Pregnancy outcomes in 1869 pregnancies in a large cohort from the Spanish Society of Rheumatology Lupus Register (RELESSER).

INTRODUCTION: Obstetric complications are more common in women with systemic lupus erythematosus (SLE) than in the general population. OBJECTIVE: To assess pregnancy outcomes in women with SLE from the RELESSER cohort after 12 years of follow-up. METHODS: A multicentre retrospective observational study was conducted. In addition to data from the RELESSER register, data were collected on obstetric/gynaecological variables and treatments received. The number of term pregnancies was compared between women with pregnancies before and after the diagnosis of SLE. Further, clinical and laboratory characteristics were compared between women with pregnancies before and after the diagnosis, on the one hand, and with and without complications during pregnancy, on the other. Bivariate and multivariate analyses were carried out to identify factors potentially associated with complications during pregnancy. RESULTS: A total of 809 women were included, with 1869 pregnancies, of which 1395 reached term. Women with pregnancies before the diagnosis of SLE had more pregnancies (2.37 vs 1.87) and a higher rate of term pregnancies (76.8% vs 69.8%, p < 0.001) compared to those with pregnancies after the diagnosis. Women with pregnancies before the diagnosis were diagnosed at an older age (43.4 vs 34.1 years) and had more comorbidities. No differences were observed between the groups with pregnancies before and after diagnosis in antibody profile, including anti-dsDNA, anti-Sm, anti-Ro, anti-La, lupus anticoagulant, anticardiolipin or anti-beta-2-glycoprotein. Overall, 114 out of the 809 women included in the study experienced complications during pregnancy, including miscarriage, preeclampsia/eclampsia, foetal death, and/or preterm birth. Women with complications had higher rates of antiphospholipid syndrome (40.5% vs 9.9%, p < 0.001) and higher rates of positivity for IgG anticardiolipin (33.9% vs 21.3%, p = 0.005), IgG anti-beta 2 glycoprotein (26.1% vs 14%, p = 0.007), and IgM anti-beta 2 glycoprotein (26.1% vs 16%, p = 0.032) antibodies, although no differences were found regarding lupus anticoagulant. Among the treatments received, only heparin was more commonly used by women with pregnancy complications. We did not find differences in corticosteroid or hydroxychloroquine use. CONCLUSIONS: The likelihood of term pregnancy is higher before the diagnosis of SLE. In our cohort, positivity for anticardiolipin IgG and anti-beta-2- glycoprotein IgG/IgM, but not lupus anticoagulant, was associated with a higher risk of poorer pregnancy outcomes.

New species and records of earthworms (Annelida, Oligochaeta: Crassiclitellata) in small holder farming systems in the Peruvian Amazon.

We examined external characters and internal anatomy, after dorsal dissection, of 11 species of Oligochaeta from the Peruvian Amazonia Loreto department. Four new species of families Glossoscolecidae and Rhinodrilidae and genera Righiodrilus and Martiodrilus are described here. Righiodrilus omagua, sp. nov., differs from other Righiodrilus by the presence of tubercula pubertatis in segments ½15, 15- ½18, 18; male pores located in intersegment 16/17; large seminal vesicles in segment 12 that extend until segment 24. Martiodrilus (Maipure) yurimaguensis, sp. nov., has a saddle-shaped clitellum in 14-1/4 25 and tubercula pubertatis between segments 1/318 -1/2 25. Martiodrilus (Maipure) tapiai, sp. nov., is differentiated from the others by the position of the tubercula pubertatis in 19-24, and the shape and size of spermathecae, common setae, ornamentation of genital setae and the location of male pores in intersegment 18/19. Martiodrilus (Martiodrilus) alegrei sp. nov., differs from other species of the genus by extension of tubercula pubertatis from 21 to 26, the number and shape of spermathecae. It is the only species of the genus that presents a single pair of spermathecae in segment 6. Additional records for the Peruvian Republic and the Amazonian region are also reported for Martiodrilus (Maipure) pano, Periscolex yuya, Pontoscolex (Pontoscolex) corethrurus, Rhinodrilus lavellei, Rhinodrilus pahanasii, Dichogaster (Diplothecodrilus) modiglianii and Ocnerodrilus occidentalis. With these new records, the earthworm fauna of Perú recorded so far increases to 36 species (21 native and 15 exotic), including eight native from Peruvian Amazonia Region. Many more species are still expected to be found.

Genome-wide analysis of Claviceps paspali: insights into the secretome of the main species causing ergot disease in Paspalum spp.

BACKGROUND: The phytopatogen Claviceps paspali is the causal agent of Ergot disease in Paspalum spp., which includes highly productive forage grasses such as P. dilatatum. This disease impacts dairy and beef production by affecting seed quality and producing mycotoxins that can affect performance in feeding animals. The molecular basis of pathogenicity of C. paspali remains unknown, which makes it more difficult to find solutions for this problem. Secreted proteins are related to fungi virulence and can manipulate plant immunity acting on different subcellular localizations. Therefore, identifying and characterizing secreted proteins in phytopathogenic fungi will provide a better understanding of how they overcome host defense and cause disease. The aim of this work is to analyze the whole genome sequences of three C. paspali isolates to obtain a comparative genome characterization based on possible secreted proteins and pathogenicity factors present in their genome. In planta RNA-seq analysis at an early stage of the interaction of C. paspali with P. dilatatum stigmas was also conducted in order to determine possible secreted proteins expressed in the infection process. RESULTS: C. paspali isolates had compact genomes and secretome which accounted for 4.6-4.9% of the predicted proteomes. More than 50% of the predicted secretome had no homology to known proteins. RNA-Seq revealed that three protein-coding genes predicted as secreted have mayor expression changes during 1 dpi vs 4 dpi. Also, three of the first 10 highly expressed genes in both time points were predicted as effector-like. CAZyme-like proteins were found in the predicted secretome and the most abundant family could be associated to pectine degradation. Based on this, pectine could be a main component affected by the cell wall degrading enzymes of C. paspali. CONCLUSIONS: Based on predictions from DNA sequence and RNA-seq, unique probable secreted proteins and probable pathogenicity factors were identified in C. paspali isolates. This information opens new avenues in the study of the biology of this fungus and how it modulates the interaction with its host. Knowledge of the diversity of the secretome and putative pathogenicity genes should facilitate future research in disease management of Claviceps spp.

Relevance of gastrointestinal manifestations in a large Spanish cohort of patients with systemic lupus erythematosus: what do we know?

OBJECTIVE: SLE can affect any part of the gastrointestinal (GI) tract. GI symptoms are reported to occur in >50% of SLE patients. To describe the GI manifestations of SLE in the RELESSER (Registry of SLE Patients of the Spanish Society of Rheumatology) cohort and to determine whether these are associated with a more severe disease, damage accrual and a worse prognosis. METHODS: We conducted a nationwide, retrospective, multicentre, cross-sectional cohort study of 3658 SLE patients who fulfil ≥4 ACR-97 criteria. Data on demographics, disease characteristics, activity (SLEDAI-2K or BILAG), damage (SLICC/ACR/DI) and therapies were collected. Demographic and clinical characteristics were compared between lupus patients with and without GI damage to establish whether GI damage is associated with a more severe disease. RESULTS: From 3654 lupus patients, 3.7% developed GI damage. Patients in this group (group 1) were older, they had longer disease duration, and were more likely to have vasculitis, renal disease and serositis than patients without GI damage (group 2). Hospitalizations and mortality were significantly higher in group 1. Patients in group 1 had higher modified SDI (SLICC Damage Index). The presence of oral ulcers reduced the risk of developing damage in 33% of patients. CONCLUSION: Having GI damage is associated with a worse prognosis. Patients on a high dose of glucocorticoids are at higher risk of developing GI damage which reinforces the strategy of minimizing glucocorticoids. Oral ulcers appear to decrease the risk of GI damage.

New Draft Genome Sequence of the Ergot Disease Fungus Claviceps paspali.

Here, we report a new draft genome sequence of an isolate of the ascomycete Claviceps paspali that is responsible for ergot disease in grasses of the Paspalum genus. This new draft genome sequence will provide useful data for evaluating intraspecies and interspecies genome variation in C. paspali and other Claviceps genus members.

Associated factors to serious infections in a large cohort of juvenile-onset systemic lupus erythematosus from Lupus Registry (RELESSER).

OBJECTIVE: To assess the incidence of serious infection (SI) and associated factors in a large juvenile-onset systemic lupus erythematosus (jSLE) retrospective cohort. METHODS: All patients in the Spanish Rheumatology Society Lupus Registry (RELESSER) who meet ≥4 ACR-97 SLE criteria and disease onset <18 years old (jSLE), were retrospectively investigated for SI (defined as either the need for hospitalization with antibacterial therapy for a potentially fatal infection or death caused by the infection). Standardized SI rate was calculated per 100 patient years. Patients with and without SI were compared. Bivariate and multivariate logistic and Cox regression models were built to calculate associated factors to SI and relative risks. RESULTS: A total of 353 jSLE patients were included: 88.7% female, 14.3 years (± 2.9) of age at diagnosis, 16.0 years (± 9.3) of disease duration and 31.5 years (±10.5) at end of follow-up. A total of 104 (29.5%) patients suffered 205 SI (1, 55.8%; 2-5, 38.4%; and ≥6, 5.8%). Incidence rate was 3.7 (95%CI: 3.2-4.2) SI per 100 patient years. Respiratory location and bacterial infections were the most frequent. Higher number of SLE classification criteria, SLICC/ACR DI score and immunosuppressants use were associated to the presence of SI. Associated factors to shorter time to first infection were higher number of SLE criteria, splenectomy and immunosuppressants use. CONCLUSIONS: The risk of SI in jSLE patients is significant and higher than aSLE. It is associated to higher number of SLE criteria, damage accrual, some immunosuppressants and splenectomy.

The protective effect of extra-virgin olive oil in the experimental model of multiple sclerosis in the rat.

This study has evaluated the effect of EVOO (Extra-Virgin olive oil), OA (oleic acid) and HT (hydroxytyrosol) in an induced model of MS through experimental autoimmune encephalomyelitis (EAE).Dark Agouti 2-month old rats (25 males) were divided into five groups: (i) control group, (ii) EAE group, (iii) EAE+EVOO, (iv) EAE+HT, and (v) EAE+OA. At 65 days, the animals were sacrificed and the glutathione redox system and bacterial lipopolysaccharide (LPS) and LPS-binding protein (LBP) products of the microbiota in brain, spinal cord, and blood were evaluated.Gastric administration of EVOO, OA, and HT reduced the degree of lipid and protein oxidation, and increased glutathione peroxidase, making it a diet-based mechanism for enhancing protection against oxidative damage. In addition, it reduced the levels of LPS and LBP, which appeared as being increased in the EAE correlated with the oxidative stress produced by the disease.

Tratamiento conservador del cáncer de mama y factores pronósticos de recidiva local / Conservative treatment of invasive breast cancer and prognostic factors of local recurrence

Introducción Actualmente, la cirugía conservadora seguida de radioterapia es el tratamiento de elección para los estadios tempranos de cáncer de mama ya que ha demostrado ser equivalente a la mastectomía en cuanto a la sobrevida. Sin embargo, la posibilidad de recidiva local luego del tratamiento conservador existe, y se han descripto diferentes factores pronósticos vinculados a ella. Objetivos Estimar la tasa de recidiva local en las pacientes con tratamiento quirúrgico conservador e identificar los parámetros relacionados con mayor riesgo de recidiva local de cáncer de mama. Material y método Se analizaron en forma retrospectiva y comparativa 450 pacientes operadas con cirugía conservadora con diagnóstico de cáncer de mama invasor, intervenidas entre enero de 2006 y diciembre de 2012. Se evaluaron las siguientes variables para recidiva local: edad, estado menopáusico, tamaño tumoral, tipo histológico, grado histológico, compromiso axilar, invasión linfovascular, componente intraductal extenso, receptores hormonales, her2, márgenes y multifocalidad. Resultados Con un seguimiento medio de 71,2 meses, la tasa de recidiva fue del 6,2% (28 de 450). El tiempo medio hasta la recidiva fue de 53 meses. En el análisis univariado, la edad menor a 35 años (p=0,0008), el estado premenopáusico (p=0,036), el tamaño tumoral mayor a 1 cm (p=0,04), el compromiso axilar (p=0,008), la invasión linfovascular (p=0,033) y el componente intraductal extenso (p=0,007) mostraron estar asociados a un mayor riesgo de recidiva local. En cambio, el tipo y grado histológico, los receptores hormonales, el her2, los márgenes y la multifocalidad no tuvieron relevancia en el desarrollo de la misma. Conclusiones Mediante este estudio, pudimos observar que la edad joven, la premenopausia, el tamaño tumoral, la enfermedad axilar y la presencia de invasión linfovascular y componente intraductal extenso en el tumor representan factores pronósticos de recidiva de cáncer de mama luego del tratamiento quirúrgico conservador.

Introduction Nowadays, breast conserving surgery followed by radiation therapy is the treatment of choice for early stage breast cancer, since it has proven to be equivalent to mastectomy in terms of survival. However, there is a possibility of recurrence after conservative treatment and there are different prognostic factor associated with it. Objectives To estimate the rate of local recurrence in patients with conservative treatment and identify the parameters related to the higher risk of breast cancer local recurrence. Materials and method Four hundred and fifty (450) patients operated on conservative surgery, between January 2006 and December 2012, with diagnose of invasive breast cancer, have been analyzed in a retrospective a comparative way. The following risk variables have been evaluated for local recurrence: age, menopausal status, tumor size, histologic type, histologic grade, nodal status, lymphovascular invasion, extensive intraductal component, hormone receptors, her2, margins status and multifocal tumors. Results For an average follow up of 72.2 months, the average rate of recurrence was 6.2% (28/450). The average relapse time was 53 months. On the univariate analysis, age lower than 35 years (p=0.0008), premenopausal status (p=0.036), tumor size larger than 1 cm (p=0.04), nodal status (p=0.008), lymphovascular invasion presence (p=0.033) and the extensive intraductal component presence (p=0.007) have shown to be associated with higher risk for local recurrence. On the other hand, histological type and grade, hormone receptors, her2, margin status and multifocal tumors had no relevance for development of local recurrence. Conclusions Through this study we were able to observe that young age, premenopausal, tumor size, nodal status, lymphovascular invasion presence, extensive intraductal component presence are indicators of an increased risk of local recurrence after conservative treatment.

Dose-dependent S-allyl cysteine ameliorates multiple sclerosis disease-related pathology by reducing oxidative stress and biomarkers of dysbiosis in experimental autoimmune encephalomyelitis.

Garlic is a component of the Mediterranean diet. S-allyl cysteine (SAC), the most common organosulphur present in garlic, possesses neuroprotective properties. This investigation was performed to evaluate the dose-dependent protective action of SAC on oxidative damage, inflammation and gut microbiota alterations biomarkers. Experimental autoimmune encephalomyelitis (EAE) as a model of multiple sclerosis (MS) was induced by the myelin oligodendrocyte glycoprotein (MOG), whose effects were quantified by examining the changes in: clinical score, lipid peroxidation products, carbonylated proteins, glutathione system, tumor necrosis factor alpha (TNFα), and lipopolysaccharide membrane bacteria (LPS). Our results reveal that MOG induces paralysis, oxidative damage and increases in LPS binding protein (LBP) and LPS levels. In this work, two doses of SAC were compared with two dose of N-acetyl cysteine (NAC). SAC was more effective than NAC and it prevented the harmful effects induced by MOG more effectively at the dose of 50mg/kg than that of 18mg/kg. Surprisingly, NAC increases LBP levels while SAC had not such negative effect. In conclusion the data show the ability of SAC to modify EAE evolution.

Macrosystematics of eutherian mammals combining HTS data to expand taxon coverage.

In the last few years high-throughput sequencing technologies have permitted significant advances in mammalian phylogenetic studies from a genomic perspective. However, these studies have been restricted to a sparse number of species with available reference genomes. Thus, several issues inside the eutherian mammals phylogeny remain unresolved. This may be due in part to limited taxon sampling, as taxonomic density is known to affect phylogenetic resolution. In this context, we present a protocol to increase taxon coverage using high-throughput sequencing data (RNA or DNA) generated for other biological studies and available in public databases. Following this procedure we addressed pending or controversial issues concerning the phylogenetic position of Dermoptera, Pholidota and Chiroptera, considering multiple and independent loci. Also for Chiroptera and Arctoidea we evaluated the relationships of the lineages that compose it. Although the maximum number of genes used is moderate (95), in some cases taxon coverage doubles that of previous related studies. Globally, all coalescent-based (STAR, MP-EST and ASTRAL) and concatenated (IQ-TREE and BEAST2) methods used for species tree reconstruction were consistent to each other and most of interrogated nodes received high statistical support.

Abdominal pain and syndrome of inappropriate antidiuretic hormone secretion as clinical presentation of acute intermittent porphyria. / Dolor abdominal y síndrome de secreción inadecuada de hormona antidiurética, forma de presentación de porfiria aguda intermitente.

Acute intermittent porphyria (AIP) is a rare condition characterized by abdominal pain and a wide range of nonspecific symptoms. We report the case of a woman with abdominal pain and syndrome of inappropriate antidiuretic hormone secretion (SIADH) as clinical presentation of AIP. The diagnosis was achieved through the etiologic study of the SIADH.

Genetic diversity analysis of the Uruguayan Creole cattle breed using microsatellites and mtDNA markers.

The Uruguayan Creole cattle population (N = 600) is located in a native habitat in south-east Uruguay. We analyzed its genetic diversity and compared it to other populations of American Creole cattle. A random sample of 64 animals was genotyped for a set of 17 microsatellite loci, and the D-loop hyper-variable region of mtDNA was sequenced for 28 calves of the same generation. We identified an average of 5.59 alleles per locus, with expected heterozygosities between 0.466 and 0.850 and an expected mean heterozygosity of 0.664. The polymorphic information content ranged from 0.360 to 0.820, and the global FIS index was 0.037. The D-loop analysis revealed three haplotypes (UY1, UY2 and UY3), belonging to the European matriline group, with a haplotype diversity of 0.532. The history of the population, changes in the effective population size, bottlenecks, and genetic drift are possible causes of the genetic variability patterns that we detected.

Neuroprotective effects of extremely low-frequency electromagnetic fields on a Huntington's disease rat model: effects on neurotrophic factors and neuronal density.

There is evidence to suggest that the neuroprotective effect of exposure of extremely low-frequency electromagnetic fields (ELF-EMF) may be due, at least in part, to the effect of these fields on neurotrophic factors levels and cell survival, leading to an improvement in behavior. This study was undertaken to investigate the neuroprotective effects of ELFEF in a rat model of 3-nitropropionic acid (3NP)-induced Huntington's disease. Behavior patterns were evaluated, and changes in neurotrophic factor, cell damage, and oxidative stress biomarker levels were monitored in Wistar rats. Rats were given 3NP over four consecutive days (20 mg/kg body weight), whereas ELFEF (60 Hz and 0.7 mT) was applied over 21 days, starting after the last injection of 3NP. Rats treated with 3NP exhibited significantly different behavior in the open field test (OFT) and the forced swim test (FST), and displayed significant differences in neurotrophic factor levels and oxidative stress biomarkers levels, together with a neuronal damage and diminished neuronal density, with respect neuronal controls. ELFEF improved neurological scores, enhanced neurotrophic factor levels, and reduced both oxidative damage and neuronal loss in 3NP-treated rats. ELFEF alleviates 3NP-induced brain injury and prevents loss of neurons in rat striatum, thus showing considerable potential as a therapeutic tool.

Life begins when the sea lion is ashore: microhabitat use by a louse living on a diving mammal host.

Among Anoplura, the family Echinophthiriidae includes species that infest pinnipeds and otters. Previous evidence obtained from pinnipeds infested by echinophthiriids, specifically from seals, indicates that flippers are the preferred infestation sites, while lice from fur seals select areas in the pelage. We studied habitat selection of Antarctophthirus microchir on South American sea lion pups (Otaria flavescens Shaw, 1800) from Patagonia, Argentina, during the austral summer of 2009. We found a clear pattern of habitat selection: eggs are laid on the dorsal surface; nymphs 1 hatch there and then migrate to the belly, where they develop into adults and copulate; and then ovigerous females return to the dorsal surface. On the one hand, nymphs 1 are characterised by their low locomotory ability; therefore, the fact that they migrate as soon as they hatch suggests a clear pressure leading to microhabitat restriction. On the other hand, the described pattern of microhabitat selection seems to respond to the physiological requirements of each stage, which vary according to the physiological process considered, e.g. oviposition, morphogenesis, hatching and development. Accordingly, it appears that A. microchir would prefer the host's ventral area for development and copulation and the dorsal area for oviposition. However, the causes of this pattern are not clear, and many factors could be involved. Considering that sea lion pups periodically soak at high tides, and that prolonged immersion and very high humidity are known to be lethal for lice eggs, selecting the dorsal area would be advantageous for oviposition because it dries much faster. Furthermore, because humidity should be retained for longer periods on the ventral surface of the pup, wetter conditions on the sea lion would prevent desiccation of the nymphs in the very arid environment where O. flavescens breeds.

Olfactory bulbectomy induced oxidative and cell damage in rat: protective effect of melatonin.

In this study we analyzed the effects of melatonin (Mel, 1 mg/kg ip) on behavioral changes as well as cell and oxidative damage prompted by bilaterally olfactory bulbectomy. Olfactory bulbectomy caused an increase in lipid peroxidation products and caspase-3, whereas it prompted a decrease of reduced glutathione (GSH) content and antioxidative enzymes activities. Additionally, olfactory bulbectomy induced behavioral changes characterized by the enhancement of immobility time in the forced swim test and hyperactivity in the open field test. All these changes were normalized by treatment of Mel (14 days). Our data show that Mel has a beneficial neuropsychiatric action against oxidative stress, cell damage and behavior alterations.

[Study of rituximab efficacy, cost, safety, and compliance of its package leaflet in a tertiary hospital]. / Estudio de adecuación a la ficha técnica, efectividad, seguridad y coste del rituximab en un hospital de tercer nivel.

INTRODUCTION: The appearance of monoclonal antibodies, and specifically, rituximab, has provided a new approach to treating non-Hodgkin's lymphomas and rheumatoid arthritis. The purpose of this study is to analyse whether this drug is used according to its package leaflet in clinical practice, evaluate the treatment's efficacy and determine its cost. METHODS: Ambispective, observational single-centre study of medication use set up as a prescription evaluation for the indication of rituximab in a tertiary hospital between March 2003 and 31 December 2007. RESULTS: 82 of the 221 patients who were treated (37.1 %) received the drug for a condition that does not appear in the package leaflet. 51.1 % and 27.5 % of response and progression were registered for approved diagnoses and 34.9 % and 47 % for non-approved diagnoses; the death rate was 25.3 % and 41.5 % respectively. The mean cost per treatment episode was the highest for idiopathic thrombocytopenic purpura (11,683 euro), whilst the highest treatment cost per patient was associated with follicular lymphoma (15,940 euro). DISCUSSION: We found that the main cause of the high rate of non-compliance with the package leaflet is patient lack of response to standard treatments, together with clinical practice guides that support the use of rituximab for conditions other than those for which it is indicated. Nevertheless, most of the clinical trials evaluating the efficacy of rituximab for these unauthorized diagnostic profiles have poor methodology, are in phase II, are open studies, have low patient numbers, or in some cases, are not comparative.

Neuroprotective effect of carvedilol and melatonin on 3-nitropropionic acid-induced neurotoxicity in neuroblastoma.

In neurodegenerative diseases, progressive oxidative stress is a major event that precedes neuronal death. Oxidative stress is characterized by an imbalance between oxidants and antioxidants. This imbalance induced oxidative molecular and cell damage, reducing cellular viability. 3-Nitropropionic acid (3NP) causes oxidative stress and other molecular and cellular changes similar to those observed in neurons of patients with Huntington's disease. Since carvedilol and melatonin act as free-radical scavengers, this study examined the effect of carvedilol (10(-5) M) and melatonin (10(-5) M) on oxidative and cell damage induced by 3NP in N1E-115 neuroblastoma cells. Carvedilol and melatonin prevented the increases in lipid peroxidation and total LDH activity, as well as the depletion of reduced glutathione (GSH) and the reduction of antioxidative enzymes activities in N1E-115 cells incubated with 100 mM 3NP. All these carvedilol and melatonin effects were more intense when the drugs were added before rather than after inducing the damage by 3NP. These results also provided evidence supporting the hypothesis that carvedilol and melatonin can be useful for treating neurodegenerative diseases, such as Huntington's disease.