Changes in mitochondrial morphology modulate LPS-induced loss of calcium homeostasis in BV-2 microglial cells.

Microglial activation involves both fragmentation of the mitochondrial network and changes in cellular Ca2+ homeostasis, but possible modifications in mitochondrial calcium uptake have never been described in this context. Here we report that activated microglial BV-2 cells have impaired mitochondrial calcium uptake, including lower calcium retention capacity and calcium uptake rates. These changes were not dependent on altered expression of the mitochondrial calcium uniporter. Respiratory capacity and the inner membrane potential, key determinants of mitochondrial calcium uptake, are both decreased in activated microglial BV-2 cells. Modified mitochondrial calcium uptake correlates with impaired cellular calcium signaling, including reduced ER calcium stores, and decreased replenishment by store operated calcium entry (SOCE). Induction of mitochondrial fragmentation through Mfn2 knockdown in control cells mimicked this effect, while inhibiting LPS-induced mitochondrial fragmentation by a dominant negative form of Drp1 prevented it. Overall, our results show that mitochondrial fragmentation induced by LPS promotes altered Ca2+ homeostasis in microglial cells, a new aspect of microglial activation that could be a key feature in the inflammatory role of these cells.

Effects of a randomized controlled trial of a brief, student-nurse led, parent-based sexual health intervention on parental protective factors and HPV vaccination uptake.

BACKGROUND: Parents play a pivotal role in adolescent sexual health and Human Papillomavirus (HPV) vaccination. Nurses are on the frontlines of healthcare and play a critical role in promoting HPV vaccination and parent-child sexual health communication. We enhanced the Families Talking Together (FTT) parent-based sexual health curriculum to include adolescent vaccinations herein, FTT + HPV, and trained student nurses to provide a strong HPV vaccination and parent-child sexual health communication endorsement. METHODS: Using a randomized attention-controlled trial design, we examined the efficacy of FTT + HPV among 519 parents and their 11-14 year old youth recruited from medically underserved communities between 2015 and 2018. Participants were recruited from 22 after-school programs (e.g., Boys and Girls Clubs) and 19 charter schools. For parents, we examined protective factors including parent-child sexual health communication and parental involvement. For youth, we examined sexual health knowledge, parent-child sexual health communication, and parent-child connectedness. To assess HPV vaccination initiation and completion, we searched IMMTRAC immunization registry records for 85% of youth and used parental report for youth without registry records. Group differences were calculated using the estimated mean difference at one- and six months post-intervention with significance set at the p < 0.05 level. RESULTS: Baseline rates of HPV vaccination were low at 55.7%. No significant difference between the groups was seen in vaccination initiation or completion rates by one-month post-intervention. However, by six-months post intervention, there was a significant difference between the groups with 70.3% of the intervention group initiating the HPV vaccination series vs. 60.6% for the control group (p = 0.02). No difference between the groups was found for HPV series completion at six-months. There were significant differences in condom knowledge (p = 0.04), parent-child connectedness (p = 0.04), and communication frequency (p = 0.001) with greater improvement in the intervention vs. the control group. Rates of sexual activity remained low in both groups throughout the six-month follow-up period. CONCLUSION: A brief parent-based adolescent sexual health and HPV vaccination intervention delivered by student nurses can improve sexual health outcomes including protective parental factors, adolescent sexual health knowledge, and HPV vaccination initiation rates. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02600884 . Prospectively registered September 1, 2015.

Wild carnivores, domestic dogs and ticks: shared parasitism in the Brazilian Cerrado.

The increase of contact between natural and rural areas is prominent in Brazil, due to agricultural activities and concern with the environmental conservation. In this context, domestic animals, wild fauna and humans are exposed to mutual exchange of parasites, microorganisms and diseases. We studied tick parasitism of wild carnivores and domestic dogs, and the environmental of questing ticks, in extensive cattle ranch areas intermingled with natural vegetation, and in a natural reserve, both in a region of Cerrado biome, Midwestern Brazil. From 2008 to 2015, we inspected 119 wild carnivores from nine species, and collected six tick species (Amblyomma sculptum, Amblyomma ovale, Amblyomma dubitatum, Amblyomma tigrinum, Dermacentor nitens and Rhipicephalus microplus). The most numerous and infested hosts were Cerdocyon thous, Lycalopex vetulus, Chrysocyon brachyurus, Puma concolor and Conepatus amazonicus. From 139 domestic dogs, we collected A. sculptum, Rhipicephalus sanguineus and R. microplus. From vegetation, samplings resulted in A. sculptum, A. dubitatum, A. ovale, Amblyomma rotundatum and R. microplus, with dominance of A. sculptum. Domestics and wild animals presented high overlapping of infestations by A. sculptum, a generalist and anthropophilic tick species. This tick is the most important vector of the Brazilian spotted fever, a lethal human disease. This fact elicits attention and requires efforts to monitor the presence of pathogens vectored by ticks circulating in this type of agroecosystem, including in other regions of the Brazil, because the most of the natural vegetation remaining have been increasingly immersed in pastures and agricultural matrix.

[Prevalence of transmitted drug resistance in HIV-infected treatment-naive patients in Chile]. / Prevalencia de resistencia transmitida a drogas antirretrovirales en pacientes con infección por VIH en Chile (2014-2018).

BACKGROUND: Transmitted drug resistance (TDR) occurs in patients with HIV infection who are not exposed to antiretroviral drugs but who are infected with a virus with mutations associated with resistance. AIM: To determine the prevalence of TDR and characterize HIV reverse transcriptase and protease mutation patterns. MATERIAL AND METHODS: HIV infected antiretroviral treatment-naive patients treated in three centers between 2014 and 2018 were studied. A genotyping study was carried out. The HIVdb Program (Stanford University) and the World Health Organization (WHO) TDR surveillance mutation list were used to register resistance-associated mutations. RESULTS: We enrolled 220 patients aged a median of 29 (interquartile range (IQR) 24-34) years, 99% men. Median CD4 count was 365 cells/µL (IQR 250-499 cells/µL) and median viral load was 39.150 copies/mL (IQR 9,270 -120,000). The overall prevalence of RTD was 10.45% (95% CI 6.7-15.2, N = 23/220). The higher frequency of TDR was against non-nucleoside reverse transcriptase inhibitors, reaching 9.0% (95% CI 5.6-13.6), followed by nucleoside reverse transcriptase inhibitors reaching 1.8% (95% CI 0.49-4.5) and protease inhibitors reaching 0.45% (95% CI 0.01-2.5). The mutations in reverse transcriptase were M41L, L210W, D67N, K70E, M184V, K103N (6.36%, 95% CI 3.5-10.4), G190A, E138A, K101E, and I84V in protease. CONCLUSIONS: These results should prompt a change in recommendations for starting antiretoviral therapy, especially in first-line regimens that include non-nucleoside reverse transcriptase inhibitors.

Correction to: Occurrence of anti-Leptospira spp. antibodies in Rhipidomys spp. from a forest fragment of the Brazilian Cerrado.

The original version of this article unfortunately contains an error. Vanessa do Nascimento Ramos was not included in the original article as one of the contributors. The name is now included in the authorgroup.

Excessive body fat linked to blunted somatosensory cortex response to general reward in adolescents.

BACKGROUND AND AIMS: The brain reward system is key to understanding adolescent obesity in the current obesogenic environment, rich in highly appetising stimuli, to which adolescents are particularly sensitive. We aimed to examine the association between body fat levels and brain reward system responsivity to general (monetary) rewards in male and female adolescents. METHODS: Sixty-eight adolescents (34 females; mean age (s.d.)= 16.56 (1.35)) were measured for body fat levels with bioelectric impedance, and underwent a functional magnetic resonance imaging (fMRI) scan during the Monetary Incentive Delay (MID) task. The MID task reliably elicits brain activations associated with two fundamental aspects of reward processing: anticipation and feedback. We conducted regression analyses to examine the association between body fat and brain reward system responsivity during reward anticipation and feedback, while controlling for sex, age and socioeconomic status. We also analysed the moderating impact of sex on the relationship between fat levels and brain responsivity measures. Brain imaging analyses were corrected for multiple comparisons, with a cluster-defining threshold of P<0.001, and minimum cluster size of 38 contiguous voxels. RESULTS: Higher body fat levels were associated with lower activation of the primary somatosensory cortex (S1) and the supramarginal gyrus during reward feedback after controlling for key sociodemographic variables. Although we did not find significant associations between body fat and brain activations during reward anticipation, S1/supramarginal gyrus activation during feedback was linked to increased negative prediction error, that is, less reward than expected, in illustrative post hoc analyses. Sex did not significantly moderate the association between body fat and brain activation in the MID task. CONCLUSIONS: In adolescents, higher adiposity is linked to hypo-responsivity of somatosensory regions during general (monetary) reward feedback. Findings suggest that adolescents with excess weight have blunted activation in somatosensory regions involved in reward feedback learning.

Predictive factors of flares in systemic lupus erythematosus patients: data from a multiethnic Latin American cohort.

Purpose The purpose of this paper is to determine the factors predictive of flares in systemic lupus erythematosus (SLE) patients. Methods A case-control study nested within the Grupo Latino Americano De Estudio de Lupus (GLADEL) cohort was conducted. Flare was defined as an increase ≥4 points in the SLEDAI. Cases were defined as patients with at least one flare. Controls were selected by matching cases by length of follow-up. Demographic and clinical manifestations were systematically recorded by a common protocol. Glucocorticoid use was recorded as average daily dose of prednisone and antimalarial use as percentage of time on antimalarial and categorized as never (0%), rarely (>0-25%), occasionally (>25%-50%), commonly (˃50%-75%) and frequently (˃75%). Immunosuppressive drugs were recorded as used or not used. The association between demographic, clinical manifestations, therapy and flares was examined using univariable and multivariable conditional logistic regression models. Results A total of 465 cases and controls were included. Mean age at diagnosis among cases and controls was 27.5 vs 29.9 years, p = 0.003; gender and ethnic distributions were comparable among both groups and so was the baseline SLEDAI. Independent factors protective of flares identified by multivariable analysis were older age at diagnosis (OR = 0.929 per every five years, 95% CI 0.869-0.975; p = 0.004) and antimalarial use (frequently vs never, OR = 0.722, 95% CI 0.522-0.998; p = 0.049) whereas azathioprine use (OR = 1.820, 95% CI 1.309-2.531; p < 0.001) and SLEDAI post-baseline were predictive of them (OR = 1.034, 95% CI 1.005-1.064; p = 0.022). Conclusions In this large, longitudinal Latin American cohort, older age at diagnosis and more frequent antimalarial use were protective whereas azathioprine use and higher disease activity were predictive of flares.

Early referral and control of disease's flares prevent Orthopedic and Hand Surgery Indication (OHSI) in a dynamic cohort of Hispanic early rheumatoid arthritis patients.

BACKGROUND: Reconstructive joint surgery is an indicator of poor prognosis in rheumatoid arthritis (RA). Objectives of this study were to describe the incidence rate of orthopedic and hand surgery indication (OHSI) in an ongoing cohort of Hispanic early RA patients treated according to a T2T strategy and to investigate predictors. METHODS: Through February 2018, the cohort comprised 185 patients recruited from 2004 onwards, with variable follow-up, and rheumatic assessments at fixed intervals that included prospective determination of OHSI. Charts were reviewed by a single data abstractor. OHSI incidence rate was calculated. A case-control study nested within a cohort investigated the predictors; cases (OHSI patients) were paired with controls (1:4) according to age, sex and autoantibodies. A logistic regression model included baseline and cumulative (up to OHSI or equivalent) variables related to disease activity, treatment and to persistence with therapy. The IRB approved the study. RESULTS: Patients from the cohort were predominantly middle-aged (mean ± SD age: 38.5 ± 12.9 years) females (87.6%) with 5.4 ± 2.6 months of disease duration. The cohort contributed to 1538 patient-years of follow-up. Twelve patients received incidental OHSI at a follow-up of 85 ± 44.5 months. The OHSI incident global rate was 8/1000 patient-years. Longer symptom duration at cohort referral (OR: 1.313, 95%CI: 1.02-1.68, p = 0.032) and a higher number of flares/patient (OR: 1.608, 95%CI: 1.05-1.61, p = 0.015) predicted OHSI. OHSI patients had more severe flares than their counterparts, and the opposite figure was true for mild flares. CONCLUSION: Early referral for appropriate management and flare control may prevent OHSI in Hispanic recent-onset RA patients.

Lack of efficacy of levetiracetam in oromandibular and cranial dystonia.

OBJECTIVE: To determine the efficacy of levetiracetam in oromandibular or cranial dystonia. METHODS: We recruited seven subjects with oromandibular or cranial dystonia. Five completed the study, median age was 71 years (range 42-79 years), median disease duration was 12 years (range 2-30 years). Participants were randomized to receive levetiracetam or placebo and were then crossed over. They titrated up to a total daily dose of 4000 mg or the maximum tolerated dose over 3 weeks and maintained that dose for another 3 weeks. The primary endpoint was the percent change of the eyes, mouth, speech, and swallowing Burke-Fahn-Marsden (BFM) subscores from baseline to weeks 6 and 14. Additional endpoints included the BFM subscore at weeks 3 and 11, and the global dystonia severity (GDS) subscore at weeks 3, 6, 11, and 14, as well as all adverse side effects. RESULTS: The mean percent increase in the BFM subscore (placebo: 31.25%, levetiracetam: 12.16%) was not significantly different between the two arms according to the Friedman analysis. The Wilcoxon signed-rank test showed that these percent changes were not significant, indicating that there was no statistical clinical worsening in either arm. The mean percent change of the BFM subscore at weeks 3 and 11 and the mean percent change of the GDS subscore at weeks 3, 6, 11, and 14 were not significantly different between the two arms, and the Wilcoxon signed-rank test did not show statistical significance. CONCLUSION: Levetiracetam does not appear to be efficacious in patients with oromandibular or cranial dystonia.

The added value of musculoskeletal ultrasound to clinical evaluation in the treatment decision of rheumatoid arthritis outpatients: physician experience matters.

BACKGROUND: Musculoskeletal ultrasound improves the accuracy of detecting the level of disease activity (DA) in RA patients, although its impact on the final treatment decision in a real clinical setting is uncertain. The objectives were to define the percentage of clinical scenarios from an ongoing cohort of RA outpatients in which the German Ultrasound Score on 7 joints (GUS-7) impacted the treatment and to explore if the impact differed between a senior rheumatologist (SR) vs. a trainee (TR). METHODS: Eighty-five consecutive and randomly selected RA outpatients underwent 170 assessments, 85 each by the SR and the TR. Initially, both physicians (blinded to each other) performed a rheumatic assessment and recommended a preliminary treatment. Then, the patients underwent the GUS-7 evaluation by an experienced rheumatologist blinded to clinical evaluations; selected joints of the clinically dominant hand were assessed by gray-scale and power Doppler (PD). In the final step, the TR and the SR integrated the GUS-7 findings with their previous evaluation and reviewed their recommendations. The patients received the final recommendation from the SR to avoid patient confusion. The study was approved by the Internal Review Board and all the patients signed informed consent. GUS-7 usefulness was separately evaluated by the SR and the TR according to a visual analogue scale (0 = not useful at all, 10 = very useful). Descriptive statistics were used. RESULTS: The patients were primarily middle-aged females (91.4%) with (mean ± SD) disease duration of 7.5 ± 3.9 years. The majority of them (69.2% according to TR and 71.8% to SR) were in DAS28-ESR-remission. In 34 of 170 clinical scenarios (20%), the GUS-7 findings modified the final treatment proposal; 24 of these scenarios were determined by the TR vs. 10 by the SR: 70.5% vs. 29.5%, p = 0.01. Treatment changes (increase, decrease and joint injection) were similar between both specialists. As expected, the TR rated the GUS-7 usefulness higher than the SR, particularly in the clinical scenarios where the GUS-7 findings impacted treatment. CONCLUSIONS: Musculoskeletal ultrasound added to standard rheumatic assessments impacted the treatment proposal in a limited number of patients; the impact was greater in the TR.

Hantavirus pulmonary syndrome and rodent reservoirs in the savanna-like biome of Brazil's southeastern region.

This paper describes the diversity of rodent fauna in an area endemic for hantavirus cardiopulmonary syndrome (HCPS) in Brazil, the population dynamics and the relationship of rodents with hantavirus in the Cerrado (savanna-like) biome. Additionally, an analysis is made of the partial S segment sequences of the hantaviruses obtained from serologically confirmed human HCPS cases and from rodent specimens. Rodents were collected during four campaigns. Human serum samples were collected from suspected cases of HCPS at hospitals in the state of Minas Gerais. The samples antibody-reactive by ELISA were processed by RT-PCR. The PCR product was amplified and sequenced. Hantavirus was detected only in Necromys lasiurus, the wild rodent species most prevalent in the Cerrado biome (min-max: 50-83·7%). All the six human serum samples were hantavirus seropositive and five showed amplified PCR products. The analysis of the nucleotide sequences showed the circulation of a single genotype, the Araraquara hantavirus. The environmental changes that have occurred in the Cerrado biome in recent decades have favoured N. lasiurus in interspecific competition of habitats, thus increasing the risk of contact between humans and rodent species infected with hantavirus. Our data corroborate the definition of N. lasiurus as the main hantavirus reservoir in the Cerrado biome.

Late-onset systemic lupus erythematosus in Latin Americans: a distinct subgroup?

OBJECTIVE: To examine the characteristics of patients who developed late onset systemic lupus erythematosus (SLE) in the GLADEL (Grupo Latino Americano de Estudio del Lupus) cohort of patients with SLE. METHODS: Patients with SLE of less than two years of disease duration, seen at 34 centers of nine Latin American countries, were included. Late-onset was defined as >50 years of age at time of first SLE-related symptom. Clinical and laboratory manifestations, activity index (SLEDAI), and damage index (SLICC/ACR- DI) were ascertained at time of entry and during the course (cumulative incidence). Features were compared between the two patient groups (<50 and ≥50) using descriptive statistics and hypothesis tests. Logistic regression was performed to examine the association of late-onset lupus, adjusting for other variables. RESULTS: Of the 1480 patients included, 102 patients (6.9 %) had late-onset SLE, 87% of which were female. Patients with late-onset SLE had a shorter follow-up (3.6 vs. 4.4 years, p < 0.002) and a longer time to diagnosis (10.1 vs. 5.8 months, p < 0.001) compared to the younger onset group. Malar rash, photosensitivity, and renal involvement were less prevalent while interstitial lung disease, pleural effusions, and sicca symptoms were more frequent in the older age group (p > 0.05). In multivariable analysis, late onset was independently associated with higher odds of ocular (OR = 3.66, 95% CI = 2.15-6.23), pulmonary (OR = 2.04, 95% CI = 1.01-4.11), and cardiovascular (OR = 1.76, 95% CI = 1.04-2.98) involvement and lower odds of cutaneous involvement (OR = 0.41, 95% CI = 0.21-0.80), number of cumulative SLE criteria (OR = 0.79, 95% CI = 0.64-0.97), use of cyclophosphamide (OR = 0.47, 95% CI = 0.24-0.95), and anti-RNP antibodies (OR = 0.43, 95% CI = 0.20-0.91). A Cox regression model revealed a higher risk of dying in older onset than the younger-onset SLE (OR = 2.61, 95% CI = 1.2-5.6). CONCLUSION: Late-onset SLE in Latin Americans had a distinct disease expression compared to the younger-onset group. The disease seems to be mild with lower cumulative SLE criteria, reduced renal/mucocutaneous involvements, and less use of cyclophosphamide. Nevertheless, these patients have a higher risk of death and of ocular, pulmonary, and cardiovascular involvements.

Rational application of adenosine deaminase activity in cerebrospinal fluid for the diagnosis of tuberculous meningitis.

PURPOSE: Tuberculous meningitis (TBM) is one of the most serious and difficult to diagnose manifestations of TB. An ADA value >9.5 IU/L has great sensitivity and specificity. However, all available studies have been conducted in areas of high endemicity, so we sought to determine the accuracy of ADA in a low endemicity area. METHODS: This retrospective study included 190 patients (105 men) who had ADA tested in CSF for some reason. Patients were classified as probable/certain TBM or non-TBM based on clinical and Thwaite's criteria. Optimal ADA cutoff was established by ROC curves and a predictive algorithm based on ADA and other CSF biochemical parameters was generated. RESULTS: Eleven patients were classified as probable/certain TBM. In a low endemicity area, the best ADA cutoff was 11.5 IU/L with 91 % sensitivity and 77.7 % specificity. We also developed a predictive algorithm based on the combination of ADA (>11.5 IU/L), glucose (<65 mg/dL) and leukocytes (≥13.5 cell/mm(3)) with increased accuracy (Se: 91 % Sp: 88 %). CONCLUSIONS: Optimal ADA cutoff value in areas of low TB endemicity is higher than previously reported. Our algorithm is more accurate than ADA activity alone with better sensitivity and specificity than previously reported algorithms.

Localized surface plasmon sensing based investigation of nanoscale metal oxidation kinetics.

The localized surface plasmon resonance (LSPR) of nanoparticles can be a powerful and sensitive probe of chemical changes in nanoscale volumes. Here we have used the LSPR of silver (Ag) to study the oxidation kinetics of nanoscopic volumes of cobalt (Co) metal. Bimetal nanoparticles of the immiscible Co-Ag system prepared by pulsed laser dewetting were aged in ambient air and the resulting changes to the LSPR signal and bandwidth were used to probe the oxidation kinetics. Co was found to preferentially oxidize first. This resulted in a significant enhancement by a factor of 8 or more in the lifetime of stable Ag plasmons over that of pure Ag. Theoretical modeling based on optical mean field approximation was able to predict the oxidation lifetimes and could help design stable Ag-based plasmonic nanoparticles for sensing applications.

The mental and subjective skin: Emotion, empathy, feelings and thermography.

We applied thermography to investigate the cognitive neuropsychology of emotions, using it as a somatic marker of subjective experience during emotional tasks. We obtained results that showed significant correlations between changes in facial temperature and mental set. The main result was the change in the temperature of the nose, which tended to decrease with negative valence stimuli but to increase with positive emotions and arousal patterns. However, temperature change was identified not only in the nose, but also in the forehead, the oro-facial area, the cheeks and in the face taken as a whole. Nevertheless, thermic facial changes, mostly nasal temperature changes, correlated positively with participants' empathy scores and their performance. We found that temperature changes in the face may reveal maps of bodily sensations associated with different emotions and feelings like love.

Jumping to Conclusions bias, BADE and Feedback Sensitivity in schizophrenia and schizotypy.

Several studies about schizophrenia have shown a cognitive bias named "Jumping to Conclusions" (JTC), defined as a decision made quickly on the basis of little evidence that occurs in these patients when performing probabilistic reasoning paradigms. The main objective of this study is to compare JTC bias and BADE (Bias Against Disconfirmatory Evidence) in patients with schizophrenia vs. participants with high/low schizotypy to understand the underlying mechanism of these cognitive biases. Probabilistic reasoning was assessed using a modified version of Drawing to Decision task. In addition to the traditional parameters of this task (Plausibility Rating (PR), Draws to Decision (DTD), BADE) we also calculated new parameters, overall accuracy and one named Feedback Sensitivity (FS) which lower scores shows greater use of feedback. The results of the study suggest a context effect: in the cued condition, there were not main differences between groups. In the uncued condition, we found higher JTC bias at stage 1 for patients. At the same time, PR at first stages related positively with Feedback Sensitivity and negatively with accuracy for patients and high schizotypy participants (high confidence is associated with worse performance and lower feedback use). BADE seems unrelated to JTC bias and FS. The results are discussed in terms of JTC like as a clinical bias and whether patients with schizophrenia are less able to use feedback.

3D phantom for image quality assessment of mammography systems.

Objective.To present an innovative approach for the design of a 3D mammographic phantom for medical equipment quality assessment, estimation of the glandular tissue percentage in the patient's breast, and emulation of microcalcification (µC) breast lesions.Approach.Contrast-to noise ratio (CNR) measurements, as well as spatial resolution and intensity-to-glandularity calibrations under mammography conditions were performed to assess the effectiveness of the phantom. CNR measurements were applied to different groups of calcium hydroxyapatite (HA) and aluminum oxide (AO)µCs ranging from 200 to 600µm. Spatial resolution was characterized using an aluminum plate contained in the phantom and standard linear figures of merit, such as the line spread function and modulation transfer function (MTF). The intensity-to-glandularity calibration was developed using an x-ray attenuation matrix within the phantom to estimate the glandular tissue percentage in a breast with a compressed thickness of 4 cm.Main results.For the prototype studied, the minimum confidence level for detecting HAµCs is 95.4%, while for AOµCs is above 68.3%. It was also possible to determine that the MTF of the commercial mammography machine used for this study at the Nyquist frequency is 41%. Additionally, a one-to-one intensity-to-glandularity calibration was obtained and verified with Monte-Carlo simulation results.Significance.The phantom provides traditional arrangements presented in accreditation phantoms, which makes it competitive with available devices, but excelling in regarding affordability, modularity, and inlays distribution. Moreover, its design allows to be positioned in close proximity to the patient's breast during a medical screening for a simultaneous x-ray imaging, such that the features of the phantom can be used as reference values to specify characteristics of the real breast tissue, such as proportion of glandular/adipose composition and/orµC type and size lesions.

Early disease activity suppression and younger age predict excellent outcome of recent-onset rheumatoid arthritis patients treated with conventional disease modifying anti-rheumatic drugs.

OBJECTIVES: Sustained remission (SR) is the target of treatment offered to patients with rheumatoid arthritis (RA). The objective of the present paper is to describe predictors of favourable outcomes in a cohort of early RA patients. METHODS: Data from 89 patients with 3 years of consecutive assessments and traditional treatment were analysed. SR was defined as ≥ 6 consecutive months with 2011 ACR/EULAR remission criteria. Excellent outcome (EO) was defined according to patient's perception. Descriptive statistics, logistic regression models and Cox regression were used. RESULTS: At baseline, patients were predominantly females (n=78), had rheumatoid factor (n=70) and (mean ± SD) age of 38.8 ± 13.6 years. After (mean ± SD) 37.1 ± 2.5 months, 75 patients achieved ≥ 1 SR state and 35 an EO. The former had lower disease activity, disability and comorbidity and better functional status at baseline than their counterparts (p ≤ 0.05); they also accumulated lesser disability (p ≤ 0.03). Lower C-reactive protein and disease activity and lesser comorbidity predict SR (p ≤ 0.04). Patients with EO were younger, better educated, had lower disease activity, better functional status and lesser comorbidity at baseline than their counterparts (p ≤ 0.05). They achieved a first sustained remission state (p ≤ 0.001) sooner and accumulated lesser disability and incident erosive disease (p ≤ 0.002). Younger age and lower disease activity were prognosticators of EO (p ≤ 0.02). When age, baseline disease activity and time to first SR were investigated as predictors of EO, younger age (HR:0.95, 95% CI: 0.91-0.98, p=0.003) and earlier SR (HR:0.49, 95% CI: 0.39-0.61, p ≤ 0.001) were relevant. CONCLUSIONS: Younger patients with lower disease activity achieved earlier SR which, in addition to age, was predictor of EO.

Self-organized bimetallic Ag-Co nanoparticles with tunable localized surface plasmons showing high environmental stability and sensitivity.

We demonstrate a promising synthesis route based on pulsed laser dewetting of bilayer films (Ag and Co) to make bimetallic nanoparticle arrays. By combining experiment and theory we establish a parameter space for the independent control of composition and diameter for the bimetallic nanoparticles. As a result, physical properties, such as the localized surface plasmon resonance (LSPR), that depend on particle size and composition can be readily tuned over a wavelength range one order of magnitude greater than for pure Ag nanoparticles. The LSPR detection sensitivity of the bimetallic nanoparticles with narrow size distribution was found to be high-comparable with pure Ag (∼60 nm/RIU). Moreover, they showed significantly higher long-term environmental stability over pure Ag.