Are the cut-offs of the rheumatoid factor and anti-cyclic citrullinated peptide antibody different to distinguish rheumatoid arthritis from their primary differential diagnoses?

OBJECTIVE: Rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (anti-CCP) are commonly used for diagnosis of rheumatoid arthritis (RA), although other rheumatic diseases with arthritis can test positive. This study aimed to determine the cutoff values for RF and anti-CCP with the best diagnostic performance in a sample of patients with RA, compared with other rheumatic diseases. METHODS: This was a descriptive, prospective study. EUROINMMUN enzyme-linked immunosorbent assays for RF isotypes immunoglobulin (Ig) A (IgA), IgG and IgM and third-generation assay IgG for anti-CCP were used in serum samples of patients with RA, other rheumatic diseases and healthy subjects. The cutoff with the best diagnostic performance was determined by the Youden Index and receiver operating characteristic analysis Results: Three hundred and thirty-two serum samples were analysed. The cutoffs proposed in our population were for RF in RA patients versus other rheumatic diseases, and healthy subjects IgM 135 IU/mL, for each disease, compared with RA, were psoriatic arthritis (Psa) IgA 47.2 IU/mL, clinically suspicious arthralgia (CSA) IgA 39.5 IU/mL, primary Sjögren's syndrome (pSS) IgM 180.6 IU/mL, systemic lupus erythematosus (SLE) IgA 42.6 IU/mL, primary fibromyalgia (pFM) IgM 68.6 IU/mL, osteoarthritis (OA) IgM 48 IU/mL, gout IgM 117 IU/mL and healthy IgM 16.3 IU/mL. For anti-CCP, in RA patients versus other rheumatic diseases, and healthy subjects 6.95 IU/mL, for each disease, compared with RA, were Psa 6.8 IU/mL, CSA 9.95 IU/mL, pSS 20.7 IU/mL, SLE 6 IU /mL, pFM 11.8 IU/mL, OA 11.9 IU/mL, gout 5 IU/mL and healthy 5 IU/mL. CONCLUSION: Irrespective of the manufacturer's suggested cutoff, the RA versus differential diagnosis cutoffs must be considered.

Synthetic negative genome screen of the GPN-loop GTPase NPA3 in Saccharomyces cerevisiae.

The GPN-loop GTPase Npa3 is encoded by an essential gene in the yeast Saccharomyces cerevisiae. Npa3 plays a critical role in the assembly and nuclear accumulation of RNA polymerase II (RNAPII), a function that may explain its essentiality. Genetic interactions describe the extent to which a mutation in a particular gene affects a specific phenotype when co-occurring with an alteration in a second gene. Discovering synthetic negative genetic interactions has long been used as a tool to delineate the functional relatedness between pairs of genes participating in common or compensatory biological pathways. Previously, our group showed that nuclear targeting and transcriptional activity of RNAPII were unaffected in cells expressing exclusively a C-terminal truncated mutant version of Npa3 (npa3∆C) lacking the last 106 residues naturally absent from the single GPN protein in Archaea, but universally conserved in all Npa3 orthologs of eukaryotes. To gain insight into novel cellular functions for Npa3, we performed here a genome-wide Synthetic Genetic Array (SGA) study coupled to bulk fluorescence monitoring to identify negative genetic interactions of NPA3 by crossing an npa3∆C strain with a 4,389 nonessential gene-deletion collection. This genetic screen revealed previously unknown synthetic negative interactions between NPA3 and 15 genes. Our results revealed that the Npa3 C-terminal tail extension regulates the participation of this essential GTPase in previously unknown biological processes related to mitochondrial homeostasis and ribosome biogenesis.

Transcriptome Analysis Unveils Gln3 Role in Amino Acids Assimilation and Fluconazole Resistance in Candida glabrata.

After Candida albicans, Candida glabrata is one of the most common fungal species associated with candidemia in nosocomial infections. Rapid acquisition of nutrients from the host is important for the survival of pathogens which possess the metabolic flexibility to assimilate different carbon and nitrogen compounds. In Saccharomyces cerevisiae, nitrogen assimilation is controlled through a mechanism known as Nitrogen Catabolite Repression (NCR). NCR is coordinated by the action of four GATA factors; two positive regulators, Gat1 and Gln3, and two negative regulators, Gzf3 and Dal80. A mechanism in C. glabrata similar to NCR in S. cerevisiae has not been broadly studied. We previously showed that in C. glabrata, Gln3, and not Gat1, has a major role in nitrogen assimilation as opposed to what has been observed in S. cerevisiae in which both factors regulate NCR-sensitive genes. Here, we expand the knowledge about the role of Gln3 from C. glabrata through the transcriptional analysis of BG14 and gln3Δ strains. Approximately, 53.5% of the detected genes were differentially expressed (DEG). From these DEG, amino acid metabolism and ABC transporters were two of the most enriched KEGG categories in our analysis (Up-DEG and Down-DEG, respectively). Furthermore, a positive role of Gln3 in AAA assimilation was described, as was its role in the transcriptional regulation of ARO8. Finally, an unexpected negative role of Gln3 in the gene regulation of ABC transporters CDR1 and CDR2 and its associated transcriptional regulator PDR1 was found. This observation was confirmed by a decreased susceptibility of the gln3Δ strain to fluconazole.

Efectos conductuales de la Terapia de Aceptación y Compromiso con pacientes de un hospital pediátrico / Behavioral Effects in pediatric hospital patients after Acceptance and Commitment Therapy

Actualmente existe una alta demanda de atención hospitalaria de pacientes pediátricos con comorbilidad de trastornos mentales. Por ello, se han desarrollado alternativas de tratamientos psicológicos, como la Terapia de Aceptación y Compromiso (ACT, por sus siglas en inglés). Esta se ha utilizado en poblaciones con diferentes diagnósticos médicos y psicológicos, y la evidencia ha mostrado resultados en población infantil. El presente estudio es cualitativo con enfoque fenomenológico, se usaron técnicas de observación con observadores como participantes, entrevista semiestructurada y registros conductuales previos y posteriores a la intervención. El objetivo de esta terapia grupal basada en ACT fue conocer los efectos conductuales en pacientes pediátricos que contaran con diagnósticos médicos y/o psicológicos. Participaron cinco pacientes escolares con condiciones médicas y problemas en el área afectiva, conductual y/o social. Los resultados muestran que los participantes presentaron mejorías conductuales, principalmente en la regulación emocional, conductas prosociales, habilidades sociales con pares y en la comunicación, las cuales se mantuvieron seis meses después. Asimismo, se observó mayor flexibilidad psicológica. Este estudio propone un nuevo protocolo de intervención basado en ACT, en formato grupal, pictórico y adaptado a pacientes en etapa escolar

At the present time, research literature has reported a high demand for pediatric patients, for hospital attention, but who are also diagnosed with mental disorders. Due to this, several psychological treatments have been developed, such as the Acceptance and Commitment Therapy (ACT). This therapy, whose evidence has shown results in child population, has been used in groups with different medical and psychological diagnoses. The present phenomenological qualitative study used the observation method, observers as participants, a semi-structured interview, and behavioral recordings before and after the intervention. The aim of this ACT based group intervention was to find out about the behavioral effects in pediatric patients with medical and psychological diagnoses. Five scholar patients with medical conditions and problems in the affective, behavioral and/or social areas, participated. Results report that the participants showed behavioral improvement mainly in emotional regulation, prosocial behavior, peer social and communication skills, all of which were maintained six months after, also psychological flexibility increased as well. This study suggests a new ACT based intervention protocol, in group format, pictorial-like, and adapted to school age patients

Removal of Cu2+ and Ni2+ from Aqueous Solution using SnO2 Nanomaterial effect of: pH, Time, Temperature, interfering cations.

Tin oxide, SnO2, nanomaterial was synthesized and tested for the removal of Cu2+ and Ni2+ ions from aqueous solutions. Various parameters for the binding were investigated in batch studied, which included pH, time, temperature, and interferences. In addition, isotherm studied were performed to determine the maximum binding capacity for both Cu2+ and Ni2+ ions. The optimal binding pH determined from the effects of pH were to be at pH 5 for both the Cu2+ and Ni2+ ions. The isotherm studies were performed at temperatures of 4°C, 25 °C, and 45 °C for both the Cu2+ and Ni2+ ions and were found to follow the Langmuir isotherm model. The binding capacities for the Cu2+ ions were 2.63 mg/g, 2.95 mg/g and 3.27 mg/g at the aforementioned temperatures, respectively. Whereas the binding capacities for Ni2+ were 0.79 mg/g, 1.07 mg/g, and 1.46 mg/g at the respective temperatures. The determined thermodynamic parameters for the binding showed that the binding processes for the reactions were endothermic, as the ΔG was observed to decrease with decreasing temperatures. As well the ΔH was 28.73 kJ/mol for Cu2+ (III) and 13.37 kJ/mol for Ni2+. The ΔS was observed to be 92.65 J/mol for Cu2+ and 54.53 J/mol for Ni2+. The free energy of adsorption for the Cu2+ was determined to be 13.99 kJ/mol and the activation energy for the binding of Ni2+ was determined to be 8.09 KJ/mol. The activation energy data indicate that the reaction was occurring through chemisorption.

Candida glabrata encodes a longer variant of the mating type (MAT) alpha2 gene in the mating type-like MTL3 locus, which can form homodimers.

The fungal pathogen Candida glabrata is a haploid asexual yeast. Candida glabrata contains orthologs of the genes that control mating and cell-type identity in other fungi, which encode putative transcription factors localized in the MAT locus in Saccharomyces cerevisiae or MTL in other fungi. Candida glabrata contains three copies of the CgMTL locus but only CgMTL1 correctly expresses the information encoded in it. CgMTL1 can encode the Cg A1: gene ( A: information), or the Cgalpha1 and Cgalpha2 genes (alpha information). CgMTL2 contains an identical copy of the Cg A1: gene. CgMTL3 contains an identical copy of the Cgalpha1 gene but a longer variant of the Cgalpha2 gene that we termed Cgalpha3. In S. cerevisiae diploid cells, that express Sc A: and Scalpha information, Sc A1: and Scalpha2 proteins form a heterodimer, which represses genes expressed only in haploid cells and some genes involved in stress response. We constructed C. glabrata strains that simultaneously express Cg A1: and Cgalpha2 or Cg A1: and Cgalpha3 genes. We did not find any phenotype in these strains when grown under a large variety of stress and nutritional conditions. However, we detected an interaction between Cg A1: and Cgalpha2 but not between Cg A1: and Cgalpha3 by Bimolecular Fluorescence Complementation and co-immunoprecipitation assays.

The superoxide dismutases of Candida glabrata protect against oxidative damage and are required for lysine biosynthesis, DNA integrity and chronological life survival.

The fungal pathogen Candida glabrata has a well-defined oxidative stress response, is extremely resistant to oxidative stress and can survive inside phagocytic cells. In order to further our understanding of the oxidative stress response in C. glabrata, we characterized the superoxide dismutases (SODs) Cu,ZnSOD (Sod1) and MnSOD (Sod2). We found that Sod1 is the major contributor to total SOD activity and is present in cytoplasm, whereas Sod2 is a mitochondrial protein. Both SODs played a central role in the oxidative stress response but Sod1 was more important during fermentative growth and Sod2 during respiration and growth in non-fermentable carbon sources. Interestingly, C. glabrata cells lacking both SODs showed auxotrophy for lysine, a high rate of spontaneous mutation and reduced chronological lifespan. Thus, our study reveals that SODs play an important role in metabolism, lysine biosynthesis, DNA protection and aging in C. glabrata.

The mating type-like loci of Candida glabrata / Los loci de apareamiento de Candida glabrata

Candida glabrata, a haploid and opportunistic fungal pathogen that has not known sexual cycle, has conserved the majority of the genes required for mating and cell type identity. The C. glabrata genome contains three mating-type-like loci called MTL1, MTL2 and MTL3. The three loci encode putative transcription factors, a1, α1 and α2 that regulate cell type identity and sexual reproduction in other fungi like the closely related Saccharomyces cerevisiae. MTL1 can contain either a or α information. MTL2, which contains a information and MTL3 with α information, are relatively close to two telomeres. MTL1 and MTL2 are transcriptionally active, while MTL3 is subject to an incomplete silencing nucleated at the telomere that depends on the silencing proteins Sir2, Sir3, Sir4, yKu70/80, Rif1, Rap1 and Sum1. C. glabrata does not seem to maintain cell type identity, as cell type-specific genes are expressed regardless of the type (or even absence) of mating information. These data highlight important differences in the control of mating and cell type identity between the non-pathogenic yeast S. cerevisiae and C. glabrata, which might explain the absence of a sexual cycle in C. glabrata. The fact that C. glabrata has conserved the vast majority of the genes involved in mating might suggest that some of these genes perhaps have been rewired to control other processes important for the survival inside the host as a commensal or as a human pathogen. This manuscript is part of the series of works presented at the "V International Workshop: Molecular genetic approaches to the study of human pathogenic fungi" (Oaxaca, Mexico, 2012) (AU)

Candida glabrata, una levadura patógena haploide y oportunista, que carece de ciclo sexual conocido (asexual), conserva la mayoría de genes ortólogos requeridos en los procesos de apareamiento, esporulación y la identidad del tipo celular. El genoma de C. glabrata contiene 3 loci de apareamiento llamados MTL1, MTL2 y MTL3 que codifican los presuntos factores de transcripción a1, α1 y α2 que controlan la reproducción sexual e identidad celular en otros hongos, como Saccharomyces cerevisiae con el cual tiene una estrecha relación filogenética. MTL1 puede contener información a o α; MTL2 contiene información a, y MTL3 que contiene información α1 y α2 son loci próximos a 2 telómeros. MTL1 y MTL2 son activos transcripcionalmente mientras que MTL3 está sujeto a un silenciamiento que no es completo, que proviene del telómero y depende de las proteínas Sir2, Sir3, Sir4, yKu70/80, Rif1, Rap1 y Sum1. C. glabrata parece no mantener identidad de tipo celular ya que varios genes específicos de un tipo celular se expresan en todas las células con independencia del tipo de información de apareamiento en los loci MTL, o incluso, en su ausencia. Estos datos ilustran varias diferencias importantes entre la levadura no patógena S. cerevisiae y C. glabrata que podrían explicar la característica asexual en esta última. El hecho de que en C. glabrata se hayan conservado los genes necesarios para el apareamiento podría indicar que es posible que algunos de estos genes se hayan «reorganizado» para controlar otros procesos importantes en la supervivencia de C. glabrata en su huésped, como comensal o como patógeno.Este artículo forma parte de una serie de estudios presentados en el «V International Workshop: Molecular genetic approaches to the study of human pathogenic fungi» (Oaxaca, México, 2012) (AU)

The mating type-like loci of Candida glabrata.

Candida glabrata, a haploid and opportunistic fungal pathogen that has not known sexual cycle, has conserved the majority of the genes required for mating and cell type identity. The C. glabrata genome contains three mating-type-like loci called MTL1, MTL2 and MTL3. The three loci encode putative transcription factors, a1, α1 and α2 that regulate cell type identity and sexual reproduction in other fungi like the closely related Saccharomyces cerevisiae. MTL1 can contain either a or α information. MTL2, which contains a information and MTL3 with α information, are relatively close to two telomeres. MTL1 and MTL2 are transcriptionally active, while MTL3 is subject to an incomplete silencing nucleated at the telomere that depends on the silencing proteins Sir2, Sir3, Sir4, yKu70/80, Rif1, Rap1 and Sum1. C. glabrata does not seem to maintain cell type identity, as cell type-specific genes are expressed regardless of the type (or even absence) of mating information. These data highlight important differences in the control of mating and cell type identity between the non-pathogenic yeast S. cerevisiae and C. glabrata, which might explain the absence of a sexual cycle in C. glabrata. The fact that C. glabrata has conserved the vast majority of the genes involved in mating might suggest that some of these genes perhaps have been rewired to control other processes important for the survival inside the host as a commensal or as a human pathogen. This manuscript is part of the series of works presented at the "V International Workshop: Molecular genetic approaches to the study of human pathogenic fungi" (Oaxaca, Mexico, 2012).