Acceptance and Commitment Therapy versus Cognitive Behavior Therapy for Children With Anxiety: Outcomes of a Randomized Controlled Trial.

Acceptance and Commitment Therapy (ACT) has a growing empirical base in the treatment of anxiety among adults and children with other concerns. This study reports on the main outcomes of a randomized controlled trial of ACT and traditional cognitive behavioral therapy (CBT) in children with a Diagnostic and Statistical Manual of Mental Disorders (4th ed.) anxiety disorder. Participants were 193 children from urban Sydney, Australia, who were block-randomized to a 10-week group-based program of ACT or CBT or a 10-week waitlist control (WLC). Completers included 157 children (ACT = 54, CBT = 57, WLC = 46; M = 11 years, SD = 2.76; 78% Caucasian, 58% female). Pretreatment, posttreatment, and 3 months posttreatment assessments included clinician/self/parent-reported measures of anxiety, quality of life (QOL; anxiety interference, psychosocial and physical health-related QOL), and acceptance/defusion outcomes. Completer and intention-to-treat analyses revealed that ACT and CBT were both superior to WLC across outcomes, reflecting statistically and clinically significant differences, with gains maintained at 3 months posttreatment. Both completer and intention-to-treat analyses found ACT and CBT to produce similar outcomes. There was some support for ACT having greater effect sizes for QOL outcomes but not for avoidance/fusion. Although this study does not suggest that ACT is equivalent to CBT or should be adopted in its place, it does provide evidence that ACT might be another empirically supported treatment option for anxious youth. Further research is needed to replicate these findings.

RNA-stable-isotope probing shows utilization of carbon from inulin by specific bacterial populations in the rat large bowel.

Knowledge of the trophisms that underpin bowel microbiota composition is required in order to understand its complex phylogeny and function. Stable-isotope ((13)C)-labeled inulin was added to the diet of rats on a single occasion in order to detect utilization of inulin-derived substrates by particular members of the cecal microbiota. Cecal digesta from Fibruline-inulin-fed rats was collected prior to (0 h) and at 6, 12, 18 and 24 h following provision of the [(13)C]inulin diet. RNA was extracted from these cecal specimens and fractionated in isopycnic buoyant density gradients in order to detect (13)C-labeled nucleic acid originating in bacterial cells that had metabolized the labeled dietary constituent. RNA extracted from specimens collected after provision of the labeled diet was more dense than 0-h RNA. Sequencing of 16S rRNA genes amplified from cDNA obtained from these fractions showed that Bacteroides uniformis, Blautia glucerasea, Clostridium indolis, and Bifidobacterium animalis were the main users of the (13)C-labeled substrate. Culture-based studies of strains of these bacterial species enabled trophisms associated with inulin and its hydrolysis products to be identified. B. uniformis utilized Fibruline-inulin for growth, whereas the other species used fructo-oligosaccharide and monosaccharides. Thus, RNA-stable-isotope probing (RNA-SIP) provided new information about the use of carbon from inulin in microbiota metabolism.

Comparison of the compositions of the stool microbiotas of infants fed goat milk formula, cow milk-based formula, or breast milk.

The aim of the study was to compare the compositions of the fecal microbiotas of infants fed goat milk formula to those of infants fed cow milk formula or breast milk as the gold standard. Pyrosequencing of 16S rRNA gene sequences was used in the analysis of the microbiotas in stool samples collected from 90 Australian babies (30 in each group) at 2 months of age. Beta-diversity analysis of total microbiota sequences and Lachnospiraceae sequences revealed that they were more similar in breast milk/goat milk comparisons than in breast milk/cow milk comparisons. The Lachnospiraceae were mostly restricted to a single species (Ruminococcus gnavus) in breast milk-fed and goat milk-fed babies compared to a more diverse collection in cow milk-fed babies. Bifidobacteriaceae were abundant in the microbiotas of infants in all three groups. Bifidobacterium longum, Bifidobacterium breve, and Bifidobacterium bifidum were the most commonly detected bifidobacterial species. A semiquantitative PCR method was devised to differentiate between B. longum subsp. longum and B. longum subsp. infantis and was used to test stool samples. B. longum subsp. infantis was seldom present in stools, even of breast milk-fed babies. The presence of B. bifidum in the stools of breast milk-fed infants at abundances greater than 10% of the total microbiota was associated with the highest total abundances of Bifidobacteriaceae. When Bifidobacteriaceae abundance was low, Lachnospiraceae abundances were greater. New information about the composition of the fecal microbiota when goat milk formula is used in infant nutrition was thus obtained.

Trauma and psychotic symptoms: data from a pediatric mental health inpatient unit.

This study describes differences in symptoms in young people with psychosis, with and without a history of trauma. The files of 118 mental health inpatients, aged 8 to 18 years, all reporting hallucinations and/or delusions, were reviewed for a history of trauma. Symptoms reported by inpatients with and without a history of trauma were compared. Variables found to be significantly associated with trauma in the univariate analysis were entered into a logistic regression analysis. Variables were entered if they met a significance of p < .05 or an adjusted odds ratio of < 2. Young people with a history of trauma reported a highly significant increase in disturbed behavior, particularly those with a history of sexual assault. This study illustrates the importance of obtaining an adequate assessment of children and adolescents with psychotic symptoms to ensure they receive the most effective treatment.

A new macrocyclic antibiotic, fidaxomicin (OPT-80), causes less alteration to the bowel microbiota of Clostridium difficile-infected patients than does vancomycin.

Clostridium difficile infection (CDI) is the most common identifiable cause of diarrhoea in hospitalized patients. Current therapies rely on the administration of metronidazole or vancomycin, which reduce vegetative populations of C. difficile in the bowel. Recurrence of the disease when treatment with these antibiotics ceases indicates that metronidazole and vancomycin affect not only C. difficile but also commensal populations that normally mediate competitive exclusion. Fidaxomicin is a new antibiotic that inhibits C. difficile. Our study shows that fidaxomicin had little effect on the composition of the faecal microbiota in terms of its major phylogenetic clusters. Notably, clostridial clusters XIVa and IV, and Bifidobacterium, were much less affected by fidaxomicin compared to vancomycin treatment. These findings help to explain the substantially reduced rates of relapse following treatment of CDI with fidaxomicin in recent clinical trials.

Bifidobacterium pseudocatenulatum is associated with atopic eczema: a nested case-control study investigating the fecal microbiota of infants.

BACKGROUND: Exposure to specific bacterial bowel commensals may increase/reduce the risk of atopic diseases. OBJECTIVE: To compare fecal bacterial communities of young infants with/without eczema. METHODS: Nested case-control study. Infants age 3 to 6 months with eczema (cases, n = 37) and without (controls, n = 24) were matched for sex, age, feeding (breast/bottle/mixed/solids), ethnicity. Information was collected on maternal/infant antibiotic exposure, feeding, gastrointestinal symptoms, family history of allergy. Eczema severity scoring was used (Severity Scoring of Atopic Dermatitis index). Samples were taken for determination of allergen-specific serum IgE (cases) and urinary/fecal eosinophilic protein X. Gastrointestinal permeability was measured. The compositions of fecal bacterial communities were analyzed (culture-independent, nucleic acid-based analyses). RESULTS: There was no difference in overall profiles of fecal bacterial communities between cases and controls. Family history of allergy increased likelihood of bifidobacteria detection (history, 86%; no history, 56%; P = .047); breast-fed infants were more likely to harbor Bifidobacterium bifidum (odds ratio, 5.19; 95% CI, 1.47-18.36; P = .01). Bifidobacterium pseudocatenulatum was detected more commonly in feces of non-breast-fed children (odds ratio, 5.6; 95% CI, 1.3-24.3; P = .02) and children with eczema (eczema, 26%; no eczema, 4%; P = .04). There were no significant associations between clinical measurements and detection of B pseudocatenulatum. CONCLUSION: Presence of B pseudocatenulatum in feces was associated with eczema and with exclusive formula-feeding; B bifidum was associated with breast-feeding.

Differentiation of Bifidobacterium longum subspecies longum and infantis by quantitative PCR using functional gene targets.

BACKGROUND: Members of the genus Bifidobacterium are abundant in the feces of babies during the exclusively-milk-diet period of life. Bifidobacterium longum is reported to be a common member of the infant fecal microbiota. However, B. longum is composed of three subspecies, two of which are represented in the bowel microbiota (B. longum subsp. longum; B. longum subsp. infantis). B. longum subspecies are not differentiated in many studies, so that their prevalence and relative abundances are not accurately known. This may largely be due to difficulty in assigning subspecies identity using DNA sequences of 16S rRNA or tuf genes that are commonly used in bacterial taxonomy. METHODS: We developed a qPCR method targeting the sialidase gene (subsp. infantis) and sugar kinase gene (subsp. longum) to differentiate the subspecies using specific primers and probes. Specificity of the primers/probes was tested by in silico, pangenomic search, and using DNA from standard cultures of bifidobacterial species. The utility of the method was further examined using DNA from feces that had been collected from infants inhabiting various geographical regions. RESULTS: A pangenomic search of the NCBI genomic database showed that the PCR primers/probes targeted only the respective genes of the two subspecies. The primers/probes showed total specificity when tested against DNA extracted from the gold standard strains (type cultures) of bifidobacterial species detected in infant feces. Use of the qPCR method with DNA extracted from the feces of infants of different ages, delivery method and nutrition, showed that subsp. infantis was detectable (0-32.4% prevalence) in the feces of Australian (n = 90), South-East Asian (n = 24), and Chinese babies (n = 91), but in all cases at low abundance (<0.01-4.6%) compared to subsp. longum (0.1-33.7% abundance; 21.4-100% prevalence). DISCUSSION: Our qPCR method differentiates B. longum subspecies longum and infantis using characteristic functional genes. It can be used as an identification aid for isolates of bifidobacteria, as well as in determining prevalence and abundance of the subspecies in feces. The method should thus be useful in ecological studies of the infant gut microbiota during early life where an understanding of the ecology of bifidobacterial species may be important in developing interventions to promote infant health.

Comprehensive analysis of the bacterial content of stool from patients with chronic pouchitis, normal pouches, or familial adenomatous polyposis pouches.

BACKGROUND: Chronic pouchitis is an important long-term complication following ileal pouch-anal anastomosis for ulcerative colitis. Antibiotic administration reduces symptoms of pouchitis, indicating that bacteria have a role in pathogenesis. The aim of the research was to investigate the bacterial content of pouches using nucleic acid-based methods. METHODS: Stool microbiota of 17 patients with normal pouches (NP), 17 patients with pouchitis (CP) utilizing samples collected from each patient when antibiotic-treated (CP-on, asymptomatic) and when untreated (CP-off, symptomatic), and 14 familial adenomatous polyposis (FAP) patients were analyzed by high-throughput sequencing, fluorescence in situ hybridization technologies, and quantitative polymerase chain reaction (qPCR). RESULTS: Fluorescence in situ hybridization analysis revealed an expanded phylogenetic gap in NP and CP-off patients relative to FAP. Antibiotic treatment reduced the gap in CP stool. The phylogenetic gap of CP-off patients was due to members of the bacterial families Caulobacteriaceae, Sphingomonadaceae, Comamonadaceae, Peptostreptococcaceae, and Clostridiaceae. There was a greater diversity of phylotypes of Clostridiaceae in CP-off subjects. The phylogenetic gap of NP stool was enriched by Ruminococcaceae and Bifidobacteriaceae. CP stool microbiota had reduced diversity relative to NP and FAP stool due largely to a reduction in Lachnospiraceae/Insertae Sedis XIV/clostridial cluster IV groups. CONCLUSIONS: Bacterial groups within the expanded phylogenetic gap of pouch patients may have roles in the pathogenesis of pouchitis. Further research concerning the physiology of cultured members of these groups will be necessary to explain their specific roles. Members of the Lachnospiraceae, Incertae Sedis XIV, and clostridial cluster IV could be useful biomarkers of pouch health.

Do New Zealand children with non-cystic fibrosis bronchiectasis show disease progression?

BACKGROUND: There is minimal literature available on the long-term outcome of pediatric non-cystic fibrosis (CF) bronchiectasis. AIM: To document 5-year outcomes of children with chest computerized tomography (CT) scan diagnosed bronchiectasis from a tertiary New Zealand (NZ) respiratory clinic. METHODS: Review of a clinical database identified 91 children. Demographics, clinical data, lung function, chest X-ray (CXR), sputum, presumed etiology, admission data, and the NZ deprivation index (NZDep) were collected. Univariate and multivariate regression were used to correlate clinical findings with lung function data and CXR scores using the Brasfield Scoring System. RESULTS: Of the 91 children, 53 (59%) were Pacific Island, 22 (24%) Maori, 14 (15%) European, and 2 (2%) Other. The median follow-up period was 6.7 years (range 5.0-15.3 years) and median age at diagnosis was 7.3 years (range 11 months-16 years). Lung function data (n = 64) showed a mean decline of -1.6% predicted/year. In 30 children lung function declined (mean FEV(1) -4.4% predicted/year, range 1-17%), remained stable in 13 and improved in 21 children (mean FEV(1) of +3% predicted/year, range 1-15%). Reduced lung function was associated with male gender, chronic Haemophilus influenzae infection, longevity of disease, and Maori and Pacific Island ethnicity. There was a significant correlation with FEV(1) and CXR score at beginning (n = 47, r = 0.45, P = 0.001) and end (n = 26, r = 0.59, P = 0.002) of the follow-up period. The only variable consistently related to CXR score was chronic Haemophilus influenzae infection occurring in 27 (30%) (r(2) = 0.52, P = <0.0001). Only four children were chronically infected with Pseudomonas species. Six children died. CONCLUSION: In our experience despite management in a tertiary multidisciplinary bronchiectasis clinic, progression of lung disease continues in a group of children and young adults.

Testing probiotic strain Escherichia coli Nissle 1917 (Mutaflor) for its ability to reduce carriage of multidrug-resistant E. coli by elderly residents in long-term care facilities.

A high carriage rate of multidrug-resistant Escherichia coli (MDREC) was observed in elderly residents in long-term care facilities. A double-blinded, placebo-controlled trial was carried out to determine whether the probiotic product E. coli strain Nissle 1917 (Mutaflor) would compete with MDREC in the bowel and thereby reduce the prevalence of the multiresistant bacteria in faeces and urine. Sixty-nine patients excreting norfloxacin-resistant E. coli were randomized to probiotic or placebo groups and administered capsules twice daily. The daily dose of probiotic was 5×10(9)-5×10(10) bacteria. Faecal and urine samples were cultured at baseline and during and after the treatment period. A reduction in baseline carriage was not influenced by probiotic administration. The probiotic strain was detected in faecal specimens collected during the treatment period of only two out of 12 probiotic group subjects that were tested. Genotyping of norfloxacin-resistant E. coli isolates showed that 32 strains were prevalent among the patients. Thus, E. coli Nissle 1917 does not have the capacity to compete effectively with MDREC in the bowel of elderly patients.

EWS/FLI1 suppresses retinoblastoma protein function and senescence in Ewing's sarcoma cells.

Ewing's Family Tumors (EFTs) most commonly harbor a specific t(11;22) translocation that generates the EWS/FLI1 fusion protein responsible for malignant transformation. Many potential downstream targets of EWS/FLI1 have been identified but a detailed mechanism by which the fusion protein brings about transformation remains unknown. In this report, we show that depletion of EWS/FLI1 in Ewing's cell lines results in a senescence phenotype, a marked increase in expression of the G1/S regulatory proteins p27(kip1) and p57(kip2), and a significant decrease in cyclin D1 and CDK2. We also demonstrate for the first time, to our knowledge, that knockdown of EWS/FLI1 leads to hypophosphorylation and functional activation of the retinoblastoma (pRb) family of proteins. Consistent with activation of the pRb proteins, E2F-responsive genes such as cyclin A are repressed in EWS/FLI1-depleted cells. Together, these results support the role of EWS/LI1 as an inhibitor of cellular senescence and implicate the retinoblastoma family of proteins as key mediators of this inhibition.

Identification, detection, and enumeration of human bifidobacterium species by PCR targeting the transaldolase gene.

Methods that enabled the identification, detection, and enumeration of Bifidobacterium species by PCR targeting the transaldolase gene were tested. Bifidobacterial species isolated from the feces of human adults and babies were identified by PCR amplification of a 301-bp transaldolase gene sequence and comparison of the relative migrations of the DNA fragments in denaturing gradient gel electrophoresis (DGGE). Two subtypes of Bifidobacterium longum, five subtypes of Bifidobacterium adolescentis, and two subtypes of Bifidobacterium pseudocatenulatum could be differentiated using PCR-DGGE. Bifidobacterium angulatum and B. catenulatum type cultures could not be differentiated from each other. Bifidobacterial species were also detected directly in fecal samples by this combination of PCR and DGGE. The number of species detected was less than that detected by PCR using species-specific primers targeting 16S ribosomal DNA (rDNA). Real-time quantitative PCR targeting a 110-bp transaldolase gene sequence was used to enumerate bifidobacteria in fecal samples. Real-time quantitative PCR measurements of bifidobacteria in fecal samples from adults correlated well with results obtained by culture when either a 16S rDNA sequence or the transaldolase gene sequence was targeted. In the case of samples from infants, 16S rDNA-targeted PCR was superior to PCR targeting the transaldolase gene for the quantification of bifidobacterial populations.

Impact of consumption of oligosaccharide-containing biscuits on the fecal microbiota of humans.

Human subjects consumed biscuits containing either galacto-oligosaccharides or fructo-oligosaccharides in a double-blinded, crossover study. The impact of supplementing the diet with three biscuits per day on the fecal microbiota was evaluated by selective culture of particular bacterial groups, measurement of beta-galactosidase activity, and nucleic acid-based analytical methods (PCR-denaturing gradient gel electrophoresis [PCR-DGGE] and fluorescent in situ hybridization). The composition of the bifidobacterial populations was monitored at the level of species (PCR-DGGE) and strains (pulsed-field gel electrophoresis of DNA digests), and representative cultures were tested quantitatively for their ability to use galacto-oligosaccharides. Technical improvements to DGGE analysis of the microbiota were made by the use of an internal standard that allowed valid comparisons of fragment staining intensities to be made between profiles, the use of S1 nuclease digestion to remove single-stranded DNA to facilitate cloning of DNA sequences cut from gels, and the extraction of RNA to be used as the template in reverse transcription-PCR-DGGE. RNA-DGGE profiles were markedly different (Dice's similarity coefficient, 58.5%) from those generated by DNA-DGGE. Neither the sizes of the bacterial populations nor the DNA-DGGE profiles of the microbiota were altered by the consumption of the biscuits, but the RNA-DGGE profiles were altered by the detection or increased staining intensity of 16S rRNA gene sequences originating from Bifidobacterium adolescentis and/or Colinsella aerofaciens in the feces of 11 of 15 subjects. beta-Galactosidase activity was elevated in the feces of some subjects as a result of biscuit consumption. Subjects differed in the ability of the bifidobacterial strains harbored in their feces to use galacto-oligosaccharides. Our observations suggest that a phylogenetic approach to analysis of the gut ecosystem may not always be optimal and that a more physiological (biochemical) method might be more informative.