Acquisition and Use of 'Priors' in Autism: Typical in Deciding Where to Look, Atypical in Deciding What Is There.
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ABSTRACT:
SUBMITTER: Allenmark F
PROVIDER: S-EPMC8460564 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:OBJECTIVE:Clinical diagnosis of autism spectrum disorder (ASD) relies on time-consuming subjective assessments. The primary purpose of this study was to investigate the utility of salivary microRNAs for differentiating children with ASD from peers with typical development (TD) and non-autism developmental delay (DD). The secondary purpose was to explore microRNA patterns among ASD phenotypes. METHOD:This multicenter, prospective, case-control study enrolled 443 children (2-6 years old). ASD diagnoses were based on DSM-5 criteria. Children with ASD or DD were assessed with the Autism Diagnostic Observation Schedule II and Vineland Adaptive Behavior Scales II. MicroRNAs were measured with high-throughput sequencing. Differential expression of microRNAs was compared among the ASD (n = 187), TD (n = 125), and DD (n = 69) groups in the training set (n = 381). Multivariate logistic regression defined a panel of microRNAs that differentiated children with ASD and those without ASD. The algorithm was tested in a prospectively collected naïve set of 62 samples (ASD, n = 37; TD, n = 8; DD, n = 17). Relations between microRNA levels and ASD phenotypes were explored. RESULT:Fourteen microRNAs displayed differential expression (false discovery rate < 0.05) among ASD, TD, and DD groups. A panel of 4 microRNAs (controlling for medical/demographic covariates) best differentiated children with ASD from children without ASD in training (area under the curve = 0.725) and validation (area under the curve = 0.694) sets. Eight microRNAs were associated (R > 0.25, false discovery rate < 0.05) with social affect, and 10 microRNAs were associated with restricted/repetitive behavior. CONCLUSION:Salivary microRNAs are "altered" in children with ASD and associated with levels of ASD behaviors. Salivary microRNA collection is noninvasive, identifying ASD-status with moderate accuracy. A multi-"omic" approach using additional RNA families could improve accuracy, leading to clinical application. CLINICAL TRIAL REGISTRATION INFORMATION:A Salivary miRNA Diagnostic Test for Autism; https://clinicaltrials.gov/; NCT02832557.
| S-EPMC6764899 | biostudies-literature
Project description:The beliefs that antipsychotic drugs (APDs) are 1) effective only to treat delusions and hallucinations (positive symptoms), 2) that typical and atypical APDs differ only in ability to cause extrapyramidal side effects, and 3) that their efficacy as antipsychotics is due solely to their dopamine D2 receptor blockade are outmoded concepts that prevent clinicians from achieving optimal clinical results when prescribing an APD. Atypical APDs are often more effective than typical APDs in treating negative symptoms, cognitive impairment, and mood symptoms as well as reducing the risk for suicide and decreasing aggression. This applies not only to those diagnosed with schizophrenia or schizoaffective disorder but also to bipolar disorder, major depression, and other psychiatric diagnoses. The greater advantage of an atypical APD is not evident in all patients for every atypical APD due, in part, to individual differences in genetic and epigenetic endowment and differences in the pharmacology of the atypical APDs, their mode of action being far more complex than that of the typical APDs. A common misconception is that among the atypical APDs, only clozapine is effective for reducing psychosis in treatment-resistant schizophrenia. Aripiprazole, lurasidone, olanzapine, and risperidone also can be more effective than typical APDs for treatment-resistant schizophrenia; clozapine is uniquely indicated for reducing the risk for suicide. The ability of the atypical APDs to improve cognition and negative symptoms in some patients together with lower propensity to cause tardive dyskinesia (an underappreciated advantage) leads to better overall outcomes. These advantages of the atypical APDs in efficacy and safety are due, in part, to initiation of synaptic plasticity via direct and indirect effects of the atypical APDs on a variety of proteins, especially G proteins, and release of neurotrophins (e.g., brain-derived neurotrophic factor). The typical APDs beneficial effects on psychosis are mainly the result of D2 receptor blockade, which can be associated with serious side effects and lack of tolerability.
| S-EPMC8412155 | biostudies-literature
Project description:Prominent theories suggest that symptoms of schizophrenia stem from learning deficiencies resulting in distorted internal models of the world. To test these theories further, we used a visual statistical learning task known to induce rapid implicit learning of the stimulus statistics. In this task, participants are presented with a field of coherently moving dots and are asked to report the presented direction of the dots (estimation task), and whether they saw any dots or not (detection task). Two of the directions were more frequently presented than the others. In controls, the implicit acquisition of the stimuli statistics influences their perception in two ways: (i) motion directions are perceived as being more similar to the most frequently presented directions than they really are (estimation biases); and (ii) in the absence of stimuli, participants sometimes report perceiving the most frequently presented directions (a form of hallucinations). Such behaviour is consistent with probabilistic inference, i.e. combining learnt perceptual priors with sensory evidence. We investigated whether patients with chronic, stable, treated schizophrenia (n = 20) differ from controls (n = 23) in the acquisition of the perceptual priors and/or their influence on perception. We found that although patients were slower than controls, they showed comparable acquisition of perceptual priors, approximating the stimulus statistics. This suggests that patients have no statistical learning deficits in our task. This may reflect our patients' relative wellbeing on antipsychotic medication. Intriguingly, however, patients experienced significantly fewer (P = 0.016) hallucinations of the most frequently presented directions than controls when the stimulus was absent or when it was very weak (prior-based lapse estimations). This suggests that prior expectations had less influence on patients' perception than on controls when stimuli were absent or below perceptual threshold.
| S-EPMC6734996 | biostudies-literature
Project description:Three- to five-year-old children produce speech that is characterized by a high level of variability within and across individuals. This variability, which is manifest in speech movements, acoustics, and overt behaviors, can be input to subgroup discovery methods to identify cohesive subgroups of speakers or to reveal distinct developmental pathways or profiles. This investigation characterized three distinct groups of typically developing children and provided normative benchmarks for speech development. These speech development profiles, identified among 63 typically developing preschool-aged speakers (ages 36-59 mo), were derived from the children's performance on multiple measures. These profiles were obtained by submitting to a k-means cluster analysis of 72 measures that composed three levels of speech analysis: behavioral (e.g., task accuracy, percentage of consonants correct), acoustic (e.g., syllable duration, syllable stress), and kinematic (e.g., variability of movements of the upper lip, lower lip, and jaw). Two of the discovered group profiles were distinguished by measures of variability but not by phonemic accuracy; the third group of children was characterized by their relatively low phonemic accuracy but not by an increase in measures of variability. Analyses revealed that of the original 72 measures, 8 key measures were sufficient to best distinguish the 3 profile groups.
| S-EPMC3362276 | biostudies-literature
Project description:Clinical electrophysiology has made the traditional classification of rapid atrial rhythms into flutter and tachycardia of little clinical use. Electrophysiological studies have defined multiple mechanisms of tachycardia, both re-entrant and focal, with varying ECG morphologies and rates, authenticated by the results of catheter ablation of the focal triggers or critical isthmuses of re-entry circuits. In patients without a history of heart disease, cardiac surgery or catheter ablation, typical flutter ECG remains predictive of a right atrial re-entry circuit dependent on the inferior vena cava-tricuspid isthmus that can be very effectively treated by ablation, although late incidence of atrial fibrillation remains a problem. Secondary prevention, based on the treatment of associated atrial fibrillation risk factors, is emerging as a therapeutic option. In patients subjected to cardiac surgery or catheter ablation for the treatment of atrial fibrillation or showing atypical ECG patterns, macro-re-entrant and focal tachycardia mechanisms can be very complex and electrophysiological studies are necessary to guide ablation treatment in poorly tolerated cases.
| S-EPMC5522718 | biostudies-other
Project description:Study Design Retrospective study of a prospectively maintained database. Objective Our aim was to retrospectively review management and outcomes of patients with low-grade hangman's fractures, specifically looking at differences in outcomes between collars and halo immobilization. We also studied fracture patterns and their treatment outcomes. Methods Forty-one patients with hangman's fractures were identified from 105 patients with axis fractures between 2007 and 2013. Typical hangman's fractures were defined as traumatic spondylolisthesis of the axis causing a bilateral pars interarticularis fracture. Fractures involving the posterior cortex of C2 on one or both sides or an asymmetrical pattern were defined as atypical. Results There were 41 patients with a mean age of 59 years, with 13 (31.7%) typical and 28 (68.2%) atypical fractures. There were 22 (53.6%) type 1 fractures, 7 (41.4%) type 2 fractures, and 2 (4.9%) type 2a fractures in this series. Cervical collars were used to manage 11 patients (27% of all patients with hangman's fractures) and halo orthosis was used in 27 (65.8%). Three (7.3%) patients underwent surgical fixation of the fracture. Bony union was achieved in all patients on radiologic follow-up. Permanent neurologic deficit occurred in one patient due to associated injuries. Neck pain and stiffness were reported more commonly in the atypical group, but this finding was not statistically significant. Conclusions The majority of hangman type fractures can be treated nonoperatively. We found no difference in outcomes between a rigid collar or halo immobilization for treatment of low-grade fractures. Radiologic follow-up is essential to identify cases of nonunion.
| S-EPMC4836940 | biostudies-other
Project description:Background:Typical and atypical carcinoids represent approximately 2% of all lung tumors. Survival of patients with typical bronchial carcinoids, unlike the survival of patients with most lung tumors, is generally long but dependent on stage. We report the findings of the Ochsner Medical Center/Louisiana State University (LSU) Health Sciences Center neuroendocrine tumor (NET) program. Methods:A database with all patients seen at the Ochsner Medical Center/LSU NET program was queried for patients with bronchopulmonary NET. We included patients who had confirmed pathologic bronchopulmonary carcinoid and who had at least 1 clinic visit. Patients with large or small cell NETs or diffuse idiopathic pulmonary neuroendocrine cell hyperplasia were excluded. Results:A total of 169 patients seen from January 1996 to March 2015 met the inclusion criteria. The mean age at diagnosis was 53 years. Of the tumors, 51% percent (86/169) were well-differentiated, 12% (21/169) were moderately differentiated, and 85% and 53% were positive on positron emission tomography and octreotide scanning, respectively. The 5- and 10-year survival rates were 88% and 81% for well-differentiated tumors and 80% and 42% for moderately differentiated tumors, respectively. The 10-year survival rates stratified by Ki-67 index ranges 0-2%, >2%-10%, and >10% were 90%, 72%, and 44%, respectively (P<0.05). Conclusion:Overall, patients with bronchial carcinoids have long 5- and 10-year survival rates. We found significant survival differences between nodal status, differentiation status, and carcinoid phenotype. Interestingly, the difference in survival stratified by Ki-67 indices was statistically significant despite its absence in the World Health Organization grading system. As with gastroenteropancreatic NETs, Ki-67 index could become a valuable prognostic indicator for bronchial carcinoids.
| S-EPMC5718446 | biostudies-literature
Project description:The 22q11.2 microduplication syndrome shows variable phenotypes with reduced penetrance compared to the 22q11.2 deletion syndrome. We report a woman with overgrowth and macrocephaly, mild mental retardation, heart defect, kidney anomalies, and dysmorphic features. Array-CGH analysis revealed a 246-kb duplication at the 22q11.2 region. No additional clinically significant CNVs were found. The case resembles a previously published case also showing overgrowth and macrocephaly with an almost identical 22q11.2 duplication of 252 kb.
| S-EPMC8117256 | biostudies-literature
Project description:BackgroundVisceral leishmaniasis (VL) is in elimination phase in India while cutaneous leishmaniasis (CL) is being reported from new foci. In Himachal Pradesh (HP), a foci of CL had been reported along Satluj River, but the causative agent poses a dilemma, hence the present study was undertaken in Shimla, Kullu and Kinnaur districts.MethodsA total of 28 CL patients from Indira Gandhi Medical College and Hospital Shimla (IGMC) in 2018, were tested by rK39., Twelve fresh cases were subjected to microscopic detection of Leishmania parasite, PCR and sequencing. Skin biopsies of 3-4 mm diameter were cultured, as well as imprints were prepared for the detection of Leishmania amastigotes. Biopsy samples were inoculated into different culture media (M199, RPMI 1640, NNN) and were incubated at 22-24 °C. Polymerase chain reaction (PCR) was performed to characterize Leishmania parasite species.ResultsOf 28 patients, one was positive by rK39 dipstick test and one imprint was found positive for Leishmania amstigotes. Twelve biopsy DNA samples subjected to PCR for Leishmania kDNA, were found Lesihmania positive. Identification of Leishmania species was confirmed by PCR-RFLP and sequencing method. Of 12 Leishmania positive samples, six were identified as L. donovani, three L. tropica, two L.major and one remained unidentified.ConclusionsThis study revealed the existence of three species of parasites i.e., L. donovani, L. tropica and L. major indicating the existence of typical and atypical leishmaniasis in Himachal Pradesh. The occurrence of CL cases in HP, Kerala or elsewhere should not be ignored considering them just cases of CL alone. Further studies are warranted to confirm the existence of L.donovani zymodeme MON37 from cases of CL in HP or L.donovani zymodeme MON2 strain causing VL in Bihar. Elimination of CL should also be considered along with goal of Kala -Azar elimination.
| S-EPMC8220184 | biostudies-literature
Project description:ObjectiveTo characterize in vivo signatures of pathological diagnosis in a large cohort of patients with primary progressive aphasia (PPA) variants defined by current diagnostic classification.MethodsExtensive clinical, cognitive, neuroimaging, and neuropathological data were collected from 69 patients with sporadic PPA, divided into 29 semantic (svPPA), 25 nonfluent (nfvPPA), 11 logopenic (lvPPA), and 4 mixed PPA. Patterns of gray matter (GM) and white matter (WM) atrophy at presentation were assessed and tested as predictors of pathological diagnosis using support vector machine (SVM) algorithms.ResultsA clinical diagnosis of PPA was associated with frontotemporal lobar degeneration (FTLD) with transactive response DNA-binding protein (TDP) inclusions in 40.5%, FTLD-tau in 40.5%, and Alzheimer disease (AD) pathology in 19% of cases. Each variant was associated with 1 typical pathology; 24 of 29 (83%) svPPA showed FTLD-TDP type C, 22 of 25 (88%) nfvPPA showed FTLD-tau, and all 11 lvPPA had AD. Within FTLD-tau, 4R-tau pathology was commonly associated with nfvPPA, whereas Pick disease was observed in a minority of subjects across all variants except for lvPPA. Compared with pathologically typical cases, svPPA-tau showed significant extrapyramidal signs, greater executive impairment, and severe striatal and frontal GM and WM atrophy. nfvPPA-TDP patients lacked general motor symptoms or significant WM atrophy. Combining GM and WM volumes, SVM analysis showed 92.7% accuracy to distinguish FTLD-tau and FTLD-TDP pathologies across variants.InterpretationEach PPA clinical variant is associated with a typical and most frequent cognitive, neuroimaging, and neuropathological profile. Specific clinical and early anatomical features may suggest rare and atypical pathological diagnosis in vivo. Ann Neurol 2017;81:430-443.
| S-EPMC5421819 | biostudies-literature