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Adults with Down syndrome (DS) are at increased risk of developing Alzheimer's disease (AD) due to genetic predisposition. Identification of patients with AD is difficult since intellectual disabilities (ID) may confound diagnosis. The objective of this study was to evaluate the ability of the French version of the modified cued recall test (mCRT) to distinguish between subjects with and without AD in the adult DS population.This was a retrospective, single-centre, medical records study including data between March 2014 and July 2020. Adults aged ≥30 years with DS who had at least one mCRT record available were eligible. Age, sex and ID level were extracted, and subjects were attributed to three groups: patients with AD, patients with co-occurring conditions that may impact cognitive function and subjects without AD. mCRT scores, adjusted by sex, age and ID level, were compared between groups. The optimal cut-off value to distinguish between patients with and without AD was determined using the receiver operating characteristic curve. The impact of age and ID level on mCRT scores was assessed.Overall, 194 patients with DS were included: 12 patients with AD, 94 patients with co-occurring conditions and 88 healthy subjects. Total recall scores were significantly lower (P 0.0001) in patients with AD compared with healthy subjects. The optimal cut-off value to discriminate between patients with AD and healthy subjects was 22, which compares well with the cut-off value of 23 originally reported for the English version of the mCRT. Patients aged 30-44 years had higher mCRT total recall scores compared with patients aged ≥45 years (P = 0.0221). Similarly, patients with mild ID had higher mCRT scores compared with patients with severe ID (P 0.0001).The mCRT is a sensitive tool that may help in the clinical diagnosis of AD in subjects with DS. Early recognition of AD is paramount to deliver appropriate interventions to this vulnerable population.

Background In the last decade, the number of individuals over 60 years of age with AIDS has increased in Brazil, with the need to know the trend of the mortality of the disease to subsidize educational and preventive actions for service users and health professionals. The objective was to describe the trend of mortality from HIV/AIDS in the elderly in the Federal District (DF), Brazil, from 2007 to 2016. Methods Descriptive study, ecological type of time series, from secondary data on mortality obtained from the Brazilian Ministry of Health. Linear regression was performed to analyze trends by sex and by age group, using the Statistical Package for the Social Sciences (SPSS). Results Deaths were predominant in men (74.1%) aged 60 to 69 years (70.4%). The sex ratio was 2.85. The married / stable union (43.0%) and white (52%) were the majority. There was a significant increase in males, while in females, it was slightly decreasing in the same period. In the age groups of 60-69 years and 70-79 years, there was a tendency to increase in mortality, decreasing for ≥ 80 years. Conclusions There was a predominance and an increasing tendency in young male elderly, demonstrating that prevention actions need to achieve greater reach in this population, with the breaking of barriers related to prejudice and the stigma of the disease. A better organization of the care network for the elderly is suggested, enabling approaches to suspected cases and providing early diagnosis, to ensure greater quality survival for the elderly. Key messages There was a tendency to increase mortality from HIV / AIDS in elderly men, aged 60-79 years. There is a need to improve educational activities and early diagnosis and timely treatment for this group.

The interactions of π-systems with lone-pairs of electrons are known and have been described in biological systems, involving lone-pairs derived from metals, metalloids, sulfur, oxygen and nitrogen. This study describes a bibliographic survey of the disulfide-bound sulfur(lone-pair) interactions with π-systems residing in the flavin adenine dinucleotide (FAD) cofactor of oxidoreductase enzymes (flavoenzymes). Thus, of the 172 oxidoreductase enzymes evaluated for gamma-S(lone-pair)…π(FAD) interactions, 96 proteins (56%) exhibited these interactions corresponding; 61% of 350 the constituent monomers featured at least one gamma-S(lone-pair)…π(FAD) interaction. Two main points of association between the S(lone-pair) and the isoalloxazine moiety of FAD were identified, namely at the centroid of the bond linking the uracil and pyrazine rings (60%), and the centroid of the uracil ring (37%). Reflecting the nature of the secondary structure in three prominent classes of oxidoreductase enzymes: glutathione disulfide reductases (GR; 21 proteins), trypanothione disulfide reductases (TR, 14) and sulfhydryl oxidases (SOX, 22), the approach of the gamma-S(lone-pair) to the FAD residue was to the si-face of the isoalloxazine ring system, i.e. to the opposite side as the carbonyl residue, for all GR and TR examples, and to the re-face for all SOX examples. Finally, the attractive nature of the gamma-S(lone-pair)…π(FAD) interactions was confirmed qualitatively by an examination of the non-covalent interaction plots.

Differentiation between psoriatic arthritis (PsA) sine psoriasis and rheumatoid arthritis (RA) may be a challenge, especially in the early stages, hence the need for new instrumental markers to assist their diagnosis. In this study, we investigated possible dermoscopic differences in vascular appearance of nail fold and elbow (a classic site of repeated trauma) in these two conditions. Fifteen patients with PsA sine psoriasis, 12 patients with RA and 12 controls were included in the study. Regarding the nail fold vascular appearance in PsA sine psoriasis and RA cohorts, the presence of diffuse reddish background with or without sparse dotted vessels was significant in the former, whereas the evidence of parallel dotted/short linear vessels ("fish school-like" pattern) or irregular/ramified, blurry, purple vessels were significant in the latter; none of these patterns were detected in the control group. Regarding the elbow, the pattern significantly associated with PsA sine psoriasis consisted of diffusely distributed, red, dotted vessels. On the other hand, RA patients and controls displayed similar dermoscopic findings, with three possible vascular patterns being observed: (i) irregular, blurry, purple vessels; (ii) avascular appearance; and (iii) sparse, dotted, purple vessels. In conclusion, dermoscopy may be a useful supportive tool for differentiating early PsA sine psoriasis from RA.

RATIONALE AND OBJECTIVES To evaluate the impact on perceived report quality of referring rheumatologists for a chest high-resolution computed tomography (HRCT) structured report (SR) template for patients with connective tissue disease (CTD), compared to the traditional narrative report (NR). MATERIALS AND METHODS We retrospectively considered 123 HRCTs in patients with CTD. Three radiologists, blinded to the original NRs they wrote during clinical routine, re-reported each HRCT using an SR dedicated template. We then divided all NR-SR couples into three groups (41 HRCT each). Each group was evaluated by one of three rheumatologists (R1, R2, R3), who expressed their perceived report quality for the respective pools of NRs and SRs in terms of completeness, clarity (both on a 10-points scale), and clinical relevance (on a 5-points scale). The Wilcoxon test and the McNemar test were used for statistical analysis. RESULTS For each rheumatologist, SR received higher ratings compared to NR for completeness (median ratings: R1, 10 vs. 7; R2, 10 vs. 8; R3, 10 vs. 6, all p

Background Identify the preclinical phase of arthritis could be clinically relevant. In this scenario, musculoskeletal ultrasonography (US) may play an important role, since it may detect subclinical disease. Psoriatic Arthritis (PsA) is a perfect disease to identify risk factors, since the risk pool group [i.e. patients with only cutaneous Psoriasis (Pso)] is known. Objectives To evaluate in Pso patients, with and without clinical arthralgia (CA), defined by the presence of joint pain without other clinical evidence of musculoskeletal inflammation: I) the prevalence of subclinical US inflammation in joints, enthesis, tendons and bursae; II) the prevalence of US structural damage; III) the relationship between US lesions and clinical data. Methods Cross-sectional prevalence study of US abnormalities in Pso patients with or without CA and healthy controls (HCs). Inclusion and exclusion criteria (e.g. osteoarthritis and fibromyalgia) are pre-defined. Forty-four joints (MCP, PIP and DIP joints, wrists, knees, MTP joints) and 12 enthesis (achilles, quadriceps, proximal and distal patellar, plantar aponeurosis and common extensor tendon enthesis) were scanned in each patient. US scans were performed using a ESAOTE MyLabClassC equipped with a high frequency linear probe. Active synovitis was defined by the presence of a grade ≥2 for grey scale (GS) and ≥1 for PD, while active enthesitis if there was hypoecogenity in GS and an entheseal PD signal (≤2 mm from bone insertion). Results Sixty-four Pso patients and 21 HCs were included; globally 2816 joints and 768 entheses were scanned. Twenty-three out of 64 (35.9%) Pso patients displayed CA. Baseline characteristics are reported in table 1. Active synovitis was found, in at least one joint, in 20/64 (31.3%) Pso patients and 0/21 HCs (p=0.002), while active enthesitis in 14/64 (21.9%) Pso patients and 0/21 HCs (p=0.017). No significant differences were found for active synovitis or enthesitis between the two subgroups of Pso, with or without CA. In the Pso cohort, 5/23 (23.8%) patients with CA and 2/41 (5%) without CA displayed tenosynovitis or paratenonitis (p=0.042). Furthermore, active synovitis, as well as GS-synovitis ≥2, was associated with higher NAPSI (9.7±8.0 vs 4.6±7.1, p=0.04 for GS ≥2), whereas active enthesitis was associated with higher PASI (5.4±3.0 vs 3.7±2.9, p=0.02). No significant differences were found between Pso patients and HCs for the structural damage (i.e. osteoproliferation and erosions), both for joints and enthesis. Conclusions In Psoriasis subclinical US active synovitis and/or enthesitis are present in 20%–30% of patients. In Pso the comparison between groups, with or without CA, show no significant difference in active subclinical synovitis or enthesitis, but Pso patients with CA present more frequently US tenosynovitis or paratenonitis. In Pso subclinical US synovitis or enthesitis are significantly associated with higher NAPSI and PASI. The relevance of these results, to possibly identify a subgroup of Pso more prone to develop PsA, deserve further investigation and prospective evaluation. Disclosure of Interest None declared

Over the past several decades, female consumer culture has changed as a result of fundamental societal shifts in American culture owing, among other factors, to the increasing focus on the self and successive waves of feminism and changing roles of women (Branchik and Chowdhury 2017). These changes result from a series of historical developments and can be reflected in age-based differences in female consumers. These significant differences impact women’s attitudes and behaviors associated with consumption and media. To date, few studies have assessed these generational differences relative to activity in the marketplace.

The genetic predisposition to a long-term efficacy of anti-tumor necrosis factor (TNF)α treatment in seronegative spondyloarthritis (SpA) was investigated by analysing the possible correlation between several single nucleotide gene polymorphisms and the retention rate of anti-TNFα therapies. We compared patients needing to switch the first anti-TNFα (Sw, No. 64) within at least 12 months of follow-up with patients not needing to switch (NSw, No. 123), observing at least 6 months of treatment to establish anti-TNFα failure, leading to treatment change. Response to treatment was evaluated by standardised criteria (BASDAI for axial involvement, DAS28-EULAR for peripheral involvement). The TNFα -308 A allele and the interleukin (IL)-6 -174GG homozygosis resulted as independent biomarkers predicting survival of the first anti-TNFα therapy in SpA patients (P=0.007, odds ratio (OR): 4.4, 95% confidence interval (CI)=1.5-13.1 and P=0.035, OR: 2.1, 95% CI=1.1-4.4). Also, the male gender (P=0.001, OR: 3.4, 95% CI=1.6-7.1) associated with the NSw phenotype, whereas no association was found either with the specific diagnosis or the predominant joint involvement.

Background and aims: Owing to the multiplicity of the key components of metabolic syndrome (MetS), its diagnosis is very complex. The lack of a unique definition is responsible for the prevalence variability observed among studies; therefore, a definition based on contin- uous variables was recommended. The aim of this study was to compare competing models of the MetS factor structure for selecting the one that explains the best clustering pattern and to propose an algorithm for computing MetS as a continuous variable. Methods and results: Data were from isolated Sardinian populations (n Z 8102). Confirmatory factor analysis (CFA) and two-group CFA by gender were performed to evaluate the sex- specific factor structure of MetS. After selecting the best model, an algorithm was obtained using factor loadings/residual variances. The quality of the MetS score was evaluated by the receiver operating characteristics curve and the area under the curve. Cross-validation was performed to validate the score and to determine the best cut point. The best fit model was a bifactor one with a general factor (MetS) and three specific factors (f1: obesity/adiposity trait; f2: hyper- tension/blood pressure trait; and f3: lipid trait). Gender-specific algorithms were implemented to obtain MetS scores showing a good diagnostic performance (0.80 specificity and 0.80 sensitivity for the cut point). Furthermore, cross-validation confirmed these results. Conclusion: These analyses suggested that the bifactor model was the most representative one. In addition, they provided a score and a cut point that are both clinically accessible and interpret- able measures for MetS diagnosis and likely useful for evaluating the association with adverse cardiovascular disease and diabetes and for investigating the MetS genetic component.

This paper outlines the use of psychological testing in a community clinic. The emphasis is on the use of projective techniques in designing treatment plans for youth in disadvantaged communities. These assessments fall into three categories of testing referrals: determining mental impairment for disability, learning disability assessments, and diagnostic clarifications and treatment recommendations for therapists. The demands of psychological testing often require that the psychological evaluation play a role in how the client progresses in a system of care. Placement and risk decisions are often made in the psychological report. Projective techniques are stressed as a means to answer the most common questions asked from community referral agents such as schools, child protective case workers, courts, and human services agencies involved with residential programs. The relative strength of projective testing is compared with the value of empirical approaches stressed in modern psychology. Copyright © 2014 John Wiley & Sons, Ltd.

Aims Several studies confirmed the growing rate of Type 1 diabetes mellitus in childhood coinciding with increasing diagnosis of viral infections. A study investigating the incidence of Type 1 diabetes during 1996-1997 showed a higher notification of viral infections in the Pavia District. The aim was to confirm these results. Methods This study evaluated the relationship between new cases of Type 1 diabetes and those of measles, mumps and rubella in 1996-2001, analysing data of newly-diagnosed Type 1 diabetes children, aged 0-14 years and enrolled into the RIDI (Italian Insulin-dependent Diabetes Registry) during the same years. Measles, rubella and mumps rates were calculated using as denominator the estimated 'population at risk', represented by the number of 0- to 14 year-old subjects who did not undergo the MMR (measles, mumps and rubella) vaccination. In order to investigate the association between Type 1 diabetes incidence and measles, rubella and mumps respectively, Spearman's rank correlation was used. Results The analysis of the whole Registries data did not at first show any statistical significance between age-standardized Type 1 diabetes incidence density and estimated rates of measles, mumps and rubella notifications. Excluding data from Sardinia Registry, a significant association was observed between Type 1 diabetes incidence and mumps (P = 0.034) and rubella (P = 0.014), respectively, while there was no statistical significance between the incidence of measles cases and diabetes rates (P = 0.269). Conclusions According to our findings, mumps and rubella viral infections are associated with the onset of Type 1 diabetes. The statistical significance observed after exclusion of the Sardinian data suggests that other environmental factors may operate over populations with different genetic susceptibility.

The purpose of this study was to investigate the changes between 2000 and 2006 in pregnancy outcome when a diagnosis of either isolated or associated fetal corpus callosum agenesis (CCA) was made, given that beginning in 2003, the information provided to couples facing this problem related a good prognosis in nearly 80 % of cases of isolated CCA and a poor prognosis in 20 % of cases. We retrospectively analyzed all pregnancies with a fetal diagnosis of CCA between 2000 and 2006 (n=155) and compared two periods: the first group from 2000 to June 2003, the second from July 2003 to 2006. For each group, we analyzed the type of CCA during pregnancy - either isolated or associated - and the outcome of pregnancy. We compared the rate of pregnancy termination before and after 2003 and analyzed the accuracy of the prenatal CCA diagnosis. Of the 155 patients studied, 62 terminated the pregnancy. The overall rate of termination decreased from 31/70 to 31/85. When CCA was said to be isolated prenatally, the rate of pregnancy termination fell from 13/35 to 9/44 (-17 %) (p

Babesia bovis is a tick-borne pathogen that remains an important constraint for the development of cattle industries in tropical and subtropical regions of the world. Effective control can be achieved by vaccination with live attenuated phenotypes of the parasite. However, these phenotypes have a number of drawbacks, which justifies the search for new, more efficient immunogens based mainly on recombinant protein technology. In the present paper, ribosomal phosphoprotein P0 from a Brazilian isolate of B. bovis was produced and evaluated with regard to conservation and antigenicity. The protein sequence displayed high conservation between different Brazilian isolates of B. bovis and several Apicomplexa parasites such as Theileria, Neospora and Toxoplasma. IgG from cattle experimentally and naturally infected with B. bovisas well as IgG1 and IgG2 from naturally infected cattle reacted with the recombinant protein. IgG from cattle experimentally infected with Babesia bigemina cross-reacted with B. bovis recombinant P0. These characteristics suggest that P0 is a potential antigen for recombinant vaccine preparations against bovine babesiosis.

A trial was conducted to evaluate the association between polymorphisms in, or close to, candidate genes and faecal egg counts (FEC) in sheep. Corriedale and Polwarth weaned ewe lambs from commercial flocks were submitted to three successive experimental challenges in naturally contaminated pastures in Southern Brazil. During the trial, Haemonchus contortus was the predominant parasite species. Individuals were phenotyped according to their post-challenge FEC averages. Polymorphisms at interleukin genes (IL-3, IL-4 and IL-5), located at sheep chromosome 5 (OAR5) and the microsatellite markers BM1815, CSRD226, OarHH56, and OMHCI, located at sheep chromosome 20 (OAR20), were tested. A forced PCR-RFLP method to genotype ovine IL-5 was also developed and described. Associations between phenotypes and genotypes were tested by allele substitution analyses. There was no significant association between logFEC and the polymorphisms examined here, except for IL-4 in the Corriedale population. Results showed that FEC averages were significantly reduced when IL-4 * B allele, the most frequent allele, was replaced by either IL-4 * A or IL-4 * C alleles ( P

Bovine babesiosis is a tick-borne disease caused by Babesia spp. haemoprotozoans. The disease is of great importance at tick enzootic unstable areas and hampers cattle production in several developing countries. The available immunisation alternatives are pre-immunition and attenuated vaccines. Despite being efficient and protective, they are unsafe as they use cattle blood cells as inoculum and may potentially spread other diseases. Another alternative to help in babesiosis control would be the identification of genetically resistant cattle to Babesia bovis infection. The objective of this work was to phenotype cattle based on primary response against B. bovis infection. Two-hundred and forty half-sib Hereford and Aberdeen Angus heifers (120 animals from each breed), 12-18-month-old naïve cattle, originated from a tick-free area in Southern Brazil, were used in the experiment. Animals were monitored following an inoculation with 1x10(7)B. bovis parasitised erythrocytes. Results showed three different phenotypes: 1-'susceptible', animals with babesiosis clinical signs that received treatment to avoid death; 2-'intermediate', animals with clinical signs: parasitaemia,or=21.5% reduction in packed cell volume (PCV) and increase in body temperature when compared to their pre-challenge physiological parameters, no specific treatment was needed as animals self recovered from the disease, and 3-'resistant', animals without clinical signs that showed B. bovis presence in blood smears,21.5% PCV reductions, with little or no increase in body temperature and no need for babesiosis treatment. The frequencies of each phenotype were: 45.4, 26.7, and 27.9%, respectively, demonstrating the existence of phenotypic variation for B. bovis in Bos taurus cattle.

Background and Purpose - The best time for administering anticoagulation therapy in acute cardioembolic stroke remains unclear. This prospective cohort study of patients with acute stroke and atrial fibrillation, evaluated (1) the risk of recurrent ischemic event and severe bleeding; (2) the risk factors for recurrence and bleeding; and (3) the risks of recurrence and bleeding associated with anticoagulant therapy and its starting time after the acute stroke. Methods - The primary outcome of this multicenter study was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding within 90 days from acute stroke. Results - Of the 1029 patients enrolled, 123 had 128 events (12.6%): 77 (7.6%) ischemic stroke or transient ischemic attack or systemic embolism, 37 (3.6%) symptomatic cerebral bleeding, and 14 (1.4%) major extracranial bleeding. At 90 days, 50% of the patients were either deceased or disabled (modified Rankin score ≥3), and 10.9% were deceased. High CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large ischemic lesion and type of anticoagulant were predictive factors for primary study outcome. At adjusted Cox regression analysis, initiating anticoagulants 4 to 14 days from stroke onset was associated with a significant reduction in primary study outcome, compared with initiating treatment before 4 or after 14 days: hazard ratio 0.53 (95% confidence interval 0.30-0.93). About 7% of the patients treated with oral anticoagulants alone had an outcome event compared with 16.8% and 12.3% of the patients treated with low molecular weight heparins alone or followed by oral anticoagulants, respectively (P=0.003). Conclusions - Acute stroke in atrial fibrillation patients is associated with high rates of ischemic recurrence and major bleeding at 90 days. This study has observed that high CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large ischemic lesions, and type of anticoagulant administered each independently led to a greater risk of recurrence and bleedings. Also, data showed that the best time for initiating anticoagulation treatment for secondary stroke prevention is 4 to 14 days from stroke onset. Moreover, patients treated with oral anticoagulants alone had better outcomes compared with patients treated with low molecular weight heparins alone or before oral anticoagulants. © 2015 American Heart Association, Inc.

To assess the relationship between tumor necrosis factor receptor II (TNF-RII) gene polymorphisms and sTNFRII plasma levels in healthy blood donors (HBDs) and in rheumatoid arthritis (RA) patients. 113 HBDs and 49 RA patients were genotyped for the T/G polymorphism in exon 6 of the TNF-RII gene. In the same cases, sTNF-RII plasma levels were determined by an enzyme-linked immunosorbent assay (ELISA) procedure. sTNF-RII levels were higher in RA patients than in HBDs (p0.0001). No difference in sTNF-RII levels arose between RA patients on low oral doses of glucocorticoids versus those not taking glucocorticoids. In healthy controls, we observed lower levels of the sTNF-RII in carriers of the TT genotype compared to TG/GG genotype (p = 0.04). In RA there was the same behaviour between TT and TG/GG carriers, even though the difference was not statistically significant. When analyzing the correlation between sTNF-RII plasma levels and disease activity parameters, significant correlations were seen with disease activity score (r = 0.40, p = 0.01), swollen joint count (r = 0.38, p = 0.01), and tender joint count (r = 0.42, p = 0.01), but not with erythrocyte sedimentation rate (r = 0.22, p = ns) nor with C-reactive protein (r = 0.14, p = NS). The correlation remained significant only in the RA subgroup carrying the TT genotype. Healthy donors carrying the TT genotype showed lower sTNF-RII plasma levels than carriers of the TG/GG genotypes, while in RA patients we observed only a trend.

This study analyses the associations between alleles at seven microsatellite markers located at the sheep chromosome 5—where the interleukin IL-3, IL-4 and IL-5 genes were mapped—and faecal egg counts (FEC) in two different flocks. The associations were analysed by estimating the average excess of alleles at each microsatellite marker on FEC. Three of the studied markers (CSRD2138, OarAE129 and TGLA176) showed significant associations with FEC in the Corriedale flock. Seven alleles at these microsatellite loci were associated with FEC and their effects ranged from −28 to +20%, relative to the FEC population mean. On the other hand, four alleles at CSRD2138 and TGLA176 microsatellite markers had significant associations with FEC in the Polwarth mob, with effects varying from −22 to −5%, relative to the FEC population mean. All microsatellites investigated presented high diversity in both flocks. Some alleles were breed specific. The CSRD2138 ∗ A allele was the only marker associated with consistent reductions in FEC for both breeds. These results indicate that markers or genes nearby the interleukin genes, such as the CSRD2138, might enhance host resistance to internal parasites in sheep by probably increasing effector cells and antibody responses.

To evaluate the usefulness of monitoring the pharmacokinetic of mycophenolic acid (MPA) in lupus nephritis (LN), in order to optimize the mycophenolate mofetil (MMF) dose in the single patient. Five consecutive patients with active LN were studied. After standard induction therapy with MMF, MMF was titrated to achieve a stable target of MPA-AUC0-12h of 45–60 mg.h/l during the maintenance treatment. For MPA assays, blood samples were collected at 0, ½, 1 ¼, 2, 4, 6, 8 and 12 h after the morning dose. Plasma MPA concentration was measured using a validated high-performance liquid chromatography. Treatment response was evaluated at baseline, i.e. at the end of the induction therapy and during maintenance therapy with MMF. The average whole follow-up was 21.4 months. At the last visit, a complete renal response was registered in all the five patients. No renal flares were observed. Glucocorticoids were suspended in all. The mean MPA-AUC0-12h of MMF at the last visit [56.74 (±2.9) mg.h/l] was significantly lower than MPA-AUC0-12h at baseline [98.7 (±24.6) mg.h/l] (p = 0.009), since the dose of MMF was significantly reduced in all the patients [from 2.8 g/day (±0.4) to 1.9 g/day (±0.4) (p = 0.018)] based on the target MPA-AUC. No severe adverse events were observed. Assessment of MPA pharmacokinetics may be useful to optimize the maintenance therapy of lupus nephritis with MMF, possibly improving the efficacy and minimizing the side effects.

Background Studies on the inflammatory process in the large airways of patients with mild/moderate COPD have shown a prevalent T lymphocyte and macrophage infiltration of the bronchial mucosa. However, bronchial inflammation in more severe disease has not been extensively studied. Objective The aim of the present study was to characterize the lymphocyte infiltration in the bronchial mucosa of subjects with severe, compared to mild, COPD, and to examine the relationship between airflow limitation and T lymphocyte numbers in the bronchial mucosa. Methods We examined bronchial biopsies obtained from nine smokers with severe airflow limitation, nine smokers with mild/moderate airflow limitation and 14 smokers with normal lung function. Immunohistochemical methods on cryostat sections were used to assess the number of CD3+, CD4+, CD8+ cells and the number of CD3+ cells coexpressing the chemokine receptor CCR5 (CCR5+CD3+) in the subepithelium. Results Subjects with severe COPD had lower numbers of CD3+, CD8+ and CCR5+CD3+ cells than mild/moderate COPD (P

Background A prolonged disease duration is associated to a lower chance to achieve disease remission in rheumatoid arthritis. Onset of the disease can be defined in a number of ways and, when possible, the following data should be recorded: 1) first musculoskeletal (MSK) symptoms relevant to the current compliant 2) first persistent patient-reported joint swelling 3) initial fulfilment of criteria for RA based on data obtained retrospectively 1 . Objectives The aim of this study was to identify the variables associated with ACR/EULAR remission 2 in a cohort of early rheumatoid arthritis (ERA). In particular, the different types of disease onset, as defined 1 , were investigated. Methods All the patients, referred to the Early Arthritis Clinic of the University Rheumatology Clinic of Udine between October 2013 and October 2015, with a diagnosis of RA and fulfilling ACR/EULAR 2010 criteria, were included. The EULAR recommendations for treat to target were followed. At the first visit, 13 clinical and laboratory variables associated with RA, including the different type of onset 1 , were recorded. The variables associated with remission at the 12th month (+12) of therapy by univariate analyses were included in a multivariate logistic regression model. Receiver operator characteristic (ROC) curves were used to evaluate the discriminative capability of the different types of onset. Results Ninety-two patients with ERA were assessed and 65 completed 12-month evaluation. 15/65 (23,1%) reached ACR/EULAR remission at +12. Two variables were selected in the logistic regression analysis (i.e. BMI and time to fulfilment of ACR/EULAR classification criteria). A low BMI (OR 0,54; CI 95% 0,33 to 0,86; p=0,01) predicted remission and 23,5 being the optimal BMI cut-off value. Time to fulfilment of ACR/EULAR classification criteria for RA was also significantly associated with remission at +12 (OR 0,21; CI 95% 0,05–0,92; p=0,039) and 2,5 months was the cut-off value showing the best discriminative power for remission achievement. By contrast, a shorter time from the onset of MSK symptoms (5.5 months showing the best discriminative power) was selected only by univariate analysis. Conclusions From a clinical perspective the present preliminary data may be reassuring if confirmed by larger analyses: a shorter time from the fulfilment of ACR/EULAR classification criteria of RA, when treatment has been frequently started (thus, not necessarily the time from the onset of MSK symptoms) is associated with disease remission at +12 in ERA. From a biologic point of view, starting the treatment as soon as disease begins (i.e. onset of MSK symptoms) may be more effective, but the currently available prognostic, diagnostic and treatment tools do not allow this recommendation yet. Furthermore remission is related to BMI, since patients with BMI >24 showed a lower chance to achieve remission References Gerlag D et al. Ann Rheum Dis. 2012 May;71(5):638–41.2012; Felson DT et al. Arthritis Rheum. 2011 Mar;63(3):573–86; Disclosure of Interest None declared

Situs viscerum inversus totalis is a rare defect with a genetic predisposition, which can present difficulties in the management of abdominal pathology, especially in laparoscopic surgery (mirror-image anatomy). We report the case of a 52-year-old female with situs viscerum inversus totalis, known from pediatric age, with a medical history of colic pain in the epigastrium radiating to the right abdominal quadrant. Laparoscopic cholecistectomy was safely performed with a three trocar technique. To the best of our knowledge this is the first time that laparoscopic cholecistectomy by three trocars was performed in a patient with situs viscerum inversus. We also review the relevant literature concerning this issue.

During rat liver regeneration, at the onset of S-phase of the first cell cycle, an enhanced mevalonate incorporation into prenylated proteins is observed. The analysis of the lipid moieties of such proteins shows a 20-fold increased content of geraniol and farnesol. The expected increase of farnesylated and geranylgeranylated proteins in pre-S phase is confirmed by an increased level of lamin A, B, C and of several GTP-binding proteins. These results suggest a relevance of both farnesylation and geranylgeranylation in this phase of the cell cycle.

Light-addressable potentiometric sensors (LAPS) based on metal/amorphous silicon/insulator structures, with Pd gate electrodes, have been fabricated and successfully operated as hydrogen sensors. The device response show a very good reproducibility and high stability allowing the possibility to detect a very low H 2 concentration.

Variations in membrane potential difference (PD) were observed between root cortical cells ofAllium porrum plants, uninfected and infected withGlomus E3: cell membrane potential was constantly hyperpolarised in the latter during the time course of infection and at all degrees of infection. This hyperpolarisation persisted in the presence of an inhibitor (2,4-dinitrophenol) and of an activator (fusicoccin) of transport membrane processes, suggesting that long-distance signals generated by the fungus could be involved.

Project mission was to mitigate the adverse economic effects of closing the U.S. Department of Energy's Pinellas Plant in Largo, Florida. This project was to facilitate the physical renovation of the plant and to help maintain and create jobs for the employees that worked at the plant when DOE terminated its operations. It also included finding and attracting high technology, industrial manufacturing and related firms to utilize the space and high tech equipment to remain at the plant. Stakeholders included the affected plant employees, local government and related public organizations, and businesses and universities in the Tampa Bay Florida area. The $17.6 million funded for this project helped produce 2,780 jobs at the Young - Rainey STAR Center at an average cost of $6,328. Rental income from STAR Center tenants and third party cash input amounted to approximately $66 million over the project period of 13.3 years.

PVTOL provides an object-oriented C++ API that hides the complexity of multicore architectures within a PGAS programming model, improving programmer productivity. Tasks and conduits enable data flow patterns such as pipelining and round-robining. Hierarchical maps concisely describe how to allocate hierarchical arrays across processor and memory hierarchies and provide a simple API for moving data across these hierarchies. Functors encapsulate computational kernels; new functors can be easily developed using the PVTOL API and can be fused for more efficient computation. Existing computation and communication technologies that are optimized for various architectures are used to achieve high performance. PVTOL abstracts the details of the underlying processor architectures to provide portability. We are actively developing PVTOL for Intel, PowerPC and Cell architectures and intend to add support for more computational kernels on these architectures. FPGAs are becoming popular for accelerating computation in both the high performance computing (HPC) and high performance embedded computing (HPEC) communities. Integrated processor-FPGA technologies are now available from both HPC and HPEC vendors, e.g. Cray and Mercury Computer Systems. We plan to support FPGAs as co-processors in PVTOL. Finally, automated mapping technology has been demonstrated with pMatlab. We plan to begin implementing automated mapping in PVTOL next year. Similar to PVL, as PVTOL matures and is used in more projects at Lincoln, we plan to propose concepts demonstrated in PVTOL to HPEC-SI for adoption into future versions of VSIPL++.

Background One of the most important outcomes of treatment in SpA is the retention rate of therapy in the long term. Many genetic studies in chronic polyarthritis reported a correlation between response to anti-TNF therapy and several single nucleotide polymorphisms (SNPs), but the usefulness of this finding when related to the clinical outcome is ill defined. Objectives The primary endpoint of this study was to establish a possible correlation between several genetic polymorphisms, including ones never investigated before in SpA, and the retention rate of the first TNFa blocking agent, by comparing patients needing to switch the first anti-TNFa agent (Sw) to patients not needing to switch (NSw). To distinguish these two groups, a follow-up of at least one year was required. Methods 187 consecutive SpA patients (124 males and 63 females; mean age 52±30 years) were studied. All the patients had been followed up for at least 12 months after the introduction of the first anti-TNFα agent. The mean disease duration was 30±28 years (range 2-58 years). Seventy-four (39.6%) patients were diagnosed as affected by psoriatic arthritis (PsA), 66 (35.3%) by ankylosing spondylitis (AS) and 47 (25.1%) by undifferentiated spondyloarthritis (uSpA). Six SNPs were analysed: TNFα -308A>G (rs1800629), TNFR2 196M>R, IL-6 -174G>C (rs1800795), IL-6Ra, FCGR3A 158V>F (rs396991) and TGF-beta 869T>C (rs 19822073). The chi-squared or Fisher9s exact test and Mann–Whitney9s U-test were used. Results The TNFα and the IL-6 promoter polymorphisms were significantly associated with the NSw phenotype in SpA. In particular, the TNFα -308 AA/AG genotypes were found in 24.4% NSw vs 10.9% Sw patients (p=0.03) and the GG homozygosis of the IL-6 promoter polymorphism in 49.6% NSw vs 34.4% Sw patients (p=0.047). By multivariate analysis, the TNFα -308A allele as well as the presence of the IL-6 -174GG homozygosis resulted as independent biomarkers predicting survival of the first anti-TNFα therapy in SpA (p=0.007, OR 4.4, 95%CI 1.5-13.1, and p=0.035, OR 2.1, 95%CI 1.1-4.4, respectively). Also the male gender (p=0.001, OR 3.4, 95%CI 1.6-7.1) resulted an independent variable associated with the NSw phenotype. The other SNPs, located in the genes encoding TNFR2, IL-6Ra, TGFb and FCGR3A, did not show any significant association. No association was found between the BASDAI or DAS28 response at month +6 (for axial or peripheral involvement, respectively) and all the investigated polymorphisms. The exposure time to the anti-TNFα therapies was significantly higher in NSw in comparison with Sw (NSw: 58±25.9 months vs Sw: 30.8±20.2 months, p Conclusions The TNFα -308 and the IL-6 -174 promoter polymorphisms appear significantly associated with a higher efficacy of anti-TNFa therapy in SpA, expressed by the retention rate of the first anti-TNFα agent. This confirms the importance of the genetic background to optimize the management of the biologic agents in SpA. Disclosure of Interest None declared

The case of a 59-year-old man with a history of recurrent severe gastrointestinal bleeding due to Meckel's diverticulum is described. The diagnosis was achieved by means of capsule endoscopy. The histological examination revealed the presence of Meckel's diverticulum with ectopic gastric mucosa. The use of capsule endoscopy for the detection of Meckel's diverticulum is discussed.

Thrombocytopenia frequently complicates systemic lupus erythematosus (SLE), and its long-term management may be problematic. Intravenous immunoglobulins and high doses of steroids are often effective as induction therapy, but thrombocytopenia frequently relapses during steroid tapering. Several immunosuppressive agents have been evaluated as induction or maintenance therapy in small series or in case reports. We describe six consecutive unselected SLE patients where cyclosporin-A (CyA) was effective and safe in the long-term management of thrombocytopenia and allowed steroid tapering. One relapse occurred during CyA reduction and responded to CyA dose adjustment. Steroids could be stopped in three out of six patients, and were maintained at very low doses in the remaining patients. CyA was stopped in one patient after one year of treatment, without relapse at month 11+ from discontinuation. No severe side effects were documented. Overall, these data suggest that CyA may prove to be an effective and safe therapeutic option for SLE-related thrombocytopenia.

The aim of the present study was to analyze the role played by norepinephrine and epinephrine in Symptomatic (S) vs Non-Symptomatic (NS) subjects within a group of healthy volunteers undergoing a 4-hour-head-down bed rest study at -6 degrees.

Orthostatic intolerance is the most serious symptom of cardiovascular deconditioning induced by microgravity exposure. In fact the neural control mechanisms of the cardiovascular system are significantly affected by this condition. Non-invasive measurement of Heart Rate Variability (HRV) have been used as a valuable tool to characterize the ability of neuroendocrine regulatory systems to modulate the cardiovascular function by analyzing the spontaneous fluctuations of arterial pressure and heart period on a beat-to-beat basis. Concerning this, conflicting results have been reported on the heart rate and blood pressure variability responses during exposure to microgravity. These differences seem to be due to different experimental designs used. Moreover, the different behavior of normal subjects in response to orthostatic stress after HD, i.e. Symptomatic (S) or Non Symptomatic (NS), could play some roles in producing these discrepancies. Therefore the aim of the present study was to examine BP and HR variability before and after 4 hours of HD in two groups of normal subjects with and without symptoms of orthostatic intolerance to orthostatic stress.

Orthostatic intolerance, induced by microgravity exposure, has been hypothesized to be related to a disorder of the autonomic control of the cardiovascular system. Non-invasive measurement of Heart Rate Variability (HRV) have been used as a valuable tool to characterize the ability of the autonomic system to modulate the cardiovascular function by analyzing the spontaneous fluctuations of arterial pressure and heart period on a beat-to-beat basis. Concerning this, conflicting results have been reported on the heart rate and blood pressure variability responses during exposure to microG. These differences seem to be due to different experimental designes used. Moreover, the different behavior of normal subjects in response to orthostatic stress after HD, i.e. Symptomatic (S) or Non Symptomatic (NS), could play some role in producing these discrepancies [correction of dicrepancies]. In this study we suggest the analysis of "magnitude" or "volatility" as a new method to study HRV variability. The volatility is a measure of the beat-to-beat excursion capability of the heart, regardless to its direction (positive or negative): the higher the volatility, the greater the excursion. The aim of the present study was to examine R-R volatility before and after 4 hours of HD -6 degrees in normal subjects.

Objectives: To study –238 and +489 TNF-α polymorphisms in severe-unresponsive (more than 6 swollen joints and still active disease despite at least 6 months of DMARDs combination therapy) and mild-responsive (less than 3 swollen joints and good response to MTX or other conventional DMARDs) rheumatoid arthritis (RA). Methods: We investigated 100 RA patients (56 with severe and 44 with mild disease activity) and 45 healthy blood donors (HBDs). Genotyping was performed by PCR-restriction fragment lenght polymorphism procedure. Several clinical and serological parameters were also examined. Results: Severe RA patients disclosed the –238 GG genotype in 100% of the cases versus 95.5% in the mild-responsive patients and 91.2% in the HBDs. The +489 GG genotype disclosed only a trend towards a prevalence in severe RA patients. However the +489 A allele seems to associates with early onset, longer disease duration and longer responsiveness to conventional therapy. Conclusion: The -238 AG genotype is absent in severe-unresponsive RA, but present in mild-responsive RA subjects. Thus –238 GG homozygosity associates with severity and unresponsiveness. In contrast the +489 polymorphism does not segregate differently between responsive and unresponsive RA patients.

ABSTRACT A classification of nonmalignant lymphoproliferation in Sjogren's syndrome is presented, based on the results of international meetings regarding Sjogren's syndrome-associated lymphomagenesis and on our results of a clinico-pathologic and molecular study and long-term follow-up in well-characterized patients. Sjogren's syndrome pathobiology has similarities to hepatitis C virus-related B-cell lymphoproliferation. Antigen stimulation with the preferential expansion of rheumatoid factor-positive clones and specific immunoglobulin gene expression and recombination represent key biologic events in lymphoproliferation. This classification is based on the couplingof molecular and histological studies and may result in more selective treatment approaches.

Cardiovascular deconditioning and orthostatic intolerance are the main symptoms experienced by astronauts after space flights. Alterations in the cardiovascular neural regulation have been implicated in the genesis of these disorders, but the mechanisms have not been clearly established. Alterations in the reflex control of circulation from the arterial and cardiopulmonary baroreceptive areas have been mainly hypothesized on the basis of long-term simulated microgravity studies. However, symptoms of orthostatic intolerance, and even fainting, are also observed after short-term exposure to simulated micro-G conditions. The possibility does exist that short-term exposure to micro-G conditions could affect the cardiovascular regulation differently from long-term exposure. Previous studies from this laboratory have shown that arterial baroreflex control of heart rate is not altered after 4 hours Head Down (HD) at -6 degrees, whereas it is significantly decreased after 28 days. Again, the role played by possible disturbances of the vasomotor regulation in the genesis of orthostatic intolerance after short term exposure to simulated microgravity has not yet been clarified. The aim of this study was therefore to evaluate peripheral blood flow changes following 2 and 4 h HD -6 degrees in healthy volunteers.

Background TNF-α is thought to be the key driving cytokine in Rheumatoid Arthritis (RA) and recently became a therapeutic target for treatment of patients particularly resistant to conventional therapy. In our study we looked for a genetic background that should indicate some criteria to address RA patients towards more aggressive treatments with anti-TNF-α agents. Objectives We assessed the role of the -238 and +489 TNF-α gene polymorphisms in a series of patients with severe aggressive disease who were treated with anti-TNF-α therapy because of their poor response to a DMARDs combination strategy. The phenotypes of these patients were compared to those of a cohort of patients who had a good response to Methotrexate (MTX), thus revealing a mild/moderate disease. Methods One hundred and thirty-eight (138) RA patients and sixty-four (64) controls (Healthy Blood Donors, HBD) entered the study. RA patients were divided into 2 subgroups. Group A: 72 rheumatoids, called MTX-responders (MTX-R), who were in stable partial remission since at least six months after MTX treatment (15 mg/w weekly, range 10–25 mg/w). Stable partial remission was defined when patients had less than 3 swollen joints and a morning stiffness of less than 20’. Group B: 68 rheumatoids with still active disease (more than 6 swollen joints and a morning stiffness of at least 60’) despite 6 months of combination therapy (MTX + Sulphasalazine + Hydroxychloroquine or MTX + Cyclosporine, including low doses of prednisone, 5 mg/day). This group subsequently received anti-TNF-α therapy and was labelled as anti-TNF-treated, (TNF-T). Genotyping for -238 and +489 TNF-α polymorphisms was made according to Weiss et al.1 Statistical analyses (Odds Ratio, 95% Confidence Interval) were performed using Prism Software (Graph-Pad, S. Diego, CA 92121-USA). Results MTX-R had an overall frequency of GG homozygousity for the -238 polymorphism of 91.6% vs 92.2% in HBD, while in TNF-T subgroup the GG genotype had a frequency of 100% (OR = 13, CI = 0.7–240, p = 0.008 vs MTX-R). The comparison between TNF-T and HBD is similarly striking (POR = 12, CI = 0.7–230, p = 0.01). The major finding concerning the +489 polymorphism is the lower frequency of the AA genotype in RA in general (OR = 4.2, CI = 1–18, p = 0.01) and in TNF-T in particular. Conclusion The GG genotype for the -238 TNF-α polymorphism marks all patients who received anti-TNF-α therapy. This group of patients also showed a significant reduction of the AA genotype of the +489 polymorphism. This latter finding supports the hypothesis that the A allele of the +489 TNF-α intronic polymorphism is linked to a genetic setting that offers a less aggressive phenotype in RA. Reference Weiss, et al. N Engl J Med. 1996;334:1090–94

Background Non-neoplastic B-cell lymphoproliferation (NNBLP) is a common feature in Sjoegre’s syndrome (SS) and predisposes to non-Hodgkin’s lymphoma (NHL). It is characterised by extranodal or nodal organ involvement or by the presence of an M-component in biologic fluids, in particular mixed monoclonal cryglobulinemia (MMC). Objectives To better address the issue of SS-NNLP of Mucosa-Associated Lymphoid Tissue (MALT), usually involving the major salivary glands, we investigated 13 consecutive patients with primary SS and persistent parotid swelling (12F, 1M; mean age 59.5 years). Methods Clinical and pathologic results were integrated with molecular analyses of B-cell clonal expansion in synchronous and metachronous biopsies (mean follow-up: 5.3 years). Results At baseline 6/13 patients presented a parotid MESA with lymphoproliferative lesion (Group 1) and 7/13 a MESA with fully benign lymphoid infiltrate (Group 2), according to strict pathologic criteria.1 Tissue B-cell clonal expansion was monoclonal in 5/6 cases in Group 1 and oligo-polyclonal in 6/7 cases in Group 2. B-cell NHL evolution was observed in 2/6 cases in Group 1 and in 0/7 in Group 2. Only the 2 cases evolved into NHL presented previous molecular evidence of ongoing expansion of the same clone or clonal dissemination in multiple biopsies. By contrast, the clinical and laboratory features were not relevant either for the diagnosis of NNLP vs NHL or to predict NHL evolution. MMC was detected in 2/13 cases, not evolved into NHL. Conclusion Pathologic features are crucial to distinguish between non-neoplastic and neoplastic extranodal LP in SS. Molecular analyses of B-cell clonal expansion appear relevant to identify a subset of patients with higher risk of NHL progression. When considering the whole spectrum of NNLP in SS and a practical diagnostic approch (“real” disease entities,1–3), the following classification is proposed: a) Fully benign lymphoproliferation: fully benign lymphoid infiltrates in MALT sites or reactive lymphoadenopathy in the lack of M-component; b) Lymphoproliferative disorder: lymphoproliferative lesions in MALT sites, nodal atypical lymphoproliferative disorder or persistent MMC or M-component in biologic fluids. A consensus on the classification of NNLP in SS will allow cooperative studies to clarify disease pathobiology and the risk of NHL evolution and to optimise follow-up and treatment. References De Vita, et al. Arthritis Rheum. 1997;40:318 Skopouli, et al. Semin Arthritis Rheum. 2000;29:296 De Vita, et al. Arthritis Rheum. 2000;43:94

Background The importance of Fibronectin (Fn) in RA chronic synovial inflammation is increasing. There are at least 6 restriction fragment length polymorphisms (RFLPs) described so far in the Fn gene, but very few is known about their possible functional relevance. Objectives In this study we assessed the role of the Msp-I Fn gene polymorphism in a series of patients with severe aggressive disease who were treated with anti-TNF-α therapy because of their poor response to a DMARDs combination strategy. The phenotype of these patients were compared to those of a cohort of patients who had a good response to Methotrexate (MTX), thus revealing a mild/moderate disease. Methods Seventy-nine (79) RA patients and sixty-one (61) controls (Healthy Blood Donors, HBD) entered the study. RA patients were split into 2 subgroups: 57 rheumatoids in stable partial remission (less than 3 swollen joints and a morning stiffness of less than 20’) since at least six months after MTX treatment (15 mg/w weekly, range 10–25 mg/w), thus called MTX-responders (MTX-R) and 22 rheumatoids with still active disease (more than 6 swollen joints and a morning stiffness of at least 60’) despite 6 months of combination therapy (MTX + Sulphasalazine + Hydroxychloquine or MTX + Cyclosporine, including low doses of prednisone, 5 mg/day). This latter group received anti-TNF-α therapy and was then labelled anti-TNF-treated (TNF-T). Genotyping for the Msp-I Fn gene polymorphism was made according to Avila et al.,1 who named C the allele resistant to enzyme’s digestion and D the variant susceptible. Statistical analyses (Odds Ratio, 95% Confidence Interval) were performed using Prism software (Graph-Pad, S. Diego, CA 92121-USA). Results MTX-R had an overall frequency of DD homozygousity of 56.1% vs 52.5% in HBD, while in TNF-T subgroup the DD genotype had a frequency of 81.8% (OR = 4.1, CI = 1.2–13, p = 0.008 vs HBD). The comparison between TNF-T and MTX-R is similarly striking (OR = 3.5, CI = 1.1–12, p = 0.01). Conclusion The DD genotype for Msp-I Fn gene polymorphism marks the patients who received anti-TNF-α therapy and may lead to a more aggressive phenotype in RA. Reference Avila JJ, et al. Am J Respir Cell Mol Biol. 1999;20:106

On the basis of their personal experience, the Authors try to identify the salient aspects of the occupational stress and of the consequent burn-out syndrome in the health personnel of the Alzheimer Units of Lombardy. In these structures, the initial motivations, the emotional involvement, and the effort required by the job make the staff at high risk. The syndrome generally evolves through four stages (idealistic enthusiasm, stagnation, frustration, apathy) and may easily become a collective problem, with worsening of the quality of care and dispersion of economical resources. The occupational physician, possibly with the collaboration of the psychologist, should adopt adequate preventive, therapeutic, and rehabilitative measures, regarding both the work organization (stress reduction, creation of a group consciousness) and the single (professional training, psychological support, health surveillance).

Fas is a receptor of the tumor necrosis factor (TNF)/ nerve growth factor (NGF) receptor superfamily that mediates apoptosis and some inflammatory changes. As the central administration of TNF is known to activate the hypothalamus-pituitary-adrenal axis (HPAA) and to induce peripheral responses including induction of serum interleukin (IL)-6 and serum amyloid A (SAA), we investigated the effects of intracerebroventricular (i.c.v.) administration of agonist anti-Fas monoclonal antibody Jo2. Centrally administered anti-Fas (1 microg/mouse, i.c.v.) induced elevated levels of corticosterone, IL-6, and SAA comparable to those observed after i.c.v. administration of recombinant murine TNF. On the other hand, administration of murine NGF did not elevate serum corticosterone or IL-6, but induced SAA. Thus, Fas can trigger a centrally mediated anti-inflammatory response (HPAA activation) and induce a peripheral acute-phase response comparable to that induced with TNF, whereas NGF induces only acute-phase proteins.