Intraspecific C-value variation and the outcomes in Psidium cattleyanum Sabine essential oil.

Polyploidy, a numerical alteration of the karyotype, is one of the most important mechanisms in plant speciation and diversification, but could also be detected among populations, the cytotypes. For example, Psidium cattleyanum, a polyploid complex, has chromosome numbers ranging from 2n=3x=33 to 2n=12x=132. Polyploidization causes an increase in DNA content, and both modifications may cause alteration in plant growth, physiology, and epigenetics. Based on this possibility, here we aim to verify the influence of the polyploidization on the production of P. cattleyanum essential oil chemotypes. Differences in the DNA contents, as a proxy to different ploidies, were observed and three distinct chemotypes were identified through the chromatographic profile analysis. The Psidium cattleyanum DNA content and qualitative and quantitative characteristics of the essential oils presented a positive relationship. Plants with higher DNA contents presented higher levels of oil production, which was mostly composed of hydrogenated sesquiterpenes, while plants with lower DNA contents produced lower amount of oil, which was mostly composed of hydrogenated monoterpenes. Based on the importance of essential oils, polyploid plants, which present higher DNA content, are recommended as possible matrices for the propagation of new plants with the potential to produce major compounds of agronomic and pharmacological interest.

Phytotoxicity and cytogenetic action mechanism of leaf extracts of Psidium cattleyanum Sabine in plant bioassays.

The search for more environmental friendly herbicides, aiming at the control of agricultural pests, combinated with less harmfulness to human health and the environment has grown. An alternative used by researchers is the application of products of secondary plant metabolism, which are investigated due to their potential bioactivities. Thus, species belonging to the Myrtaceae family are potential in these studies, since this family is recognized for having high biological activity. A species belonging to this genus is Psidium cattleyanum, which has a medicinal effect and its fruits are used in human food. Thus, the objective of this research was to evaluate and compare the phyto-cyto-genotoxicity of aqueous and ethanolic leaf extracts of the specie P. cattleyanum, from plant bioassays, as well as to identify the main classes of compounds present in the extracts. For this, the extracts were prepared, characterized and biological tests were carried out by evaluating, in seeds and seedlings of lettuce and sorghum, the variables: percentage of germination, germination speed index, root growth and aerial growth; and in meristematic lettuce cells the variables: mitotic phases, mitotic index, nuclear alterations and chromosomal alterations. Flavones, flavonones, flavonols, flavononols, flavonoids, alkaloids, resins, xanthones and anthraquinone glycoside were characterized in the ethanolic extract. Both evaluated extracts, in the highest concentration, inhibited the initial plant development. All treatments caused alterations in the mitotic phases and inhibited mitotic index. In addition, the treatments promoted an increase in nuclear and chromosomal alterations. The mechanism of action presented was aneugenic, clastogenic and determined in epigenetic alterations. The ethanolic extract was more cytotoxic, since it had a more expressive effect at a lower concentration. Despite the cytotoxicity of the extracts under study, they promoted alterations at lower levels than the glyphosate positive control.

Multimodality imaging in connective tissue disease-related interstitial lung disease.

Interstitial lung disease is a well-recognised manifestation and a major cause of morbidity and mortality in patients with connective tissue diseases. Interstitial lung disease may arise in the context of an established connective tissue disease or be the initial manifestation of an otherwise occult autoimmune disorder. Early detection and characterisation are paramount for adequate patient management and require a multidisciplinary approach, in which imaging plays a vital role. Computed tomography is currently the imaging method of choice; however, other imaging techniques have recently been investigated, namely ultrasound, magnetic resonance imaging, and positron-emission tomography, with promising results. The aim of this review is to describe the imaging findings of connective tissue disease-related interstitial lung disease and explain the role of each imaging technique in diagnosis and disease characterisation.

Ventromedial medullary pathway mediating cardiac responses evoked from periaqueductal gray.

Periaqueductal gray (PAG) is a midbrain region that projects to areas controlling behavioral and autonomic outputs and is involved in the behavioral and physiological components of defense reactions. Since Raphe Pallidus (RPa) is a medial medullary region comprising sympathetic premotor neurons governing heart function, it is worth considering the PAG-RPa path. We assessed: i) whether PAG projects to RPa; ii) the amplitude of cardiac responses evoked from PAG; iii) whether cardiovascular responses evoked from PAG rely on RPa. Experiments conducted in Wistar rats (±300 g) were approved by Ethics Committee CEUA-UFG (092/18). Firstly, (n = 3), monosynaptic retrograde tracer Retrobeads was injected into RPa; PAG slices were analyzed. Other two groups (n = 6 each) were anesthetized with urethane (1.4 g/kg) and chloralose (120 mg/kg) and underwent craniotomy, tracheostomy, catheterization of femoral artery and vein and of cardiac left ventricle. In one group, we injected the GABAA receptor antagonist, bicuculline methiodide (BMI - 40 pmol/100 nL) into lateral/dorsolateral PAG. Another group was injected (100 nL) with the GABAA receptor agonist muscimol (20 mM) into RPa, 20 min before BMI into PAG. The results were: i) retrogradely labelled neurons were found in PAG; ii) PAG activation by BMI caused positive chronotropism and inotropism, which were accompanied by afterload increases; iii) RPa inhibition with Muscimol reduced heart rate, arterial and ventricular pressures; iv) the subsequent PAG activation still increased arterial pressure, cardiac chronotropy and inotropy, but these responses were significantly attenuated. In conclusion, PAG activation increases cardiac chronotropy and inotropy, and these responses seem to rely on a direct pathway reaching ventromedial medullary RPa neurons.

Ocular involvement in systemic lupus erythematosus patients: a paradigm shift based on the experience of a tertiary referral center.

OBJECTIVE: To evaluate ocular involvement in a cohort of systemic lupus erythematosus (SLE) patients of a tertiary referral center and to compare the results with the existing literature. METHODS: Patients underwent a complete ophthalmological evaluation, including visual acuity, slit-lamp examination, fluorescein staining, Schirmer-I test, Goldmann applanation tonometry, fundoscopy, 10-2 automated threshold visual fields, fundus autofluorescence and spectral-domain optical coherence tomography to screen for hydroxychloroquine (HCQ) macular toxicity. RESULTS: A total of 161 patients (16 men and 145 women) were enrolled in this study. The mean age was 47.6 years and the mean disease duration was 11.5 years. Fifty patients (31.1%) had at least one ocular manifestation of SLE. The most frequent manifestation was dry eye syndrome (12.4%), immediately followed by cataracts (11.2%) and HCQ macular toxicity (11.2%). Among patients with HCQ maculopathy, two presented with an atypical spectral-domain optical coherence tomography pattern. Five patients (3.1%) presented with glaucoma, two patients (1.2%) presented with SLE retinopathy while only one presented with lupus choroidopathy (0.6%). CONCLUSIONS: Compared with previous studies, we conclude there has been a significant reduction in disease-related ocular complications, particularly those associated with poor systemic disease control. On the other hand, drug and age-related complications are assuming a prominent role in the ophthalmic care of these patients.

DISSEQT-DIStribution-based modeling of SEQuence space Time dynamics.

Rapidly evolving microbes are a challenge to model because of the volatile, complex, and dynamic nature of their populations. We developed the DISSEQT pipeline (DIStribution-based SEQuence space Time dynamics) for analyzing, visualizing, and predicting the evolution of heterogeneous biological populations in multidimensional genetic space, suited for population-based modeling of deep sequencing and high-throughput data. The pipeline is openly available on GitHub (https://github.com/rasmushenningsson/DISSEQT.jl, accessed 23 June 2019) and Synapse (https://www.synapse.org/#!Synapse: syn11425758, accessed 23 June 2019), covering the entire workflow from read alignment to visualization of results. Our pipeline is centered around robust dimension and model reduction algorithms for analysis of genotypic data with additional capabilities for including phenotypic features to explore dynamic genotype-phenotype maps. We illustrate its utility and capacity with examples from evolving RNA virus populations, which present one of the highest degrees of genetic heterogeneity within a given population found in nature. Using our pipeline, we empirically reconstruct the evolutionary trajectories of evolving populations in sequence space and genotype-phenotype fitness landscapes. We show that while sequence space is vastly multidimensional, the relevant genetic space of evolving microbial populations is of intrinsically low dimension. In addition, evolutionary trajectories of these populations can be faithfully monitored to identify the key minority genotypes contributing most to evolution. Finally, we show that empirical fitness landscapes, when reconstructed to include minority variants, can predict phenotype from genotype with high accuracy.

Vulnerability of seagrass blue carbon to microbial attack following exposure to warming and oxygen.

Seagrass meadows store globally-significant quantities of organic 'blue' carbon. These blue carbon stocks are potentially vulnerable to anthropogenic stressors (e.g. coastal development, climate change). Here, we tested the impact of oxygen exposure and warming (major consequences of human disturbance) on rates of microbial carbon break-down in seagrass sediments. Active microbes occurred throughout seagrass sediment profiles, but deep, ancient sediments (~5000 yrs. old) contained only 3% of the abundance of active microbes as young, surface sediments (<2 yrs. old). Metagenomic analysis revealed that microbial community structure and function changed with depth, with a shift from proteobacteria and high levels of genes involved in sulfur cycling in the near surface samples, to a higher proportion of firmicutes and euraracheota and genes involved in methanogenesis at depth. Ancient carbon consisted almost entirely (97%) of carbon considered 'thermally recalcitrant', and therefore presumably inaccessible to microbial attack. Experimental warming had little impact on carbon; however, exposure of ancient sediments to oxygen increased microbial abundance, carbon uptake and sediment carbon turnover (34-38 fold). Overall, this study provides detailed characterization of seagrass blue carbon (chemical stability, age, associated microbes) and suggests that environmental disturbances that expose coastal sediments to oxygen (e.g. dredging) have the capacity to diminish seagrass sediment carbon stocks by facilitating microbial remineralisation.

Comparación intraindividual de la PET/TC con 68Ga-DOTATATE vs. PET/TC con 11C-colina en pacientes con cáncer de próstata en recaída bioquímica: evaluación in vivo de la expresión de receptores de la somatostatina / Intraindividual comparison of 68Ga-DOTATATE PET / CT vs 11C-Choline PET / CT in patients with prostate cancer in biochemical relapse: in vivo evaluation of the expression of somatostatin receptors

Antecedentes y objetivos: Comparar prospectivamente la tasa de detección de la PET/TC con 68Ga-DOTATATE versus 11C-colina en pacientes con cáncer de próstata en recaída bioquímica y evaluar in vivo la expresión de receptores de la somatostatina con el fin de planificar terapias dirigidas (177Lu-DOTATATE). Material y métodos: Analizamos prospectivamente 64 pacientes con recaída bioquímica (mediana PSA: 4,25 ng/mL). Se realizó una PET/TC con 11C-colina y otra con 68Ga-DOTATATE. Se midió el SUVmáx en todas las lesiones. Se consideraron como patrón de referencia las imágenes correlativas, histopatología y/o seguimiento clínico y bioquímico. Resultados: La tasa de detección global por paciente fue del 48,43% para 68Ga-DOTATATE y de 46,87% para 11C-colina. Los resultados fueron concordantes en 53 casos (82,81%). El SUV máximo de la 11C-colina fue significativamente mayor que el correspondiente al 68Ga-DOTATATE para todas las lesiones concordantes (n = 130): 6,17 (1,7-15,5) versus 4,38 (1,37-26,7), mediana (rango), para cada radiotrazador, respectivamente (P < 0,0001). Los valores por paciente de sensibilidad y especificidad fueron los mismos para ambas técnicas: 0,82 (0,65-0,93) y 0,9 (0,73-0,98), respectivamente. Aunque la diferencia no fue estadísticamente significativa, la sensibilidad fue menor para pacientes con niveles de PSA inferiores: 0,63 vs. 0,89; p = 0,13. Se encontró una correlación significativa entre el SUVmáx de ambos trazadores (r = 0,41, n = 130, p < 0,0001). Conclusiones: La PET/TC con 68Ga-DOTATATE y la PET/TC con 11C-colina parecen poseer alta capacidad de detección de lesiones patológicas en la evaluación de los pacientes con cáncer de próstata en recaída bioquímica. Se necesitan más estudios con el fin de probar el posible valor clínico complementario de estas técnicas PET/TC, y para el 68Ga-DOTATATE para la potencial planificación de terapias mediadas por los receptores de somatostatina (177Lu-DOTATATE)

Background and objectives: To prospectively compare the detection rate of 68Ga-DOTATATE versus 11C-choline PET/CT in patients with prostate cancer in biochemical relapse, and to evaluate somatostatin receptor expression in vivo to plan targeted therapies (177Lu-DOTATATE). Material and methods: We prospectively analysed 64 patients with biochemical relapse (median PSA: 4.25 ng/mL). A PET/CT was performed with 11C-choline, and another with 68Ga-DOTATATE. The SUVmax was measured in all lesions. The correlative images, histopathology and/or clinical and biochemical follow-up were taken as the reference standard. Results: The overall detection rate per patient was 48.43% for 68Ga-DOTATATE and 46.87% for 11C-choline. The results were concordant in 53 cases (82.81%). The maximum SUV of 11C-choline was significantly higher than that of 68Ga-DOTATATE for all the concordant lesions (n=130): 6.17 (1.7-15.5) versus 4.38 (1.37-26.7), median (range) for each radiotracer, respectively (p < .0001). The sensitivity and specificity values per patient were the same for both techniques: 0.82 (0.65-0.93) and 0.9 (0.73-0.98), respectively. Although the difference was not significant, the sensitivity was lower in patients with lower PSA levels: 0.63 vs. 0.89; p=.13. A significant correlation was found between the SUVmax of both tracers (r = 0.41, n = 130, p <.0001). Conclusions: 68Ga-DOTATATE PET/CT and 11C-choline PET/CT seem to have a high capacity to detect pathological lesions in the assessment of patients with prostate cancer with biochemical relapse. Further studies are required to test the potential complementary value of these PET/CT techniques, and to evaluate the potential role of 8Ga-DOTATATE for planning somostatin receptor-mediated therapies (177Lu-DOTATATE)

Intraindividual comparison of 68Ga-DOTATATE PET / CT vs 11C-Choline PET / CT in patients with prostate cancer in biochemical relapse: in vivo evaluation of the expression of somatostatin receptors. / Comparación intraindividual de la PET/TC con 68Ga-DOTATATE vs. PET/TC con 11C-colina en pacientes con cáncer de próstata en recaída bioquímica: evaluación in vivo de la expresión de receptores de la somatostatina.

BACKGROUND AND OBJECTIVES: To prospectively compare the detection rate of 68Ga-DOTATATE versus 11C-choline PET/CT in patients with prostate cancer in biochemical relapse, and to evaluate somatostatin receptor expression in vivo to plan targeted therapies (177Lu-DOTATATE). MATERIAL AND METHODS: We prospectively analysed 64 patients with biochemical relapse (median PSA: 4.25 ng/mL). A PET/CT was performed with 11C-choline, and another with 68Ga-DOTATATE. The SUVmax was measured in all lesions. The correlative images, histopathology and/or clinical and biochemical follow-up were taken as the reference standard. RESULTS: The overall detection rate per patient was 48.43% for 68Ga-DOTATATE and 46.87% for 11C-choline. The results were concordant in 53 cases (82.81%). The maximum SUV of 11C-choline was significantly higher than that of 68Ga-DOTATATE for all the concordant lesions (n=130): 6.17 (1.7-15.5) versus 4.38 (1.37-26.7), median (range) for each radiotracer, respectively (p < .0001). The sensitivity and specificity values per patient were the same for both techniques: 0.82 (0.65-0.93) and 0.9 (0.73-0.98), respectively. Although the difference was not significant, the sensitivity was lower in patients with lower PSA levels: 0.63 vs. 0.89; p=.13. A significant correlation was found between the SUVmax of both tracers (r = 0.41, n = 130, p <.0001). CONCLUSIONS: 68Ga-DOTATATE PET/CT and 11C-choline PET/CT seem to have a high capacity to detect pathological lesions in the assessment of patients with prostate cancer with biochemical relapse. Further studies are required to test the potential complementary value of these PET/CT techniques, and to evaluate the potential role of 8Ga-DOTATATE for planning somostatin receptor-mediated therapies (177Lu-DOTATATE).

Hallazgo incidental de captación focal del colon en estudios 18F-FDG PET/TC / Incidental focal colonic uptake in studies 18F-FDG PET/CT

Objetivos. Evaluar la frecuencia de la captación focal de colon como observación incidental en estudios 18F-FDG PET/TC. Correlacionar dicho hallazgo con resultados histopatológicos. Material y métodos. Se analizaron de forma sistemática 30 estudios en los que se constató captación focal del colon de un total de 3.176 PET/TC con 18F-FDG. Se excluyeron pacientes con neoplasia colorrectal conocida. Se consignó el valor del SUV máximo (SUVm) y el hallazgo morfológico de la TC. Los estudios fueron informados por un médico radiólogo y un médico nuclear. Los hallazgos fueron correlacionados con la endoscopia y la anatomía patológica. Resultados. De los 30 pacientes con lesiones focales hipermetabólicas del colon (0,94%), 15 eran hombres y 15 mujeres con edades comprendidas entre los 27 y 73 años (media 55 años). Los motivos de realización de la PET/TC fueron: cáncer broncopulmonar (4), cáncer de mama (4), tumor de origen desconocido (4), melanoma (3), carcinoma renal (3), neoplasia de cuello uterino (2), adenocarcinoma de ovario (2) y otros (8). Se realizaron 23 fibrocolonoscopias (FCC): 10 pacientes (43,4%) presentaron lesiones malignas, 6 pacientes (26,1%) lesiones premalignas y en 7 pacientes (30,4%) no se identificó ninguna lesión o esta fue benigna. En 7 pacientes no se hizo endoscopia por diversos motivos (rechazo del paciente para realizar el estudio, enfermedad oncológica avanzada). Se correlacionó con valores de SUVm y no se encontraron diferencias estadísticamente significativas entre lesiones malignas-premalignas y las lesiones benignas. Conclusiones. La captación focal en colon de 18F-FDG tiene relevancia clínica sobre todo asociada a lesión morfológica en TC, puede tratarse de un segundo tumor o una lesión premaligna. Se recomienda que todas las captaciones focales del colon sean valoradas con endoscopia, tengan o no alteraciones en TC (AU)

Objectives. To assess the frequency of focal colonic uptake as an incidental observation in 18F-FDG PET/CT studies, and to correlate this finding with histopathological results. Material and methods. Out of a total of 3,176 PET/CT studies with 18F-FDG systematic analysis was carried out on 30 studies in which colonic focal uptake was observed. Patients with known colorectal neoplasia were excluded. The maximum standardised uptake values (SUVm) and the morphological findings provided by the CT were recorded. The studies were reported by a radiologist and a nuclear medicine doctor. The findings were compared with endoscopy and pathology findings. Results. Of the 30 patients with focal hypermetabolic lesions of the colon (0.94%), 15 were men and 15 were women with ages between 27 and 73 (mean 55 years). The reasons for PET/CT were bronchopulmonary cancer (4), breast cancer (4), tumour of unknown origin (4), melanoma (3), renal carcinoma (3), cervical neoplasia (2), adenocarcinoma of ovary (2), and others (8). Of the 23 colonoscopies performed, 10 patients (43.4%) had malignant lesions, 6 (26.1%) had pre-malignant lesions, and in 7 patients (30.4%) no lesion was identified or was benign. No endoscopy was performed on 7 patients for various reasons (patient refusal to perform the study, advanced oncological disease). An analysis was performed with the SUVm, with no statistically significant differences being found between malignant-premalignant lesions and benign lesions. Conclusions. Focal uptake in the colon of 18F-FDG has clinical relevance, and is mainly associated with morphological lesions in CT. It should be evaluated, as it may be a second tumour or a pre-malignant lesion. It is recommended that all focal uptakes of the colon be evaluated with endoscopy (AU)

Incidental focal colonic uptake in studies 18F-FDG PET/CT. / Hallazgo incidental de captación focal del colon en estudios 18F-FDG PET/TC.

OBJECTIVES: To assess the frequency of focal colonic uptake as an incidental observation in 18F-FDG PET/CT studies, and to correlate this finding with histopathological results. MATERIAL AND METHODS: Out of a total of 3,176 PET/CT studies with 18F-FDG systematic analysis was carried out on 30 studies in which colonic focal uptake was observed. Patients with known colorectal neoplasia were excluded. The maximum standardised uptake values (SUVm) and the morphological findings provided by the CT were recorded. The studies were reported by a radiologist and a nuclear medicine doctor. The findings were compared with endoscopy and pathology findings. RESULTS: Of the 30 patients with focal hypermetabolic lesions of the colon (0.94%), 15 were men and 15 were women with ages between 27 and 73 (mean 55 years). The reasons for PET/CT were bronchopulmonary cancer (4), breast cancer (4), tumour of unknown origin (4), melanoma (3), renal carcinoma (3), cervical neoplasia (2), adenocarcinoma of ovary (2), and others (8). Of the 23 colonoscopies performed, 10 patients (43.4%) had malignant lesions, 6 (26.1%) had pre-malignant lesions, and in 7 patients (30.4%) no lesion was identified or was benign. No endoscopy was performed on 7 patients for various reasons (patient refusal to perform the study, advanced oncological disease). An analysis was performed with the SUVm, with no statistically significant differences being found between malignant-premalignant lesions and benign lesions. CONCLUSIONS: Focal uptake in the colon of 18F-FDG has clinical relevance, and is mainly associated with morphological lesions in CT. It should be evaluated, as it may be a second tumour or a pre-malignant lesion. It is recommended that all focal uptakes of the colon be evaluated with endoscopy.

Immunodeficiency and autoimmunity coming together: a nearly missed diagnosis.

The coexistence of human immunodeficiency virus (HIV) and systemic lupus erythematosus (SLE) appears to be unusual and the prevalence of patients who carry the dual diagnosis is currently unknown. We hereby present a case of a C4 deficient HIV-1 positive Caucasian female under highly active antiretroviral therapy for the past eight years, admitted to hospital with an aggressive and potentially fatal clinical presentation of SLE. There was a favorable outcome despite a significant diagnostic delay. Despite its rarity, the case highlights that this association is remarkable and may be overlooked by clinicians familiar with either condition.

Estudio comparativo de los niveles plasmáticos de homocisteína, vitamina B12 y ácido fólico en pacientes epilépticos frente a controles / Comparative case-control study of homocysteine, vitamin B12, and folic acid levels in patients with epilepsy

Introducción: El aumento de homocisteína en sangre constituye un conocido factor de riesgo cardiovascular. Los pacientes epilépticos en tratamiento crónico con fármacos antiepilépticos pueden presentar niveles más elevados de homocisteína y, en consecuencia, un potencial aumento del riesgo cardiovascular. Material y métodos: Estudio observacional de casos y controles para la comparación de los niveles plasmáticos de homocisteína, ácido fólico y vitamina B12. Resultados: Se reclutó a un total de 88 sujetos, 52 de ellos epilépticos y 36 controles. Se observó una tendencia a niveles de homocisteína más elevados (p=0,084) en los pacientes epilépticos y unos valores de ácido fólico más bajos (p<0,05). Conclusiones: Por su potencial efecto como factor de riesgo cardiovascular, es importante prestar atención a los niveles de homocisteína en los pacientes epilépticos en tratamiento crónico con fármacos antiepilépticos y en caso de encontrar niveles elevados sugerimos la instauración de tratamiento específico (AU)

Introduction: Increased blood homocysteine levels are a known cardiovascular risk factor. Epileptic patients on long-term treatment with antiepileptic drugs may present higher homocysteine levels and, consequently, a potential increase in cardiovascular risk. Material and methods: We conducted an observational case-control study to compare plasma levels of homocysteine, folic acid, and vitamin B12. Results: Our study included a total of 88 subjects: 52 patients with epilepsy and 36 controls. Epileptic patients showed higher homocysteine levels (P=.084) and lower levels of folic acid (P<.05). Conclusion: Homocysteine levels should be monitored in epileptic patients on long-term treatment with antiepileptic drugs. We suggest starting specific treatment in patients with high homocysteine levels (AU)

Exposure to crack cocaine causes adverse effects on marine mussels Perna perna.

Our study aimed to evaluate crack cocaine effects in different life stages of the marine mussel Perna perna. For this purpose, fertilization rate, embryo-larval development, lysosomal membrane stability and DNA strand breaks were assessed. Effect concentrations in gametes and in larval development were found after 1h (IC50=23.53mg·L-1) and 48h (IC50=16.31mg·L-1), respectively. The highest tested concentration showing no acute toxicity (NOEC) was 10mg·L-1, while the lowest observed effect concentration (LOEC) was 20mg·L-1. NOEC concerning embryo-larval development was 0.625mg·L-1, while the LOEC was 1.25mg·L-1. Cyto-genotoxic effects were evidenced in mussels exposed to crack cocaine concentrations ranging from 5 to 500µg·L-1. Our results report the first data on effects of an illicit drug to marine organisms and should encourage further ecotoxicological studies of these contaminants of emerging concern in coastal ecosystems.

Two separate effects contribute to regulatory T cell defect in systemic lupus erythematosus patients and their unaffected relatives.

Forkhead box P3 (FoxP3)+ regulatory T cells (Tregs ) are functionally deficient in systemic lupus erythematosus (SLE), characterized by reduced surface CD25 [the interleukin (IL)-2 receptor alpha chain]. Low-dose IL-2 therapy is a promising current approach to correct this defect. To elucidate the origins of the SLE Treg phenotype, we studied its role through developmentally defined regulatory T cell (Treg ) subsets in 45 SLE patients, 103 SLE-unaffected first-degree relatives and 61 unrelated healthy control subjects, and genetic association with the CD25-encoding IL2RA locus. We identified two separate, uncorrelated effects contributing to Treg CD25. (1) SLE patients and unaffected relatives remarkably shared CD25 reduction versus controls, particularly in the developmentally earliest CD4+ FoxP3+ CD45RO- CD31+ recent thymic emigrant Tregs . This first component effect influenced the proportions of circulating CD4+ FoxP3high CD45RO+ activated Tregs . (2) In contrast, patients and unaffected relatives differed sharply in their activated Treg CD25 state: while relatives as control subjects up-regulated CD25 strongly in these cells during differentiation from naive Tregs , SLE patients specifically failed to do so. This CD25 up-regulation depended upon IL2RA genetic variation and was related functionally to the proliferation of activated Tregs , but not to their circulating numbers. Both effects were found related to T cell IL-2 production. Our results point to (1) a heritable, intrathymic mechanism responsible for reduced CD25 on early Tregs and decreased activation capacity in an extended risk population, which can be compensated by (2) functionally independent CD25 up-regulation upon peripheral Treg activation that is selectively deficient in patients. We expect that Treg -directed therapies can be monitored more effectively when taking this distinction into account.

EULAR recommendations for women's health and the management of family planning, assisted reproduction, pregnancy and menopause in patients with systemic lupus erythematosus and/or antiphospholipid syndrome.

OBJECTIVES: Develop recommendations for women's health issues and family planning in systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS). METHODS: Systematic review of evidence followed by modified Delphi method to compile questions, elicit expert opinions and reach consensus. RESULTS: Family planning should be discussed as early as possible after diagnosis. Most women can have successful pregnancies and measures can be taken to reduce the risks of adverse maternal or fetal outcomes. Risk stratification includes disease activity, autoantibody profile, previous vascular and pregnancy morbidity, hypertension and the use of drugs (emphasis on benefits from hydroxychloroquine and antiplatelets/anticoagulants). Hormonal contraception and menopause replacement therapy can be used in patients with stable/inactive disease and low risk of thrombosis. Fertility preservation with gonadotropin-releasing hormone analogues should be considered prior to the use of alkylating agents. Assisted reproduction techniques can be safely used in patients with stable/inactive disease; patients with positive antiphospholipid antibodies/APS should receive anticoagulation and/or low-dose aspirin. Assessment of disease activity, renal function and serological markers is important for diagnosing disease flares and monitoring for obstetrical adverse outcomes. Fetal monitoring includes Doppler ultrasonography and fetal biometry, particularly in the third trimester, to screen for placental insufficiency and small for gestational age fetuses. Screening for gynaecological malignancies is similar to the general population, with increased vigilance for cervical premalignant lesions if exposed to immunosuppressive drugs. Human papillomavirus immunisation can be used in women with stable/inactive disease. CONCLUSIONS: Recommendations for women's health issues in SLE and/or APS were developed using an evidence-based approach followed by expert consensus.