Neuronal basis of emotion processing and regulation in conduct disorder

Emotion regulation, a key component of healthy development, has been shown to be deficient in several psychiatric conditions, including conduct disorder. Conduct disorder is a neuropsychiatric disorder of childhood and adolescence characterized by severe aggressive behavior and violation of societal norms. It is highly prevalent and results in substantial economic costs and negative social consequences. Neuroimaging evidence has revealed brain activity alterations in several regions, including prefrontal, temporal, and limbic cortex (amygdala, insula, and cingulate gyrus). While the neuronal basis of emotion processing in conduct disorder has been intensely investigated, the brain correlates of implicit and explicit emotion regulation remain unclear. The main aim of this dissertation was to extend current knowledge by investigating the neuronal mechanisms of emotion regulation in children and adolescents with conduct disorder. First, we conducted a meta-analysis in order to identify the neuronal correlates of emotion processing in adolescents with aggressive behavior. We then developed an affective Stroop task designed to investigate the interplay between emotion and cognition in a paediatric population, and validated it in healthy young adults. We then employed the task to study the neuronal characteristics of implicit emotion-cognition interaction in children and adolescents with conduct disorder. Finally, we investigated explicit emotion regulation by cognitive reappraisal (i.e., reinterpretation of the meaning of an emotional stimulus) in conduct disorder. We here present findings on altered brain function during tasks assessing implicit and explicit emotion regulation in adolescents with conduct disorder that are in agreement with behaviorally observed deficits. Our meta-analysis on emotion processing in conduct disorder summarized previous literature indicating prefrontal and limbic brain structure and function alterations. The results from our study employing the affective Stroop task in healthy adults validated the usefulness of our task design and replicated previous findings suggesting that emotion significantly impacts cognition on a behavioral and neuronal level. Using the affective Stroop and cognitive reappraisal tasks in adolescents with conduct disorder revealed neuronal alterations within prefrontal and limbic regions, brain areas implicated in both emotion and cognition. Overall, the results of this dissertation provide novel evidence on the neuronal basis of emotion regulation deficits in conduct disorder. Future studies shall further investigate emotion regulation in specific subgroups of conduct disorder, for example those with psychopathic traits or high levels of anxiety with the ultimate goal of influencing the child’s immediate environment and society as a whole

A microarray configuration to quantify expression levels and relative abundance of splice variants

Over the past decade, alternative RNA splicing has raised a great interest appearing to be of high importance in the generation of expression diversity. This regulatory process plays a critical role in the normal development and its impact on the initiation and development of human disorders as well as on the pharmacological properties of drugs is increasingly being recognized. Only few studies describe specific alternative splicing expression profiling. Microarray strategies have been conceived to address alternative splicing events but with very few experimental data related to their abilities to provide true quantification values. We have developed a specific microarray configuration relying on a few, well optimized probes per splice event. Basically, five probes of 24mer are used to fully characterize a splice event. These probes are of two types, exon probes and junction probes, and are either specific to a splice event or not. The performances of such a ‘splice array’ were validated on synthetic model systems and on complex biological materials. The results indicate that DNA chips based on this design combining exon and junction derived probes enable the detection and, absolute and relative quantification of splice variants. In addition, this strategy is compatible with all the microarrays that use oligonucleotide probes

Sex Ex Libris: Abstinence Messages in High School Health Textbooks Cultivate Sex Negativity Among Teens

The vast majority of high schools require some form of sex education. Despite numerous concerns about the efficacy of abstinence-only education programs and their failure to demonstrate a reduction in the onset of teenage sexual activity, such curricula remains widespread in U.S. public schools. One resource in formal sex education is health textbooks. Six widely used high school health textbooks were investigated. Through qualitative content analysis of the written material, a shared emphasis on abstinence was identified, specifically in relation to premarital relationships, decision-making, and risk prevention. Textbooks emphasize that marriage is the only appropriate place for people to have sex, aim to instruct teens on how to make responsible decisions and how to refuse engaging in deviant behavior, and stress that sex is a high-risk activity that teens should avoid in favor of abstinence. Using the data from these high school health textbooks, I develop a theory of patronizing exclusivism to explain the implicit and explicit messages about abstinence and identify six primary features: perpetuation of the stereotypical ideal family, denial of demographic realities, assumption that teens are impulsive, conflation of sex with morality, encouragement of stigma of the sexually active, and promotion of sex negativity. Promotion of sex negativity is the root strategy and facilitates the implicit and explicit messages about abstinence in high school health textbooks. The theory of patronizing exclusivism has implications relevant to dialogue about how sex education should be taught and what should be included

Do magnification loupes affect the precision of cavity preparations made by undergraduates? A randomized crossover study.

BACKGROUND Evidence on the effect of magnification devices on procedure quality in restorative dentistry is scant. This study therefore aimed to assess, under simulated clinical conditions, if magnification loupes affect the quality of preparations carried out by undergraduate dental students. METHODS 59 undergraduate dental students underwent two visual acuity tests, based on which they were divided into a "low visual acuity group" (visus < 1) and a "good visual acuity group" (visus ≥ 1). In a randomized crossover experiment, participants performed a two-dimensional S and a three-dimensional O figure preparation with a dental handpiece on standardized acrylic blocs designed for preclinical restorative training. Each participant carried out the preparation tasks twice, once with magnification loupes (2.5×) and once without. Two blinded investigators independently evaluated parameters of preparation precision. Data were analyzed using Spearman rank correlation coefficients, intra-class correlation coefficients, and Wilcoxon rank-sum tests (α = 0.05). RESULTS Participants from the "low visual acuity group" did not show a statistically significant improvement in accuracy when they used magnification loupes for the S figure preparation (p ≥ 0.0625). Participants from the "high visual acuity group" obtained a higher level of accuracy (p ≤ 0.0012) when they used magnification loupes for the S figure preparation. The use of magnification loupes had no statistically significant effect on the accuracy parameters of the O figure cavity preparations (p ≥ 0.1865). Participants with high visual acuity achieved only a marginally better accuracy than participants with a visus < 1. CONCLUSIONS This study suggests that loupes with 2.5× magnification increase the accuracy of two-dimensional preparations while they have no significant effect, favorable or otherwise, on the accuracy of complex, three-dimensional cavity preparations of untrained dental students

Low iron availability in continuous in vitro colonic fermentations induces strong dysbiosis of the child gut microbial consortium and a decrease in main metabolites

Iron (Fe) deficiency affects an estimated 2 billion people worldwide, and Fe supplements are a common corrective strategy. The impact of Fe deficiency and Fe supplementation on the complex microbial community of the child gut was studied using in vitro colonic fermentation models inoculated with immobilized fecal microbiota. Chyme media (all Fe chelated by 2,2′-dipyridyl to 26.5 mg Fe L−1) mimicking Fe deficiency and supplementation were continuously fermented. Fermentation effluent samples were analyzed daily on the microbial composition and metabolites by quantitative PCR, 16S rRNA gene 454-pyrosequencing, and HPLC. Low Fe conditions (1.56 mg Fe L−1) significantly decreased acetate concentrations, and subsequent Fe supplementation (26.5 mg Fe L−1) restored acetate production. High Fe following normal Fe conditions had no impact on the gut microbiota composition and metabolic activity. During very low Fe conditions (0.9 mg Fe L−1 or Fe chelated by 2,2′-dipyridyl), a decrease in Roseburia spp./Eubacterium rectale, Clostridium Cluster IV members and Bacteroides spp. was observed, while Lactobacillus spp. and Enterobacteriaceae increased consistent with a decrease in butyrate (−84%) and propionate (−55%). The strong dysbiosis of the gut microbiota together with decrease in main gut microbiota metabolites observed with very low iron conditions could weaken the barrier effect of the microbiota and negatively impact gut healt

Microstructural white matter alterations in the corpus callosum of girls with conduct disorder

Objective Diffusion tensor imaging (DTI) studies in adolescent conduct disorder (CD) have demonstrated white matter alterations of tracts connecting functionally distinct fronto-limbic regions, but only in boys or mixed-gender samples. So far, no study has investigated white matter integrity in girls with CD on a whole-brain level. Therefore, our aim was to investigate white matter alterations in adolescent girls with CD. Method We collected high-resolution DTI data from 24 girls with CD and 20 typically developing control girls using a 3T magnetic resonance imaging system. Fractional anisotropy (FA) and mean diffusivity (MD) were analyzed for whole-brain as well as a priori−defined regions of interest, while controlling for age and intelligence, using a voxel-based analysis and an age-appropriate customized template. Results Whole-brain findings revealed white matter alterations (i.e., increased FA) in girls with CD bilaterally within the body of the corpus callosum, expanding toward the right cingulum and left corona radiata. The FA and MD results in a priori−defined regions of interest were more widespread and included changes in the cingulum, corona radiata, fornix, and uncinate fasciculus. These results were not driven by age, intelligence, or attention-deficit/hyperactivity disorder comorbidity. Conclusion This report provides the first evidence of white matter alterations in female adolescents with CD as indicated through white matter reductions in callosal tracts. This finding enhances current knowledge about the neuropathological basis of female CD. An increased understanding of gender-specific neuronal characteristics in CD may influence diagnosis, early detection, and successful intervention strategies

Clostridium difficile colonization and antibiotics response in PolyFermS continuous model mimicking elderly intestinal fermentation

Abstract Background Clostridium difficile (CD), a spore-forming and toxin-producing bacterium, is the main cause for antibiotic-associated diarrhea in the elderly. Here we investigated CD colonization in novel in vitro fermentation models inoculated with immobilized elderly fecal microbiota and the effects of antibiotic treatments. Methods Two continuous intestinal PolyFermS models inoculated with different immobilized elder microbiota were used to investigate selected factors of colonization of CD in proximal (PC, model 1) and transverse-distal (TDC, model 1 and 2) colon conditions. Colonization of two CD strains of different PCR ribotypes, inoculated as vegetative cells (ribotype 001, model 1) or spores (ribotypes 001 and 012, model 2), was tested. Treatments with two antibiotics, ceftriaxone (daily 150 mg L−1) known to induce CD infection in vivo or metronidazole (twice daily 333 mg L−1) commonly used to treat CD, were investigated in TDC conditions (model 2) for their effects on gut microbiota composition (qPCR, 16S pyrosequencing) and activity (HPLC), CD spore germination and colonization, and cytotoxin titer (Vero cell assay). Results CD remained undetected after inoculating vegetative cells in PC reactors of model 1, but was shown to colonize TDC reactors of both models, reaching copy numbers of up to log10 8 mL−1 effluent with stable production of toxin correlating with CD cell numbers. Ceftriaxone treatment in TDC reactors showed only small effects on microbiota composition and activity and did not promote CD colonization compared to antibiotic-free control reactor. In contrast, treatment with metronidazole after colonization of CD induced large modifications in the microbiota and decreased CD numbers below the detection limit of the specific qPCR. However, a fast CD recurrence was measured only 2 days after cessation of metronidazole treatment. Conclusions Using our in vitro fermentation models, we demonstrated that stable CD colonization in TDC reactors can be induced by inoculating CD vegetative cells or spores without the application of ceftriaxone. Treatment with metronidazole temporarily reduced the counts of CD, in agreement with CD infection recurrence in vivo. Our data demonstrate that CD colonized an undisturbed microbiota in vitro, in contrast to in vivo observations, thus suggesting an important contribution of host-related factors in the protection against CD infection

Investigating the Influences of Language Delay and/or Familial Risk for Dyslexia on Brain Structure in 5-Year-Olds

Early language delay has often been associated with atypical language/literacy development. Neuroimaging studies further indicate functional disruptions during language and print processing in school-age children with a retrospective report of early language delay. Behavioral data of 114 5-year-olds with a retrospective report of early language delay in infancy (N = 34) and those without (N = 80) and with a familial risk for dyslexia and those without are presented. Behaviorally, children with a retrospective report of early language delay exhibited reduced performance in language/reading-related measures. A voxel-based morphometry analysis in a subset (N = 46) demonstrated an association between reduced gray matter volume and early language delay in left-hemispheric middle temporal, occipital, and frontal regions. Alterations in middle temporal cortex in children with a retrospective report of early language delay were observed regardless of familial risk for dyslexia. Additionally, while children with isolated familial risk for dyslexia showed gray matter reductions in temporoparietal and occipitotemporal regions, these effects were most profound in children with both risk factors. An interaction effect of early language delay and familial risk was revealed in temporoparietal, occipital, and frontal cortex. Our findings support a cumulative effect of early behavioral and genetic risk factors on brain development and may ultimately inform diagnosis/treatment

Mother-child similarity in brain morphology: A comparison of structural characteristics of the brain\u27s reading network

Background: Substantial evidence acknowledges the complex gene-environment interplay impacting brain development and learning. Intergenerational neuroimaging allows the assessment of familial transfer effects on brain structure, function and behavior by investigating neural similarity in caregiver-child dyads. Methods: Neural similarity in the human reading network was assessed through well-used measures of brain structure (i.e., surface area (SA), gyrification (lG), sulcal morphology, gray matter volume (GMV) and cortical thickness (CT)) in 69 mother-child dyads (children\u27s age~11 y). Regions of interest for the reading network included left-hemispheric inferior frontal gyrus, inferior parietal lobe and fusiform gyrus. Mother-child similarity was quantified by correlation coefficients and familial specificity was tested by comparison to random adult-child dyads. Sulcal morphology analyses focused on occipitotemporal sulcus interruptions and similarity was assessed by chi-square goodness of fit. Results: Significant structural brain similarity was observed for mother-child dyads in the reading network for lG, SA and GMV (r = 0.349/0.534/0.542, respectively), but not CT. Sulcal morphology associations were non-significant. Structural brain similarity in lG, SA and GMV were specific to mother-child pairs. Furthermore, structural brain similarity for SA and GMV was higher compared to CT. Conclusion: Intergenerational neuroimaging techniques promise to enhance our knowledge of familial transfer effects on brain development and disorders

Novel defensin subfamily from spinach (Spinacia oleracea)

Antimicrobial peptides (So-D1-7) were isolated from a crude cell wall preparation from spinach leaves (Spinacia oleracea cv. Matador) and, judged from their amino acid sequences, six of them (So-D2-7) represented a novel structural subfamily of plant defensins (group IV). Group-IV defensins were also functionally distinct from those of groups I–III. They were active at concentrations <20 μM against Gram-positive (Clavibacter michiganensis) and Gram-negative (Ralstonia solanacearum) bacterial pathogens, as well as against fungi, such as Fusarium culmorum, F. solani, Bipolaris maydis, and Colletotrichum lagenarium. Fungal inhibition occurred without hyphal branching. Group-IV defensins were preferentially distributed in the epidermal cell layer of leaves and in the subepidermal region of stems