Morphology of the toe flexor muscles in older people with toe deformities

Objective: Despite suggestions that atrophied, or weak toe flexor muscles are associated with the formation of toe deformities, there has been little evidence to support this theory. This study aimed to determine whether the size of the toe flexor muscles differed in older people with and without toe deformities. Methods: Forty-four older adults (>60 years) were recruited for the study. Each participant had their feet assessed for the presence of hallux valgus or lesser toe deformities. Intrinsic and extrinsic toe flexor muscles were imaged with an ultrasound system using a standardised protocol. Assessor blinded muscle thickness and cross-sectional area was measured using Image J software. Results: Participants with lesser toe deformities (n=20) were found to have significantly smaller quadratus plantae (p=0.003), flexor digitorum brevis (p=0.013), abductor halluces (p=0.004) and flexor halluces brevis (p=0.005) muscles than the participants without any toe deformities (n=19). Female participants with hallux valgus (n=10) were found to have significantly smaller abductor hallucis (p=0.048) and flexor halluces brevis (p=0.013) muscles than the female participants without any toe deformities (n=10; p<0.05). Conclusion: This is the first study to use ultrasound to investigate the size of the toe flexor muscles in older people with hallux valgus and lesser toe deformities compared to otherwise healthy older adults. The size of the abductor hallucis and flexor hallucis brevis muscles were decreased in participants with hallux valgus whereas the quadratus plantae, flexor digitorum brevis, abductor hallucis and flexor halluces brevis muscles were smaller in those participants with lesser toe deformities

Adipocyte-hepatocyte crosstalk in cellular models of obesity: Role of soluble factors

Hepatic steatosis is often a consequence of obesity. Adipose tissue is an important endocrine regulator of metabolic homeostasis in the body. In obesity, adipocytes become hypertrophic and develop an inflammatory phenotype, altering the panel of secreted adipokines. Moreover, excess fatty acids are, in part, released by ad-ipocytes and delivered to the liver. These multiple pathways of adipose-liver crosstalk contribute to the devel-opment and progression of liver disease: TNF alpha induces hepatocyte dysfunction, excess of circulating fatty acids promotes hepatic steatosis and inflammation, whilst adipokines mediate and exacerbate liver injury. In this study, we investigated in vitro the effects and mechanisms of the crosstalk between adipocytes and hepatocytes, as a function of the different adipocyte status (mature vs hypertrophic) being mediated by soluble factors. We employed the conditioned medium method to test how mature and hypertrophic adipocytes distinctively affect the liver, leading to metabolic dysfunction. The media collected from adipocytes were characterized by high triglyceride content and led to lipid accumulation and fat-dependent dysfunction in hepatocytes. The present findings seem to suggest that, in addition to triglycerides, other soluble mediators, cytokines, are released by mature and hypertrophic adipocytes and influence the metabolic status of liver cells. Understanding the precise factors involved in the pathogenesis and pathophysiology of NAFLD in obesity will provide important insights into the mechanisms responsible for the metabolic complications of obesity, paving the way for new possible approaches

Beneficial Effects of Carvacrol on In Vitro Models of Metabolically-Associated Liver Steatosis and Endothelial Dysfunction: A Role for Fatty Acids in Interfering with Carvacrol Binding to Serum Albumin

Background: Carvacrol, a plant phenolic monoterpene, is largely employed as food additive and phytochemical. Objective: We aimed to assess the lipid lowering and protective effects of carvacrol in vitro using cellular models of hepatic steatosis and endothelial dysfunction. We also investigated if and how the binding of carvacrol to albumin, the physiological transporter for small compounds in the blood, might be altered by the presence of high levels of fatty acids (FAs). Methods: Hepatic FaO cells treated with exogenous FAs mimic hepatosteatosis; endothelial HECV cells exposed to hydrogen peroxide are a model of endothelial dysfunction. In these models, we measured spectrophotometrically lipid accumulation and release, lipoperoxidation, free radical production, and nitric oxide release before and after treatment with carvacrol. The carvacrol binding to albumin in the presence or absence of high levels of FAs was assessed by absorption and emission spectroscopies. Results: Carvacrol counteracted lipid accumulation and oxidative stress in hepatocytes and protected endothelial cells from oxidative stress and dysfunction. Moreover, high levels of FAs reduced the binding of carvacrol to albumin. Conclusion: The results suggest the good potential of carvacrol in ameliorating dysfunction of hepatic and endothelial cells in vitro. High levels of circulating FAs might compete with carvacrol for binding to albumin thus influencing its transport and bio-distribution

Antitumor Activity of Ethanolic Extract From Thymbra Spicata L. Aerial Parts: Effects On Cell Viability And Proliferation, Apoptosis Induction, STAT3 And Nfkb Signaling

Thyme-like plants including Thymbra spicata L. are widely used as food and folk medicinal remedies in the Mediterranean area. The present study aimed to explore the in vitro antitumor potential of polyphenol-enriched extracts from aerial parts of T. spicata. The ethanolic extract significantly inhibited proliferation of different human tumor cell lines, without significant effects on non-neoplastic cells. A deeper investigation of the molecular mechanism sustaining the in vitro antitumor activity of the extract was carried on the human breast cancer cells MCF-7 in comparison with the normal breast cells MCF-10A. The effects on MCF-7 cells were associated to: (i) production of reactive oxygen species (ROS) and release of nitric oxide; (ii) apoptosis induction; (iii) reduction in STAT3 and NF-kB phosphorylation. The ethanolic extract from T. spicata leaves might represent a novel therapeutic tool in combination with conventional chemotherapy to reduce the adverse side effects and drug resistance

Long-term Outcome of Children Born to Women with Autoimmune Rheumatic Diseases: A Multicentre, Nationwide Study on 299 Randomly Selected Individuals

The concern about the offspring's health is one of the reasons for a reduced family size of women with rheumatic diseases (RD). Increased risk of autoimmune diseases (AD) and neurodevelopmental disorders (ND) has been reported in children born to patients with RD. Within a nationwide survey about reproductive issues of women with RD, we aimed at exploring the long-term outcome of their children. By surveying 398 patients who received their diagnosis of RD during childbearing age (before the age of 45), information about the offspring were obtained from 230 women who declared to have had children. A total of 148 (64.3%) patients were affected by connective tissue diseases (CTD) and 82 (35.7%) by chronic arthritis. Data on 299 children (156 males, 52.1%; mean age at the time of interview 17.1\ub19.7years) were collected. Twelve children (4.0%), who were born to patients with CTD in 75% of the cases, were affected by AD (8 cases of celiac disease). Eleven children had a certified diagnosis of ND (3.6%; 6 cases of learning disabilities); 9 of them were born to mothers with CTD (5 after maternal diagnosis). No association was found between ND and prenatal exposure to either maternal autoantibodies or anti-rheumatic drugs. Absolute numbers of offspring affected by AD and ND were low in a multicentre cohort of Italian women with RD. This information can be helpful for the counselling about reproductive issues, as the health outcomes of the offspring might not be an issue which discourage women with RD from having children

Long-Term Retention Rate of Tofacitinib in Rheumatoid Arthritis: An Italian Multicenter Retrospective Cohort Study

Background: Tofacitinib (TOFA) was the first Janus kinase inhibitor (JAKi) to be approved for the treatment of rheumatoid arthritis (RA). However, data on the retention rate of TOFA therapy are still far from definitive. Objective: The goal of this study is to add new real-world data on the TOFA retention rate in a cohort of RA patients followed for a long period of time. Methods: A multicenter retrospective study of RA subjects treated with TOFA as monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) was conducted in 23 Italian tertiary rheumatology centers. The study considered a treatment period of up to 48 months for all included patients. The TOFA retention rate was assessed with the Kaplan–Meier method. Hazard ratios (HRs) for TOFA discontinuation were obtained using Cox regression analysis. Results: We enrolled a total of 213 patients. Data analysis revealed that the TOFA retention rate was 86.5% (95% CI: 81.8–91.5%) at month 12, 78.8% (95% CI: 78.8–85.2%) at month 24, 63.8% (95% CI: 55.1–73.8%) at month 36, and 59.9% (95% CI: 55.1–73.8%) at month 48 after starting treatment. None of the factors analyzed, including the number of previous treatments received, disease activity or duration, presence of rheumatoid factor and/or anti-citrullinated protein antibody, and presence of comorbidities, were predictive of the TOFA retention rate. Safety data were comparable to those reported in the registration studies. Conclusions: TOFA demonstrated a long retention rate in RA in a real-world setting. This result, together with the safety data obtained, underscores that TOFA is a viable alternative for patients who have failed treatment with csDMARD and/or biologic DMARDs (bDMARDs). Further large, long-term observational studies are urgently needed to confirm these results

Development and First Validation of a Disease Activity Score for Gout

none51OBJECTIVE: To develop a new composite disease activity score for gout and provide its first validation. METHODS: Disease activity has been defined as the ongoing presence of urate deposits that lead to acute arthritis and joint damage. Every measure for each Outcome Measures in Rheumatology core domain was considered. A 3-step approach (factor analysis, linear discriminant analysis, and linear regression) was applied to derive the Gout Activity Score (GAS). Decision to change treatment or 6-month flare count were used as the surrogate criteria of high disease activity. Baseline and 12-month followup data of 446 patients included in the Kick-Off of the Italian Network for Gout cohort were used. Construct- and criterion-related validity were tested. External validation on an independent sample is reported. RESULTS: Factor analysis identified 5 factors: patient-reported outcomes, joint examination, flares, tophi, and serum uric acid (sUA). Discriminant function analysis resulted in a correct classification of 79%. Linear regression analysis identified a first candidate GAS including 12-month flare count, sUA, visual analog scale (VAS) of pain, VAS global activity assessment, swollen and tender joint counts, and a cumulative measure of tophi. Alternative scores were also developed. The developed GAS demonstrated a good correlation with functional disability (criterion validity) and discrimination between patient- and physician-reported measures of active disease (construct validity). The results were reproduced in the external sample. CONCLUSION: This study developed and validated a composite measure of disease activity in gout. Further testing is required to confirm its generalizability, responsiveness, and usefulness in assisting with clinical decisions.noneScirè, Carlo A; Carrara, Greta; Viroli, Cinzia; Cimmino, Marco A.; Taylor, William J.; Manara, Maria; Govoni, Marcello; Salaffi, Fausto; Punzi, Leonardo; Montecucco, Carlomaurizio; Matucci-Cerinic, Marco; Minisola, Giovanni; Ariani, Alarico; Galossi, Alessandra; Lauriti, Ciro; Fracassi, Elena; Idolazzi, Luca; Bardelli, Marco; Selvi, Enrico; Tirri, Enrico; Furini, Federica; Inverardi, Flora; Calabrò, Andrea; Porta, Francesco; Bittelli, Raffaele; Venturino, Francesco; Capsoni, Franco; Prevete, Immacolata; Sebastiani, Giandomenico; Selmi, Carlo; Fabbriciani, Gianluigi; D'Avola, Giovanni; Botticella, Giulia; Serale, Francesca; Seminara, Giulia; D'Alessandro, Giuseppe; Santo, Leonardo; Longato, Lorena; Zaccara, Eleonora; Sinigaglia, Luigi; Atteritano, Marco; Broggini, Marco; Caprioli, Marta; Favero, Marta; Sallì, Salvatore; Scarati, Marco; Parisi, Simone; Malavolta, Nazzarena; Corvaglia, Stefania; Scarpato, Salvatore; Veneto, VittorioScirè, Carlo A; Carrara, Greta; Viroli, Cinzia; Cimmino, Marco A.; Taylor, William J.; Manara, Maria; Govoni, Marcello; Salaffi, Fausto; Punzi, Leonardo; Montecucco, Carlomaurizio; Matucci Cerinic, Marco; Minisola, Giovanni; Ariani, Alarico; Galossi, Alessandra; Lauriti, Ciro; Fracassi, Elena; Idolazzi, Luca; Bardelli, Marco; Selvi, Enrico; Tirri, Enrico; Furini, Federica; Inverardi, Flora; Calabrò, Andrea; Porta, Francesco; Bittelli, Raffaele; Venturino, Francesco; Capsoni, Franco; Prevete, Immacolata; Sebastiani, Giandomenico; Selmi, Carlo; Fabbriciani, Gianluigi; D'Avola, Giovanni; Botticella, Giulia; Serale, Francesca; Seminara, Giulia; D'Alessandro, Giuseppe; Santo, Leonardo; Longato, Lorena; Zaccara, Eleonora; Sinigaglia, Luigi; Atteritano, Marco; Broggini, Marco; Caprioli, Marta; Favero, Marta; Sallì, Salvatore; Scarati, Marco; Parisi, Simone; Malavolta, Nazzarena; Corvaglia, Stefania; Scarpato, Salvatore; Veneto, Vittori