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Personalized AAC intervention refers to an approach in which intervention is tailored to the individual's needs and skills, the needs and priorities of the individual's family and other social environments, the evidence base, and the individual's response to intervention. This approach is especially relevant to AAC intervention for young children with complex communication needs given their unique constellations of strengths and challenges, and the qualitative and quantitative changes that they experience over time as they develop, as well as the diversity of their families, schools, and communities. This paper provides detailed documentation of personalized AAC intervention over a six-month period for a 3-year-old girl with developmental delay and complex communication needs. The paper describes (1) personalization of multimodal AAC supports to provide this child with the tools to communicate; (2) personalized intervention to build semantic and morphosyntactic skills; and, (3) personalized instruction in literacy skills (i.e., letter-sound correspondences, sound blending, decoding, sight word recognition, reading simple stories, reading comprehension, and encoding skills). Specific goals, instructional materials, and procedures are described; data on speech, language, and literacy outcomes are presented.

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About 20% of the population suffers from "functional syndromes". Since these syndromes overlap greatly in terms of co-morbidity, pathophysiology (including aberrant autonomic activity) and treatment responses, common predisposing genetic factors have been postulated. We had previously showed that two common mitochondrial DNA (mtDNA) polymorphisms at positions 16519 and 3010 are statistically associated with the functional syndromes of migraine, cyclic vomiting syndrome and non-specific abdominal pain. Herein, among individuals with mtDNA haplogroup H (HgH), the presence of these two mtDNA polymorphisms were ascertained in additional functional syndromes: chronic fatigue syndrome, complex regional pain syndrome, sudden infant death syndrome, and major depressive disorder. Polymorphic prevalence rates were compared between disease and control groups, and within each disease group in participants with and without specific clinical findings. In all four conditions, one or both of the polymorphisms was significantly associated with the respective condition and/or co-morbid functional symptomatology. Thus, we conclude that these two mtDNA polymorphisms likely modify risk for the development of multiple functional syndromes, likely constituting a proportion of the postulated common genetic factor, at least among individuals with HgH. Pathophysiology likely involves broad effects on the autonomic nervous system.

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Several studies have demonstrated altered brain functional connectivity in the resting state in depression. However, no study has investigated interregional networking in patients with persistent depressive disorder (PDD). The aim of this study was to assess differences in brain perfusion distribution and connectivity between large groups of patients and healthy controls. Participants comprised 91 patients with PDD and 65 age- and sex-matched healthy controls. Resting state perfusion was investigated by single photon emission computed tomography, and group differences were assessed by Statistical Parametric Mapping. Brain connectivity was explored through a voxel-wise interregional correlation analysis using as covariate of interest the normalized values of clusters of voxels in which perfusion differences were found in group analysis. Significantly increased regional brain perfusion distribution covering a large part of the cerebellum was observed in patients as compared with controls. Patients showed a significant negative functional connectivity between the cerebellar cluster and caudate, bilaterally. This study demonstrated inverse relative perfusion between the cerebellum and the caudate in PDD. Functional uncoupling may be associated with a dysregulation between the role of the cerebellum in action control and of the caudate in action selection, initiation and decision making in the patients. The potential impact of the resting state condition and the possibility of mitochondrial impairment are discussed.

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Psychiatric diagnoses are not reflections of the aetiology of the disorder, but rather lists of symptoms with considerable overlaps, which hamper research and may cause confusion. The diagnoses of autism spectrum disorder, attention deficit hyperactivity disorder and tic disorder are often comorbid along with a number of other symptomatic syndromes. Individual immune responsivity is possibly involved in pathophysiological mechanisms. Multiple environmental factors may contribute to the clinical phenotypes. Recent research supports to some extent the involvement of dietary and nutritional factors in ADHD. In spite of impressive progress in the molecular biological understanding of the pathophysiology of these disorders, treatment options are still limited and more research is warranted.

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Oxidative stress has been implicated in the cognitive decline, especially in memory impairment. The purpose of this study was to determine the concentration of malondialdehyde (MDA) in patients with recurrent depressive disorders (rDD) and to define relationship between plasma levels of MDA and the cognitive performance. The study comprised 46 patients meeting criteria for rDD. Cognitive function assessment was based on: The Trail Making Test , The Stroop Test, Verbal Fluency Test and Auditory-Verbal Learning Test. The severity of depression symptoms was assessed using the Hamilton Depression Rating Scale (HDRS). Statistically significant differences were found in the intensity of depression symptoms, measured by the HDRS on therapy onset versus the examination results after 8 weeks of treatment (P < 0.001). Considering the 8-week pharmacotherapy period, rDD patients presented better outcomes in cognitive function tests. There was no statistically significant correlation between plasma MDA levels, and the age, disease duration, number of previous depressive episodes and the results in HDRS applied on admission and on discharge. Elevated levels of MDA adversely affected the efficiency of visual-spatial and auditory-verbal working memory, short-term declarative memory and the delayed recall declarative memory. 1. Higher concentration of plasma MDA in rDD patients is associated with the severity of depressive symptoms, both at the beginning of antidepressants pharmacotherapy, and after 8 weeks of its duration. 2. Elevated levels of plasma MDA are related to the impairment of visual-spatial and auditory-verbal working memory and short-term and delayed declarative memory.

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For many years, a deficiency of monoamines including serotonin has been the prevailing hypothesis on depression, yet research has failed to confirm consistent relations between brain serotonin and depression. High degrees of overlapping comorbidities and common drug efficacies suggest that depression is one of a family of related conditions sometimes referred to as the "affective spectrum disorders", and variably including migraine, irritable bowel syndrome, chronic fatigue syndrome, fibromyalgia and generalized anxiety disorder, among many others. Herein, we present data from many different experimental modalities that strongly suggest components of mitochondrial dysfunction and inflammation in the pathogenesis of depression and other affective spectrum disorders. The three concepts of monoamines, energy metabolism and inflammatory pathways are inter-related in many complex manners. For example, the major categories of drugs used to treat depression have been demonstrated to exert effects on mitochondria and inflammation, as well as on monoamines. Furthermore, commonly-used mitochondrial-targeted treatments exert effects on mitochondria and inflammation, and are increasingly being shown to demonstrate efficacy in the affective spectrum disorders. We propose that interactions among monoamines, mitochondrial dysfunction and inflammation can inspire explanatory, rather than mere descriptive, models of these disorders.

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BACKGROUND: Comorbidity between Attention Deficit Hyperactivity Disorder (ADHD) and mood disorders is common. Alterations of the cerebellum and frontal regions have been reported in neuro-imaging studies of ADHD and major depression. METHODS: Thirty chronically depressed adult females of whom 16 had scores below, and 14 scores above, cut-offs on the 25-items Wender Utah Retrospective Scale (WURS-25) and the Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS) were divided into subgroups designated "Depression" and "Depression + ADHD", respectively. Twenty-one of the patients had some audiological symptom, tinnitus and/or hearing impairment. The patients were investigated with other rating scales and 99mTc-HMPAO SPECT. Controls for 99mTc-HMPAO SPECT were 16 healthy females. SPECT was analyzed by both statistical parametric mapping (SPM2) and the computerized brain atlas (CBA). Discriminant analysis was performed on the volumes of interest generated by the CBA, and on the scores from rating scales with the highest group differences. RESULTS: The mean score of a depression rating scale (MADRS-S) was significantly lower in the "Depression" subgroup compared to in the "Depression + ADHD" subgroup. There was significantly decreased tracer uptake within the bilateral cerebellum at both SPM and CBA in the "Depression + ADHD" subgroup compared to in the controls. No decrease of cerebellar tracer uptake was observed in "Depression". Significantly increased tracer uptake was found at SPM within some bilateral frontal regions (Brodmann areas 8, 9, 10, 32) in the "Depression + ADHD" subgroup compared to in "Depression". An accuracy of 100% was obtained for the discrimination between the patient groups when thalamic uptake was used in the analysis along with scores from Socialization and Impulsivity scales. CONCLUSION: The findings confirm the previous observation of a cerebellar involvement in ADHD. Higher bilateral frontal 99mTc-HMPAO uptake in "Depression + ADHD" compared to in "Depression" indicate a difference between these subgroups. 99mTc-HMPAO uptake mechanisms are discussed.

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INTRODUCTION: 99mTc-d,l-hexamethylpropylene amine oxime (99mTc-HMPAO) retention in brain is proportional to cerebral blood flow and related to both the local hemodynamic state and to the cellular content of reduced glutathione. Alterations of the regional distribution of 99mTc-HMPAO retention, with discrepant results, have been reported at functional brain imaging of unipolar depression. Since mitochondrial involvement has been reported in depressed patients, the aim of the study was to explore whether the 99mTc-HMPAO retention at single-photon emission computed tomography in depressed patients may relate to different levels of mitochondrial function. METHODS: All patients had audiological and muscular symptoms, somatic symptoms that are common in depression. Citrate synthase (CS) activity assessed in muscle mitochondria correlated strongly with the activities of three mitochondrial respiratory chain enzymes and was used as a marker of mitochondrial function. K-means clustering performed on CS grouped eight patients with low and 11 patients with normal CS. Voxel-based analysis was performed on the two groups by statistical parametric mapping. RESULTS: Voxel-based analysis showed significantly higher 99mTc-HMPAO retention in the patients with low CS compared with the patients with normal CS in the posterior and inferior frontal cortex, the superior and posterior temporal cortex, the somato-sensory cortex, and the associative parietal cortex. CONCLUSION: Low muscle CS in depressed patients is related to higher regional 99mTc-HMPAO retention that may reflect cerebrovascular adaptation to impaired intracellular metabolism and/or intracellular enzymatic changes, as previously reported in mitochondrial disorder. Mitochondrial dysfunction in varying proportions of the subjects may explain some of the discrepant results for 99mTc-HMPAO retention in depression.

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AIMS: Somatic symptomatology is common in depression, and is often attributed to the Freudian-inspired concept of "somatization". While the same somatic symptoms and depression are common in mitochondrial disease, in cases with concurrent mood symptoms the diagnosis of a mitochondrial disorder and related therapy are typically delayed for many years. A short screening tool that can identify patients with depression at high risk for having underlying mitochondrial dysfunction is presented. METHODS: Six items of the Karolinska Scales of Personality (KSP) were found to differentiate among 21 chronically-depressed Swedish subjects with low versus normal muscle ATP production rates. A screening tool consisting of the six KSP questions was validated in the relatives of American genetics clinic patients, including in 24 matrilineal relatives in families with maternally inherited mitochondrial disease and in 30 control relatives. RESULTS: Among the depressed Swedish patients, the screening tool was positive in 13/14 with low and 1/7 with normal mitochondrial function (P = 0.0003). Applied to the American relatives of patients, the screening tool was positive in 13/24 matrilineal relatives and in 1/30 control relatives (P = 2 x 10-5). CONCLUSION: Our preliminary data suggest that a small number of specific somatic-related questions can be constructed into a valid screening tool for cases at high risk for having a component of energy metabolism in their pathogenesis.

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PURPOSE: Neurobiological abnormalities underlying atypical depression have previously been suggested. The purpose of this study was to explore differences at functional brain imaging between depressed patients with and without atypical features and healthy controls. METHODS: Twenty-three out-patients with chronic depressive disorder recruited from a service for patients with audiological symptoms were investigated. Eleven fulfilled the DSM-IV criteria for atypical depression (mood reactivity and at least two of the following: weight gain, hypersomnia, leaden paralysis and interpersonal rejection sensitivity). Twenty-three healthy subjects served as controls. Voxel-based analysis was applied to explore differences in (99m)Tc-HMPAO uptake between groups. RESULTS: Patients in the atypical group had a higher prevalence of bilateral hearing impairment and higher depression and somatic distress ratings at the time of SPECT. Significantly higher tracer uptake was found bilaterally in the atypical group as compared with the non-atypicals in the sensorimotor (Brodmann areas, BA1-3) and premotor cortex in the superior frontal gyri (BA6), in the middle frontal cortex (BA8), in the parietal associative cortex (BA5, BA7) and in the inferior parietal lobule (BA40). Significantly lower tracer distribution was found in the right hemisphere in the non-atypicals compared with the controls in BA6, BA8, BA44, BA45 and BA46 in the frontal cortex, in the orbito-frontal cortex (BA11, BA47), in the postcentral parietal cortex (BA2) and in the multimodal association parietal cortex (BA40). CONCLUSION: The differences found between atypical and non-atypical depressed patients suggest different neurobiological substrates in these patient groups. The putative links with the clinical features of atypical depression are discussed. These findings encourage the use of functional neuroimaging in psychiatric disorders.

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OBJECTIVE: To evaluate the performance of a rapid HIV antibody test used with whole blood and oral fluid in settings where the test is likely to be used. DESIGN: In four separate studies, we compared the accuracy of the rapid test performed on whole blood and oral fluid specimens with the results of conventional HIV tests. METHODS: Oral fluid and whole blood from persons of unknown HIV status recruited from clinics, labor and delivery units, and outreach venues were tested with the OraQuick Advance rapid HIV-1/2 antibody test. Sensitivity and specificity were compared with results of the enzyme immunoassay (EIA) and Western blot algorithm used by the study sites. RESULTS: OraQuick sensitivity was 99.7% with whole blood and 99.1% with oral fluid from 327 persons who were HIV antibody positive by the conventional algorithm. OraQuick specificity was 99.9% with whole blood and 99.6% with oral fluid from 12 010 HIV-negative persons; EIA specificity was 99.7%. A cluster of 16 false-positive oral fluid tests occurred in one study, in which specificity was lower (99.0%) than in the other three studies (99.6-99.8%). CONCLUSIONS: In diverse settings in four studies, the OraQuick test showed high sensitivity and specificity for HIV antibody in whole blood and oral fluid specimens. Slightly more false-positive and false-negative results occurred with oral fluid than with whole blood, but performance with both specimen types was similar to, or better than, that of conventional EIAs.

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BACKGROUND: Several studies have reported a high degree of association of the common conditions of depression, bowel dysmotility and migraine. Mitochondrial dysfunction and mitochondrial DNA (mtDNA) sequence variants have been linked individually to each of these three conditions, providing a plausible hypothesis for the reported association. If this hypothesis is correct, the matrilineal relatives (who all share essentially the same mtDNA sequence) of patients with mitochondrial disease secondary to inherited mtDNA mutations would be expected to have an elevated prevalence of each of these three conditions. METHODS: Families were recruited by an advertisement posted on the United Mitochondrial Disease Foundation website and invited to participate in an on-line questionnaire if at least one member was diagnosed with mitochondrial disease by a physician. Based upon the reported family histories, families were assigned by the investigators to either the probable maternal inheritance (PMI) group (55 families) or the probable non-maternal inheritance (PnMI) group (111 families). RESULTS: Bowel disorders, migraine and depression were reported at very high prevalence in the PMI mothers (60%, 54% and 51%, respectively), but were present at significantly lower prevalence rates among the PnMI mothers (16%, 26% and 12%; P<0.0001 for each) and the fathers of both groups (range 9-16%; P < 2 x 10(-6) for each). Similar data was obtained comparing the prevalence rates among maternal and paternal grandmothers, aunts and uncles. LIMITATIONS: Our data was obtained from families ascertained by the presence of a severely affected individual, and may not be applicable to families lacking this proband. CONCLUSIONS: Depression, bowel dysmotility and migraine are common manifestations in individuals with mtDNA sequence-related mitochondrial dysfunction, which supports our hypothesis that mitochondrial dysfunction is a major common factor underlying the association of these three conditions.

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