Multivariate characterization of white matter heterogeneity in autism spectrum disorder.

The complexity and heterogeneity of neuroimaging findings in individuals with autism spectrum disorder has suggested that many of the underlying alterations are subtle and involve many brain regions and networks. The ability to account for multivariate brain features and identify neuroimaging measures that can be used to characterize individual variation have thus become increasingly important for interpreting and understanding the neurobiological mechanisms of autism. In the present study, we utilize the Mahalanobis distance, a multidimensional counterpart of the Euclidean distance, as an informative index to characterize individual brain variation and deviation in autism. Longitudinal diffusion tensor imaging data from 149 participants (92 diagnosed with autism spectrum disorder and 57 typically developing controls) between 3.1 and 36.83 years of age were acquired over a roughly 10-year period and used to construct the Mahalanobis distance from regional measures of white matter microstructure. Mahalanobis distances were significantly greater and more variable in the autistic individuals as compared to control participants, demonstrating increased atypicalities and variation in the group of individuals diagnosed with autism spectrum disorder. Distributions of multivariate measures were also found to provide greater discrimination and more sensitive delineation between autistic and typically developing individuals than conventional univariate measures, while also being significantly associated with observed traits of the autism group. These results help substantiate autism as a truly heterogeneous neurodevelopmental disorder, while also suggesting that collectively considering neuroimaging measures from multiple brain regions provides improved insight into the diversity of brain measures in autism that is not observed when considering the same regions separately. Distinguishing multidimensional brain relationships may thus be informative for identifying neuroimaging-based phenotypes, as well as help elucidate underlying neural mechanisms of brain variation in autism spectrum disorders.

Avaliação microbiológica do sorvete de creme elaborado com soro de leite fluído pasteurizado

No Brasil, foi relatada a ocorrência de um surto de gastrenterite no Amapá, por Salmonella Paratyphi C, veiculado por sorvete . Existem para os gelados comestíveis padrões microbiológicos estabelecidos pela Comissão Nacional de Normas e Padrões para Alimentos do Ministério da Saúde, que tolera nesses produtos, no máximo 100 bactérias do grupo coliformes totais / g e 200.000 UFC / g de bactérias mesófilas.

Intact Prototype Formation but Impaired Generalization in Autism.

Cognitive processing in autism has been characterized by a difficulty with the abstraction of information across multiple stimuli or situations and subsequent generalization to new stimuli or situations. This apparent difficulty leads to the suggestion that prototype formation, a process of creating a mental summary representation of multiple experienced stimuli that go together in a category, may be impaired in autism. Adults with high functioning autism and a typically developing comparison group matched on age and IQ completed a random dot pattern categorization task. Participants with autism demonstrated intact prototype formation in all four ways it was operationally defined, and this performance was not significantly different from that of control participants. However, participants with autism categorized dot patterns that were more highly distorted from the category prototypes less accurately than did control participants. These findings suggest, at least within the constraints of the random dot pattern task, that although prototype formation may not be impaired in autism, difficulties may exist with the generalization of what has been learned about a category to novel stimuli, particularly as they become less similar to the category's prototype.

DNA repair signature is associated with anthracycline response in triple negative breast cancer patients.

We hypothesized that a subset of sporadic triple negative (TN) breast cancer patients whose tumors have defective DNA repair similar to BRCA1-associated tumors are more likely to exhibit up-regulation of DNA repair-related genes, anthracycline-sensitivity, and taxane-resistance. We derived a defective DNA repair gene expression signature of 334 genes by applying a previously published BRCA1-associated expression pattern to three datasets of sporadic TN breast cancers. We confirmed a subset of 69 of the most differentially expressed genes by quantitative RT-PCR, using a low density custom array (LDA). Next, we tested the association of this DNA repair microarray signature expression with pathologic response in neoadjuvant anthracycline trials of FEC (n = 50) and AC (n = 16), or taxane-based TET chemotherapy (n = 39). Finally, we collected paraffin-fixed, formalin-embedded biopsies from TN patients who had received neoadjuvant AC (n = 28), and tested the utility of the LDA to discriminate response. Correlation between RNA expression measured by the microarrays and 69-gene LDA was ascertained. This defective DNA repair microarray gene expression pattern was significantly associated with anthracycline response and taxane resistance, with the area under the ordinary receiver operating characteristic curve (AUC) of 0.61 (95% CI = 0.45-0.77), and 0.65 (95% CI = 0.46-0.85), respectively. From the FFPE samples, the 69-gene LDA could discriminate AC responders, with AUC of 0.79 (95% CI = 0.59-0.98). In conclusion, a promising defective DNA repair gene expression signature appears to differentiate TN breast cancers that are sensitive to anthracyclines and resistant to taxane-based chemotherapy, and should be tested in clinical trials with other DNA-damaging agents and PARP-1 inhibitors.

Decreased left posterior insular activity during auditory language in autism.

BACKGROUND AND PURPOSE: Individuals with autism spectrum disorders often exhibit atypical language patterns, including delay of speech onset, literal speech interpretation, and poor recognition of social and emotional cues in speech. We acquired functional MR images during an auditory language task to evaluate systematic differences in language-network activation between control and high-functioning autistic populations. MATERIALS AND METHODS: Forty-one right-handed male subjects (26 high-functioning autistic subjects, 15 controls) were studied by using an auditory phrase-recognition task, and areas of differential activation between groups were identified. Hand preference, verbal intelligence quotient (IQ), age, and language-function testing were included as covariables in the analysis. RESULTS: Control and autistic subjects showed similar language-activation networks, with 2 notable differences. Control subjects showed significantly increased activation in the left posterior insula compared with autistic subjects (P < .05, false discovery rate), and autistic subjects showed increased bilaterality of receptive language compared with control subjects. Higher receptive-language scores on standardized testing were associated with greater activation of the posterior aspect of the left Wernicke area. A higher verbal IQ was associated with greater activation of the bilateral Broca area and involvement of the prefrontal cortex and lateral premotor cortex. CONCLUSIONS: Control subjects showed greater activation of the posterior insula during receptive language, which may correlate with impaired emotive processing of language in autism. Subjects with autism showed greater bilateral activation of receptive-language areas, which was out of proportion to the differences in hand preference in autism and control populations.

Medical care of overweight children under real-life conditions: the German BZgA observation study.

OBJECTIVE: Current care for overweight children is controversial, and only few data are available concerning the process of care, as well as the outcome under real-life conditions. METHODS: A nationwide survey of treatment programs for overweight children and adolescents in Germany identified 480 treatment centers. From 135 institutions that had agreed to participate in this study of process of care and outcome, 48 randomly chosen institutions were included in the study. All 1916 overweight children (mean age 12.6 years, 57% female, mean body mass index 30.0 kg/m(2)), who presented at these institutions for lifestyle interventions, were included in this study. Diagnostic procedures according to guidelines and effect of lifestyle interventions on weight status at end of treatment were analyzed. RESULTS: Children treated <3 months were older and more obese, whereas children with >3 months treatment duration demonstrated more cardiovascular risk factors at baseline. On the basis of an intention-to-treat analysis, 75% of the children reduced their overweight. The reduction of overweight varied widely between the treatment institutions (intracluster correlation coefficient 0.15 in the multiple regression model reflecting the intracenter correlation). Screening for hypertension, disturbed glucose metabolism and dyslipidemia was performed in 52% of the children at baseline and in 10% at the end of intervention. CONCLUSION: Overweight reduction is achievable with lifestyle intervention in clinical practice. However, because the clientele, treatment approach and outcome varied widely between different institutions, and screening for comorbidities was seldomly performed as recommended, quality criteria for institutions have to be implemented to improve medical care of overweight children under real-life conditions.

The value of FDG-PET and bone scintigraphy with SPECT in the primary diagnosis and follow-up of patients with chronic osteomyelitis of the mandible.

OBJECTIVE: To appraise the value of FDG-PET and bone scintigraphy using SPECT in the primary diagnosis and follow-up of patients with chronic osteomyelitis of the mandible (COM). METHODS: In a prospective study the pattern of tracer uptake was investigated using 2 diagnostic methods in 42 patients. Results were compared with histology and radiographs as well as clinical and laboratory parameters. RESULTS: The use of FDG-PET in the primary diagnosis of COM resulted in a sensitivity of 64% and a specificity of 77.7%. The sensitivity of SPECT was 84% and the specificity 33.3%. During the follow-up period of these patients the sensitivity of SPECT increased to 93.7%, while the specificity decreased (6.6%). The sensitivity and specificity of FDG-PET for this follow-up group were 62.5 and 80%, respectively. CONCLUSION: Because of its high sensitivity, SPECT is vastly superior to other diagnostic methods in initiating treatment. In the follow-up period it might be replaced by FDG-PET, which reflects the disease course better and indicates the time of clinical remission.

Transgenic ablation of rod photoreceptors alters the circadian phenotype of mice.

The impact of photoreceptor loss on the circadian system was examined by utilizing a transgenic mouse model (rdta) in which rod photoreceptors were specifically ablated. These mice were able to phase-shift their circadian locomotor behaviour in response to light, but features of this circadian behaviour were markedly altered. The amplitude of circadian responses to light were approximately 2.5 greater, the circadian period (tau) was reduced (c. 20 min) and the total duration of activity (alpha) was increased (c. 50 min) when compared to wild type (+/+) and rd/rd mice (retinal degeneration, mice which also lack rod photoreceptors) of the same genetic background. The pattern of Fos expression in the suprachiasmatic nuclei (the site of the primary circadian clock in mammals) was indistinguishable between +/+ and rdta mice. However, Fos expression in the retina suggested that rod loss in rdta mice resulted in a functional reorganization of the retina and the constitutive activation of a population of retinal ganglion cells. Although it has been known for several years that the entraining photoreceptors of mammals are ocular, and that rod photoreceptors are not required for light regulation of the clock, these are the first data to show that features of the circadian phenotype (amplitude of the phase response curve, alpha, tau) can be influenced by photoreceptor ablation. These data support the hypothesis that the circadian phenotype of mammals is the product of an interaction between the suprachiasmatic nuclei and the retina. Thus, mammals which show an altered circadian behaviour can no longer be assumed to have defects associated only with specific clock genes; genes that affect photoreceptor survival may also modify circadian behaviour.

Photopigments and circadian systems of vertebrates.

In the retinal degeneration (rd) mouse the absence of rod cells and the progressive loss of cones does not result in a decrease in circadian phase shifting responses to light. By contrast, rd/rd mice are unable to perform simple visual tasks. In addition, rodless transgenic mice, and mice homozygous for the retinal degeneration slow (rds) mutation, show unattenuated circadian responses to light. Collectively these data suggest that cone cells lacking outer segments are sufficient to maintain normal circadian responses to light, or some unidentified photoreceptor within the retina. An action spectrum for circadian responses to light in rd/rd mice, and molecular analysis of retinally degenerate mice and blind mole rat eyes, suggests the involvement of a mid-to-long wavelength sensitive cone opsin in photoentrainment. Extraocular photoreceptors of non-mammalian vertebrates are currently being analyzed in order to identify functional and evolutionary similarities between visual and non-visual photoreceptor systems.