The fMRI success rate of children and adolescents: Typical development,epilepsy, attention deficit/hyperactivity disorder,and autism spectrum disorders

Functional magnetic resonance imaging (fMRI) in children is increasingly used in clinical application and in developmental research; however, little is known how pediatric patient and typically developing populations successfully complete studies. We examined pediatric success rates with epilepsy, attention deficit/hyperactivity disorder (ADHD), autism spectrum disorders (ASD), and typically developing children (TYP). We also examined the affect of age, and, for ADHD populations, medication status on success rates. We defined a successful fMRI individual run when the data were interpretable and included in group statistics. For unsuccessful runs, datasets with excessive motion or floor task performance were categorized when possible. All clinical groups scanned less successfully than controls; medication status did not affect ADHD success (epilepsy, 80%; ADHD (off methylphenidate), 77%; ADHD (on methylphenidate), 81%; ASD, 70%; TYP, 87%). Ten to 18‐year‐old had a significantly greater scan success rate than 4‐ to 6‐year‐old; adolescents (13‐ to 18‐year‐old) demonstrated greater scan success rates than 7‐ to 9‐year‐old. Success rate for completing an entire battery of experimental runs (n = 2–6), varied between 50–59% for patient populations and 69% for TYP (79% when excluding 4‐ to 6‐year‐old). Success rate for completing one run from a battery was greater than 90% for all groups, except for ASD (81%). These data suggest 20–30% more children should be recruited in these patient groups, but only 10–20% for TYP for research studies. Studies with 4‐ to 6‐year‐olds may require 20–40% additional participants; studies with 10‐ to 18‐year‐olds may require 10–15% additional participants. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.     

Belief models in first episode schizophrenia in South India

Background Existing evidence indicates that dissonance between patients’ and professionals’ explanatory models affects engagement of patients with psychiatric services in Western and non-Western countries. Aims To assess qualitatively the explanatory models (EMs) of psychosis and their association with clinical variables in a representative sample of first episode patients with schizophrenia in South India. Method One hundred and thirty one patients with schizophrenia presenting consecutively were assessed. Measures included the patient’s explanatory models, and clinician ratings of insight, symptoms of psychosis, and functioning on standard scales. Results The majority of patients (70%) considered spiritual and mystical factors as the cause of their predicament; 22% held multiple models of illness. Patients who held a biomedical concept of disease had significantly higher scores on the insight scale compared to those who held non-medical beliefs. Multivariate analyses identified three factors associated with holding of spiritual/mystical models (female sex, low education and visits to traditional healers); and a single factor (high level of insight) for the endorsement of biological model. Conclusions Patients with schizophrenia in this region of India hold a variety of non-medical belief models, which influence patterns of health seeking. Those holding non-medical explanatory models are likey to be rated as having less insight.     

The concept of neurosis in a cross-cultural perspective

PURPOSE OF REVIEW: The aim of this review is to discuss the current state of research on the concept of neurosis across cultures and to document the advances made in this field over the previous year. RECENT FINDINGS: There has been a significant alteration in the concept of neurosis in most cultures, with the relative abandonment of the term 'neurosis' and replacing the concept with that of common mental disorders. The state of research on the aetiopathogenesis of neurosis has moved towards neurobiological, neurophysiological and genetic factors. Neuroticism as a personality trait has retained its role in the development of neurotic disorders. The epidemiological studies on neurotic disorders are equivocal across cultures. Besides, studies on clinical presentation of common mental disorders, somatization and abnormal illness behaviour show some cultural variations. Though there are no significant advances in the management of neurosis equivalents, it seems that the specific serotonin receptor inhibitors may have a role in management of these conditions. SUMMARY: The recent literature shows acceptance of common mental disorders across cultures replacing neurotic disorders. Other conceptual equivalents of neurosis are seen in somatoform disorders, somatization and abnormal illness behaviour. Some traditional culture-bound neurotic syndromes and idioms of distress persist.     

Are there ethnicity-based differences in the evaluation of individuals with abnormal liver biochemistries?

BACKGROUND/AIMS: Recent studies suggested NAFLD is less infrequent in African Americans (AA) than in Caucasians but it is unclear if this difference is biological or due to under-recognition/under-referral. This study examined if there is an ethnicity-based difference in obtaining liver biochemistries or evaluating abnormal liver biochemistries by primary care physicians. METHODS: This study consisted of 45,016 AA and 49,660 Caucasians seen at our primary care clinics over a 3-year period. From these two groups, we identified patients with elevated aminotransferases (AA: 3676, Caucasians: 4644) and elevated bilirubin (AA: 1295, Caucasians: 1199) based on predefined criteria. Subsequently, we assessed the proportion of patients in each group who had liver-specific evaluation (viral serologies, abdominal imaging or GI clinic visit). RESULTS: Among patients with elevated aminotransferases, compared to Caucasians, AA did not have lower testing for viral hepatitis (26% vs. 25%), imaging (16% vs. 13%) or GI clinic visits (17% vs. 17%). Similarly, we did not observe clinically significant difference in the evaluation of elevated bilirubin between AA and Caucasians (viral serologies: 22% vs. 22%; imaging: 25% vs. 27%; GI clinic: 15% vs. 21%). CONCLUSIONS: Under-recognition and under-referral are not likely to explain the reported ethnic differences in the prevalence of NAFLD.     

Network of general and specialty J protein chaperones of the yeast cytosol

J proteins are obligate cochaperones of Hsp70s, stimulating their ATPase activity and thus allowing them to function in multiple cellular processes. In most cellular compartments, an Hsp70 works with multiple, structurally divergent J proteins. To better understand the functional specificity of J proteins and the complexity of the Hsp70:J protein network, we undertook a comprehensive analysis of 13 J proteins of the cytosol of the yeast Saccharomyces cerevisiae. Phenotypes caused by the absence of four proteins, Sis1, Jjj1, Jjj3, and Cwc23, could not be rescued by overexpression of any other cytosolic J protein, demonstrating the distinctive nature of J proteins. In one case, that of Zuo1, the phenotypic effects of the absence of a J protein could be rescued by overexpression of only one other J protein, Jjj1, which, like Zuo1, is ribosome-associated. In contrast, the severe growth phenotype caused by the absence of the cytosol's most abundant J protein, Ydj1, was substantially rescued by expression of J domain-containing fragments of many cytosolic J proteins. We conclude that many functions of Hsp70 chaperone machineries only require stimulation of Hsp70's ATPase activity by J protein partners. However, a subset of Hsp70 functions requires specific J protein partners, likely demanding either sublocalization within the compartment or binding to specific client proteins.     

Arsenic-induced hepatic mitochondrial toxicity in rats and its amelioration by dietary phosphate

The present study was aimed to test the hypothesis that inorganic phosphate may reduce arsenic toxicity by decreasing its intestinal transference. Co-administration of inorganic phosphate (6.56 M) and arsenic (6.07 mM) in the intestinal loops of rats, in situ, caused significant reduction of arsenic transference. Short-term arsenic exposure (3mg/kg body weight/day for 30 days) caused liver damage evidenced by activities of liver enzymes and necroinflammatory changes. These effects of arsenic were coupled with enhanced mitochondrial swelling, inhibition of cytochrome c oxidase, Ca(2+)-ATPase, a decrease in mitochondrial calcium content, changes in indices of hepatic mitochondrial oxidative stress and iNOS expression. Arsenic also increased hepatic caspase 3 activity and DNA fragmentation. All these apoptosis-related molecular changes caused by arsenic could be alleviated by supplementation with inorganic phosphate, which likely suggests a protective role of phosphate against arsenic-induced hepatotoxic changes.     

From the Cover: Hypoxia inducible microRNA 210 attenuates keratinocyte proliferation and impairs closure in a murine model of ischemic wounds

Ischemia complicates wound closure. Here, we are unique in presenting a murine ischemic wound model that is based on bipedicle flap approach. Using this model of ischemic wounds we have sought to elucidate how microRNAs may be implicated in limiting wound re-epithelialization under hypoxia, a major component of ischemia. Ischemia, evaluated by laser Doppler as well as hyperspectral imaging, limited blood flow and lowered tissue oxygen saturation. EPR oximetry demonstrated that the ischemic wound tissue had pO₂ <10 mm Hg. Ischemic wounds suffered from compromised macrophage recruitment and delayed wound epithelialization. Specifically, epithelial proliferation, as determined by Ki67 staining, was compromised. In vivo imaging showed massive hypoxia inducible factor-1α (HIF-1α) stabilization in ischemic wounds, where HIF-1α induced miR-210 expression that, in turn, silenced its target E2F3, which was markedly down-regulated in the wound-edge tissue of ischemic wounds. E2F3 was recognized as a key facilitator of cell proliferation. In keratinocytes, knock-down of E2F3 limited cell proliferation. Forced stabilization of HIF-1α using Ad-VP16- HIF-1α under normoxic conditions up-regulated miR-210 expression, down-regulated E2F3, and limited cell proliferation. Studies using cellular delivery of miR-210 antagomir and mimic demonstrated a key role of miR-210 in limiting keratinocyte proliferation. In summary, these results are unique in presenting evidence demonstrating that the hypoxia component of ischemia may limit wound re-epithelialization by stabilizing HIF-1α, which induces miR-210 expression, resulting in the down-regulation of the cell-cycle regulatory protein E2F3.