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Abstract: Pregnancy is a sensitive period when women experience major hormonal and psychological changes. A high prevalence of the symptoms of depression and manifested major depression rates have been reported during this period, leading to negative outcomes both for mothers and the offspring. Despite its prevalence, the aetiology of depression is not yet fully understood. Nonetheless, alterations in cortisol levels have been proposed as a reliable biomarker to identify pregnant women at risk of perinatal depression. Hair cortisol has recently been extensively used in bio-psychological studies as a suitable non-invasive biomarker for several neuropsychiatric disorders. Various studies have published evidence regarding the relationship between cortisol fluctuations during the perinatal period, measured both in hair and in other substrates, and the onset of perinatal symptoms of depression. This current review provides an overview of cortisol level changes measured in women’s hair during pregnancy or the postpartum period and its association with perinatal symptoms of depression. Further studies, including repetitive measurement of both hair cortisol and depression throughout the prenatal period, must be performed to clarify the relationship between cortisol levels and perinatal symptoms of depression.

Objectives To investigate the association between patient–physician discordance in the assessment of disease activity and residual US synovitis/tenosynovitis in a cohort of patients with RA in clinical remission. Methods A post hoc analysis of the STARTER study, promoted by the Musculoskeletal-US (MSUS) Study Group of the Italian Society for Rheumatology, was performed using data from 361 consecutive patients with RA in clinical remission. The global assessment of disease activity by each patient (PGA) and evaluator/physician (EGA) was recorded on a 100-mm visual analogue scale. The PGA-EGA discordance was classified as positive (PGA>EGA) or negative (PGA Results The mean (s.d.) PGA and EGA scores were 6.1 (7.1) and 8.8 (12) mm, respectively, with a median (IQR) absolute difference of 4 (0–10) mm. Positive and negative discordances were recorded in 39 (10.8%) and 65(18.0%) patients, respectively. The GS-S (adjOR 1.099) and PD-S (adjOR 1.167) scores were associated with positive discordance (P Conclusions Patient–physician discordance is associated with the lack of US remission in patients with RA and may represent a further indication for MSUS.

To evaluate the association between C-reactive protein (CRP) and 10-year risk of cardiovascular (CV) events using the Expanded Cardiovascular Risk Prediction Score for Rheumatoid Arthritis (ERS-RA), based on conventional and RA-specific risk factors but not CRP, in RA patients without previous cardiovascular events.ERS-RA was calculated in 1,251 "Cardiovascular Obesity and Rheumatic Disease Study (CORDIS)" database patients [(age 60.4(9.3) years; 78% female; disease duration, 11.6(8) years; CDAI, 9(9); CRP, 6.8(12) mg/L].The mean (SD) 10-year risk of CV events was 12.9% (10). After adjusting for the use of DMARDs and biologics, CRP concentrations were significantly associated with 10-year risk of CV events (coefficient=0.005 for each 10 mg/L CRP increment; 95%CI 0.000-0.111; p = 0.047). In mediation analysis, the association between CRP and ERS-RA was not explained by disease activity.In a large cohort of RA patients without previous cardiovascular events, a 20 mg/L increase in CRP concentrations was associated with a 1% increase in 10-year risk of CV events. This suggests that actively targeting residual inflammatory risk beyond conventional and RA-specific risk factors might further reduce CV event rates in RA patients.

Background: Providing quality end-of-life care to individuals with advanced dementia is crucial. To date, little attention has been paid to palliative care knowledge and attitudes toward palliative care for people with advanced dementia in Spain Objectives: To investigate the knowledge of and attitudes toward palliative care for advanced dementia among registered nurses and physicians in Spain. Design and Methods: A descriptive, cross-sectional survey design was used. This study included a convenience sample of 402 nurses (n = 290) and physicians (n = 112). Two instruments were administered: demographic characteristics and Spanish version of the Questionnaire of Palliative Care for Advanced Dementia (qPAD-SV). Descriptive statistics and multiple regression were used for data analysis. Results: Overall, the nurses and physicians had moderate mean scores for both knowledge of and attitudes regarding palliative care for advanced dementia. Physicians had a higher level of knowledge (p Conclusion: This study indicates the need to provide nurses and physicians with more education for select groups of professionals who have had limited education and experience in caring for older adults with advanced dementia.

Background: We investigated the relationship between respiratory function measured by spirometry analysis and anthropometric variables (skeletal and fat mass) and nutritional status in the institutionalized elderly, particularly at high-risk for adverse outcomes after respiratory infections and malnutrition. Design: This is a multicenter cross-sectional study with a quantitative approach conducted among older people institutionalized living in nursing homes. Methods: Respiratory function was assessed by measuring the forced vital capacity, forced expiratory volume in the first second, the ratio between FEV1 and FVC (FEV1/FVC), and peak expiratory flow in percentage by means of spirometric analysis (values of the forced expiratory volume measured during the first second of the forced breath (FEV1) and forced vital capacity (FVC)). Nutritional assessment and anthropometry analyses were performed to evaluate under or over nutrition/weight. Results: There was a significant (p70% with FEV1 and FVC150 mg/dl) (OR=5.59). Conclusion: The relationship between a restrictive pattern of respiratory function and fat mass deserves future investigation to manage these parameters as a possible modifiable factor of altered respiratory function in overweight institutionalized older individuals.

Background Perineuronal nets (PNNs) are specialized extracellular matrix structures mainly found around fast-spiking parvalbumin (FS-PV) interneurons. In the adult, their degradation alters FS-PV-driven functions, such as brain plasticity and memory, and altered PNN structures have been found in neurodevelopmental and central nervous system disorders such as Alzheimer’s disease, leading to interest in identifying targets able to modify or participate in PNN metabolism. The serine protease tissue-type plasminogen activator (tPA) plays multifaceted roles in brain pathophysiology. However, its cellular expression profile in the brain remains unclear and a possible role in matrix plasticity through PNN remodeling has never been investigated. Result By combining a GFP reporter approach, immunohistology, electrophysiology, and single-cell RT-PCR, we discovered that cortical FS-PV interneurons are a source of tPA in vivo. We found that mice specifically lacking tPA in FS-PV interneurons display denser PNNs in the somatosensory cortex, suggesting a role for tPA from FS-PV interneurons in PNN remodeling. In vitro analyses in primary cultures of mouse interneurons also showed that tPA converts plasminogen into active plasmin, which in turn, directly degrades aggrecan, a major structural chondroitin sulfate proteoglycan (CSPG) in PNNs. Conclusions We demonstrate that tPA released from FS-PV interneurons in the central nervous system reduces PNN density through CSPG degradation. The discovery of this tPA-dependent PNN remodeling opens interesting insights into the control of brain plasticity.

Background: Speciation analysis is defined as the analytical activities of identifying and/or measuring the quantities of one or more individual chemical species in a sample. The knowledge of elemental species provides more complete information about mobility, bioavailability and the impact of elements on ecological systems or biological organisms. It is no longer sufficient to quantitate the total elemental content of samples to define toxicity or essentiality. Thus speciation analysis is of vital importance and generally offers a better understanding of a specific element. Discussion: Thorough speciation scheme consisting of sampling, sample preparation, species analysis and evaluation were described. Special emphasis is placed on recent speciation analysis approaches including both direct and coupling methods. A current summary of advantages and limitations of the various methods as well as an illustrative method comparison are presented. Certain elements and species of interest are briefly mentioned and practical examples of speciation applications in tobacco and other important economic crops are also discussed. Aim/Conclusion: This review aims to offer comprehensive knowledge about elemental speciation and provide readers with valuable information. Many strategies have been developed for the determination of multiple elemental species in tobacco and other important economic crops. Nevertheless, it is an eternal pursuit to establish speciation methods which can balance accuracy, agility as well as universality.

OBJECTIVES In bio-naïve patients with Psoriatic arthritis (PsA) initiating a Tumour Necrosis Factor inhibitor (TNFi), we aimed to identify baseline predictors of Disease Activity index for PsA in 28 joints (DAPSA28) remission (primary objective) and DAPSA28 moderate response at 6 months, as well as drug retention at 12 months across 13 European registries. METHODS Baseline demographic and clinical characteristics were retrieved and the three outcomes investigated per registry and in pooled data, using logistic regression analyses on multiply imputed data. In the pooled cohort, selected predictors that were either consistently positive or negative across all three outcomes, were defined as common predictors. RESULTS In the pooled cohort (n = 13 369), six-month proportions of remission, moderate response and 12-month drug retention were 25%, 34% and 63% in patients with available data (n = 6,954, n = 5,275 and n = 13 369, respectively). Baseline predictors of remission, moderate response and 12-month drug retention were identified, five common across all three outcomes. Odds ratios (95% confidence interval) for DAPSA28 remission were: age, per year: 0.97 (0.96-0.98); disease duration, years (< 2 years as reference): 2-3 years: 1.20 (0.89-1.60), 4-9 years: 1.42 (1.09-1.84), ≥10 years: 1.66 (1.26-2.20); men vs women: 1.85 (1.54-2.23); CRP >10 vs ≤ 10 mg/l: 1.52 (1.22-1.89) and one mm increase in patient fatigue score: 0.99 (0.98-0.99). CONCLUSION Baseline predictors of remission, response and adherence to TNFi were identified, of which five were common for all three outcomes, indicating that the predictors emerging from our pooled cohort may be considered generalisable from the country- to disease-level.

Contexte et problématique : La société des savoirs constitue un changement de paradigme sur la forme et sur le fond. La science ouverte (SO) est un mouvement mondial qui vise à rendre accessible les produits de la recherche et qui s’accélère avec les potentialités technologiques. Elle s’appuie sur un certain nombre de principes : accès et diffusion large et sans entrave, partage et retombée des produits de la recherche avec la société civile. Contenu et analyse : La SO comporte un accès libre et gratuit aux articles, un accès aux données sources, une analyse des données, la mise à disposition de pré-prints, l’évaluation ouverte. Dans ce contexte, la francophonie, par l’hétérogénéité de ses situations et son homogénéité linguistique, apparaît comme un terrain privilégié d’observation et d’expérimentation. Le Groupe de réflexion et d’information en science ouverte francophone (GRISOF), qui œuvre à l’amélioration de la recherche francophone dans la science médicale et en santé, propose, à partir de ses acquis, quelques clés pratiques pour le chercheur clinicien, le chercheur en biomédical et en santé publique, oriente sa réflexion vers l’évaluation et intensifie sa feuille de route sur la formation. Si l’anglais est la langue prédominante, le traitement automatique du langage (TAL) constitue une opportunité technologique. L’accès libre aux articles donne une opportunité aux travaux en français de mieux se faire connaître, de même que la traduction numérisée permet d’accéder aux articles d’autres langues. Conclusion : L’accès libre aux articles permet d’améliorer la profondeur et l’étendue des connaissances des étudiants. Il constitue une composante essentielle des apprentissages de recherche. Faire participer les étudiants à la publication ouverte de leurs propres travaux est un moyen de les sensibiliser aux pratiques scientifiques ouvertes.

Aim. To assess the efficacy of belimumab in joint and skin manifestations in a nationwide cohort of patients with SLE. Methods. All patients with skin and joint involvement enrolled in the BeRLiSS cohort were considered. Belimumab (intravenous, 10 mg/kg) effectiveness in joint and skin manifestations was assessed by DAS28 and CLASI, respectively. Attainment and predictors of DAS28 remission (

In this prospective observational study, data were collected from 34 rheumatology clinics in Italy in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) who started golimumab (GLM) as a second anti-TNFα drug. The primary objective was to evaluate the effectiveness of GLM after 6 months. Changes in quality of life using the EQ-5D-5L were also assessed. A total of 194 patients aged 53.2 ± 12 years started GLM as a second anti-TNF drug: 39 (20.1%) with RA, 91 (46.9%) with PsA and 64 (32.9%) with axSpA. After 6 months of GLM treatment, 68% of RA patients achieved low disease activity (LDA; DAS28-CRP ≤ 3.2), 31.9% of PsA patients achieved minimal disease activity and 32.5% of axSpA patients achieved LDA (ASDAS-CRP < 2.1). Good/moderate EULAR response was achieved in 61.9% and 73.8% of patients with RA and PsA, respectively, and 16% of axSpA patients achieved a 50% improvement in BASDAI. Across all indications, improvements in disease activity measures and EQ-5D-5L domains were observed over 6 months. The main reasons for GLM interruption were lack/loss of efficacy (7.2%) or adverse events (2%). This study confirms the effectiveness of GLM as a second-line anti-TNF for the treatment of RA, PsA and axSpA in a real-world setting in Italy.

This paper aims to outline the effect of implementing Content and Language Integrated Learning (CLIL) approach in teaching Business English through task-based practice. This includes gap-filling exercises, words in context activities, reading comprehension of ESP texts, translation of specialized terms, and oral presentation rubric. Students were divided into a CLIL and a Non-CLIL group. The aim was to assess students’ speaking skills in terms of acquisition of subject-specific profession-related terms depending on the used approach. The obtained qualitative data revealed higher progress of the students in the CLIL group. The results support the importance of CLIL methodology as a relatively new and more effective approach for an overall improvement of language skills and more specifically for the development of communicative competence in terms of teaching Business English terminology and ESP as an important part of preparation for problem solving in real-life situations enhancing future career opportunities.

Background: Melatonin is a biomarker of the central circadian clock and its chronobiotic actions entraining circadian rhythms to the light-dark cycle are well known. Reduction in melatonin levels and altered circadian rhythms have been associated with a high risk of breast cancer. Melatonin has also shown to display anti-proliferative effects on breast cancer growth and proliferation. Evaluation of melatonin circadian rhythm alterations in patients bearing breast cancer may have interesting prognostic and therapeutic applications. Objective: To review studies evaluating the circadian rhythm of melatonin in breast cancer patients. The effects of surgery and chemotherapy on melatonin secretion were also reviewed. Methods: Electronic databases including PubMed/MEDLINE and Scopus were searched from their inception to May 2020, using the keywords "Melatonin", "Circadian rhythm" and "Breast cancer". Result: Patients with breast cancer maintain a circadian rhythm of melatonin secretion with relatively high levels during the night, and low levels during the day however a reduction of nocturnal melatonin peak and decreased amplitude of melatonin circadian rhythms in these patients have been also reported. Melatonin levels can influence estrogen receptor concentrations in hormone-dependent estrogen-positive breast cancer. Chemotherapy alters melatonin levels, and breast surgery tends to alter melatonin secretion at first day post-operation. Melatonin levels correlate with clinical and psychological symptoms of breast cancer, such as sleep quality and depression severity. Conclusion: Circadian rhythm and the concentration of melatonin in blood are altered in patients with breast cancers and it can modify not only sleep-wake cycle and thus patients’ quality of life but due to melatonin’s antioxidant effects is can modulated the effect of therapies. Due to the heterogonous protocols used to assess melatonin and variable environmental factors during sampling, further studies need to control such variables in order to tailor clinical trial based on melatonin rhythm adjustment and/or supplementation in breast cancer patients.

ObjectiveAxial involvement in patients with psoriatic arthritis (PsA) is a common subset of this condition, but a unanimous definition has yet to be established. It has been defined by using different criteria, ranging from the presence of at least unilateral grade 2 sacroiliitis to those used for ankylosing spondylitis (AS), or simply the presence of inflammatory low back pain (IBP). Our aim was to identify and evaluate the efficacy of therapeutic interventions for treatment of axial disease in PsA.MethodsThis systematic review is an update of the axial PsA (axPsA) domain of the treatment recommendations project by the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA).ResultsThe systematic review of the literature showed that new biologic and targeted synthetic disease-modifying antirheumatic drug classes, namely interleukin (IL)-17A and Janus kinase inhibitors, could be considered for the treatment of axPsA. This would be in addition to previously recommended treatments such as nonsteroidal antiinflammatory drugs, physiotherapy, simple analgesia, and tumor necrosis factor inhibitors. Conflicting evidence still remains regarding the use of IL-12/23 and IL-23 inhibitors.ConclusionFurther studies are needed for a better understanding of the treatment of axPsA, as well as validated outcome measures.

The Mediterranean diet (MD), a well-established quality diet model, and regular physical activity are associated with reducing the appearance or progression of several chronic diseases and reducing morbidity and mortality. However, reduction of these goals, adherence to the MD, and regular physical activity occur at all ages, including older individuals in Mediterranean countries such as Spain, where at least adherence to the MD is culturally rooted. Objective: To evaluate the degree of adherence to the MD and physical activity in older individuals. Methods: The sample comprises 679 older adults aged 60 and over who attended activities in municipal centers for older adults in Valencia. Adherence to the Mediterranean diet, frequency of physical activity, and anthropometric assessment were used. Results: High adherence (score ≥ 9) to MD was observed only in 23.7% of the study sample. Smoking habits or having meals in fast-food restaurants on a weekly basis were significantly (p < 0.05) associated with lower MD adherence. Age, BMI, marital status, and physical activity were not significantly associated with MD adherence. Physical activity was significantly (p < 0.05) lower in individuals who were divorced or widow/ers and in those taking care of their grandchildren several times a week. Conclusions: Adherence to the MD in a big Spanish city is low among older individuals. Socio-family factors seem to play a role. Public health and governmental strategies should reinforce adherence to the MD among older individuals as a gold standard for nutrition.

Background: Chronic wounds are commonly associated with polymicrobial biofilm infections. In the last years, the extensive use of antibiotics has generated several antibiotic-resistant variants. To overcome this issue, alternative natural treatments have been proposed, including the use of microorganisms like probiotics. The aim of this manuscript was to review current literature concerning the application of probiotics for the treatment of infected chronic wounds. Methods: Relevant articles were searched in the Medline database using PubMed and Scholar, using the keywords “probiotics” and “wound” and “injuries”, “probiotics” and “wound” and “ulcer”, “biofilm” and “probiotics” and “wound”, “biofilm” and “ulcer” and “probiotics”, “biofilm” and “ulcer” and “probiotics”, “probiotics” and “wound”. Results: The research initially included 253 articles. After removal of duplicate studies, and selection according to specific inclusion and exclusion criteria, 19 research articles were included and reviewed, accounting for 12 in vitro, 8 in vivo studies and 2 human studies (three articles dealing with animal experiments included also in vitro testing). Most of the published studies about the effects of probiotics for the treatment of infected chronic wounds reported a partial inhibition of microbial growth, biofilm formation and quorum sensing. Discussion: The application of probiotics represents an intriguing option in the treatment of infected chronic wounds with multidrug-resistant bacteria; however, current results are difficult to compare due to the heterogeneity in methodology, laboratory techniques, and applied clinical protocols. Lactobacillus plantarum currently represents the most studied strain, showing a positive application in burns compared to guideline treatments, and an additional mean in chronic wound infections. Conclusions: Although preliminary evidence supports the use of specific strains of probiotics in certain clinical settings such as infected chronic wounds, large, long-term clinical trials are still lacking, and further research is needed.

Pharmacological therapy targeting the HER2 protein is one of the major breakthroughs in the treatment of cancer patients overexpressing HER2 who have increased survival rates. Despite improved survival, it is important to determine the less frequent adverse effects in order to tailor treatments more personalized to the patients’ features. The possible impact of cancer treatments on cognitive functions is huge, and the effects of anti-HER 2 therapies on this issue have not been reviewed and are the objective of this study. Analysis of PubMed, Scopus, Cochrane library and Web of Science databases revealed six studies performed in breast and serous uterine cancer patients analyzing cognitive function under chemotherapy regimens including anti-HER2 drugs. Four of these studies reported small to significant worsening of cognitive function following chemotherapy regimens containing trastuzumab (the most widely used anti-HER2 drug). In neoadjuvant settings, and in breast cancer patients, treatment with the new anti-HER-2 drug trastuzumab emtansine seems to induce less cognitive impairment than therapeutic regimens containing chemotherapy and trastuzumab. Acute administration of trastuzumab induced cognitive impairment in gastric cancer mice models, confirming its ability to alter cognitive function in patients. More studies analyzing the impact of anti-HER2 therapy on cognitive function are necessary at preclinical and clinical levels in order to personalize pharmacological treatment and offer cancer patients a better quality of life.

A systematic review and meta-analysis were conducted, according to the PRISMA methodology, to summarize current evidence on the prevalence and predictors of long-term glucocorticoid (GC) treatment and disease relapses in the real-life management of polymyalgia rheumatica (PMR).Out of 5442 retrieved studies, 21 were eligible for meta-analysis and 24 for qualitative analysis. The pooled proportions of patients still taking GCs at 1, 2, and 5 years were respectively 77% (95%CI 71–83%), 51% (95%CI 41–61%), and 25% (95CI% 15–36%). No significant difference was recorded by distinguishing study cohorts recruited before and after the issue of the international recommendations in 2010. The pooled proportion of patients experiencing at least one relapse at 1 year from treatment initiation was 43% (95%CI 29–56%). Female gender, acute-phase reactants levels, peripheral arthritis, starting GCs dosage, and tapering speed were the most frequently investigated potential predictors of prolonged GC treatment and relapse, but with inconsistent results. Only a few studies and with conflicting results evaluated the potential role of early treatment with methotrexate in reducing the GC exposure and the risk of relapse in PMR.This study showed that a high rate of prolonged GC treatment is still recorded in the management of PMR. The relapse rate, even remarkable, can only partially explain the long-term GC treatment, suggesting that other and not yet identified factors may be involved. Additional research is needed to profile patients with a higher risk of long-term GC treatment and relapse and identify more effective steroid-sparing strategies.Key Points:• High rate of long-term glucocorticoid (GC) treatment is recorded in polymyalgia rheumatica (PMR), being 77%, 51%, and 25% of patients still on GCs after respectively 1, 2, and 5 years.• A pooled relapse rate of 43% at 1 year, even remarkable, can only partially explain the long-term GC treatment in PMR.• Several studies have attempted to identify potential predictors of prolonged treatment with GCs and relapse, but with inconsistent results.• Additional research is needed to profile patients with a higher risk of long-term GC treatment and relapse and identify more effective steroid-sparing strategies.

First-line treatment in postmenopausal women with estrogen- and/or progesterone-positive breast cancer consists of aromatase inhibitors (AROi). The ability of AROi to promote or worsen cognitive function, depressive symptoms, sleep quality and performance in basic activities of daily life as primary and concomitant outcomes in long longitudinal studies in post-menopausal women has been seldom investigated. This study is a cohort trial which aimed to determine if there were differences in cognitive function assessment, depressive symptoms, and sleep quality after 1 year under AROi treatment and to determine the interrelations between these symptoms.A prospective 1-year longitudinal study was performed in a representative sample of tertiary hospital. Women with localized breast cancer newly treated with AROi therapy were evaluated for cognitive functions, depressive symptoms, sleep problems and ability to perform basic activities of the daily life at baseline and after 6 months and 12 months under adjuvant AROi treatment.Analysis of cognitive functions by the Mini-Mental State Examination (MMSE) scores did not show significantly worsening under AROi treatment after 6 months and 12 months of treatment compared to the baseline. Analysis of depressive symptoms with the Geriatric Depression Scale and sleep quality with the Athens Insomnia Scale (AIS) scores showed significant (p 0.05) changes after 6 and 12 months of treatment with AROi, with women describing more depressive symptoms and more sleep disturbances.Our study found impairments in sleep quality and an increase in depressive symptoms, which has important implications for clinicians as they impair quality of life and adherence to treatment.

Background: Physical activity is associated with a higher quality of life (QoL) in older adults, but there is no evidence whether its effects on healthy individuals or individuals with a mild disability performing a medium-intensity exercise program can be assessed. Objective: This randomized controlled trial aims to evaluate whether moderate exercise training can improve QoL, and whether this model is suitable for older adults with mild chronic diseases living in the community. Methods: 120 participants, randomized 1/1 to either perform a physical exercise protocol or to undergo a social program (control group), were recruited in a 12-week randomized controlled trial registered at ClinicalTrials.Gov (NCT03858114). QoL was measured through the Health-Related Quality of Life Survey Short Form - 12 items tool (SF-12). Results: The participants involved in the exercise-training program had a moderate QoL improvement, compared to those involved in cultural activities, who experienced no change or even a worsening of their QoL. However, the between-groups differences did not attain the statistically significant threshold, when globally assessed, F[1, 103] = 2.98, p = .087, nor when the analysis was restricted to the physical (F[1, 103] = 2.78, p = .099) or mental components (F[1, 103] = 3.83, p = .053). Conclusion: Data from this study are not conclusive, although suggestive of possible efficacy. An effort to collect a larger amount of evidence is advisable. Research published only as protocols, not providing final results, might be useful to demonstrate or reject the hypothesis that physical exercise improves QoL in older adults. On a heuristic level, the sum of results that are not conclusive individually might be decisive if meta-analyzed. (Randomized Controlled Blind trial NCT03858114).

We sought to determine whether the increased risk of atrial fibrillation and stroke in rheumatoid arthritis (RA) can be accounted for by an increased prevalence of electrocardiographic markers of atrial myopathy.We retrospectively evaluated clinical and electrocardiographic data of 218 RA patients prospectively enrolled in the Endothelial Dysfunction Evaluation for Coronary Heart Disease Risk Estimation in Rheumatoid Arthritis study (EDRA study ClinicalTrials.gov: NCT02341066) and 109 controls matched by age and gender. The prevalence of interatrial blocks (IAB, partial - pIAB or advanced - aIAB), abnormal P-wave terminal force in lead V1 (aPtfV1) and atrial myopathy (electrocardiographically defined as the presence of 1) aIAB, or 2) pIAB plus abnormal aPtfV1) was assessed in each group. RA patients were followed-up for 5 years for incident atrial fibrillation and cardiovascular events.Barring the prevalence of hyperlipidaemia and obesity, the demographic characteristics and cardiovascular risk profile of RA patients and controls were comparable. All subjects enrolled in the study were free from previous cardiovascular disease and atrial fibrillation. Compared to controls, RA patients had longer P-wave duration (118±12 vs. 112±10 ms, p0.001) and higher prevalence of pIAB (43% vs. 21%, p0.001) and abnormal PtfV1 (27% vs. 10%, p0.001). Accordingly, atrial myopathy was significantly more prevalent (15% vs 4%, p=0.003) in RA patients. In multiple regression, male gender (OR [95% CI] = 3.09 [1.48-6.47], p=0.003) and RA (OR [95% CI] = 4.83 [1.58-14.73], p=0.006) were independently associated with atrial myopathy. Atrial myopathy was not significantly associated with incident atrial fibrillation or cardiovascular events in RA patients after 5 years of follow-up.Electrocardiographic markers of atrial myopathy are independently associated with RA. Further studies with larger sample size and longer follow-up are needed to determine whether the increased prevalence of atrial myopathy contributes to the increased risk of atrial fibrillation and stroke in this group.

Patients with rheumatoid arthritis (RA), a chronic and disabling autoimmune condition that is characterized by articular and extra-articular manifestations and a pro-inflammatory and pro-oxidant state, suffer from premature atherosclerosis and excessive cardiovascular disease burden. A key step in the pathogenesis of atherosclerosis is impaired synthesis of the endogenous messenger nitric oxide (NO) by endothelial cells which, in turn, alters local homeostatic mechanisms and favors vascular damage and plaque deposition. While the exact mechanisms of endothelial dysfunction in RA remain to be established, there is good evidence that RA patients have relatively high circulating concentrations of the methylated arginine asymmetric dimethylarginine (ADMA), a potent endogenous inhibitor of endothelial NO synthase (eNOS). This review discusses the biological and pathophysiological role of ADMA, the interplay between ADMA, inflammation and oxidative stress, and the available evidence on the adverse impact of ADMA on endothelial function and atherosclerosis and potential ADMA-lowering therapies in RA patients.

Objective Our objective was to update the understanding of the development of paradoxical immune-mediated glomerular disorders (IGDs) in patients with rheumatic diseases treated with biologics and targeted synthetic drugs (ts-drugs). Methods A systematic literature review was performed by searching PubMed for articles published between 1 January 2014 and 1 January 2020 reporting on the development of IGD in adult patients with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis or systemic lupus erythematosus (SLE) who were receiving biologics or ts-drugs. IGDs were classified on the basis of clinical, laboratory and histopathological data as (1) glomerulonephritis associated with systemic vasculitis (GNSV), (2) isolated autoimmune renal disorder (IARD) or (3) glomerulonephritis in SLE and in lupus-like syndrome (GNLS). The World Health Organization-Uppsala Monitoring Centre (WHO-UMC) system for standardized case causality assessment was applied to evaluate the causal relationship between IGD and specific drugs. The classification was based on a six-category scale, where the “certain” and “probable” categories were deemed clinically relevant relationships. Results The literature search retrieved 875 articles. Of these, 16 articles reported IGD data, for a total of 25 cases. According to the WHO-UMC assessment, the strength of the causal relationship between IGDs and investigated drugs was higher for anti-tumor necrosis factor-α agents (a clinically relevant relationship was found in four of six cases), abatacept (one of two cases), tocilizumab (two cases), ustekinumab (one case) and tofacitinib (one case) than for rituximab (nine cases), belimumab (three cases) or secukinumab (one case), which showed a weak causal relationship with these paradoxical events. No cases associated with apremilast or baricitinib were found. The retrieved cases were classified as 11 GNLS, seven IARD and seven GNSV. Conclusions Biologics and ts-drugs can cause IGDs. These events are rare, and the causative effect of a specific drug is hard to establish. When a patient is suspected of having an IGD, the drug should be discontinued, and treatment for the new-onset renal disorder should be promptly started.

Childhood obesity is a major public health concern. We wanted to evaluate the effectiveness of a multidisciplinary program based on healthy eating, exercise, cognitive-behavioral therapy, and health education to achieve weight loss and improve metabolic parameters in overweight and obese children. A randomized, controlled clinical trial with long-term follow-up (24 months) was conducted at a community care center in overweight and obese individuals aged 6–12 years. A sample of 108 children was divided into an experimental and a control group receiving a standard care program. The experimental groups received a 12-month interdisciplinary program; the results were evaluated at 4 months, the end of the intervention, and at follow-up 12 months later. Anthropometric and biological marker measurements related to metabolic alterations, dyslipidemia (based on total cholesterol), hyperglycemia, fasting glycaemia, triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol in blood were recorded. The intervention had a significant effect ( p < 0.001) in terms of decreased body mass index, skinfolds, and waist and arm circumferences. These changes were accompanied by biochemical changes underlying an improvement in metabolic parameters, such as a significant reduction in total cholesterol, low-density lipoprotein-cholesterol, triglycerides, and hyperglycemia and a significant increase in high-density lipoprotein-cholesterol. These effects were still significant for markers of excess weight or obesity in the experimental group 12 months after the end of the intervention, suggesting that an enduring change in healthy lifestyles had been maintained period. This interdisciplinary, nurse-led program helped to reduce childhood and adolescent excess weight and obesity and had long-lasting effects.

The year 2020 marked the 95th anniversary of Francesco De Pinedo and Ernesto Campanelli's record-breaking flight of 55,000 km, from Italy to Australia, Japan and back, in a seaplane named Gennariello. Their achievement was lauded worldwide, especially in Australia, where the press reported on it intensively. This paper reconstructs the story of the flight by analysing the Australian press accounts and De Pinedo's diary, to understand how the Australian public perceived the event. It investigates the aviators’ arrival in Perth, Adelaide and Melbourne, where their popularity was greatest and where the local Italian communities enthusiastically welcomed them. The analysis shows that the flight engendered increased public interest and paid dividends in terms of image for the commercial companies involved, while fascism exploited it to display its progress in aviation. The paper concludes by exploring the legacy of the endeavour in modern Italy and Australia, emphasising the differences between the countries.

BACKGROUND: Although targeted biological treatments have transformed the outlook for patients with rheumatoid arthritis, 40% of patients show poor clinical response, which is mechanistically still unexplained. Because more than 50% of patients with rheumatoid arthritis have low or absent CD20 B cells-the target for rituximab-in the main disease tissue (joint synovium), we hypothesised that, in these patients, the IL-6 receptor inhibitor tocilizumab would be more effective. The aim of this trial was to compare the effect of tocilizumab with rituximab in patients with rheumatoid arthritis who had an inadequate response to anti-tumour necrosis factor (TNF) stratified for synovial B-cell status. METHODS: This study was a 48-week, biopsy-driven, multicentre, open-label, phase 4 randomised controlled trial (rituximab vs tocilizumab in anti-TNF inadequate responder patients with rheumatoid arthritis; R4RA) done in 19 centres across five European countries (the UK, Belgium, Italy, Portugal, and Spain). Patients aged 18 years or older who fulfilled the 2010 American College of Rheumatology and European League Against Rheumatism classification criteria for rheumatoid arthritis and were eligible for treatment with rituximab therapy according to UK National Institute for Health and Care Excellence guidelines were eligible for inclusion in the trial. To inform balanced stratification, following a baseline synovial biopsy, patients were classified histologically as B-cell poor or rich. Patients were then randomly assigned (1:1) centrally in block sizes of six and four to receive two 1000 mg rituximab infusions at an interval of 2 weeks (rituximab group) or 8 mg/kg tocilizumab infusions at 4-week intervals (tocilizumab group). To enhance the accuracy of the stratification of B-cell poor and B-cell rich patients, baseline synovial biopsies from all participants were subjected to RNA sequencing and reclassified by B-cell molecular signature. The study was powered to test the superiority of tocilizumab over rituximab in the B-cell poor population at 16 weeks. The primary endpoint was defined as a 50% improvement in Clinical Disease Activity Index (CDAI50%) from baseline. The trial is registered on the ISRCTN database, ISRCTN97443826, and EudraCT, 2012-002535-28. FINDINGS: Between Feb 28, 2013, and Jan 17, 2019, 164 patients were classified histologically and were randomly assigned to the rituximab group (83 [51%]) or the tocilizumab group (81 [49%]). In patients histologically classified as B-cell poor, there was no statistically significant difference in CDAI50% between the rituximab group (17 [45%] of 38 patients) and the tocilizumab group (23 [56%] of 41 patients; difference 11% [95% CI -11 to 33], p=0·31). However, in the synovial biopsies classified as B-cell poor with RNA sequencing the tocilizumab group had a significantly higher response rate compared with the rituximab group for CDAI50% (rituximab group 12 [36%] of 33 patients vs tocilizumab group 20 [63%] of 32 patients; difference 26% [2 to 50], p=0·035). Occurrence of adverse events (rituximab group 76 [70%] of 108 patients vs tocilizumab group 94 [80%] of 117 patients; difference 10% [-1 to 21) and serious adverse events (rituximab group 8 [7%] of 108 vs tocilizumab group 12 [10%] of 117; difference 3% [-5 to 10]) were not significantly different between treatment groups. INTERPRETATION: The results suggest that RNA sequencing-based stratification of rheumatoid arthritis synovial tissue showed stronger associations with clinical responses compared with histopathological classification. Additionally, for patients with low or absent B-cell lineage expression signature in synovial tissue tocilizumab is more effective than rituximab. Replication of the results and validation of the RNA sequencing-based classification in independent cohorts is required before making treatment recommendations for clinical practice. FUNDING: Efficacy and Mechanism Evaluation programme from the UK National Institute for Health Research. ispartof: LANCET vol:397 issue:10271 pages:305-317 ispartof: location:England status: published

Contexte et problématique : Le concept de responsabilité sociale en santé (RSS) prend une importance majeure au moment où les systèmes de santé, comme la société en général, vivent un bouleversement inédit sous l’effet d’une pandémie qui remet au centre de nos préoccupations un nécessaire changement de paradigme. Objectif : Cet article offre une courte rétrospective de ce concept en repartant de l’origine et de l’évolution du concept de RS dans l’entreprise, et réinterroge sous l’éclairage des sciences humaines (philosophie, anthropologie, sociologie) la notion de la responsabilité en tant que telle, mais aussi au sein de l’exercice professionnel en santé. Exégèse : Comment intégrer les préoccupations sociales et environnementales dans la pratique médicale au quotidien sans accabler le professionnel de santé du poids d’une responsabilité déjà prégnante ? Plusieurs hypothèses conditionnent ce processus, parmi lesquelles l’instauration d’une pensée systémique, qui rend seule possible une action transformative, un engagement porté sur les valeurs, une co-gestion de l’ensemble des acteurs de santé avec les parties prenantes. Ces hypothèses dessinent les contours d’une définition élargie de la RSS.

ObjectiveTo assess the potential association between TNF-inhibitors and MOGADBackgroundThe association of tumor necrosis factor-a (TNF)-inhibitors with MS has previously been suggested, whereas little is known about MOG-IgG-associated disease (MOGAD) in the context of these drugs. We recently encountered two patients who developed MOGAD while receiving TNF-inhibitors, prompting a search for similar cases in the literature and clinical practice.Design/MethodsThe two cases were seen at Mayo Clinic, Rochester (bilateral optic neuritis) and the University-Hospital of Sassari (brainstem syndrome). Three additional cases of MOGAD presenting during treatment with TNF-inhibitors were identified through Pubmed. We searched the medical records of 336 MOGAD patients seen at the Mayo Clinic, to assess if they had been treated with TNF-inhibitors.ResultsA total of 5 patients were identified. The median age at MOGAD presentation was 40 years (range, 36-49); 4/5 were male (80%). The median time from TNF-inhibitor initiation to MOGAD presentation was 6.5 years (range, 2-18). Of 4 patients who discontinued the TNF-inhibitor due to MOGAD onset, two subsequently had a MOGAD relapse. While in another patient, neurological symptoms subsided with corticosteroids despite TNF-inhibitor being maintained. The frequency of MOGAD presenting during TNF-inhibitors treatment at Mayo Clinic was 0.3% (1/336 cases).ConclusionsWe found that MOGAD is unlikely to present during treatment with TNF-inhibitors. The outcomes in these patients seemed not to be influenced by TNF-inhibitor treatment duration or discontinuation. These findings suggest the benefit of TNF-inhibitor withdrawal is not obvious, and the choice of discontinuing vs maintaining treatment with TNF-inhibitors should be weighted based on symptoms severity and activity status of the underlying systemic disorder. When withdrawal is considered, immunosuppression with agents potentially effective for both MOGAD and the immune-mediated disease originally managed by the TNF-inhibitor, could serve as dual purpose treatment.

Background This study aimed to investigate the trajectory of damage accrual, associated factors, and impact on health-related quality of life (HR-QoL) in a multicenter cohort of patients with Behçet’s syndrome (BS) over 2 years of follow-up. Methods Patients recruited in the BS Overall Damage Index (BODI) validation study were prospectively monitored for 2 years and assessed for damage accrual, defined as an increase ≥1 in the BODI score, and HR-QoL was evaluated by the SF-36 questionnaire. Logistic and multiple linear regression models were built to determine factors associated with damage accrual and impairment in the different SF-36 domains. Results During follow-up, 36 out of 189 (19.0%) patients had an increase ≥1 in the BODI score with a mean (SD) difference of 1.7 (0.8) (p p p 0.038) were identified as predictors of damage accrual, whereas the use of immunosuppressants showed a protective effect (OR 0.20, 95% CI 0.08–0.54, p Conclusion In BS, organ damage accrues over time, also in long-standing disease, resulting in an impairment of the perceived physical and mental health. Adequate immunosuppressive treatment, preventing disease flares and minimizing exposure to GCs have a crucial role in lowering the risk of damage accrual.

Background: Chronic Pain (CP) is a crucial determinant for disability in older adults. CP amplifies the impact of other common age-related diseases and increases cardiovascular risk. Physical exercise can improve CP. Randomized Controlled Trials (RCTs) with high-intensity exercise in older adults excluded people with Moderate Chronic Illness (MCI) and CP. Objective: This study aimed at evaluating in an RCT whether moderate exercise training can improve chronic pain in a sample of older adults, including people with MCI, and if any modification persists over time. Methods: A sample of 120 older adults was randomly selected for a moderate-intensity exercise program or cultural activities (control group). Chronic pain was assessed at t0, at t12 (end of the trial), and t48 weeks, by means of the Italian version of the SIP-Roland Scale. Results: Seventy-nine participants completed the follow-up (age 72.3±4.7, women 55.3%). At the end of RCT, an improvement in the SIP scale score was found in the exercise group (p=0.035), showing a lower score than the control group; this difference was not maintained at 48 weeks (p=0.235). Conclusion: Our study highlighted that a moderate-intensity exercise intervention reduced chronic pain in older adults, but this effect disappeared at follow-up after 36 weeks from the end of the training program. These findings suggested that such kinds of programs, easily accessible to old people even with MCI, should be implemented and supported over time, thus promoting active aging and preventing CP of age-related diseases. Clinical Trial Registration: Clinical.Trials.gov.NCT03858114

Background and Objectives: Diabetes mellitus is considered a serious public health problem due to its high prevalence and related complications, including gait and posture impairments due to neuropathy and vascular alterations and the subsequent increased risk of falls. The gait of patients with diabetes is characterized by alterations of the main spatiotemporal gait parameters such as gait velocity, cadence, stride time and length, which are also known to worsen with disease course. Wearable sensor systems can be used for gait analysis by providing spatiotemporal parameters and postural control (evaluated from the perspective of body sway), useful for investigating the disease progression. Thanks to their small size and low cost of their components, inertial measurement units (IMUs) are easy to wear and are cheap tools for movement analysis. Materials and Methods: The aim of this study is to review articles published in the last 21 years (from 2000 to 2021) concerning the application of wearable sensors to assess spatiotemporal parameters of gait and body postural alterations in patients with diabetes mellitus. Relevant articles were searched in the Medline database using PubMed, Ovid and Cochrane libraries. Results: One hundred and four articles were initially identified while searching the scientific literature on this topic. Thirteen were selected and analysed in this review. Wearable motion sensors are useful, noninvasive, low-cost, and objective tools for performing gait and posture analysis in diabetic patients. The IMUs can be worn at the lumber levels, tibias or feet, and different spatiotemporal parameters of movement and static posture can be assessed. Conclusions: Future research should focus on standardizing the measurement setup and selecting the most informative spatiotemporal parameters for gait and posture analysis.

OBJECTIVE To compare the effect of achievement and maintenance of Lupus Low Disease Activity State (LLDAS) and clinical remission (CR) in preventing early damage accrual in patients with systemic lupus erythematosus (SLE). METHODS In a monocentric cohort of 116 newly diagnosed SLE patients, LLDAS and CR achievement at 6 months (T1) after treatment initiation and their maintenance over the next 12 months were assessed. Early damage was recorded after 18 months of follow-up (T2) using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index. Univariate and multivariate analyses were performed to evaluate the association of LLDAS and CR with early damage. RESULTS LLDAS was significantly more attained than CR both at T1 (42.2% versus 21.6% of patients; P < 0.001) and T2 (46.6% versus 31.9%; P = 0.022). The overlap rate between persistent LLDAS and persistent CR was 41.7% (n = 15). On multivariate analysis, achievement of CR (odds ratio [OR] 0.07 [95% confidence interval (95% CI) 0.01-0.59], P = 0.015) and LLDAS (OR 0.25 [95% CI 0.06-0.99], P = 0.049) at T1 were independently associated with lower accrual of early damage. Patients who achieved LLDAS (including CR) at T1 and steadily persisted in this condition until T2 developed significantly less damage compared to those who failed to maintain it during the T1-T2 interval (P = 0.003), those who achieved it later than T1 (P < 0.001), or those who had never been in this condition (P < 0.001). CONCLUSION Although CR is recommended as the primary treatment target in SLE, LLDAS represents a valid alternative in the early stage of SLE management. LLDAS and CR maintenance should be targeted to prevent damage.

ObjectiveThe Physician Global Assessment (PGA) is a visual analogue score that reflects the clinician’s judgement of overall SLE disease activity. The aim of this systematic literature review is to describe and analyse the psychometric properties of the PGA.MethodsThis systematic literature review was conducted by two independent reviewers in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. All articles published through 1 July 2019 in PubMed were screened, with no limitation on year of publication, language or patients’ age. Psychometric properties data were analysed according to the OMERACT Filter methodology version 2.1.ResultsThe literature search identified 91 studies. Face validity was reported in all the articles retrieved in which the PGA was used alone or as part of composite indices (Systemic Responder Index, Safety of Estrogen in Lupus Erythematosus National Assessment Flare Index, Lupus Low Disease Activity State, Definitions of Remission in Systemic Lupus Erythematosus criteria). Content validity was reported in 89 studies. Construct validity was demonstrated by a good correlation (r ≥ 0.50) between the PGA with the SLEDAI (12 studies), SLAM (4 studies), LAI, BILAG and ECLAM (2 studies each). Criterion validity was assessed exploring the PGA correlation with quality of life measurements, biomarker levels and treatment changes in 28 studies, while no study has evaluated correlation with damage. A good responsiveness for PGA was shown in eight studies. A high variability in scales was found, causing a wide range of reliability (intraclass correlation coefficient 0.67–0.98).ConclusionPGA is a valid, responsive and feasible instrument, though its reliability was impacted by the scale adopted, suggesting the major need for standardization of its scoring.

Forecasting the thermosphere (the atmosphere's uppermost layer, from about 90 to 800 km altitude) is crucial to space-related applications, from space mission design to re-entry operations, space surveillance and more. Thermospheric dynamics is directly linked to the solar dynamics through the solar UV (ultraviolet) input, which is highly variable, and through the solar wind and plasma fluxes impacting Earth's magnetosphere. The solar input is non-periodic and non-stationary, with long-term modulations from the solar rotation and the solar cycle and impulsive components, due to magnetic storms. Proxies of the solar input exist and may be used to forecast the thermosphere, such as the F10.7 radio flux and the Mg II EUV (extreme-ultraviolet) flux. They relate to physical processes of the solar atmosphere. Other indices, such as the Ap geomagnetic index, connect with Earth's geomagnetic environment. We analyse the proxies' time series comparing them with in situ density data from the ESA (European Space Agency) GOCE (Gravity Field and Steady-State Ocean Circulation Explorer) gravity mission, operational from March 2009 to November 2013, therefore covering the full rising phase of solar cycle 24, exposing the entire dynamic range of the solar input. We use empirical mode decomposition (EMD), an analysis technique appropriate to non-periodic, multi-scale signals. Data are taken at an altitude of 260 km, exceptionally low for a low-Earth-orbit (LEO) satellite, where density variations are the single most important perturbation to satellite dynamics. We show that the synthesized signal from optimally selected combinations of proxy basis functions, notably Mg II for the solar flux and Ap for the plasma component, shows a very good agreement with thermospheric data obtained by GOCE, during periods of low and medium solar activity. In periods of maximum solar activity, density enhancements are also well represented. The Mg II index proves to be, in general, a better proxy than the F10.7 index for modelling the solar flux because of its specific response to the UV spectrum, whose variations have the largest impact over thermospheric density.

Objectives This study aims to investigate the factors associated with early discontinuation (within one year) of etanercept (ETA) in rheumatoid arthritis (RA) patients who began ETA as first biologic disease-modifying antirheumatic drug (bDMARD) and who were entered into the Gruppo Italiano di Studio sulla Early Arthritis (Italian Group for the Study of Early Arthritis; GISEA) registry. Patients and methods This registry-based cohort study included 477 RA patients (95 males, 382 females; median age 53 years; range 18 to 83 years) who began ETA as first bDMARD. Patient demographics, disease features and drugs were re-evaluated after 12 months. Baseline predictors of ETA discontinuation were estimated by univariate and multivariate analyses using Cox regression model. Results Seventy patients (14.7%) discontinued ETA during the first year (for inefficacy in 55.8%, adverse events in 28.6%, and other reasons in 6.5%). Concurrent conventional synthetic DMARDs (csDMARDs) were reported in 54.3% of patients, mainly methotrexate (MTX), while 52.4% of subjects took low doses of glucocorticoids. Patients stopping ETA more frequently showed one or more comorbidities, mainly cardiovascular diseases (28.6% vs. 15.7% in patients stopping and continuing ETA, respectively, p=0.009). The presence of comorbidities and a combination therapy with csDMARDs other than MTX were independent factors associated with early discontinuation of ETA at multivariate Cox analysis. Conclusion Although ETA demonstrated a high persistence in biologic-naive RA patients, about 15% of patients discontinued the treatment within 12 months. The presence of comorbidities and a combination therapy with csDMARDs other than MTX were the main factors for an early withdrawal of the drug.

To explore the emotional experience and the perceived mental health of experienced family caregivers of people with mental disorders.Family caregiving for individuals with mental disorders differs from other health conditions, as it implies a burden, deterioration in physical and mental health, stigma and a perceived lack of support from mental health services.A mixed-method study was undertaken with family caregivers of people diagnosed with mental disorders.A total of 13 experienced family caregivers were included in the study. The qualitative data were classified into two major themes: emotions and perceived mental health. Emotions included five categories: irritability, painful emotions, pressure, emotions orientated towards coping, and positive emotions. The perceived mental health status embraced five categories: anxiety, burden and exhaustion, needing psychological or psychiatric treatment, insomnia and suicidal thoughts. An emotional path could be constructed from their discourses, starting with lack of control or irritation that evolved towards resignation, peace or satisfaction. The quantitative analysis partially replicated the qualitatively reported anxiety, depressive symptoms and insomnia.Past and present emotions related to caregiving described by experienced family caregivers were identified. Their emotional trajectories converged in that negative emotions gave way to emotions towards coping, which in turn were followed by positive emotions. The participants' descriptions about their mental status were partially reflected through objective mental health measurements.More support from mental health services could help caregivers to progress in their emotional trajectory towards coping, and improve their caregiving knowledge and skills. Mental health nurses have a role in patients and caregivers education and in the promotion of caregivers' psychological wellbeing.

Background: The elderly is characterized by a gradual decline in body function, which represents the clinical situation called "frailty". Prefrailty is the intermediate stage between frailty and the robust condition. L-carnitine (LC) plays an important role in energy production from long-chain fatty acids in mitochondria and its serum level is lower in prefrail and frail subjects. Objective: This study aims to evaluate the effect of Acetyl-L-carnitine (ALCAR) in pre frail older patients. Methods: We scheduled 3 months of treatment and then 3 months of follow-up. 92 subjects were selected from May 2009 to July 2017 in a randomized, observational, double-blind, placebo-controlled study. We scheduled 3 months of treatment and then 3 months of follow-up. ALCAR (oral 1.5 g/bis in die - BID) or placebo group. Results: After the treatment, only the treated group displayed a decrease in C reactive protein (CRP) p Conclusions: ALCAR treatment delays the incidence and severity of onset in prefrail subjects of degenerative disorders of the elderly, with improvement in memory and cognitive processes.

Frailty syndrome is associated with poor outcomes, morbidity and premature mortality. We performed a cross-sectional study to evaluate the presence of frailty syndrome based on Fried's frailty phenotype in post-menopausal women with breast cancer. We further analyzed the association between frailty syndrome with geriatric assessments and the association with the concentration of gonadotropins LH and FSH, estrogens, androgens and the aromatase activity index in the blood. We enrolled 47 post-menopausal women with localized breast cancer (mean age 66.8 +/- 1.3 years (range 52-83)) prior to the starting of adjuvant endocrine therapy. Patients were identified as "non-frail" (robust) or "prefrail/frail" if they fulfilled at least one frailty criteria. In order to determine associations among variables and to control for other variables potentially affecting frailty syndrome (age, comorbidity index and previous chemotherapy treatment), we performed a logistic regression analysis. The receiver operating characteristic curve was performed to assess the sensitivity and specificity of the hormonal concentration to discriminate prefrail/frail versus non-frail individuals. Significant positive associations were observed between the severity of frailty syndrome and estrone, FSH and LH concentrations and the aromatase activity index in the blood (p < 0.05). Further research into the role of hormonal biomarkers should be evaluated in follow-up studies in order to recommend their use as suitable biomarkers of frailty syndrome in breast cancer patients.

Additional file 1: Supplementary Figure 1. Flow chart representing the patients’ recruiting process from the BODI validation cohort.

Background: One of the physiological changes that is most closely associated with frailty is the increase in pro-inflammatory cytokines, and IL-6 in particular. Most studies have demonstrated this association using blood samples. We analyzed the relationship between frailty syndrome, individual frailty criteria, and IL-6 levels obtained by saliva tests. Methods: A cross-sectional pilot study was performed among women institutionalized in nursing homes. Frailty was defined as having three or more of the following components: low lean mass, weakness, self-reported exhaustion, low activity level, and slow walking speed; prefrailty was defined as having one or two of those components. Results: There was a significant and positive correlation between the frailty score and salivary IL-6 concentration. Regarding the associations between IL-6 and individual dichotomized frailty criteria, there were significant differences in salivary IL-6 concentration in two frailty criteria: weight loss (p = 0.002) and low physical activity (p = 0.007). Receiver operating characteristic curve analysis showed that IL-6 concentration significantly (p < 0.05) (although moderately) discriminated patients that progressed in the frailty syndrome (the area under the curve value was 0.697 with 95% CI 0.566-0.827). Conclusions: Salivary IL-6 concentration can be used as potential biomarker of frailty syndrome and as a tool to monitor the effects of interventions in frail individuals.

We present new results on the application of semantic- and knowledge-based reasoning techniques to the analysis of cloud deployments. In particular, to the security of Infrastructure as Code configuration files, encoded as description logic knowledge bases. We introduce an action language to model mutating actions; that is, actions that change the structural configuration of a given deployment by adding, modifying, or deleting resources. We mainly focus on two problems: the problem of determining whether the execution of an action, no matter the parameters passed to it, will not cause the violation of some security requirement (static verification), and the problem of finding sequences of actions that would lead the deployment to a state where (un)desirable properties are (not) satisfied (plan existence and plan synthesis). For all these problems, we provide definitions, complexity results, and decision procedures.