Subclinical Atherosclerosis in Primary Sjögren's Syndrome: Does Inflammation Matter?

Sjögren's syndrome (SS) is a systemic autoimmune disease mainly characterized by inflammatory involvement of exocrine gland. Atherosclerosis is a complex process leading to plaque formation in arterial wall with subsequent cardiovascular (CV) events. Recently, numerous studies demonstrated that SS patients bear an increased CV risk. Since activation of immune system is a key element in atherosclerosis, it is interesting to analyze whether and how the autoimmune and inflammatory events characterizing SS pathogenesis directly or indirectly contribute to atherosclerosis risk in these patients. An increase in circulating endothelial microparticles and integrins, which may be a consequence of endothelial damage and impaired repair mechanisms, has been demonstrated in SS. Increased endothelial expression of adhesion molecules with subsequent infiltration of inflammatory cells into arterial wall is also a critical event in atherosclerosis. The early inflammatory events taking place in the atherosclerotic plaque cause an increase in alarmins, such as S100A8/A9, which seems to be associated with SS disease activity and, in turn, induce up-regulation of interleukin (IL)-1β and other pro-atherogenic cytokines. Interestingly, increased IL-1β levels were also detected in tertiary lymphoid structures developing in vessel adventitia adjacent to the atherosclerotic plaque, suggesting a direct role of IL-1β in this process. Similar to these structures, germinal center-like structures arising in SS exocrine glands are also tertiary lymphoid systems where T-helper (Th) cell subsets govern the adaptive immune response. Th1 cells are the most prevalent subtype and have been shown to be strongly involved in both SS pathogenesis and atherosclerosis. Th17 cells are attracting great interest and few studies showed its importance in SS development. Albeit in low amounts, a Th17 signature was also detected in atherosclerotic plaques and some animal models demonstrated a significant pro-atherogenic role and positive effects of IL-17A blockade. Despite the fact that T cells have a pivotal role in the inflammatory process that ultimately leads to atherosclerosis, B cells have also been detected in atherosclerotic plaques, although their exact role is still mostly unknown with studies showing contrasting results. In this scenario, the role of inflammation in atherosclerosis pathogenesis in patients with SS needs to be further explored

Protective Effects of Recombinant Human Angiogenin in Keratinocytes: New Insights on Oxidative Stress Response Mediated by RNases

Human angiogenin (ANG) is a 14-kDa ribonuclease involved in different pathophysiological processes including tumorigenesis, neuroprotection, inflammation, innate immunity, reproduction, the regeneration of damaged tissues and stress cell response, depending on its intracellular localization. Under physiological conditions, ANG moves to the cell nucleus where it enhances rRNA transcription; conversely, recent reports indicate that under stress conditions, ANG accumulates in the cytoplasmic compartment and modulates the production of tiRNAs, a novel class of small RNAs that contribute to the translational inhibition and recruitment of stress granules (SGs). To date, there is still limited and controversial experimental evidence relating to a hypothetical role of ANG in the epidermis, the outermost layer of human skin, which is continually exposed to external stressors. The present study collects compelling evidence that endogenous ANG is able to modify its subcellular localization on HaCaT cells, depending on different cellular stresses. Furthermore, the use of recombinant ANG allowed to determine as this special enzyme is effectively able to counter at various levels the alterations of cellular homeostasis in HaCaT cells, actually opening a new vision on the possible functions that this special enzyme can support also in the stress response of human skin

Targeting Inflammation to Prevent Cardiovascular Disease in Chronic Rheumatic Diseases: Myth or Reality?

Evidence for increased risk of cardiovascular morbidity and mortality in chronic inflammatory rheumatic diseases has accumulated during the last years. Traditional cardiovascular risk factors contribute in part to the excess of cardiovascular risk in these patients and several mechanisms, including precocious acceleration of subclinical atherosclerotic damage, inflammation, and immune system deregulation factors, have been demonstrated to strictly interplay in the induction and progression of atherosclerosis. In this setting, chronic inflammation is a cornerstone of rheumatic disease pathogenesis and exerts also a pivotal role in all stages of atherosclerotic damage. The strict link between inflammation and atherosclerosis suggests that cardiovascular risk may be reduced by rheumatic disease activity control. There are data to suggest that biologic therapies, in particular TNFα antagonists, may improve surrogate markers of cardiovascular disease and reduce CV adverse outcome. Thus, abrogation of inflammation is considered an important outcome for achieving not only control of rheumatic disease, but also reduction of cardiovascular risk. However, the actual effect of anti-rheumatic therapies on atherosclerosis progression and CV outcome in these patients is rather uncertain due to great literature inconsistency. In this paper, we will summarize some of the main mechanisms linking the inflammatory pathogenic background underlying rheumatic diseases and the vascular damage observed in these patients, with a particular emphasis on the pathways targeted by currently available therapies. Moreover, we will analyze current evidence on the potential atheroprotective effects of these treatments on cardiovascular outcome pointing out still unresolved questions

Promoting post-traumatic growth in cancer patients: a randomized controlled trial of guided written disclosure

BackgroundCancer is a life-threatening disease that triggers not only vulnerability to distressing symptoms but also a meaning-making process that may lead to post-traumatic growth. As people often struggle to integrate cancer illness into their meaning system to reach an adaptive meaning, psychological interventions focused on a reappraisal of the illness experience can facilitate this process. This multicenter randomized controlled trial (RCT) was primarily aimed at assessing the efficacy of a writing intervention known as a guided disclosure protocol (GDP), compared to a generic writing intervention, in promoting post-traumatic growth in stage I-III breast and colon cancer patients at the end of their adjuvant chemotherapy.MethodsBetween January 2016 and August 2020 recruitment of eligible subjects took place during follow-up clinical consultations. Assessment occurred at baseline (T0), after the intervention (T1, 3 months from baseline), and at 6 months from baseline (T2). Both interventions consisted of three 20-min writing sessions to be performed once every two weeks. Change in post-traumatic growth was assessed using the Posttraumatic Growth Inventory, meaning with the Constructed Meaning Scale, and psychological distress with the Impact of Event Scale and the Hospital Anxiety and Depression Scale.ResultsIn the five participating centers, 102 eligible patients were randomized and 72 participants completed follow-up evaluation. Most patients were women (79.4%), had breast cancer (68.6%), and stage I (27.5%), or stage II (44.1%) disease. Mean differences did not reach statistical significance for any of the dependent variables. However, an effect of the GDP, although not statistically relevant, was observed after the intervention in terms of enhanced post-traumatic growth and increased distress measured with the Impact of Event Scale.ConclusionThis is the first RCT investigating the efficacy of a GDP in cancer patients having post-traumatic growth as the primary aim. Though GDP is a promising intervention in promoting post-traumatic growth, the lack of statistical significance of our findings may be due to the study being underpowered, hence this trial should be replicated with an adequate sample size, paying attention to supporting recruitment.Clinical trial registration: ClinicalTrials.gov, identifier: 2015/0024360

The assessment of mindfulness skills: the “what” and the “how”

Background: The five facets mindfulness questionnaire-short form (FFMQ-SF) is a new, brief measure for the assessment of mindfulness skills in clinical and nonclinical samples. The construct validity of the FFMQ-SF has not been previously assessed in community samples. Aims: The present study investigated the factor structure of the Italian version of the FFMQ-SF. Method: Structured equation modeling was used to test the fit of three alternative models in a sample of highly educated adults (n = 211). Results: A hierarchical model with a single second-order factor loaded by observing, describing, and acting with awareness (i.e. the mindfulness “what” skills) performed slightly better than both a five-factor model with correlated factors and a hierarchical model with a general second-order factor. The FFMQ-SF scores were significantly higher than those reported in both Dutch depressed patients and Australian undergraduate students for all facets (but nonreactivity for the Australian sample). Conclusions: Data support the multifaceted nature of mindfulness skills. Because of its brevity and simplicity of use, the FFMQ-SF is a promising questionnaire in longitudinal and clinical research. This questionnaire can serve as a guideline to help clinicians assess and monitor mindfulness skills acquisition, strengthening, and generalization, and prioritize mindfulness skills that need immediate attention

Hydraulic characterization of a pervious concrete for deep draining trenches

Reduction in pore water pressure is an useful strategy to improve the stability of slopes. Deep draining trenches can be used for this purpose. For the realization of deep trenches, the usual conventional construction techniques are not adequate and the use of adjacent vertical panels, built by means of the methods well-established for diaphragm walls, is necessary. However, unbonded materials (i.e., gravels) cannot be used, because the excavation of a panel adjacent to one already built will cause instability. For this scope a bonded material such as pervious concrete can be used. It must have high permeability; filtering capacity, in order to prevent internal erosion of the soil in which the trench drain is installed; and sufficient shear strength after a short curing time to avoid the instability of adjacent previously built panels. This paper reports the hydraulic characterization of two mixtures of pervious concrete carried out in the laboratory. Hydraulic conductivity was measured in saturated conditions. Then, the water retention functions of the mixtures were experimentally deduced by investigating different calculation options and their impact on the simulation of seepage processes through an unsaturated soil mass, in which an ideal trench is located

Remarks On The Sources Of Error In The Modelling Of Lunar Geotechnical Structures

Scale modelling should be a very useful strategy for the design of lunar structures. Preventing structural damages in the lunar environment is crucial and scale models are helpful to achieve this aim. The size of these models must be scaled to take into account the different gravitational levels. Since the lunar gravity acceleration is about one-sixth of the terrestrial one, it follows that the models on Earth will be very smaller than the prototype to be realized on the Moon. This strategy will represent an opportunity for engineers working on lunar structure design, provided that the errors, both computational and experimental, related to the change of scale are quantified, allowing reliable extension of the physical scale modelling results to the prototype. In this work, a three-dimensional finite element analysis of walls retaining lunar regolith backfill is described and discussed, in order to provide preliminary results, which can guide a future experimental investigation based on physical scale-modelling. In particular, computational errors related to the scale effects are assessed, with respect to a virtual prototype of the lunar geotechnical structure, and compared with errors from other sources of discrepancy, like the adopted constitutive model, the variability of the geotechnical parameters and the calculation section used in the 3D analysis. The results seem to suggest the soundness of this strategy of modelling and are likely to encourage new research, both numerical and experimental, supporting the structure serviceability assessment

Associations between mindfulness and emotion regulation. The key role of describing and nonreactivity

Although it has been shown that mindfulness and emotion regulation are related, the nature of the relationship and the underlying processes are still not fully understood. The present study explored the relationship between mindfulness and emotion regulation at the facet level using both bivariate correlation analysis and canonical correlation analysis. A total of 211 adults (mean age = 56.4 years, SD = 15.3; 72.0% females) completed the short forms of the Five Facet Mindfulness Questionnaire and the Heidelberg Questionnaire for the Assessment of Emotion Regulation Strategies. Three relationship clusters emerged between mindfulness facets and emotion regulation strategies: (1) a mindful emotion regulation cluster in which describing and nonreactivity were positively related with reappraisal and acceptance; (2) a suppression and nonreactivity cluster in which describing and nonreactivity were negatively and positively associated with both suppression of emotional expression and suppression of emotional experience, respectively; and (3) a negative self-monitoring cluster in which observing and nonjudging were positively and negatively related to rumination, respectively. These results suggest potential pathways through which mindfulness-based interventions might improve emotion regulation

Dimensions of Mindfulness and Their Relations with Psychological Well-Being and Neuroticism

In this study we examined whether differences in the habitual use of mindfulness skills were associated with specific well-being and neuroticism aspects. Two hundred eleven volunteers aged 21–84 years completed measures of mindfulness, neuroticism, psychological well-being (PWB), and subjective well-being (SWB). Describing, observing, and acting with awareness (i.e., the mindfulness “what” skills) were positively correlated with personal growth, purpose in life, and autonomy (i.e., the “core” eudaimonic components of PWB). Nonreactivity and nonjudging (i.e., the mindfulness “how” skills) were negatively associated with neuroticism aspects, such as withdrawal (e.g., depression) and volatility (e.g., anger). Describing and nonreactivity were the only mindfulness skills significantly correlated with the SWB measures. Acting with awareness mediated the effect of both withdrawal and volatility on eudaimonic well-being outcomes. Describing had consistent mediation effects across all well-being measures, but only for the withdrawal aspect. Nonreactivity and nonjudging did not mediated withdrawal when considering eudaimonic well-being as outcomes. Mediation effects for nonjudging and nonreactivity were found between volatility and SWB markers as well as between volatility and self-acceptance, environmental mastery, and positive relations with others (i.e., the “other” eudaimonic PWB components). In sum, the mindfulness “what” skills were important for eudaimonic well-being, especially for internalizing individuals. Authors discuss the usefulness of a facet-level analysis of mindfulness for examining incremental validity of some facets over others in accounting for different well-being outcomes measures. Clinical implications are also discussed