Q Fever Outbreak among Workers at a Waste-Sorting Plant

An outbreak of Q fever occurred in February–April 2014 among workers at a waste-sorting plant in Bilbao (Spain). The outbreak affected 58.5% of investigated employees, 47.2% as confirmed cases (PCR and/or serology) and 11.3% as probable cases (symptoms without laboratory confirmation). Only employees who had no-access to the waste processing areas of the plant were not affected and incidence of infection was significantly higher among workers not using respiratory protection masks. Detection by qPCR of Coxiella burnetii in dust collected from surfaces of the plant facilities confirmed exposure of workers inside the plant. Animal remains sporadically detected among the residues received for waste-sorting were the most probable source of infection. After cleaning and disinfection, all environmental samples tested negative. Personal protection measures were reinforced and made compulsory for the staff and actions were taken to raise farmers’ awareness of the biological risk of discharging animal carcasses as urban waste.     

Variation at interleukin-6 receptor gene is associated to joint damage in rheumatoid arthritis

IntroductionInterleukin-6 (IL-6) cytokine signaling is key in Rheumatoid Arthritis (RA) pathophysiology. Blocking IL-6 receptor (IL6R) has proven to be a highly effective treatment to prevent joint damage. This study was performed to investigate the association between the genetic variation at IL6R gene and the severity of joint damage in RA.MethodsIL6R gene tagging SNPs (n = 5) were genotyped in a discovery group of 527 RA patients from 5 different university hospitals from Spain. For each marker, a linear regression analysis was performed using an additive model and adjusting for the years of evolution of the disease, autoantibody status, gender and age. Haplotypes combining the SNPs were also estimated and tested for association with the level of joint destruction. Using an independent cohort of 705 RA patients from 6 university hospitals we performed a validation study of the SNPs associated in the discovery phase.ResultsIn the discovery group we found a highly significant association between IL6R SNP rs4845618 and the level of joint destruction in RA (P = 0.0058, P_corrected = 0.026), and a moderate association with SNP rs4453032 (P = 0.02, P_corrected = 0.05). The resulting haplotype from both SNPs was more significantly associated with joint damage (P = 0.0037, P_corrected = 0.011). Using the validation cohort, we replicated the association between the two IL-6R SNPs with the degree of joint destruction in RA (P = 0.007 and P = 0.04, meta-analysis P = 0.00011 and P = 0.0021, respectively), and the haplotype association (P = 0.0058, meta-analysis P = 6.64 e-5).ConclusionsGenetic variation at IL6R gene is associated with joint damage in RA.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-015-0737-8) contains supplementary material, which is available to authorized users.     

Electrophysiological Responses to Affective Stimuli in Neglectful Mothers

Results illustrating an atypical neural processing in the early and late differentiation of infant faces have been obtained with neglectful mothers. The present study explores whether a different pattern of response is observed when using non-infant affective pictures. We examined the event-related evoked potentials and induced delta, theta and alpha activity in 14 neglectful mothers and 14 control mothers elicited while categorizing positive, negative and neutral pictures from the International Affective Picture System. Self-reports of anhedonia and empathy were also recorded. Early posterior negativity, P200 and late positive potential components were modulated by the emotional content of pictures in both groups. However, the LPP waveform had a more delayed and more attenuated maximum in neglectful mothers than in control mothers. Oscillatory responses indicated lower power increases for neglectful mothers than for control mothers in delta (1–4 Hz), theta (4–8 Hz) and lower alpha (8–10 Hz) bands at frontal sites, and a more consistent increase for neglectful mothers in theta and lower alpha bands at occipital sites, especially for negative pictures. These findings help us to better understand the limits of emotional insensitivity in neglectful mothers.     

Immunotherapy Reduces Allergen-Mediated CD66b Expression and Myeloperoxidase Levels on Human Neutrophils from Allergic Patients

CD66b is a member of the carcinoembryonic antigen family, which mediates the adhesion between neutrophils and to endothelial cells. Allergen-specific immunotherapy is widely used to treat allergic diseases, and the molecular mechanisms underlying this therapy are poorly understood. The present work was undertaken to analyze A) the in vitro effect of allergens and immunotherapy on cell-surface CD66b expression of neutrophils from patients with allergic asthma and rhinitis and B) the in vivo effect of immunotherapy on cell-surface CD66b expression of neutrophils from nasal lavage fluid during the spring season. Myeloperoxidase expression and activity was also analyzed in nasal lavage fluid as a general marker of neutrophil activation.

Results

CD66b cell-surface expression is upregulated in vitro in response to allergens, and significantly reduced by immunotherapy (p<0.001). Myeloperoxidase activity in nasal lavage fluid was also significantly reduced by immunotherapy, as were the neutrophil cell-surface expression of CD66b and myeloperoxidase (p<0.001). Interestingly, CD66b expression was higher in neutrophils from nasal lavage fluid than those from peripheral blood, and immunotherapy reduced the number of CD66⁺MPO⁺ cells in nasal lavage fluid. Thus, immunotherapy positive effects might, at least in part, be mediated by the negative regulation of the CD66b and myeloperoxidase activity in human neutrophils.     

Detecting Falls as Novelties in Acceleration Patterns Acquired with Smartphones

Despite being a major public health problem, falls in the elderly cannot be detected efficiently yet. Many studies have used acceleration as the main input to discriminate between falls and activities of daily living (ADL). In recent years, there has been an increasing interest in using smartphones for fall detection. The most promising results have been obtained by supervised Machine Learning algorithms. However, a drawback of these approaches is that they rely on falls simulated by young or mature people, which might not represent every possible fall situation and might be different from older people''s falls. Thus, we propose to tackle the problem of fall detection by applying a kind of novelty detection methods which rely only on true ADL. In this way, a fall is any abnormal movement with respect to ADL. A system based on these methods could easily adapt itself to new situations since new ADL could be recorded continuously and the system could be re-trained on the fly. The goal of this work is to explore the use of such novelty detectors by selecting one of them and by comparing it with a state-of-the-art traditional supervised method under different conditions. The data sets we have collected were recorded with smartphones. Ten volunteers simulated eight type of falls, whereas ADL were recorded while they carried the phone in their real life. Even though we have not collected data from the elderly, the data sets were suitable to check the adaptability of novelty detectors. They have been made publicly available to improve the reproducibility of our results. We have studied several novelty detection methods, selecting the nearest neighbour-based technique (NN) as the most suitable. Then, we have compared NN with the Support Vector Machine (SVM). In most situations a generic SVM outperformed an adapted NN.     

Serum Activin A and Follistatin Levels in Gestational Diabetes and the Association of the Activin A-Follistatin System with Anthropometric Parameters in Offspring

Context

The Activin A-Follistatin system has emerged as an important regulator of lipid and glucose metabolism with possible repercussions on fetal growth.

Objective

To analyze circulating activin A, follistatin and follistatin-like-3 (FSTL3) levels and their relationship with glucose metabolism in pregnant women and their influence on fetal growth and neonatal adiposity.

Design and methods

A prospective cohort was studied comprising 207 pregnant women, 129 with normal glucose tolerance (NGT) and 78 with gestational diabetes mellitus (GDM) and their offspring. Activin A, follistatin and FSTL3 levels were measured in maternal serum collected in the early third trimester of pregnancy. Serial fetal ultrasounds were performed during the third trimester to evaluate fetal growth. Neonatal anthropometry was measured to assess neonatal adiposity.

Results

Serum follistatin levels were significantly lower in GDM than in NGT pregnant women (8.21±2.32 ng/mL vs 9.22±3.41, P = 0.012) whereas serum FSTL3 and activin A levels were comparable between the two groups. Serum follistatin concentrations were negatively correlated with HOMA-IR and positively with ultrasound growth parameters such as fractional thigh volume estimation in the middle of the third trimester and percent fat mass at birth. Also, in the stepwise multiple linear regression analysis serum follistatin levels were negatively associated with HOMA-IR (β = −0.199, P = 0.008) and the diagnosis of gestational diabetes (β = −0.138, P = 0.049). Likewise, fractional thigh volume estimation in the middle of third trimester and percent fat mass at birth were positively determined by serum follistatin levels (β = 0.214, P = 0.005 and β = 0.231, P = 0.002, respectively).

Conclusions

Circulating follistatin levels are reduced in GDM compared with NGT pregnant women and they are positively associated with fetal growth and neonatal adiposity. These data suggest a role of the Activin-Follistatin system in maternal and fetal metabolism during pregnancy.     

Evaluación de la efectividad del tratamiento con glucocorticoides intravenosos en la oftalmopatía de Graves

ObjectiveTo assess the efficacy of intermittent, high-dose treatment with intravenous glucocorticoids (IV GCs) in moderate to severe Graves’ ophthalmopathy (GO).Materials and methodsPatients with GO treated with IV GCs from August 2007 to August 2011 at the Endocrinology Department of Reina Sofía Hospital were enrolled into the study. IV pulse prednisolone (7.5 mg/kg/day) was administered twice weekly every two weeks for 6 weeks, and at half the dose for 6 additional weeks.ResultsEighteen patients (mean age, 43+/-11 years) with moderate to severe GO were analyzed (83.3% females). Four were active smokers, five former smokers, and the rest had never smoked. Hyperthyroidism due to Graves’ disease was found in 66.7% of patients, 41.6% of whom had received radioiodine therapy. Response to treatment was satisfactory in 72.2%, partial in 11.1%, and poor in 16.7%. Mild side effects were reported by 5 patients. Before treatment, 83.3% had diplopia, 33.3% eyelid retraction, 72.2% eye pain, and 44.4% exophthalmos. After treatment, only 33.3% had diplopia (P = .004), 5.6% eyelid retraction (P = .063), 16.7% eye pain (P = .002), and 11.1% exophthalmos (P = .031). Response to treatment was not related to the underlying disease (P = .866), prior radioiodine treatment (P = .447), or smoking status (P = .368).ConclusionsIntravenous glucocorticoid therapy decreased activity in patients with moderate to severe active GO, with major improvement occurring in diplopia, eye pain, and exophthalmos. Side effects were mild and uncommon. Treatment response was independent from the underlying disease, prior radioiodine treatment, or smoking status.     

Postsynaptic Kainate Receptor Recycling and Surface Expression Are Regulated by Metabotropic Autoreceptor Signalling

Kainate receptors (KARs) play fundamentally important roles in controlling synaptic function and regulating neuronal excitability. Postsynaptic KARs contribute to excitatory neurotransmission but the molecular mechanisms underlying their activity‐dependent surface expression are not well understood. Strong activation of KARs in cultured hippocampal neurons leads to the downregulation of postsynaptic KARs via endocytosis and degradation. In contrast, low‐level activation augments postsynaptic KAR surface expression. Here, we show that this increase in KARs is due to enhanced recycling via the recruitment of Rab11‐dependent, transferrin‐positive endosomes into spines. Dominant‐negative Rab11 or the recycling inhibitor primaquine prevents the kainate‐evoked increase in surface KARs. Moreover, we show that the increase in surface expression is mediated via a metabotropic KAR signalling pathway, which is blocked by the protein kinase C inhibitor chelerythrine, the calcium chelator BAPTA and the G‐protein inhibitor pertussis toxin. Thus, we report a previously uncharacterized positive feedback system that increases postsynaptic KARs in response to low‐ or moderate‐level agonist activation and can provide additional flexibility to synaptic regulation.      

The influence of cis‐acting P1 protein and translational elements on the expression of Potato virus Y helper‐component proteinase (HCPro) in heterologous systems and its suppression of silencing activity

In the Potyvirus genus, the P1 protein is the first N‐terminal product processed from the viral polyprotein, followed by the helper‐component proteinase (HCPro). In silencing suppression patch assays, we found that Potato virus Y (PVY) HCPro expressed from a P1‐HCPro sequence increased the accumulation of a reporter gene, whereas protein expressed from an HCPro sequence did not, even with P1 supplied in trans. This enhancing effect of P1 has been noted in other potyviruses, but has remained unexplained. We analysed the accumulation of PVY HCPro in infiltrated tissues and found that it was higher when expressed from P1‐HCPro than from HCPro sequences. Co‐expression of heterologous suppressors increased the steady‐state level of mRNA expressed from the HCPro sequence, but not that of protein. This suggests that, in the absence of P1 upstream, either HCPro acquires a conformation that affects negatively its activity or stability, or that its translation is reduced. To test these options, we purified HCPro expressed in the presence or absence of upstream P1, and found no difference in purification pattern and final soluble state. By contrast, alteration of the Kozak context in the HCPro mRNA sequence to favour translation increased partially suppressor accumulation and activity. Furthermore, protein activity was not lower than in protein expressed from P1‐HCPro sequences. Thus, a direct role for P1 on HCPro suppressor activity or stability, by influencing its conformation during translation, can be excluded. However, P1 could still have an indirect effect favouring HCPro accumulation. Our data highlight the relevance of cis‐acting translational elements in the heterologous expression of HCPro.