Genetic Control of the Variable Innate Immune Response to Asymptomatic Bacteriuria

The severity of urinary tract infection (UTI) reflects the quality and magnitude of the host response. While strong local and systemic innate immune activation occurs in patients with acute pyelonephritis, the response to asymptomatic bacteriuria (ABU) is low. The immune response repertoire in ABU has not been characterized, due to the inherent problem to distinguish bacterial differences from host-determined variation. In this study, we investigated the host response to ABU and genetic variants affecting innate immune signaling and UTI susceptibility. Patients were subjected to therapeutic urinary tract inoculation with E. coli 83972 to ensure that they were exposed to the same E. coli strain. The innate immune response repertoire was characterized in urine samples, collected from each patient before and after inoculation with bacteria or PBS, if during the placebo arm of the study. Long-term E. coli 83972 ABU was established in 23 participants, who were followed for up to twelve months and the innate immune response was quantified in 233 urine samples. Neutrophil numbers increased in all but two patients and in an extended urine cytokine/chemokine analysis (31 proteins), the chemoattractants IL-8 and GRO-α, RANTES, Eotaxin-1 and MCP-1, the T cell chemoattractant and antibacterial peptide IP-10, inflammatory regulators IL-1-α and sIL-1RA and the T lymphocyte/dendritic cell product sIL-2Rα were detected and variably increased, compared to sterile samples. IL-6, which is associated with symptomatic UTI, remained low and numerous specific immune mediators were not detected. The patients were also genotyped for UTI-associated IRF3 and TLR4 promoter polymorphisms. Patients with ABU associated TLR4 polymorphisms had low neutrophil numbers, IL-6, IP-10, MCP-1 and sIL-2Rα concentrations. Patients with the ABU-associated IRF3 genotype had lower neutrophils, IL-6 and MCP-1 responses than the remaining group. The results suggest that the host-specific, low immune response to ABU mainly includes innate immune mediators and that host genetics directly influence the magnitude of this response

The evolution of saline lake waters: gradual and rapid biogeochemical pathways in the Basotu Lake District, Tanzania

The biogeochemical evolution of solutes markedly alters the chemistry in the closed-basin maar lakes that comprise the Basotu Lake District (Tanzania, East Africa). Examination of 11 (out of 13) lakes in the Basotu Lake District identified two distinct evolutionary pathways: a gradual path and a rapid path. During the course of biogeochemical evolution these waters follow either the gradual path alone or a combination of the gradual and rapid paths. Solute evolution along the gradual path is determined by all of the biogeochemical processes that for these waters appear to be tightly coupled to evaporative concentration (e.g. mineral precipitation, sorption and ion exchange, C0 2 degassing, and sulfate reduction). Rapid evolution occurs when mixing events suddenly permit H 2 S to be lost to the atmosphere. The chemistry of waters undergoing rapid evolution is changed abruptly because loss of every equivalent of sulfide produces an equivalent permanent alkalinity.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42881/1/10750_2004_Article_BF00026937.pd

Prevalência de TDAH em quatro escolas públicas brasileiras ADHD prevalence in four brazilian plublic schools

OBJETIVO: Determinar a prevalência de transtorno de déficit de atenção/hiperatividade (TDAH) em crianças de quatro escolas públicas brasileiras. MÉTODO: Estudo de prevalência. A população consistiu em todos os alunos de 1ª à 4ª séries do ensino fundamental com idades entre 6 e 12 anos de quatro escolas públicas (CIEPs). Na primeira etapa do estudo, os professores efetuaram triagem para TDAH utilizando os critérios diagnósticos do Manual Diagnóstico e Estatístico de Transtornos Mentais - IV Edição (DSM-IV). A triagem resultou em dois grupos de crianças: suspeitos e não suspeitos. Na segunda etapa, os pais das crianças suspeitas foram convidados a comparecerem à escola para entrevista com os pesquisadores e preenchimento dos critérios diagnósticos de TDAH, anamnese e exame físico pediátrico e neurológico. Ao final desta etapa, as crianças foram classificadas em "casos" de TDAH e crianças "indeterminadas" (crianças que preenchiam parcialmente os critérios diagnósticos). RESULTADOS: De uma população de 602 alunos, 461 fizeram parte do estudo. A prevalência de TDAH considerando o conjunto das 4 escolas foi 13%. A proporção masculino: feminino foi 2:1. O subtipo de TDAH mais freqüente foi o misto com 61,7% dos casos. CONCLUSÃO: A prevalência de TDAH nestes escolares brasileiros (13%) é mais elevada que a prevalência tradicionalmente mencionada (3-5%). O sexo masculino foi mais acometido que o feminino e o subtipo de TDAH mais prevalente foi o misto, ambos de acordo com estudos anteriores.<br>OBJECTIVE: To define the prevalence of attention-deficit/hyperactivity disorder (ADHD) in children from four Brazilian public elementary schools. METHOD: Study population consisted of all students from the first through fourth grades, age range 6-12 years, who attended four public elementary schools (CIEPs). This prevalence study comprised two steps. During the first step, school teachers screened their own pupils for ADHD using diagnostic criteria from the Diagnostic and Statistic Manual of Mental Disorders - Fourth Edition (DSM-IV). Screening resulted in two groups of children: suspects and non-suspects. In the second step, parents of suspect children were invited for an interview with the researchers, during which they filled ADHD symptoms questionnaire, and in addition a complete history, pediatric physical exam, and neurological exam were performed. At the end of this step, students were classified as "cases" or "undetermined", i.e., those who partially met ADHD diagnostic criteria. RESULTS: From a population of 602 students, 461 were recruited. Considering all four elementary schools, ADHD prevalence was 13%. Male to female ratio was 2:1. The most frequent ADHD subtype was the combined one, accounting for 61.7% of all cases. CONCLUSION: ADHD prevalence in a sample of school-aged children (13%) was higher than the rate that traditionally has been mentioned (3-5%). Boys were more frequently affected than girls and the most prevalent ADHD subtype was the combined subtype, and the latter two findings are concordant with previous studies