Variants in toll-like receptors 2 and 9 influence susceptibility to pulmonary tuberculosis in Caucasians, African-Americans, and West Africans.

Tuberculosis (TB) is a global public health problem and a source of preventable deaths each year, with 8.8 million new cases of TB and 1.6 million deaths worldwide in 2005. Approximately, 10% of infected individuals develop pulmonary or extrapulmonary TB, suggesting that host defense factors influence development of active disease. Toll-like receptor' (TLR) polymorphisms have been associated with regulation of TLR expression and development of active TB. In the present study, 71 polymorphisms in TLR1, TLR2, TLR4, TLR6, and TLR9 were examined from 474 (295 cases and 179 controls) African-Americans, 381 (237 cases and 144 controls) Caucasians, and from 667 (321 cases and 346 controls) Africans from Guinea-Bissau for association with pulmonary TB using generalized estimating equations and logistic regression. Statistically significant associations were observed across populations at TLR9 and TLR2. The strongest evidence for association came at an insertion (I)/deletion (D) polymorphism (-196 to -174) in TLR2 that associated with TB in both Caucasians (II vs. ID&DD, OR = 0.41 [95% CI 0.24-0.68], p = 0.0007) and Africans (II vs. ID&DD, OR = 0.70 [95% CI 0.51-0.95], p = 0.023). Our findings in three independent population samples indicate that variations in TLR2 and TLR9 might play important roles in determining susceptibility to TB.

[Pragmatic difficulties in children with specific language impairment. The role of mentalistic tasks]. / Dificultades pragmáticas en el trastorno especifico del lenguaje. El papel de las tareas mentalistas.

Several subjects with Specific Language Impairment (SLI) show communicative and pragmatic problems. In this study, we suggested that mentalistic comprehension tasks would help us to find a deteriorated pragmatic profile among the population with SLI. To achieve this goal, a group of participants with conventional SLI (n=11) was compared to a group of SLI with more pragmatic problems (n=9) and their respective control group with typically developed language (n=13), of ages between 4 and 7 years. Results revealed that all the groups were able to attribute mental states in tasks where the context was structured. However, the subjects with predominant pragmatic SLI showed poorer performance than those with conventional SLI when tasks were communicative-oriented and they needed to process non-explicit information from the context. These findings suggest that it is possible to isolate a SLI subtype with more pragmatic problems and also that we can use mentalistic tasks to assess these difficulties more accurately.

NOS2A, TLR4, and IFNGR1 interactions influence pulmonary tuberculosis susceptibility in African-Americans.

Tuberculosis (TB) has substantial mortality worldwide with 5-10% of those exposed progressing to active TB disease. Studies in mice and humans indicate that the inducible nitric oxide synthase (iNOS) molecule plays an important role in immune response to TB. A mixed case-control association study of individuals with TB, relatives, or close contact controls was performed in 726 individuals (279 case and 166 control African-Americans; 198 case and 123 control Caucasians). Thirty-nine single nucleotide polymorphisms (SNPs) were selected from the NOS2A gene for single SNP, haplotype, and multilocus interaction analyses with other typed candidate genes using generalized estimating equations. In African-Americans, ten NOS2A SNPs were associated with TB. The strongest associations were observed at rs2274894 (odds ratio (OR) = 1.84, 95% confidence interval (CI) [1.23-2.77], p = 0.003) and rs7215373 (OR = 1.67, 95% CI [1.17-2.37], p = 0.004), both of which passed a false discovery rate correction for multiple comparisons (q* = 0.20). The strongest gene-gene interactions were observed between NOS2A rs2248814 and IFNGR1 rs1327474 (p = 0.0004) and NOS2A rs944722 and IFNGR1 rs1327474 (p = 0.0006). Three other SNPs in NOS2A interacted with TLR4 rs5030729 and five other NOS2A SNPs interacted with IFNGR1 rs1327474. No significant associations were observed in Caucasians. These results suggest that NOS2A variants may contribute to TB susceptibility, particularly in individuals of African descent, and may act synergistically with SNPs in TLR4 and IFNGR1.

Autism and Faux Pas. Influences of Presentation Modality and Working Memory.

People diagnosed with an autism spectrum disorder (ASD) often have difficulties on Theory of Mind (ToM) tasks involving social situations, such as 'faux pas'. The objective of this study was to find the modality of presentation (visual, verbal, or mixed) that yields the best understanding of a 'faux pas', and the possible influence of other variables, including intelligence (IQ), age, and working memory. Thirty autistic children and 30 neurotypical children, all aged 7 to 12 years old and comparable in age and IQ, participated in this study. They were asked to resolve nine 'faux pas' stories (three per modality). Significant between-groups differences were found in the visual (t = 2.99, p = .004) and verbal modalities (t = 2.64, p = .011), such that the neurotypical (NT) group had higher scores than the ASD group. The ASD group's comprehension was better via the mixed modality than the verbal modality (t = 2.48, p = .019). In addition, working memory had a bigger impact on Faux Pas understanding in cases of autism than in typical development (R2 explained between .19 and .28 of variance in Faux Pas test outcomes), and could therefore explain some of the difficulties previously reported in this area. Future research should include a measure of working memory and a control among the stimuli presented to test for group differences in faux pas understanding.

[Tuberculosis treatment. A practical guide elaborated by the tuberculosis section, Argentine Association of Respiratory Medicine]. / Tratamiento de la tuberculosis. Guia practica elaborada por la seccion tuberculosis, Asociacion Argentina de Medicina Respiratoria.

Tuberculosis is a worldwide prevalent disease. The emergence of multidrug-resistant strains spurred the search for new drugs. There are several tuberculosis treatment guidelines, international and local in a programmatic approach. An Argentinean specialists panel draw practical guidelines based in clinical criteria and the local and international bibliography through consensus meetings, including issues as: antituberculosis drugs available in Argentina, initial and re-treatement modalities, special situations treatment, adverse reactions to antituberculosis drugs, current indications of surgical treatment and new drugs under study for the treatment of the disease.

Autism and faux pas. Influences of presentation modality and working memory

People diagnosed with an autism spectrum disorder (ASD) often have difficulties on Theory of Mind (ToM) tasks involving social situations, such as 'faux pas'. The objective of this study was to find the modality of presentation (visual, verbal, or mixed) that yields the best understanding of a 'faux pas', and the possible influence of other variables, including intelligence (IQ), age, and working memory. Thirty autistic children and 30 neurotypical children, all aged 7 to 12 years old and comparable in age and IQ, participated in this study. They were asked to resolve nine 'faux pas' stories (three per modality). Significant between-groups differences were found in the visual (t = 2.99, p = .004) and verbal modalities (t = 2.64, p = .011), such that the neurotypical (NT) group had higher scores than the ASD group. The ASD group's comprehension was better via the mixed modality than the verbal modality (t = 2.48, p = .019). In addition, working memory had a bigger impact on Faux Pas understanding in cases of autism than in typical development (R2 explained between .19 and .28 of variance in Faux Pas test outcomes), and could therefore explain some of the difficulties previously reported in this area. Future research should include a measure of working memory and a control among the stimuli presented to test for group differences in faux pas understanding

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MCP1 SNPs and pulmonary tuberculosis in cohorts from West Africa, the USA and Argentina: lack of association or epistasis with IL12B polymorphisms.

The monocyte chemotactic protein-1 (MCP-1) is a chemokine that plays an important role in the recruitment of monocytes to M. tuberculosis infection sites, and previous studies have reported that genetic variants in MCP1 are associated with differential susceptibility to pulmonary tuberculosis (PTB). We examined eight MCP1 single nucleotide polymorphisms (SNPs) in a multi-ethnic, case-control design that included: 321 cases and 346 controls from Guinea-Bissau, 258 cases and 271 controls from The Gambia, 295 cases and 179 controls from the U.S. (African-Americans), and an additional set of 237 cases and 144 controls of European ancestry from the U.S. and Argentina. Two locus interactions were also examined for polymorphisms in MCP1 and interleukin 12B (IL12B), another gene implicated in PTB risk. Examination of previously associated MCP1 SNPs rs1024611 (-2581A/G), rs2857656 (-362G/C) and rs4586 (+900C/T) did not show evidence for association. One interaction between rs2857656 and IL12B SNP rs2288831 was observed among Africans but the effect was in the opposite direction in Guineans (OR = 1.90, p = 0.001) and Gambians (OR = 0.64, p = 0.024). Our data indicate that the effect of genetic variation within MCP1 is not clear cut and additional studies will be needed to elucidate its role in TB susceptibility.

Are children with Specific Language Impairment competent with the pragmatics and logic of quantification?

Specific Language Impairment (SLI) is understood to be a disorder that predominantly affects phonology, morphosyntax and/or lexical semantics. There is little conclusive evidence on whether children with SLI are challenged with regard to Gricean pragmatic maxims and on whether children with SLI are competent with the logical meaning of quantifying expressions. We use the comprehension of statements quantified with 'all', 'none', 'some', 'some…not', 'most' and 'not all' as a paradigm to study whether Spanish-speaking children with SLI are competent with the pragmatic maxim of informativeness, as well as with the logical meaning of these expressions. Children with SLI performed more poorly than a group of age-matched typically-developing peers, and both groups performed more poorly with pragmatics than with logical meaning. Moreover, children with SLI were disproportionately challenged by pragmatic meaning compared to their age-matched peers. However, the performance of children with SLI was comparable to that of a group of younger language-matched typically-developing children. The findings document that children with SLI do face difficulties with employing the maxim of informativeness, as well as with understanding the logical meaning of quantifiers, but also that these difficulties are in keeping with their overall language difficulties rather than exceeding them. The implications of these findings for SLI, linguistic theory, and clinical practice are discussed.

Interleukin 12B (IL12B) genetic variation and pulmonary tuberculosis: a study of cohorts from The Gambia, Guinea-Bissau, United States and Argentina.

We examined whether polymorphisms in interleukin-12B (IL12B) associate with susceptibility to pulmonary tuberculosis (PTB) in two West African populations (from The Gambia and Guinea-Bissau) and in two independent populations from North and South America. Nine polymorphisms (seven SNPs, one insertion/deletion, one microsatellite) were analyzed in 321 PTB cases and 346 controls from Guinea-Bissau and 280 PTB cases and 286 controls from The Gambia. For replication we studied 281 case and 179 control African-American samples and 221 cases and 144 controls of European ancestry from the US and Argentina. First-stage single locus analyses revealed signals of association at IL12B 3' UTR SNP rs3212227 (unadjusted allelic p = 0.04; additive genotypic p = 0.05, OR = 0.78, 95% CI [0.61-0.99]) in Guinea-Bissau and rs11574790 (unadjusted allelic p = 0.05; additive genotypic p = 0.05, OR = 0.76, 95% CI [0.58-1.00]) in The Gambia. Association of rs3212227 was then replicated in African-Americans (rs3212227 allelic p = 0.002; additive genotypic p = 0.05, OR = 0.78, 95% CI [0.61-1.00]); most importantly, in the African-American cohort, multiple significant signals of association (seven of the nine polymorphisms tested) were detected throughout the gene. These data suggest that genetic variation in IL12B, a highly relevant candidate gene, is a risk factor for PTB in populations of African ancestry, although further studies will be required to confirm this association and identify the precise mechanism underlying it.

Tratamiento de la tuberculosis: guia practica elaborada por la Seccion Tuberculosis, Asociacion Argentina de Medicina Respiratoria / Tuberculosis treatment: a practical guide elaborated by the Tuberculosis Section, Argentine Association of Respiratory Medicine

La tuberculosis es una enfermedad prevalente en todo el mundo. La emergencia de cepas multirresistentes del Mycobacterium tuberculosis ha incentivado la búsqueda de nuevos fármacos. Existen diversas guías de tratamiento de la enfermedad, internacionales y a nivel programático local. Un grupo de especialistas argentinos elaboró una guía práctica basada en criterios clínicos y en la bibliografía nacional e internacional sobre el tema a través de reuniones de consenso, abarcando tópicos como: fármacos antituberculosos disponibles en la Argentina, modalidades de tratamiento inicial y retratamiento, tratamiento en situaciones especiales, reacciones adversas a fármacos antituberculosos, indicaciones actuales de tratamiento quirúrgico y nuevos fármacos en estudio para el tratamiento de la enfermedad.

Tuberculosis is a worldwide prevalent disease. The emergence of multidrug-resistant strains spurred the search for new drugs. There are several tuberculosis treatment guidelines, international and local in a programmatic approach. An Argentinean specialists panel draw practical guidelines based in clinical criteria and the local and international bibliography through consensus meetings, including issues as: antituberculosis drugs available in Argentina, initial and re-treatement modalities, special situations treatment, adverse reactions to antituberculosis drugs, current indications of surgical treatment and new drugs under study for the treatment of the disease.

Dificultades pragmáticas en el trastorno específico del lenguaje. El papel de las tareas mentalistas / Pragmatic difficulties in children with specific language impairment. The role of mentalistic tasks

Gran número de sujetos con Trastorno Específico del Lenguaje (TEL) manifiestan problemas comunicativos y de tipo pragmático. Este estudio se planteó analizar el papel de las tareas de comprensión mentalista en la distinción de un perfil TEL con problemas predominantemente pragmáticos. Para ello se comparó la ejecución en tareas mentalistas de un grupo de participantes con TEL convencional (n= 11), un grupo con TEL con mayor afectación pragmática (n= 9) y un grupo con desarrollo típico del lenguaje (n= 13) de edades comprendidas entre 4 y 7 años. Los resultados revelaron que todos los grupos fueron igualmente capaces de atribuir estados mentales cuando el contexto está estructurado. Sin embargo, los sujetos con TEL pragmático tuvieron menos éxito que el grupo TEL convencional cuando las tareas estaban orientadas de manera comunicativa y necesitaban procesar información no explícita del contexto. Nuestros datos apoyan la posibilidad de aislar un subtipo de TEL con especiales problemas pragmáticos, así como el uso de tareas mentalistas para evaluar de forma más precisa estas dificultades (AU)

Several subjects with Specific Language Impairment (SLI) show communicative and pragmatic problems. In this study, we suggested that mentalistic comprehension tasks would help us to find a deteriorated pragmatic profile among the population with SLI. To achieve this goal, a group of participants with conventional SLI (n= 11) was compared to a group of SLI with more pragmatic problems (n= 9) and their respective control group with typically developed language (n= 13), of ages between 4 and 7 years. Results revealed that all the groups were able to attribute mental states in tasks where the context was structured. However, the subjects with predominant pragmatic SLI showed poorer performance than those with conventional SLI when tasks were communicative-oriented and they needed to process non-explicit information from the context. These findings suggest that it is possible to isolate a SLI subtype with more pragmatic problems and also that we can use mentalistic tasks to assess these difficulties more accurately (AU)