The pathogenesis of rheumatoid arthritis (RA) is a complex scenario that, to date, is not fully elucidated. However, scientific progress has enabled us to understand several mechanisms underlying the ...development of the disease. The breakdown of self-tolerance in genetically predisposed individuals and the aberrant activation of innate and adaptive immune responses culminate in synovial hyperplasia and bone destruction. In addition, extra-articular manifestations, as well as the burden of increased cardiovascular risk (CVR), in patients with RA represent another interesting aspect of RA pathogenesis under intense investigation. The purpose of this review article is to provide an overview of the new insights in RA pathogenesis summarising the most relevant studies published over the last year.
The TOTEM collaboration at the LHC has measured the elastic, inelastic and total proton-proton cross sections at several center of mass energies and is carrying on a rich program of measurements of ...diffractive physics together with the CMS collaboration. The talk will review the TOTEM measurements mainly focusing on the newest and most significant ones. The status of the experimental apparatus, its latest changes and the current and future technological challenges will be discussed as well.
Objective
Innate and adaptive immunity may contribute to gland dysfunction in patients with primary Sjögren's syndrome (pSS). The P2X7 receptor (P2X7R)–NLRP3 inflammasome complex modulates the ...release of the inflammatory cytokines IL‐1β and IL‐18. The presence of P2X7R in salivary glands suggests an interesting scenario for the initiation and amplification of the innate immune response in pSS. Therefore, the aim of this study was to assess the role of the P2X7R–NLRP3 inflammasome in pSS.
Subjects and Methods
Twenty‐one consecutive patients with pSS according to the American–European Consensus Group criteria and 15 patients with sicca syndrome (i.e. without Sjögren's syndrome, non‐SS) were enrolled in this study, together with six control (CTL) subjects. Expression of the P2X7R‐NLRP3 platform and IL‐18 was determined by real‐time PCR and western blotting in gland specimens and peripheral lymphomonocytes; data were related to patients\x92 clinical, serological and histopathological characteristics. The presence of IL‐18 was determined in gland and saliva samples.
Results
P2X7R expression was significantly higher in salivary glands from individuals with pSS than in those from non‐SS and CTL subjects. Accordingly, the gene expression levels of the inflammasome components NLRP3, ASC and caspase‐1 were significantly higher in pSS gland specimens, and this was paralleled by an increased expression of mature IL‐18 in pSS saliva samples. The expression of both the P2X7R and the inflammasome components was a marker of disease‐related glandular involvement, being increased in patients with anti‐Ro/SSA positivity and correlated with focus score.
Conclusion
The results of this study suggest an involvement of the P2X7R–inflammasome–caspase‐1–IL‐18 axis in the development of pSS exocrinopathy. This finding provides the basis for studying the complex mechanisms underlying pSS, as well as for developing novel potential therapeutic strategies.
Renin–angiotensin system (RAS) blockers are extensively used worldwide to treat many cardiovascular disorders, where they are effective in reducing both mortality and morbidity. These drugs are known ...to induce an increased expression of angiotensin‐converting enzyme 2 (ACE2). ACE2 acts as receptor for the novel SARS coronavirus‐2 (SARS‐CoV‐2) which raising the important issue of possible detrimental effects that RAS blockers could exert on the natural history and pathogenesis of the coronavirus disease‐19 (COVID‐19) and associated excessive inflammation, myocarditis and cardiac arrhythmias. We review the current knowledge on the interaction between SARS‐CoV‐2 infection and RAS blockers and suggest a scientific rationale for continuing RAS blockers therapy in patients with COVID‐19 infection.
Wound healing can be delayed following colonization and infection with the common bacterium
. While multiple therapies are used for their treatment, these are ineffective, expensive, and ...labour-intensive. Thus, there is an enormous unmet need for the treatment of infected wounds. Cinnamaldehyde, the major component of cinnamon oil, is well known for its antimicrobial properties. Herein, we investigated the effects of sub-inhibitory concentrations of cinnamaldehyde in the virulence of
. We also assessed its healing potential in
-infected mouse skin wounds and the mechanisms involved in this response. Sub-inhibitory concentrations of cinnamaldehyde reduced
metabolic rate and its ability to form biofilm and to cause haemolysis. Daily topical application of cinnamaldehyde on
-infected skin wounds reduced tissue bacterial load and promoted faster healing. Lower interleukin-17 (IL-17), vascular endothelial growth factor (VEGF) and nitric oxide levels were detected in cinnamaldehyde-treated wound samples. Blockage of transient receptor potential ankyrin 1, the pharmacological target of cinnamaldehyde, abrogated its healing activity and partially reversed the inhibitory actions of this compound on VEGF and IL-17 generation. We suggest that topical application of sub-inhibitory concentrations of cinnamaldehyde may represent an interesting approach to improve the healing of
-infected skin wounds.
Abstract
The realization of mathematical, multi-physics models for alkaline electrolyzers is crucial for advancing this technology. Lumped parameter models offer shorter simulation times, compared ...with other approaches, and practical industrial applications. If electrochemical models provide the polarization curve, the hydrogen production rate, and the device efficiency, thermal models solve the equations involving the electrolyte temperature. With a coupled approach, the two models can be linked together by considering the device voltage as temperature dependent. Despite the relevance of such models, few instances of their direct application on existing electrolyzers can be found in the literature, and combined electrochemical-thermal simulations are rare.
This study presents a multi-physics model applied on an alkaline electrolyzer and validated against measurements acquired on a dedicated experimental test bench.
The physics-based model accurately predicts the polarization curve, exhibiting a high precision match with experimental data. Additionally, it identifies material or geometrical imperfections in the electrolyzer, allowing for optimization in the design phase. The thermal model successfully converges to the desired electrolyte temperature of 72 °C under stationary conditions. Additional transient simulations demonstrate an average deviation of only 0.25% compared to the measured temperature trend. Finally, a sensitivity analysis explores the coupling of the electrolyzer with a wind turbine under different wind conditions.
The study showcases the effectiveness of the coupled electrochemical-thermal model in predicting electrolyzer performance, with a direct application to a wind turbine power output.
To describe the clinical spectrum of cryoglobulinemic vasculitis (CV) in primary Sjögren's syndrome (pSS), investigate its relation to lymphoma and identify the differences with hepatitis C virus ...(HCV) related CV.
From a multicentre study population of consecutive pSS patients, those who had been evaluated for cryoglobulins and fulfilled the 2011 classification criteria for CV were identified retrospectively. pSS-CV patients were matched with pSS patients without cryoglobulins (1:2) and HCV-CV patients (1:1). Clinical, laboratory and outcome features were analyzed. A data driven logistic regression model was applied for pSS-CV patients and their pSS cryoglobulin negative controls to identify independent features associated with lymphoma.
1083 pSS patients were tested for cryoglobulins. 115 (10.6%) had cryoglobulinemia and 71 (6.5%) fulfilled the classification criteria for CV. pSS-CV patients had higher frequency of extraglandular manifestations and lymphoma (OR=9.87, 95% CI: 4.7–20.9) compared to pSS patients without cryoglobulins. Purpura was the commonest vasculitic manifestation (90%), presenting at disease onset in 39% of patients. One third of pSS-CV patients developed B-cell lymphoma within the first 5 years of CV course, with cryoglobulinemia being the strongest independent lymphoma associated feature. Compared to HCV-CV patients, pSS-CV individuals displayed more frequently lymphadenopathy, type II IgMk cryoglobulins and lymphoma (OR = 6.12, 95% CI: 2.7–14.4) and less frequently C4 hypocomplementemia and peripheral neuropathy.
pSS-CV has a severe clinical course, overshadowing the typical clinical manifestations of pSS and higher risk for early lymphoma development compared to HCV related CV. Though infrequent, pSS-CV constitutes a distinct severe clinical phenotype of pSS.
Bacterial resistance to the available marketed drugs has prompted the search of novel therapies; especially in regards of anti-virulence strategies that aim to make bacteria less pathogenic and/or ...decrease their probability to become resistant to therapy. Cinnamaldehyde is widely known for its antibacterial properties through mechanisms that include the interaction of this compound with bacterial cell walls. However, only a handful of studies have addressed its effects on bacterial virulence, especially when tested at sub-inhibitory concentrations. Herein, we show for the first time that cinnamaldehyde is bactericidal against
and
multidrug resistant strains and does not promote bacterial tolerance. Cinnamaldehyde actions were stronger on
as it was able to inhibit its hemolytic activity on human erythrocytes and reduce its adherence to latex. Furthermore, cinnamaldehyde enhanced the serum-dependent lysis of
.
testing of cinnamaldehyde in
larvae infected with
, showed this compound improves larvae survival whilst diminishing bacterial load in their hemolymph. We suggest that cinnamaldehyde may represent an alternative therapy to control
-induced bacterial infections as it presents the ability to reduce bacterial virulence/survival without promoting an adaptive phenotype.
To analyse the possible morphologic and positional changes of the mandibular condyles after orthognathic surgery.
A prospective cohort study was performed. Patients with mandibular retrognathism were ...surgically treated to advance the mandible. The study group included seventeen patients (34 condyles) treated with sagittal split osteotomies alone (4 patients) or in combination with maxillary osteotomies (13 patients). Only condyles located on the mandibular side that advance during surgery were studied, therefore only 25 condyles entered this prospective study. Beside it, a group of 6 patients undergoing maxillary surgery as only procedure, maxillary group, was also studied to determinate the influence of maxillary surgery on condylar displacement. Computed tomographies and lateral cephalometric radiographs were performed two weeks before surgery and one year after the surgical procedures. Different variables which analyse the position and morphology of the mandible were studied. The data obtained were analysed statistically by computing R2 values.
In the maxillary group they were small displacements in magnitude and not significant. In the study group, 8 condyles showed morphological changes with alteration on reference points. In the remainder 17 condyles different displacements were noted after surgery. Several of these positional changes were predictable and did not affect postoperative mandibular stability.
condylar displacements that occur after sagittal split osteotomies for mandibular advancement show significant correlation with the degree of mandibular advancement and can be defined by mathematical formulae. Maxillary osteotomies do not seem to influence condylar position when bimaxillary procedures take place.
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