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Collective behavior is widely regarded as a hallmark property of living and intelligent systems. Yet, many examples are known of simple physical systems that are not alive, which nonetheless display collective behavior too, prompting simple physical models to often be adopted to explain living collective behaviors. To understand collective behavior as it occurs in living examples, it is important to determine whether or not there exist fundamental differences in how non-living and living systems act collectively, as well as the limits of the intuition that can be built from simpler, physical examples in explaining biological phenomenon. Here, we propose a framework for comparing non-living and living collectives as a continuum based on their information architecture: that is, how information is stored and processed across different degrees of freedom. We review diverse examples of collective phenomena, characterized from an information-theoretic perspective, and offer views on future directions for quantifying living collective behaviors based on their informational structure. [ABSTRACT FROM AUTHOR]

Quorum sensing (QS) is ubiquitous in distributed, multi-agent systems in nature—from bacteria to arthropods to primates—and has been proposed as a useful distributed algorithm in engineered systems—from multi-robot systems to Internet server farms. Achieving QS requires groups to collectively integrate information about their numbers and reach consensus on an action contingent upon those numbers. In nest-site selection tasks that employ QS in ants, sensitivity to encounter rate has been implicated as a mechanism for how individuals sense that quorum has been reached. However, little is known about how individual ants estimate proximity to the critical rate. Ant-inspired QS algorithms proposed by computer scientists either heavily depend on communication between agents or the ability for individual agents to accumulate information over many encounters with others. Both communication and significant memory storage may be beyond the simple capabilities of small-scale robots in large collectives. Alternatively, if cognition was embodied across the group of agents and their physical environment, cognitive abilities could far exceed the abilities of each individual. Toward this end, we propose a novel bio-inspired algorithm for QS on mobile agents within a confined space. Our approach does not require individuals to communicate or count over long sequences of encounters; instead, QS emerges from the random interaction of mobile excitable agents with each other and the physical cavity. We validate theoretical predictions for our algorithm's performance in simulation, and we also show that it has good qualitative agreement with accuracy and response-time data from real ants. More broadly, our algorithm provides a new, concrete example of how ants can serve as conceptual models for hypothetical dynamic networks of mobile neurons. [ABSTRACT FROM AUTHOR]

Prolonged remission (PR), defined as a 5-year consecutive period of no disease activity based on SLEDAI-2K, has been reported to be associated with a lower damage accrual over time in patients with systemic lupus erythematosus (SLE), as the consequence of a lower activity burden. Since disease activity is considered to play a role in the incidence of cardiovascular disease (CVD), we investigated the relationship, if any, between PR and the occurrence of a subsequent first CV event in patients with SLE. Out of 488 patients consecutively admitted to two tertiary Italian centers from November 1, 2000, to December 31, 2016, the 294 patients, who had been followed at least for 5 years, had not experienced any CV event at admission, and had been visited biannually during follow-up, were considered for the present study. The incidence of a first CV in patients who had achieved PR was compared with that registered in those who had not. Moreover, it was compared among PR patients subdivided into three groups: complete remission, clinical off-corticosteroids (offCR), and clinical on-corticosteroids remission (onCR). Kaplan-Meier curves and the log-rank test were used to analyze differences in event-free survival among groups. Cox regression was used to investigate disease and therapeutic features associated with the development of a first CV event. During 9 years median follow-up time, 24 (8.1%) CV events occurred. Out of the 294 patients, 126 (42.8%) had achieved PR. Kaplan-Meier analysis revealed a greater overall CV event-free rate in these patients as compared to both those with a shorter lasting remission and those who had never remitted (log-rank test χ2 = 14.43; p = 0.0001). In addition, CV outcome did not differ among PR patients, irrespectively the type of remission achieved (p > 0.05). At multivariate analysis, hydroxychloroquine therapy and PR resulted to be protective (HR 0.19; HR 0.18), while arterial hypertension and antiphospholipid positivity increased the risk of a first CV event (HR 2.61; HR 2.47). The PR, whichever the subtype, is associated with a better CV outcome and should be considered as a treat-to-target goal in the CV risk management of the lupus patient. [ABSTRACT FROM AUTHOR]

We present the Kilogrid, an open-source virtualization environment and data logging manager for the Kilobot robot, Kilobot for short. The Kilogrid has been designed to extend the sensory-motor abilities of the Kilobot, to simplify the task of collecting data during experiments, and to provide researchers with a tool to fine-control the experimental setup and its parameters. Based on the design of the Kilobot and compatible with existing hardware, the Kilogrid is a modular system composed of a grid of computing nodes, or modules that provides a bidirectional communication channel between the Kilobots and a remote workstation. In this paper, we describe the hardware and software architecture of the Kilogrid system as well as its functioning to accompany its release as a new open hardware tool for the swarm robotics community. We demonstrate the capabilities of the Kilogrid using a 200-module Kilogrid, swarms of up to 100 Kilobots, and four different case studies: exploration and obstacle avoidance, site selection based on multiple gradients, plant watering, and pheromone-based foraging. Through this set of case studies, we show how the Kilogrid allows the experimenter to virtualize sensors and actuators not available to the Kilobot and to automatize the collection of data essential for the analysis of the experiments. [ABSTRACT FROM AUTHOR]

This study aims to investigate pre-clinical esophageal involvement in systemic sclerosis (SSc) by high-resolution impedance manometry (HRiM), its associations with disease features including lung involvement, and its predictivity of esophageal symptoms overtime. Charts of 45 asymptomatic (no heartburn/regurgitation/dysphagia) SSc patients (96% females; mean age 46 years) with at least one follow-up (FU) visit and complete clinical, serological, functional, and radiological assessment, including high-resolution computed tomography (HRCT) of the chest and lung function tests, that had undergone esophageal HRiM were retrospectively evaluated. Esophagogastric junction-contractile integral (EGJ-CI) and esophageal body motility, as evaluated by mean distal contractile integral (DCI), were assessed. SSc patients had a normal esophageal motility in 7/45 cases, a defective EGJ-CI in 28, an ineffective esophageal motility (IEM) in 17, and aperistalsis in 12. Defective EGJ-CI was associated with IEM/aperistalsis in 20 cases, while 9 patients had isolated IEM. Defective EGJ-CI and/or IEM/aperistalsis were associated with a diffusing lung capacity for CO < 80% of predicted value (all p < 0.05), while defective EGJ-CI was also associated with interstitial lung disease on HRCT (p = 0.03). Prevalence of any HRiM abnormality was higher in anti-centromere antibody negative patients (all p < 0.05). IEM/aperistalsis independently increased the risk of esophageal symptoms by 2.3-fold (95% CI 1.1-5.7) and was associated with their higher cumulative incidence with respect to patients with other HRiM patterns at FU (χ2 = 4.63; p = 0.03). SSc patients asymptomatic for esophageal involvement can have HRiM abnormalities in up to 84% of cases. A baseline-impaired motility is a risk factor for symptomatic esophageal disease. [ABSTRACT FROM AUTHOR]

Undifferentiated connective tissue disease at risk for systemic sclerosis (UCTD-risk-SSc), otherwise referred to as very early-early SSc, is a condition characterized by Raynaud’s phenomenon with serum SSc marker autoantibodies and/or typical capillaroscopic findings and unsatisfying classification criteria for the disease. The aim of the present study was to assess the prevalence of right (RV) or left ventricular (LV) systolic and/or diastolic dysfunction by standard echocardiography and tissue Doppler imaging (TDI). Thirty patients with UCTD-risk-SSc (28 female, mean age 47 ± 13 years, range 21-70) and 30 age- and sex-matched controls underwent cardiac assessment by standard echocardiography and TDI. UCTD-risk-SSc patients and controls did not show any difference at standard echocardiography. Despite results falling within the respective normal ranges, TDI pointed out a mild impairment of LV and RV diastolic (Em 15 ± 4 vs. 19 ± 5, p = 0.0004; E/Em 6.1 ± 1.7 vs. 4.8 ± 1.2, p = 0.001; Et 14 ± 3 vs. 16 ± 2, p = 0.02; Et/At 0.9 ± 0.4 vs. 1.3 ± 0.3, p = 0.002; E/Et 3.5 ± 1.2 vs. 4.2 ± 0.9, p = 0.02) and systolic function (Sm 13 ± 3 vs. 15 ± 2 cm/s, p < 0.0003; St 14 ± 2 vs. 16 ± 3 cm/s, p < 0.0001) and increased estimated pulmonary artery wedge pressure (9 ± 2 vs. 8 ± 1, p = 0.001) in UCTD-risk-SSc patients as compared to controls. Notably, a statistically significant difference also emerged in the prevalence of TDI detected E′/A′t, (71% of UCTD-risk-SSc patients vs. 19% of controls; p < 0.0001). Our study shows that UCTD-risk-SSc patients show a previously unrecognized, mild biventricular systolic and diastolic dysfunction as compared to controls. The pathophysiologic meaning as well the predictive value of developing overt SSc await to be elucidated. [ABSTRACT FROM AUTHOR]

The aim of the study was to evaluate CXCL4 levels in undifferentiated connective tissue disease at risk for SSc (UCTD-SSc-risk) and confirm its increase and investigate its prognostic value. Serum CXCL4 levels were measured in 45 patients and 24 controls. CXCL4 was significantly higher in UCTD-SSc-risk patients than in controls. It resulted higher in patients with a shorter disease duration and in those lacking capillaroscopic alterations. We confirm that CXCL4 levels are increased in UCTD-risk-SSc patients. Further studies are needed to investigate the role of CXCL4 assessment in UCTD-risk-SSc. [ABSTRACT FROM AUTHOR]

Previous studies of the occurrence of interstitial lung disease (ILD) in undifferentiated connective tissue diseases (UCTD) were conducted in patients admitted to Respiratory Medicine Units. The aim of the present prospective study was to investigate lung involvement in UCTD patients admitted to a Rheumatology Unit. Eighty-one consecutive UCTD patients were enrolled in the study. Each patient underwent history and physical examination, routine laboratory investigations, antinuclear antibody (ANA) profiling, B-mode echocardiography, and lung function study according to previously reported methods. Lung high resolution computed tomography (HRCT) was performed in patients who provided informed consent. Six patients (7.4%) had a history of grade II dyspnea. Three of them had a DLCO ranging from 42 to 55% of the predicted value; and a HRCT-documented ILD with a non-specific interstitial pneumonia (NSIP) pattern. Symptoms in the other three patients were due to cardiac disease. None of the 75 asymptomatic patients, had relevant findings at physical examination, 26/75 had a DLCO <80% (<70% in 10 cases). Of these, 3 of the 30 patients who underwent lung HRCT were affected by NSIP-ILD. Six of the 81 enrolled were affected by ILD, which was symptomatic in three patients. A higher percentage of patients had a reduced DLCO. The latter finding may reflect a preradiographic ILD or a preechocardiographic pulmonary vascular disease. [ABSTRACT FROM AUTHOR]

In this paper, we show that non-uniform distributions in swarms of agents have an impact on the scalability of collective decision-making. In particular, we highlight the relevance of noise-induced bistability in very sparse swarm systems and the failure of these systems to scale. Our work is based on three decision models. In the first model, each agent can change its decision after being recruited by a nearby agent. The second model captures the dynamics of dense swarms controlled by the majority rule (i.e., agents switch their opinion to comply with that of the majority of their neighbors). The third model combines the first two, with the aim of studying the role of non-uniform swarm density in the performance of collective decision-making. Based on the three models, we formulate a set of requirements for convergence and scalability in collective decision-making. [ABSTRACT FROM AUTHOR]

CXCL4 is an antiangiogenic and immunomodulatory chemokine. We aimed to investigate serum levels of CXCL4 in primary Sjögren's syndrome (pSS), looking for associations with disease features. Thirty-nine consecutive pSS patients underwent clinical-serological assessment and nailfold videocapillaroscopy (NVC). Thirty-six patients and 30 controls affected by osteoarthritis were also investigated for serum levels of CXCL4 and soluble E-selectin (sE-selectin). CXCL4 was higher in pSS patients than in controls (1.79 [0.2-11.18] vs 1.023 ng/ml [0.02-14.45], p < 0.05), particularly in those without anti-La/SSB antibodies (2.89 [1.01-11.18] vs 1.69 ng/ml [0.2-2.72], p < 0.05), while it was lower in pSS patients with a focus score ≥1 at lip biopsy (1.44 [0.86-2.1] vs 2.24 ng/ml [1.64-3.25], p < 0.05) and clinically evident lymphadenopathy (1.53 [0.38-1.7] vs 2.08 ng/ml [1.45-3.03], p < 0.05). CXCL4 correlated with disease duration ( r = 0.35, p < 0.05) and sE-selectin ( r = 0.45, p < 0.01). Patients with Raynaud's phenomenon (RP) had more frequently abnormal CXCL4 levels than patients without RP (11/15 vs 3/21, p < 0.001), enlarged capillaries (14/16 vs 7/23, p < 0.001) and capillary loss at NVC (14/16 vs 6/23, p < 0.001). The hitherto unknown association of increased serum CXCL4 with features of microvascular impairment in pSS, along with the negative association with features of lymphocytic response (i.e., the absence of subset disease-specific autoantibodies, a low focus score, and the absence of lymphadenopathy) suggest clarifying the possible implication of this chemokine in pSS pathogenesis in larger studies. [ABSTRACT FROM AUTHOR]

Glucocorticoids (GC) are widely used to treat systemic sclerosis (SSc). The lack of efficacy data and patient/physician concerns may prompt therapy discontinuation. The aim of this study is to identify factors hampering GC discontinuation in patients with stable disease on oral GC for longer than 12 months. Consecutive patients fulfilling the 2013 ACR/EULAR criteria for SSc and with stable disease were prescribed a slow tapering GC regimen to achieve discontinuation. At study entry and 6 months later (T6), patients were assessed for disease activity and severity. Moreover, the Short-Form-36; the Health Assessment Questionnaire Disability Index (HAQ-DI); and visual analog scales for fatigue, pain, and general health were completed. Reasons for stopping the discontinuation regimen were recorded. Forty-eight patients (46 females, 9 diffuse SSc), with a mean ± SD age of 56±14 years and a median disease duration of 10 years (range 2-22), were enrolled. The median daily GC dose was 5 mg (range 5-10; all patients treated with prednisone). At T6, 33 (68.7 %) patients had discontinued GC. The remaining 15 patients could not discontinue GC because of arthralgia in eight, arthritis in two, puffy fingers in two, increased creatine-kinase in two, and bursitis in one patient. At multiple logistic analysis, a higher baseline HAQ-DI was the only independent factor associated with GC need (OR 2.98, 95 % CI 1.20-7.41; p = 0.01). About one third of SSc patients did not achieve a GC-free regimen. Disability as assessed by HAQ-DI was the leading factor hindering GC discontinuation. A low HAQ-DI score can identify candidates for GC discontinuation. [ABSTRACT FROM AUTHOR]

Adult-onset Still's disease (AOSD) is a systemic inflammatory condition of unknown aetiology characterized by typical episodes of spiking fever, evanescent rash, arthralgia, leukocytosis and hyperferritinemia. Given the lack of data in Italian series, we promote a multicentric data collection to characterize the clinical phenotype of Italian patients with AOSD. Data from 245 subjects diagnosed with AOSD were collected by 15 centres between March and May 2013. The diagnosis was made following Yamaguchi's criteria. Data regarding clinical manifestations, laboratory features, disease course and treatments were reported and compared with those presented in other published series of different ethnicity. The most frequent features were the following: arthritis (93 %), pyrexia (92.6 %), leukocytosis (89 %), negative ANA (90.4 %) and neutrophilia (82 %). As compared to other North American, North European, Middle Eastern and Far Eastern cohorts, Italian data show differences in clinical and laboratory findings. Regarding the treatments, in 21.9 % of cases, corticosteroids and traditional DMARDs have not been able to control the disease while biologics have been shown to be effective in 48 to 58 patients. This retrospective work summarizes the largest Italian multicentre series of AOSD patients and presents clinical and laboratory features that appear to be influenced by the ethnicity of the affected subjects. [ABSTRACT FROM AUTHOR]

Enlargement and dysfunction of the right atrium might be an early sign for pulmonary hypertension in systemic sclerosis (SSc). This is the first study to analyse right atrial morphology and function in SSc patients compared to healthy controls by speckle-tracking two-dimensional strain echocardiography (2DSE) at rest and during exercise. Furthermore, right atrial function was correlated with further clinical findings. Adult patients with SSc for >3 years ( n = 90) and 55 age- and gender-matched healthy controls underwent a panel of non-invasive assessments including transthoracic echocardiography, pulsed Doppler myocardial imaging and 2DSE at rest and during exercise. Furthermore, serological tests and high-resolution chest computed tomography were performed. SSc patients showed significant impairment of right atrial function and the right atrial enlargement, measured by 2DSE at rest and during exercise compared to controls (both p < 0.001). These findings were more evident in SSc patients with pulmonary fibrosis ( p < 0.001) and in patients with high pulmonary artery systolic pressures (PAPs) during exercise. In the SSC patients, right atrial lateral strain was significantly associated with PAPs during effort, right atrial area, left ventricle stroke volume and inferior vena cava diameter using multivariable analysis. The findings of this study suggest that a high proportion of SSc patients reveal right atrial dysfunction even without manifest pulmonary hypertension. Impaired right atrial function occurred mostly in patients with pulmonary fibrosis and/or elevated PAPs during exercise, was independently associated with prognostic factors and may therefore be useful for risk stratification. Further studies are needed to analyse if right atrial dysfunction assessed by 2DSE may help to improve early diagnosis of pulmonary hypertension. [ABSTRACT FROM AUTHOR]

Anthocyanin levels decline in some red grape berry varieties ripened under high-temperature conditions, but the underlying mechanism is not yet clear. Here we studied the effects of two different temperature regimes, representing actual Sangiovese ( Vitis vinifera L.) viticulture regions, on the accumulation of mRNAs and enzymes controlling berry skin anthocyanins. Potted uniform plants of Sangiovese were kept from veraison to harvest, in two plastic greenhouses with different temperature conditions. The low temperature (LT) conditions featured average and maximum daily air temperatures of 20 and 29 °C, respectively, whereas the corresponding high temperature (HT) conditions were 22 and 36 °C, respectively. The anthocyanin concentration at harvest was much lower in HT berries than LT berries although their profile was similar under both conditions. Under HT conditions, the biosynthesis of anthocyanins was suppressed at both the transcriptional and enzymatic levels, but peroxidase activity was higher. This suggests that the low anthocyanin content of HT berries reflects the combined impact of reduced biosynthesis and increased degradation, particularly the direct role of peroxidases in anthocyanin catabolism. Overexpression of VviPrx31 decreased anthocyanin contents in Petunia hybrida petals under heat stress condition. These data suggest that high temperature can stimulate peroxidase activity thus anthocyanin degradation in ripening grape berries. [ABSTRACT FROM AUTHOR]

Achieving fast and accurate collective decisions with a large number of simple agents without relying on a central planning unit or on global communication is essential for developing complex collective behaviors. In this paper, we investigate the speed versus accuracy trade-off in collective decision-making in the context of a binary discrimination problem-i.e., how a swarm can collectively determine the best of two options. We describe a novel, fully distributed collective decision-making strategy that only requires agents with minimal capabilities and is faster than previous approaches. We evaluate our strategy experimentally, using a swarm of 100 Kilobots, and we study it theoretically, using both continuum and finite-size models. We find that the main factor affecting the speed versus accuracy trade-off of our strategy is the agents' neighborhood size-i.e., the number of agents with whom the current opinion of each agent is shared. The proposed strategy and the associated theoretical framework can be used to design swarms that take collective decisions at a given level of speed and/or accuracy. [ABSTRACT FROM AUTHOR]

Self-organizing systems rely on positive feedback (amplification of perturbations). In particular, in swarm systems, positive feedback builds up in a transient phase until maximal positive feedback is reached and the system converges temporarily on a state close to consensus. We investigate two examples of swarm systems showing time-variant positive feedback: alignment in locust swarms and adaptive aggregation of swarms. We identify an influencing bias in the spatial distribution of agents compared to a well-mixed distribution and two features, percentage of aligned swarm members and neighborhood size, that allow us to model the time variance of feedbacks. We report an urn model that is capable of qualitatively representing all these relevant features. The increase in neighborhood sizes over time enables the swarm to lock in a highly aligned state but also allows for infrequent switching between lock-in states. We report similar occurrences of time-variant feedback in a second collective system to indicate the potential for generality of this phenomenon. Our study is concluded by applications of methods from renormalization group theory that allow us to focus on the neighborhood dynamics as scale transformations. Correlation lengths and critical exponents are determined empirically. [ABSTRACT FROM AUTHOR]

Spatially targeted communication (STC) allows a message sender to choose message recipients based on their location in space. Currently, STC in multirobot systems is limited to centralized systems. In this paper, we propose a novel communication protocol that enables STC in decentralized multirobot systems. The proposed protocol dispenses with the many aspects that underpin previous approaches, including external tracking infrastructure, a priori knowledge, global information, dedicated communication devices or unique robot IDs. We show how off-the-shelf hardware components such as cameras and LEDs can be used to establish ad-hoc STC links between robots. We present a Markov chain model for each of the two constituent parts of our proposed protocol and we show, using both model-based analysis and experimentation, that the proposed protocol is highly scalable. We also present the results of extensive experiments carried out on an autonomous, heterogeneous multirobot system composed of one aerial robot and numerous ground-based robots. Finally, two real world application scenarios are presented in which we show how spatial coordination can be achieved in a decentralized multirobot system through STC. [ABSTRACT FROM AUTHOR]

Purpose: To assess the serum profile of factors involved in endothelial, T-cell, and fibroblast interplay in patients with Raynaud's phenomenon (RP) associated with nailfold vodeocapillaroscopy (NVC) scleroderma findings and/or systemic sclerosis (SSc) marker autoantibodies, recently labeled as early SSc patients. Methods: Serum levels of soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular adhesion molecule-1 (sVCAM-1), CCL2, CXCL8, IL-13, IL-33, and transforming growth factor-β (TGF-β) were measured in 24 early SSc patients, 48 definite SSc patients, and 24 osteoarthritis/fibromyalgia controls by multiplex suspension immunoassay. All SSc patients were investigated for the presence/absence of preclinical and clinical organ involvement, SSc marker autoantibodies, and NVC abnormalities. Results: Serum sICAM-1, CCL2, CXCL8, and IL-13 were increased in all SSc patients as compared to controls, and paralleled the severity of the disease subset (early SSc < limited cutaneous SSc < diffuse cutaneous SSc; p < 0.0001). Surprisingly, IL-33 was significantly higher in early SSc patients as compared to both controls ( p < 0.01) and definite SSc patients ( p < 0.05). In early SSc there were no differences in the investigated markers according to the functional and serological features assessed. Conclusions: Our study suggests that an endothelial, T-cell and fibroblast activation can be present in patients with early SSc and it is associated with a distinct profile of circulating factors involved in the cross-talk of these cells. The marked increase of IL-33 in early SSc patients suggests new routes of investigation of cell-cell dynamics in target tissues predating overt disease manifestations, thus opening to new therapeutic approaches. [ABSTRACT FROM AUTHOR]

Glucocorticoids (GC) represent a mainstay in the therapeutical strategies of many autoimmune diseases, but their role in systemic sclerosis (SSc) is controversial. The main objective of this review is to assess the extent of and the factors associated with GC use in SSc patients, taking into account data from cohort studies and registries. We performed a search in MEDLINE databases updated to April 2013. The pooled prevalence and factors associated with GC utilization in both SSc patients collectively considered and in any of the two subsets of the disease were calculated. The pooled prevalence was 0.36 (95 % confidence interval (CI) 0.28-0.43) for overall sample. In six studies, data about the GC prescription in the two different subsets of the disease were available. The pooled prevalence was 0.52 (95 % CI 0.49-0.55) in diffuse and 0.33 (95 % CI 0.31-0.35) in limited cutaneous disease patients. Five papers reporting data about the dose of GC prescribed showed a pooled prevalence of 0.89 (95 % CI 0.87-0.91) for a daily dose of <15 mg of prednisone equivalent. Huge heterogeneity was identified across studies ( I > 75 %). No significant correlation was detected between the extent of GC utilization and either the percentage of concomitant immunosuppressants intake ( p = 0.347), diffuse subset ( p = 0.720) or female sex ( p = 0.913). Despite the limited evidence for their effectiveness, GC are frequently prescribed in SSc patients, mostly in those with the diffuse subset. The variability in the extent of their utilization in different centres is considerable and suggests the need to develop treatment recommendations. [ABSTRACT FROM AUTHOR]

The occurrence of non-Hodgkin’s lymphoma in systemic sclerosis is an uncommon event. In our scleroderma cohort, a case of primary gastric B-cell lymphoma was diagnosed in 2007. The patient was a 45-year-old woman suffering from late systemic sclerosis sine scleroderma in whom non-Hodgkin’s lymphoma presented with progressive weight loss, later with gastrointestinal symptoms. Subsequently, we retrospectively analyzed the charts of 251 systemic sclerosis patients consecutively admitted to our Unit from 2000 to 2008 to search for other non-Hodgkin’s lymphoma cases (prevalence, 0.49%). Then we performed a Pubmed search for “systemic sclerosis & non-Hodgkin’s lymphoma,” limited to the English language. Twenty detailed cases of such an association were found, pointing out the following: non-Hodgkin’s lymphoma seems to be associated to old age, female sex, diffuse cutaneous subset and early disease; B-cell lymphoma subtypes are the majority; the interval between systemic sclerosis and lymphoma onset is usually short; systemic sclerosis could present as a paraneoplastic syndrome in some cases. We concluded that, although rare, the association of systemic sclerosis and non-Hodgkin’s lymphoma may not be coincidental and the clinician should be aware of the risk for lymphoproliferative disorders in scleroderma patients. This is the first description of non-Hodgkin’s lymphoma in systemic sclerosis sine scleroderma. The insidious onset of gastric lymphomas, mimicking the most common features of gastrointestinal involvement in systemic sclerosis is underlined. [ABSTRACT FROM AUTHOR]

The aim of the present study was to evaluate the concentration of cell-free DNA (cf-DNA) in the plasma of patients with systemic sclerosis (SSc) and to examine the correlation of cf-DNA with clinical variables of the disease. The study population consisted of 122 SSc patients and 16 healthy controls. Epidemiological and clinical data were collected by direct assessment. The β-globin gene was used to determine the total amount of DNA in the plasma by real-time quantitative PCR analysis. cf-DNA was found in all patients (mean concentration 1,420.7 copies/ml) and controls (mean concentration 1,462.5), with no significant difference. In SSc patients, no correlation was found between cf-DNA and the type of organ involvement, but patients with active disease presented significantly higher cf-DNA concentrations than those with inactive disease ( p < 0.05). Our data suggest that cf-DNA could provide a useful biomarker for the assessment of disease activity in SSc patients. [ABSTRACT FROM AUTHOR]

The objective of this work is to investigate the occurrence of atherosclerosis and metabolic syndrome (MetS) in ankylosing spondylitis (AS) patients (pts). Twenty-four consecutive AS pts (men, 87.5%; median age, 50.5 years; median disease duration, 16.5 years), fulfilling the modified 1984 New York criteria for AS criteria, and 19 age- and sex-matched controls were investigated. Clinical atherosclerosis was evaluated by physical examination for cardiovascular (CV) diseases and history or drug use for CV events. Subclinical atherosclerosis was detected by mean intima media thickness (a-IMT) and maximum IMT (max-IMT) of carotid arteries using ultrasonography. Laboratory investigations including fasting plasma glucose, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides were assessed by standard methods, while homocysteine was assessed by chemiluminescence. MetS was assessed using the updated NCEP-ATP III criteria. Disease activity was defined according to the International Ankylosing Spondylitis Assessment Study criteria. The 10-year CV risk (%) profile was evaluated in agreement to the Progetto Cuore criteria. No major CV event was detected in the study population. No significant differences were found when AS pts and controls were compared according to the mean a-IMT (0.52±0.26 vs 0.51±0.13 mm), max-IMT (0.92±0.20 vs 0.85±0.39 mm), prevalence of abnormal max-IMT >1 mm (27.2 vs 5.3%), and 10-year CV risk (9.9±9.6 vs 3.6±1.8%). Systolic blood pressure ( p=0.04), triglyceride to HDL cholesterol ratio ( p=0.002), and LDL cholesterol ( p=0.03) were found significantly higher in AS pts than in controls; on the contrary, HDL cholesterol was pointed out as significantly lower ( p<0.001). MetS was found in 11/24 (45.8%) AS pts and in 2/19 (10.5%) controls ( p=0.019). No significant relationship emerged in MetS prevalence among AS pts regarding the mean value of age, disease duration, Bath Ankylosing Spondylitis Functional Index, Bath Ankylosing Spondylitis Disease Activity Index, and the Italian version of Health Assessment Questionnaire. This preliminary report points out a higher prevalence of MetS in AS pts than in controls. Further studies are needed to confirm this finding. [ABSTRACT FROM AUTHOR]

Objective: To assess the clinical and radiological features of systemic sclerosis (SSc) joint involvement in a prospective cross-sectional study.Design and Patients: Seventy-six consecutive patients with SSc divided into clinical and serological subsets were investigated. Clinical and radiological assessments of the hands and feet were carried out. Three radiological patterns of inflammatory, degenerative and fibrotic changes were predefined. The Health Assessment Questionnaire (HAQ) disability index (DI) and individual components of the HAQ-DI were also evaluated.Results: The highest impairments on the HAQ-DI (median 0.44; range 0-2.87) were detected in subdimensions such as hygiene, grip and activity components. Clinically articular involvement, arthralgia and finger contractures were seen more frequently than arthritis, and a significantly higher prevalence of finger flexion was found in patients with diffuse cutaneous SSc (P=0.03) compared with the other SSc subtypes. Radiologically, distal interphalangeal joint space narrowing and flexion deformity indicating periarticular fibrosis were frequently detected. Juxta-articular osteoporosis, joint space narrowing and flexion contractures of the fingers were seen significantly more frequently in the hands. A significantly higher frequency of fibrotic pattern were found in the hands whereas a degenerative pattern was more frequent in the feet (P<0.05). Finally, significant correlations were detected between flexion contractures and a radiological fibrotic pattern (P<0.001), and the severity scores of peripheral vascular impairment (P=0.026) and skin (P=0.007).Conclusion: This cross-sectional prospective study confirms that an arthropathy is common in SSc patients and shows that it is a major determinant of disability. A classification of radiological alterations into three specific patterns is proposed. [ABSTRACT FROM AUTHOR]

Both oral and intravenous high-dose cyclophosphamide (CYC) regimens are associated with serious side effects when used for the treatment of systemic sclerosis (SSc). The aim of the present trial was to test the safety of low-dose intravenous CYC in patients with SSc. Eight SSc patients, in whom CYC treatment was warranted, were studied at baseline and after 6 months’ intravenous CYC treatment (500 mg pulses at weeks 0, 1, 2, 6, 10, 14, 18 and 22). Side effects probably related to CYC treatment were carefully investigated. The development of amenorrhea was assessed during the period of treatment and over the following 12 months. The therapy was well tolerated overall. No patient discontinued treatment because of side effects. Leukopenia, premature ovarian failure, hemorrhagic cystitis, microscopic hematuria and liver toxicity were never detected. The most common adverse events were mild and self-limiting nausea and weakness. Our data suggest that low-dose intravenous CYC is relatively safe, at least in the short term. Further studies are needed to assess both the efficacy and the long-term safety. [ABSTRACT FROM AUTHOR]

Objective. The aim of this study was to assess intestinal permeability (IP) in patients with systemic sclerosis (SSc) and to relate the results with general disease activity and gastrointestinal involvement. Methods. Twenty-eight females and four males were studied. Patients with severe gastrointestinal involvement were excluded. Thirty-three healthy volunteers served as controls. Intestinal permeability was assessed by means of the orally administered cellobiose/mannitol sugar (Ce/Ma) test. Intestinal transit time (ITT) was investigated with the H2-lactulose breath test. Results. The mean value of IP in 32 SSc patients was significantly higher than in 33 controls (P<0.05), although it fell within the normal range. Eleven patients showed abnormally high individual IP values (>0.028) that significantly correlated to disease duration (r=0.73). Altered IP was associated with the higher but not statistically relevant presence of anti-Scl70 antibodies (9/11) and to more severe gastrointestinal involvement. More than half of the SSc patients showed slower orocecal transit times on the H2 breath test. In particular, delayed ITT was observed in 60% of patients with increased IP and in all patients with moderate gastrointestinal involvement according to the scleroderma severity scale. Conclusion. Intestinal permeability was altered in 11/32 SSc patients. Correlations between increased IP and duration of disease and degree of gastgrointestinal involvement appear to support the hypothesis of secondary involvement of the intestinal barrier, and the presence of anti-Scl70 antibodies in 82% of the patients with higher IP clearly reinforces the hypothesis of an altered immune response in these subjects. [ABSTRACT FROM AUTHOR]

Our objective was to investigate the phenotype of helper T cells in the peripheral blood of patients with systemic sclerosis (SSc). PBMC from 15 patients with SSc and 15 sex- and age-matched controls were investigated for lymphocyte subpopulations (CD3, CD4, CD8, CD19, CD16/CD56, CD3-DR); IL-2, IL-4, and IFN-γ mRNAs; and the relative cytokines in their cytoplasm. The last assay was carried out both in unstimulated and in PMA-activated PBMC. SSc patients presented a higher percentage of activated T cells, CD3+ DR+ (19.7 ± 9.9 vs 5.1 ± 2.5%; P < 0.0001); 12 of them presented IFN-γ mRNA-positive cells; and none IL-2 or IL-4 mRNAs. Under basal conditions, PBMC from six SSc patients contained IL-2, IL-4, and IFN-γ (i.e., they showed both Th1 and Th2 activation), and 1 IFN-γ only. PMA-stimulated PBMC of patients differed from those of controls only in the increased percentage of IFN-γ positive cells (52 ± 12 vs 37 ± 11%; P < 0.01). Our study demonstrates that Th1 activation occurs in the peripheral blood of SSc patients. This evidence must be faced with from both a pathogenetic and a therapeutical point of view. [ABSTRACT FROM AUTHOR]

Gastrointestinal involvement is frequent in patients with systemic sclerosis (SSc); however, studies on the proximal stomach and its regulation are lacking. It has been hypothesized that the primary event in the pathogenesis of gastrointestinal involvement in SSc is an early neural lesion. This study investigates proximal stomach function and its relation to autonomic nerve function in SSc. Twenty SSc patients classified in to clinical subsets, underwent measurement of proximal stomach function with and without glucagon by electronic barostat and an assessment of autonomic nerve function. SSc patients were not significantly different from 11 controls for gastric compliance (59.5 ± 5.0 vs 47.7 ± 4.2 ml/mm Hg, P = 0.1). The pressure–volume curves in each participant with and without glucagon were significantly different (P < 0.001). A significant positive association was found between gastric compliance and autonomic nerve function (P < 0.05). The change in gastric compliance during glucagon administration was significant associated with autonomic function (P < 0.05). The perception cumulative scores did not differ between SSc patients and control subjects (P = 0.2). In conclusion, proximal stomach function is associated with autonomic nerve function in SSc patients. This confirms the frequent association of motility disorders with autonomic dysfunction in SSc. [ABSTRACT FROM AUTHOR]

We report on an uncommon case of bilateral transient osteoporosis of the hip (TOH) occurring in a young woman during pregnancy. The clinical features and the therapeutic action of intramuscular neridronate sodium, a third-generation amino-bisphosphonate, are underlined. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to an article on early onset neutropenia after mycophenolate mofetil in systemic sclerosis that was published in one of the previous issues.