Study of the anti-JCV antibody levels in a Spanish multiple sclerosis cohort.

BACKGROUND: One of the risk factor to develop progressive multifocal leukoencephalopathy (PML) among natalizumab-treated patients is the presence and high levels of anti-JCV antibodies. Our purpose was to test the association of different clinical and demographic variables with the presence and levels of anti-JCV antibodies in a Spanish cohort of patients with multiple sclerosis (MS) during natalizumab treatment. MATERIALS AND METHODS: All patients with MS from two hospitals with at least one measure of the anti-JCV antibodies levels (2011-2014) were recruited, among them were two PML cases. Anti-JCV antibody levels were assessed using two-step ELISA. RESULTS: A total of 1061 patients (16·3% natalizumab-treated) participated in this study. The seropositivity rate of anti-JCV antibodies was 58·2%. It increased with age (Pcorrected = 0·00005) and was lower among HLA-DRB1*15:01 carriers (Pcorrected = 0·049). The two patients with PML were HLA-DRB1*15:01 carriers. We had at least three quarterly anti-JCV antibody measurements (index value) from 137 patients, whose levels did not increase during natalizumab treatment. However, 5·8% of these patients had an increase of the index value higher of one point in a maximum of 6 months, something that was more frequently observed (P = 0·054) among patients treated with immunosuppressant prior to natalizumab onset. CONCLUSIONS: Old age and HLA-DRB1*15:01 were the factors that influence positively and negatively, respectively, our anti-JCV antibody prevalence, although our both PML cases were HLA-DRB1*15:01carriers. Most of our patients showed a stable anti-JCV antibody index values during natalizumab treatment.

Constructing fused N-heterocycles from unprotected mesoionic N-heterocyclic olefins and organic azides via diazo transfer.

Mesoionic N-heterocyclic olefins (mNHOs) were first reported last year and their reactivity remains largely unexplored. Herein we report the reaction of unprotected mNHOs and organic azides as a novel synthetic route to a variety of pyrazolo[3,4-d][1,2,3]triazoles, an important structural motif in drug candidates and energetic materials. The only byproduct aniline can be easily recycled and converted back to the starting organic azide, in compliance with the green chemistry principle. The reaction mechanism has been explored through experimental and computational studies.

Emotional Intelligence Measures: A Systematic Review.

Emotional intelligence (EI) refers to the ability to perceive, express, understand, and manage emotions. Current research indicates that it may protect against the emotional burden experienced in certain professions. This article aims to provide an updated systematic review of existing instruments to assess EI in professionals, focusing on the description of their characteristics as well as their psychometric properties (reliability and validity). A literature search was conducted in Web of Science (WoS). A total of 2761 items met the eligibility criteria, from which a total of 40 different instruments were extracted and analysed. Most were based on three main models (i.e., skill-based, trait-based, and mixed), which differ in the way they conceptualize and measure EI. All have been shown to have advantages and disadvantages inherent to the type of tool. The instruments reported in the largest number of studies are Emotional Quotient Inventory (EQ-i), Schutte Self Report-Inventory (SSRI), Mayer-Salovey-Caruso Emotional Intelligence Test 2.0 (MSCEIT 2.0), Trait Meta-Mood Scale (TMMS), Wong and Law's Emotional Intelligence Scale (WLEIS), and Trait Emotional Intelligence Questionnaire (TEIQue). The main measure of the estimated reliability has been internal consistency, and the construction of EI measures was predominantly based on linear modelling or classical test theory. The study has limitations: we only searched a single database, the impossibility of estimating inter-rater reliability, and non-compliance with some items required by PRISMA.

Effect of parathyroid-hormone-related protein on human platelet activation.

Evidence suggests that PTHrP [PTH (parathyroid hormone)-related protein] can act as an inflammatory mediator in several pathological settings including cardiovascular disease. The aim of the present study was to determine whether PTHrP might be involved in human platelet activation. We used a turbidimetric method to determine platelet aggregation. The expression of PTH1R (PTH type 1 receptor) in human platelets was analysed by Western blot and flow cytometry analyses. PTHrP-(1-36) (10(-7) mol/l) by itself failed to modify the activation of platelets. However, it significantly enhanced ADP-induced platelet activation, and also increased the ability of other agonists (thrombin, collagen and arachidonic acid) to induce platelet aggregation. H89 (10(-6) mol/l) and 25 x 10(-6) mol/l Rp-cAMPS (adenosine 3',5'-cyclic monophosphorothioate Rp-isomer), two protein kinase A inhibitors, and 25 x 10(-9) mol/l bisindolylmaleimide I, a protein kinase C inhibitor, partially decreased the enhancing effect of PTHrP-(1-36) on ADP-induced platelet activation. Meanwhile, 10(-6) mol/l PTHrP-(7-34), a PTH1R antagonist, as well as 10(-5) mol/l PD098059, a MAPK (mitogen-activated protein kinase) inhibitor, or a farnesyltransferase inhibitor abolished this effect of PTHrP-(1-36). Moreover, 10(-7) mol/l PTHrP-(1-36) increased (2-fold over control) MAPK activation in human platelets. PTH1R was detected in platelets, and the number of platelets expressing it on their surface in patients during AMI (acute myocardial infarction) was not different from that in a group of patients with similar cardiovascular risk factors without AMI. Western blot analysis showed that total PTH1R protein levels were markedly higher in platelets from control than those from AMI patients. PTH1R was found in plasma, where its levels were increased in AMI patients compared with controls. In conclusion, human platelets express the PTH1R. PTHrP can interact with this receptor to enhance human platelet activation induced by several agonists through a MAPK-dependent mechanism.

Tear cytokine profile of glaucoma patients treated with preservative-free or preserved latanoprost.

PURPOSE: To determine variations in cytokine levels of glaucoma patients treated either with preservative-free latanoprost or preserved latanoprost, relative to healthy individuals. METHODS: Tear samples were collected from 39 healthy subjects, 20 glaucoma patients treated with preserved latanoprost, and 20 patients treated with preservative-free latanoprost. A set of 27 inflammatory cytokines was analyzed in each group, including interleukin (IL)-1ß, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL9, IL-10, IL-12 (p70), IL-13, IL-15, IL-17, eotaxin, fibroblast growth factor (FGF) basic, granulocyte colony stimulating factor (G-CSF), granulocyte monocyte colony stimulating factor (GM-CSF), interferon (IFN)-γ, interferon gamma-induced protein (IP)-10, monocyte chemo attractant protein (MCP)-1MCAF, macrophage inflammatory protein (MIP)-1α, MIP-1ß, platelet-derived growth factor (PDGF)-BB, regulated on activation, normal T cell expressed and secreted (RANTES), tumor necrosis factor (TNF)-α and vascular endothelial growth factor (VEGF). Cytokine concentrations were obtained by the Bio-Plex Human Cytokine Immunoassay. Non-invasive tear breakup time (NI-TBUT), tear meniscus height, corneal fluorescein staining, conjunctival hyperemia and ocular surface disease index (OSDI) were assessed in patients treated with preservative-free and preserved latanoprost. RESULTS: The levels of IL-2, IL-5, IL-10, IL-12 (p70), IL-13, IL-15, IL-17, FGF basic, PDGF-BB, and TNF-α were significantly higher in patients receiving preserved latanoprost, compared to normal controls (p < 0.05). The expression of all the cytokines studied remained statistically invariable in patients receiving preservative-free latanoprost, compared to healthy subjects (p > 0.05). Ocular surface parameters were not significantly different in both glaucoma groups, and no correlation between these clinical parameters and cytokine levels was observed. CONCLUSIONS: Treatment with preserved latanoprost has a direct impact on tear cytokine levels, whereas this effect is not observed upon preservative-free latanoprost instillation.

The HLA-DQß1 insertion is a strong achalasia risk factor and displays a geospatial north-south gradient among Europeans.

Idiopathic achalasia is a severe motility disorder of the esophagus and is characterized by a failure of the lower esophageal sphincter to relax due to a loss of neurons in the myenteric plexus. Most recently, we identified an eight-amino-acid insertion in the cytoplasmic tail of HLA-DQß1 as strong achalasia risk factor in a sample set from Central Europe, Italy and Spain. Here, we tested whether the HLA-DQß1 insertion also confers achalasia risk in the Polish and Swedish population. We could replicate the initial findings and the insertion shows strong achalasia association in both samples (Poland P=1.84 × 10(-04), Sweden P=7.44 × 10(-05)). Combining all five European data sets - Central Europe, Italy, Spain, Poland and Sweden - the insertion is achalasia associated with Pcombined=1.67 × 10(-35). In addition, we observe that the frequency of the insertion shows a geospatial north-south gradient. The insertion is less common in northern (around 6-7% in patients and 2% in controls from Sweden and Poland) compared with southern Europeans (~16% in patients and 8% in controls from Italy) and shows a stronger attributable risk in the southern European population. Our study provides evidence that the prevalence of achalasia may differ between populations.

Type 1 diabetes in the Spanish population: additional factors to class II HLA-DR3 and -DR4.

BACKGROUND: The Major Histocompatibility Complex is the main genetic contributor to susceptibility to type 1 diabetes (T1D); genome-wide scans have consistently mapped increased predisposition to this region. The highest disease risk has been associated with HLA-DR3 and HLA-DR4. In particular, the DR3-positive ancestral haplotype 18.2 was reported as highly diabetogenic. We aimed to corroborate whether this haplotype increases the susceptibility conferred by the DQ2-DR3 alleles in a Mediterranean population. We also searched for additional susceptibility factors to the classic DQ2-DR3 and DQ8-DR4. RESULTS: Genetic MHC markers were analysed in a case-control study with 302 T1D patients and 529 ethnically matched controls. DR3-TNFa1b5 carrier rate was significantly higher in DR3-positive heterozygous T1D patients than in DR3-positive heterozygous controls (p = 0.0019; odds ratio OR [95% confidence interval CI] = 2.26 [1.3-3.93]). This data was confirmed analysing the allelic frequency, which includes the information corresponding to the DR3-homozygous individuals (p = 0.001; OR = 2.09) and by using the Arlequin software to check the DR3-positive haplotypes (p = 0.004;OR = 1.93). The present results provide strong evidence of a second susceptibility region in the ancestral haplotype 18.2 in the Spanish population. Moreover, we searched for T1D susceptibility factors in addition to the MHC classical ones, within the DR2-DQ6/DR3-DQ2/DR4-DQ8 negative population. Several genetic markers in both MHC class II (DQA1*0101-DQB1*0501 [p = 0.007;OR = 2.81], DQA1*0201-DQB1*0202 [p = 0.03; OR = 2.35]) and III (TNFa2b1 [p = 0.01 OR = 2.74], BAT-2*2 [p = 0.004; OR = 3.19]) were found. These different alleles associated with T1D were not independent and we observed linkage disequilibrium among them leading us to describe two new risk haplotypes (DQA1*0101-DQB1*0501-TNFa2b1 and DQA1*0201-DQB1*0202- BAT-2*2). Finally, we studied a T1D susceptibility/protection marker located in extended class I, D6S2223; however, no association was observed in our population. CONCLUSION: Our results suggest that other associated MHC haplotypes might present susceptibility factors in loci different from HLA-class II and that the class II molecules are not necessarily the universal etiologic factor in every MHC haplotype.

Th1 cytokine polymorphisms in spanish patients with type 1 diabetes.

Several polymorphisms in regions where Th1 cytokines (IL12B and IFNG genes) are located were analyzed in 303 Spanish subjects with type 1 diabetes and compared with a control cohort (n = 548). Both groups comprised residents of the Madrid area. The haplotype frequencies were estimated by the expectation-maximization algorithm, and p values were corrected by the number of haplotypes taken into account in the study. Two haplotypes were significantly associated with the disease, one in the IL12B region (D5S2038*8/D5S1352*2/SNP1188C; OR = 3.01, p(c) = 0.0255) and another involved the IFNGgene (D12S313*9/IFNG*1; OR = 1.58, p(c) = 0.0217). Furthermore, a protective IL12B haplotype was found (D5S2038*4/D5S1352*1/SNP1188A; OR = 0.40, p(c) = 0.0405). No association was found for any of IL12B and IFNG markers individually.

Reproductive biology of Poecilia sphenops Valenciennes, 1846 (Cyprinidontiformes: Poeciliidae) at the Emiliano Zapata Reservoir in Morelos, Mexico

Poecilia sphenops es una especie nativa registrada recientemente en la cuenca del Balsas y el río Amacuzac en Morelos (México), en el cual es abundante y ampliamente distribuida. En este estudio se analizaron algunos aspectos de la biología reproductiva de Poecilia sphenops de la presa Emiliano Zapata, ubicada en el centro de México. Los especímenes fueron recolectados de Enero a diciembre de 2006, utilizando una red de 20 m de largo con una luz de malla de 5 mm. Se recolectaron un total de 581 especímenes: 407 hembras (70.0%), 83 machos (14.3%) y 91 individuos indiferenciados (15.7%). El tamaño de los peces osciló de 2 a 96 mm de longitud total y de 0.01 a 13.07 g de peso corporal. La proporción sexual de las hembras con respecto a los machos (4.9:1) se desvió significativamente de la unidad (2= 214.2, p 0.05). La variación mensual de los índices gonadosomático, hepatosomático y del desarrollo de los estadios de los ovarios, mostraron que la época de desove de P. sphenops se llevó a cabo entre julio y octubre, durante la época de lluvias. Otro pico de reproducción fue registrado en Febrero. La talla más grande registrada para los machos y para las hembras fue de 96 mm y 83 mm, respectivamente.

Poecilia sphenops is a native species recently recorded in the Balsas basin and the Amacuzac River in Morelos (Mexico), in which it is abundant and widely distributed. This study analyzed some aspects of the reproductive biology of Poecilia sphenops from the Emiliano Zapata Reservoir, in Central Mexico. Specimens were collected using a 20 m-long seine with a 5 mm mesh size, from January to December 2006. A total of 581 specimens were collected: 407 females (70.0%), 83 males (14.3%) and 91 individuals with no differentiated sex (15.7%). Fish ranged from 20 to 96 mm in total length and 0.01 to 13.07 g in body weight. The female to male sex ratio (4.9:1) deviated significantly from the unity (2= 214.2, p 0.05). Monthly variations in gonadosomatic (GSI) and hepatosomatic (HSI) indexes and ovarian development stages showed that P. sphenops spawning season occurred between July and October, concurring with the rainy season. Another reproduction peak was registered in February. The largest length registered for males and females was 96 mm and 83 mm, respectively.