Objective
To evaluate sperm DNA fragmentation analysis in non-azoospermic male systemic lupus erythematosus (SLE) patients.
Methods
Twenty-eight consecutive male SLE patients (American College of ...Rheumatology criteria) and 34 healthy controls were evaluated for demographic/exposures data, urological evaluation, hormone profile and sperm analysis (including sperm DNA fragmentation). Clinical features, disease activity/damage scores and treatment were also evaluated.
Results
The median age (33 (20–52) vs. 36.5 (25–54) years, P = 0.329) and frequency of varicocele (25% vs. 32%, P = 0.183) were similar in SLE patients and healthy controls. Sperm DNA fragmentation showed significantly higher levels of cells class III (44 (9–88) vs. 16.5 (0–80)%, P = 0.001) and cell class IV (10.5 (3–86) vs. 7 (0–36)%, P = 0.039) in SLE. The sperm DNA fragmentation index was also significantly higher in SLE patients (62 (31–97) vs. 25.5 (0–100)%, P < 0.001). Conventional sperm parameters (including sperm count, motility and morphology) were similar in both groups. In SLE patients no correlations were observed between sperm DNA fragmentation index and age, disease duration, Systemic Lupus Erythematosus Disease Activity Index 2000 and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index scores, and cumulative dose of prednisone, hydroxychloroquine, intravenous cyclophosphamide, methotrexate, azathioprine and mycophenolate mofetil (P > 0.05). Further analysis of SLE patients treated with and without intravenous cyclophosphamide showed that total sperm motility was significantly lower in the former group (64% (15–83) vs. 72% (57–86), P = 0.024). The sperm DNA fragmentation index was alike in both groups (52.5 (31–95) vs. 67.5 (34–97)%, P = 0.185).
Conclusions
To our knowledge, this is the first demonstration that male non-azoospermic SLE patients have increased sperm DNA fragmentation without evident gonadal dysfunction. Intravenous cyclophosphamide does not seem to be a major determinant for this abnormality. Future prospective study is necessary to determine the impact of this alteration in these patients' fertility.
BackgroundCompEx is a composite outcome capturing severe asthma exacerbations, and acute worsening events (based on peak expiratory flow, reliever medication use and asthma symptoms). Tezepelumab, a ...human monoclonal antibody, targets thymic stromal lymphopoietin (TSLP). In the phase 3 NAVIGATOR study (NCT03347279), tezepelumab reduced the annualized rate of severe exacerbations by 56% versus placebo in patients with severe, uncontrolled asthma.ObjectiveTo evaluate the effect of tezepelumab on CompEx in NAVIGATOR.MethodsIn NAVIGATOR, patients (12–80 years old) were randomized 1:1 to receive tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks. This pre-specified analysis assessed the annualized rate of CompEx events over 52 weeks.ResultsAmong 1059 treated patients, the annualized CompEx event rate was reduced by 55% (95% CI: 45–62) with tezepelumab versus placebo (table 1). The number of events and the annualized event rate were greater for CompEx than for severe asthma exacerbations; both were lower with tezepelumab than placebo (table 1).Abstract S49 Table 1CompEx events and severe exacerbations in NAVIGATOR Treatment group Number of patients Number of events Total time atrisk (years) Annualized event rate (95% CI ) Rate ratio, tezepelumab vs placebo (95% CI ) CompEx events Tezepelumab 210 mg 528 718 491.2 1.77 (1.53–2.04) 0.45 (0.38–0.55) Placebo 531 1358 459.2 3.89 (3.41–4.43) Severe exacerbations Tezepelumab 210 mg 528 425 504.0 0.93 (0.80– 1.07) 0.44 (0.37–0.53) Placebo 531 878 482.1 2.10 (1.84– 2.39) CI, confidence interval.ConclusionTezepelumab reduced the CompEx event rate, a composite of severe asthma exacerbations and acute worsening events, versus placebo by a similar magnitude to the reduction in the rate of severe exacerbations, further demonstrating the efficacy of tezepelumab in adults and adolescents with severe, uncontrolled asthma.Please refer to page A210 for declarations of interest related to this abstract.
•Automatic monitoring of areas with soy.•Relations between deforestation in Amazonia and annual crop.•Conversion of soil use between forest-pasture-soy.•Agreement between entities for not planting ...soy in deforested areas.
Brazil is one of the world leaders in replacing forests with agriculture. Agribusiness has responded to international public opinion by introducing the Soy Moratorium, (SoyM), an agreement that aims to inhibit the destruction of forests to plant soy in the Brazilian Amazon. This pressure led to the creation of a joint working group comprised of representatives from the civil society, soy producers, and finally the Brazilian government. In this article, we analyze all the areas that were forested in 2006 and are now planted with soy in the Amazonian municipalities in the state of Mato Grosso. During the period in which we analyzed deforestation between 2009 and 2016, we identified 54 municipalities that were not in compliance with SoyM; a total of 59,972ha had been converted to soy plantation. These results can be ascribed to several reasons, one of which is, essentially, that SoyM has not been able to reach the offending producers. If we consider deforestation starting in 2006, the amount of soy grown in violation of SoyM would be equivalent to an estimated total of 350,000 tons−1, or 9700 truckloads, only in the 2016/17 harvest. Nevertheless, even with these less satisfactory results, SoyM, the first voluntary zero-deforestation agreement implemented in the tropics, should be seen as a commendable initiative to engage all segments, including society, the productive sector, and the government, in this process. It merely needs to be refined, with all the groups involved in discussing new strategies in an international forum.
Chronic urticaria (daily or almost daily symptoms lasting for more than six weeks) is characterized by wheals and erythema, with or without itching. A few case reports have shown chronic autoimmune ...urticaria at the beginning of systemic lupus erythematosus (SLE), particularly in adults. However, the prevalence of this manifestation in a lupus paediatric population was not studied. During 27 consecutive years, 5419 patients were followed up at our University Hospital and 271 (5%) had juvenile SLE (American College of Rheumatology criteria). Two of them (0.7%) had chronic and painless autoimmune urticaria as the first manifestation of juvenile SLE, and were reported herein. One case was a five-year old female with continuous widespread urticaria (duration 120 days), antinuclear antibodies (ANA) 1:640 (dense fine speckled pattern) and elevated complement levels. The juvenile SLE diagnosis was established after one year. The other case was a 13-year old female who had chronic widespread urticaria (lasting 45 days), ANA 1:160 (fine speckled pattern) and normal complement levels. The juvenile SLE diagnosis was established after three years. In conclusion, chronic autoimmune urticaria is very rare and may be the first lupus manifestation, particularly associated with the presence of autoantibodies. This study reinforces the importance of a rigorous follow-up in children and adolescents suffering from autoimmune urticaria due to the possibility of connective tissue disorders, such as paediatric lupus.
Temporomandibular joint (TMJ) disorder caused by occlusal trauma is one of the most controversial topics in dentistry. Experimental traumatic occlusion (ETO) induced by metal crowns cemented to ...mandibular first molars in rats causes a long-lasting nociceptive response. This study aimed to elucidate whether ETO generates an increase in inflammatory mediators in the TMJ. In addition, the impact of ETO on trigeminal ganglia, neurotransmitter release, and satellite glial cell (SGC) activation was investigated. ELISA revealed enhanced inflammatory mediators, including TNF-α, IL-1β, IL-6, CX3CL1, and ADAM-17 by Western blotting, in periarticular TMJ tissue after 28 d of ETO. In the trigeminal ganglia, ETO groups increased the release of the neurotransmitters substance P and glutamate. Overexpression of the AMPA receptor and upregulation of NMDA were observed in the 0.4- and 0.7-mm ETO groups, respectively, highlighting enhanced neuronal excitation. Increased IL-1β and COX-2 mRNA levels in the 0.7-mm ETO group confirmed trigeminal ganglia SGC activation. Immunofluorescence and electrophoresis of SGC revealed increased pERK expression in the 0.7-mm ETO group. ERK phosphorylation was shown to be nociceptive specific, with its upregulation occurring in cases of chronic inflammatory pain. Increased PKA mRNA levels were observed in the 0.4-mm ETO group, while CREB mRNA levels were upregulated for both ETO groups. Electrophoresis showed overexpression of sodium channel Nav 1.7 in the 0.7-mm ETO group, while immunofluorescence revealed that Nav 1.7 is expressed in sensory trigeminal ganglia cells. The results of this study suggest that occlusal trauma induces neuroimmune crosstalk, with synthesis of proinflammatory/pronociceptive mediators, which increases neuronal activity in trigeminal ganglia via the activation of an inflammatory response cascade to develop a persistent neuroinflammatory state that leads to central sensitization.
Low-voltage ride-through (LVRT) requirements demand wind-power plants to remain connected to the network in presence of grid-voltage dips. Most dips present positive-, negative-, and zero-sequence ...components. Hence, regulators based on symmetrical components are well suited to control grid-connected converters. A neutral-point-clamped topology has been considered as an active front end of a distributed power-generation system, following the trend of increasing power and voltage levels in wind-power systems. Three different current controllers based on symmetrical components and linear quadratic regulator have been considered. The performance of each controller is evaluated on LVRT requirement fulfillment, grid-current balancing, maximum grid-current value control, and oscillating power flow. Simulation and experimental results show that all three controllers meet LVRT requirements, although different system performance is found for each control approach. Therefore, controller selection depends on the system constraints and the type of preferred performance features.
BACKGROUNDImmune checkpoint inhibitors (ICIs) revolutionized non-small-cell lung cancer (NSCLC) treatment. However, improving patients' selection for this therapy is needed. Gene expression profile ...(GEP) is a promising biomarker tool. We assessed the predictive value of 48 onco-immune GEPs in an NSCLC real-world scenario.METHODSRetrospective cohort of Brazilian NSCLC patients treated with ICIs in any line. GEP was assessed in FFPE tumor tissue using the nCounter PanCancer IO360 panel, comprising 770 cancer immune genes.RESULTSThe median age of the 135 patients was 61 years old, most male (57.8 %), history of smoking (83.6 %), ECOG-PS 0-1 (88.7 %), clinical stage IV (91.9 %) and adenocarcinoma (65.1 %). First-line ICI in 40 % of cases, alone or in combination with chemotherapy. The median follow-up was 28 months, overall survival after starting immunotherapy (post-immunotherapy survival - PIS) was 17.8 months, and real-world progression-free survival was 5.5 months. The GEP analysis was possible in 66 patients. We found that 14 different GEPs associated with PIS, namely IDO1, PD-L2, Cytotoxicity, Cytotoxic Cells, IFN Downstream, CTLA4, PD-L1, TIGIT, Lymphoid, Immunoproteasome, Exhausted CD8, IFN Gamma, TIS and APM. TIS and IFN-γ were the most significant GEPs associated with favorable outcomes. The median PIS for patients with high TIS expression was 29.2 versus 15.5 months (HR 0.42; 95 %CI; 0.17-0.67; p<0.05) for those with low expression. Similar results were observed for IFN-γ.CONCLUSIONSThe TIS (tumor inflammation signature) and IFN-γ signatures constitute predictive biomarkers to identify patients with NSCLC patients who would possibly benefit from ICI therapies.
ObjectiveTo develop and validate a diagnostic score that aids in identifying macrophage activation syndrome (MAS) in patients with systemic juvenile idiopathic arthritis (sJIA).MethodsThe clinical ...and laboratory features of 362 patients with sJIA-associated MAS and 404 patients with active sJIA without evidence of MAS were collected in a multinational collaborative project. Eighty percent of the study population was used to develop the score and the remaining 20% constituted the validation sample. A Bayesian Model Averaging approach was used to assess the role of each clinical and laboratory variables in the diagnosis of MAS and to obtain the coefficients of selected variables. The final score, named MAS/sJIA (MS) score, resulted from the linear combination of these coefficients multiplied by the values of each variable. The cut-off that best discriminated MAS from active sJIA was calculated by means of receiver operating characteristic (ROC) curve analysis. Score performance was evaluated in both developmental and validation samples.ResultsThe MS score ranges from −8.4 to 41.8 and comprises seven variables: central nervous system dysfunction, haemorrhagic manifestations, active arthritis, platelet count, fibrinogen, lactate dehydrogenase and ferritin. A cut-off value ≥−2.1 revealed the best performance in discriminating MAS from active sJIA, with a sensitivity of 0.85, a specificity of 0.95 and a kappa value of 0.80. The good performance of the MS score was confirmed in the validation sample.ConclusionThe MS score is a powerful and feasible tool that may assist practitioners in making a timely diagnosis of MAS in patients with sJIA.
Light Detection and Ranging (LiDAR) has become a common means for predicting key forest structural attributes. The aim of this study was to explore the relationship between individual tree ...LiDAR-based metrics and field data on tree attributes from a tropical rainforest in Peninsular Malaysia, to assess the correlation between LiDAR and field data at the individual-tree level for aboveground biomass (AGB) estimates. The model was developed using multiple regression analysis, with a non-linear power model being used to fit the predictive models. The AGB model was developed based on estimated AGB at the field site and LiDAR data using the following methodology; (1) pooling of both field sample and LiDAR data, using ANCOVA to justify this approach, (2) selection of independent variables, (3) regression model development and (4) model assessment and validation. LiDAR height percentile (h80) and crown width (CW) measurement were found to best fit the data as evidenced by Adj-R² value of 0.63, root mean square error (RMSE) of the model of 14.8% and analysis of the residuals. This study provides an analytic framework for developing a predictive LiDAR-AGB model at tree level as LiDAR derived information helps natural resource managers to provide details of forest that could be derived from the biomass assessment to improve management decisions.
Systemic injections of nitric oxide synthase (NOS) inhibitors have been shown to decrease exploratory behavior in rats. This effect may be related to motor impairments since these drugs can induce ...catalepsy in rodents.
To compare the effects of two NOS inhibitors in tests aimed to investigate exploratory behavior and to assess motor control.
The acute effects of the NOS inhibitors NG-nitro- L-arginine ( L-NOARG, 10-80 mg/kg IP) and 7-nitroindazole (7-NIO, 3-30 mg/kg IP) on exploratory activity were analyzed in an open field arena. Drug effects on catalepsy were examined in the hanging-bar and wire-ring test. Footprint pattern after treatment with the two NOS inhibitors was evaluated and the results compared with those obtained with the dopamine D2 receptor antagonist haloperidol (1-2 mg/kg IP). Sub-chronic (twice a day for 4 days) effects of L-NOARG (40 mg/kg) or 7-NIO (30 mg/kg) were also tested in the open field arena and catalepsy test.
L-NOARG and 7-NIO decreased locomotion and rearing in the open field arena. Both drugs induced catalepsy in the hanging-bar test but did not change footprint pattern. The cataleptic effect of L-NOARG in the hanging bar and wire-ring tests were highly correlated ( r=0.927). The exploratory and cataleptic effects of L-NOARG and 7-NIO provided evidence for tolerance after sub-chronic treatment.
These results confirm that inhibition of neuronal NO formation induces impairment of exploratory behavior. This effect does not seem to involve aspects evaluated by footprint analysis, such as weight support, trunk stability and foot placement. They could, however, be related to drug-induced catalepsy.
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