Transcriptional, epigenetic and pharmacological control of JAK/STAT pathway in NK cells

Differentiation of Natural Killer (NK) cells is a stepwise process having its origin in the bone marrow and proceeding in the periphery, where these cells follow organ specific trajectories. Several soluble factors and cytokines regulate the distinct stages of NK cell differentiation, and ultimately, their functional properties. Cytokines activating the Janus kinases (JAKs) and members of the signal transducer and activator of transcription (STAT) pathway control distinct aspects of NK cell biology, ranging from development, terminal differentiation, activation, and generation of cells with adaptive properties. Here, we discuss how the recent advances of next generation sequencing (NGS) technology have led to unravel novel molecular aspects of gene regulation, with the aim to provide genomic views of how STATs regulate transcriptional and epigenetic features of NK cells during the different functional stages

S.11.1 Influence of digital ulcer healing on disability and daily activity limitations in SSc

Objective. We previously showed that DU significantly increased global and hand disability with a significant impact on activities of daily living (ADLs) and work disability. This study aims to evaluate the impact of digital ulcer (DU) healing on disability and daily activity limitations in SSc. Methods. From January 2008 and June 2009, we prospectively evaluated 189 SSc patients for DU history, disability, employment and occupational status during meetings of the French SSc Patient Association (n = 86, 45.5%) or during hospitalization (n = 103, 54.5%)1. Among the 60 patients with at least one active DU at baseline (M0), 40 patients were followed longitudinally over 6 (3) months. These patients were evaluated for DU history, global and hand disability, health-related quality of life (HRQoL), daily activity limitation and employment status. Results. The median (IQR) age was 57.5 (43.5-68) years and the median (IQR) disease duration was 8.3 (3-16.5) years. Twenty-two (55%) patients had diffuse SSc and 34 (85%) were females. At baseline, a mean of 2.9 (2.8) DU per patient was reported. Thirty-three (82.5%) patients had ischaemic DU, 7 (17.5%) patients had >1 DU associated with calcinosis and 13 (32.5%) patients had mechanical DU. Thirteen (32.5%) patients had >4 DU at baseline. Among the 40 patients, 16 (40%) patients showed complete ulcer healing. In these patients with DU, the presence of calcinosis was associated with a lower probability of healing (P = 0.03). Comparison between healed and no-healed DU patients showed an improvement of hand disability provided by an improvement of the Cochin Hand Function score (P = 0.05)) and a trend towards HAQ domain dressing and grooming (P = 0.06) between M0 and M6 (3) visit in healed patients but not in no-healed patients. Concerning HRQoL, there were no difference for Mental and Physical component Scores of SF-36 but significant improvement of Bodily Pain score (P = 0.04) and Physical Role score (P = 0.05) between M0 and M6 (3) visit in patients with healed DU. The absence of healing was associated with significantly decreased work productivity (P = 0.05), whereas the performance in ADL was not significantly decreased (P = 0.15). Patients who were on sick-leave and who received some help for household tasks at the time of active DU were more likely to heal. Conclusion. For the first time, we provide prospective data with evidence that DU healing is associated with an improvement in hand function. Sick leave was associated with better healing of D

Clinical and ultrasonography assessment of peripheral enthesitis in ankylosing spondylitis

Objective. The aim of this study was to compare clinical examination with power Doppler US (PDUS) in the detection of entheseal abnormalities in patients with AS. Methods. Thirty-six AS patients underwent clinical and PDUS examination of the following bilateral entheseal sites: common extensor tendon at its insertion at the lateral humeral epicondyle; gluteus tendons at their insertion at the greater trochanter; quadriceps tendon at its insertion at the superior pole of the patella; patellar tendon at its proximal insertion at the inferior pole of the patella; patellar tendon at its distal insertion at the tibial tuberosity; Achilles tendon at its insertion at the calcaneus; and plantar aponeuroses at its insertion at the calcaneus. Results. Clinical and PDUS examination revealed at least one abnormal enthesis in 23 (63.9%) and 35 (97.2%) AS patients, respectively. Furthermore, of 432 entheses examined in our 36 AS patients, 64 (14.8%) were considered abnormal by clinical examination and 192 (44.4%) by PDUS. US abnormalities most commonly found were enthesophytes (31.7%), calcifications (33.7%), thickening (29.8%) and hypoechogenicity (26.6%). We found erosions and PD signals in 9.7 and 6% of examined entheseal sites, respectively. The evidence of entheseal abnormalities by clinical examination has a poor likelihood ratio (LR) for the presence of US abnormalities with vascularization (LR = 1.61), without vascularization (LR = 1.24) or erosions (LR = 1.51) at all sites. Conclusions. PDUS permits detection of structural and inflammatory abnormalities of the enthesis in AS and may complement the physical examination in order to better evaluate enthesitis

The conservative treatment of xanthoma of the Achilles tendon in patients affected with type IIA hypercholesterolemia.

Treatment of xanthoma of the Achilles tendon has up until the present been based on partial or total surgical resection of the affected tendon. Because of the different results of surgical treatment our study was aimed at using clinical and ultrasound data to reveal the effectiveness of hypocholesteremic medical therapy in 39 cases of tendinous xanthoma

Finasteride, 1 mg daily administration on male androgenetic alopecia in different age groups: 10-year follow-up

Finasteride 1 mg is indicated for the treatment of men with androgenetic alopecia (AGA). However, more than 5 years efficacy and safety has not been previously reported. To assess the efficacy over 10 years in different age groups of men with AGA. 118 men, between 20 and 61 years, with AGA receiving finasteride (1 mg/day), were enrolled in this uncontrolled study. Efficacy evaluation was assessed with standardized global photographs at T0, T1, T2, T5, T10. Statistical analysis was made using frequency tables and evaluating the chi-square index with its p-value. Better improvements are observed in patients older than 30 years (42.8% aged between 20 and 30 years did not improve also after 10 years) or with higher AGA grades (58.9% for AGA grade IV and 45.4% for AGA grade V had the first improvement just after 1 year). In 21% of cases, the treatment continuation beyond 5 years provided better results. Side effects were referred by 6% of the patients; nevertheless, some of them went on with treatment because of the great results. In our opinion, the result after the first year can help in predicting the effectiveness of the treatment. Its efficacy was not reduced as time goes on; in fact, a big proportion of subjects unchanged after 1 year, improved later on, maintaining a positive trend

Assessment of subclinical atherosclerosis in ankylosing spondylitis: correlations with disease activity indices

The aim of the study was to evaluate atherosclerosis in ankylosing spondylitis (AS) through the assessment of morphological and functional measures of subclinical atherosclerosis. Twenty patients [M/F=12/8, age (median/range) 43.5/28-69 years; disease duration (median/range) 9.7/1-36) years] with AS classified according to modified New York criteria and twenty age and sex related healthy controls with negative past medical history for cardiovascular events were enrolled in the study. In all patients and controls, the intima-media thickness (IMT) of common carotid artery, carotid bulb and internal carotid artery, and the flow-mediated dilatation (FMD) of non-dominant arm brachial artery were determined, using a sonographic probe Esaote GPX (Genoa, Italy). Furthermore, we assess the main disease activity and disability indices [bath ankylosing spondylitis disease activity index, ankylosing spondylitis disease activity score-eritrosedimentation rate (ASDAS-ESR), ASDAS-C-reactive protein (CRP), bath ankylosing spondylitis metrology index, bath ankylosing spondylitis functional index) and acute phase reactants. Plasmatic values of total cholesterol, low-density lipoprotein, high-density lipoprotein, triglyceride and homocysteine were carried out in all twenty patients. IMT at carotid bulb was significant higher in patients than in controls (0.67 mm <em>vs</em> 0.54 mm; P=0.03). FMD did not statistically differ between patients and controls (12.5% <em>vs</em> 15%; P&gt;0.05). We found a correlation between IMT at carotid bulb and ESR (rho 0.43; P=0.04). No correlation was found between FMD and disease activity and disability indices. This study showed that in AS patients, without risk factors for cardiovascular disease, carotid bulb IMT, morphological index of subclinical atherosclerosis, is higher than in controls

Changes, functional disorders, and diseases in the gastrointestinal tract of elderly Cambios, dolencias funcionales y enfermedades en el sistema gastrointestinal en personas mayores

This article describes changes in the basic digestive functions (motility, secretion, intraluminal digestion, absorption) that occur during aging. Elderly individuals frequently have oropharyngeal muscle dysmotility and altered swallowing of food. Reductions in esophageal peristalsis and lower esophageal sphincter (LES) pressures are also more common in the aged and may cause gastroesophageal reflux. Gastric motility and emptying and small bowel motility are generally normal in elderly subjects, although delayed motility and gastric emptying have been reported in some cases. The propulsive motility of the colon is also decreased, and this alteration is associated with neurological and endocrine-paracrine changes in the colonic wall. Decreased gastric secretions (acid, pepsin) and impairment of the mucous-bicarbonate barrier are frequently described in the elderly and may lead to gastric ulcer. Exocrine pancreatic secretion is often decreased, as is the bile salt content of bile. These changes represent the underlying mechanisms of symptomatic gastrointestinal dysfunctions in the elderly, such as dysphagia, gastroesophageal reflux disease, primary dyspepsia, irritable bowel syndrome, primary constipation, maldigestion, and reduced absorption of nutrients. Therapeutic management of these conditions is also described. The authors also review the gastrointestinal diseases that are more common in the elderly, such as atrophic gastritis, gastric ulcer, colon diverticulosis, malignant tumors, gallstones, chronic hepatitis, liver cirrhosis, Hepato Cellular Carcinoma (HCC), and chronic pancreatitis.Este artículo describe los cambios en las funciones digestivas básicas (motilidad, secreción, digestión intraluminal, absorción) que ocurren en el envejecimiento. Los individuos ancianos a menudo presentan una dismotilidad de la musculatura orofaríngea y una alteración de la deglución de los alimentos. Las reducciones en el peristaltismo esofágico y de las presiones del esfínter esofágico inferior (EEI) también son más frecuentes en las personas mayores y pueden causar un reflujo gastroesofágico. La motilidad y el vaciamiento gástricos así como la motilidad intestinal son, por lo general, normales en los individuos ancianos, si bien se han notificado en algunos casos una motilidad y vaciamiento gástricos retardados. La motilidad propulsora del colon también está disminuida y esta alteración se asocia con cambios neurológicos y endocrinos-paracrinos de la pared colónica. En el anciano se describen frecuentemente disminución de las secreciones gástricas (ácido, pepsina) y alteración de la barrera mucosa-bicarbonato, lo cual puede favorecer la úlcera gástrica. A menudo la secreción pancreática exocrina está disminuida, así como el contenido en sales biliares de la bilis. Estos cambios representan mecanismos subyacentes de las disfunciones gastrointestinales sintomáticas del anciano tales como disfagia, enfermedad por reflujo gastroesofágico, dispepsia primaria, síndrome del intestino irritable, estreñimiento primario, maladigestión y disminución de la absorción de nutrientes. También se describe el manejo terapéutico de estos trastornos. Los autores también revisan las enfermedades gastrointestinales que son más frecuentes en el anciano, tales como las gastritis atrófica, la úlcera gástrica, la diverticulosis colónica, los tumores malignos, los cálculos biliares, la hepatitis crónica, la cirrosis hepática, el carcinoma hepatocelular (CHC) y la pancreatitis crónica

Intima-media thickness in patients with psoriatic arthritis : a case-control study

Fil: Perrotta, F. M. University of Rome. Dipartimento di Medicina Interna e Specialità Mediche; ItaliaFil: Scarno, A. University of Rome. Dipartimento di Medicina Interna e Specialità Mediche; ItaliaFil: Carboni, A. University of Rome. Dipartimento di Medicina Interna e Specialità Mediche; ItaliaFil: Cardini, F. University of Rome. Dipartimento di Medicina Interna e Specialità Mediche; ItaliaFil: Montepaone, M. University of Rome. Dipartimento di Medicina Interna e Specialità Mediche; ItaliaFil: Lubrano, E. Università del Molise. Dipartimento di Medicina e di Scienze per la Salute; ItaliaFil: Spadaro, A. University of Rome. Dipartimento di Medicina Interna e Specialità Mediche; ItaliaAim of the study was to evaluate atherosclerosis in Psoriatic Arthritis (PsA) by assessing the morphological index of subclinical atherosclerosis in a cohort of Italian patients

Homocysteine plasmatic status in patients with psoriasis

[No abstract available