FEDER). Ministerio de Economía y Competitividad. Gobierno de España. (PI15/00164, PI15/00586, PI15/00566