The microRNA cluster C19MC is deregulated in parathyroid tumours

A subset of over-expressed microRNAs (miRNAs) identified in parathyroid carcinomas (Ca) compared to normal glands belongs to C19MC, a cluster on chromosome 19q13.4 involved in stem cell biology and tumourigenesis. In this study, the expression of C19MC-MIR371-3 clusters and the molecular mechanisms presiding their modulation were investigated in a series of six normal parathyroids, 24 adenomas (Ad), 15 Ca and five matched metastases. The general expression levels of C19MC or MIR371-3 clusters in Ad lesions did not differ from normal glands, while they distinguished Ad from Ca at unsupervised hierarchical cluster analysis (P=0.0008). MIR517C showed the most significant difference in expression between Ca and Ad (P=0.0003) and it positively correlated with serum calcium, parathormone and tumour weight. In regard to the molecular mechanism determining C19MC cluster activation, we could detect C19MC copy number (CN) gain in ten Ca (67%) extending distal to the MIR371-3 cluster in almost all samples. Conversely, only four Ad (16%) showed C19MC amplification, with one case presenting distal genomic aberration to MIR371-3. Globally, CN variations of 19q13.4 loci were significantly associated with MIR517C up-regulation (P=0.006). Opposite to normal glands where C19MC promoter was methylated, hypomethylation occurred in 15 out of 30 analysed tumours. Though the epigenetic status did not correlate with C19MC miRNA expression levels, loss of C19MC promoter methylation was significantly associated with Ca and metastatic disease (P=0.01). In conclusion, C19MC cluster aberrations are a characteristic of Ca with respect to Ad. Altogether, these evidences point towards a role for 19q13.4 miRNA clusters as oncogenes in parathyroid tumourigenesis.     

Differential cognitive performances between schizophrenic responders and non-responders to antipsychotics: Correlation with course of the illness,psychopathology, attitude to the treatment and antipsychotics doses

Multiple lines of evidence demonstrate that schizophrenia patients may perform worse than normal controls in several cognitive tasks. However, little is known on putative differences in cognitive functioning between schizophrenia patients responding to antipsychotics and those resistant to the treatment. In this cross-sectional study, 63 subjects (41 schizophrenia and schizoaffective patients and 22 age and sex-matched controls) were enrolled. Patients were divided in resistant (TRS, n=19) and non-resistant to pharmacological treatment (non-TRS, n=22) according to the American Psychiatric Association (APA) criteria for treatment resistance. The Brief Assessment of Cognition in Schizophrenia (BACS) was administered to patients and controls. The following rating scales were administered to schizophrenia patients: the Positive and Negative Syndrome Scale (PANSS), the Drug Attitude Inventory (DAI) and the Subjective Well-being under Neuroleptics (SWN). Statistically significant differences among non-TRS patients, TRS ones, and controls were detected at the BACS. TRS patients performed significantly worse than non-TRS ones on Verbal Memory task, exhibited higher PANSS total and subscales scores and were prescribed higher antipsychotic doses. Poorer performances at the BACS significantly correlated with more severe negative symptoms in TRS but not in non-TRS patients. These results may suggest that TRS patients suffer from a form of the disease with prominent cognitive impairment possibly related to negative symptoms.     

Energy expenditure,body composition and dietary habits in progressive supranuclear palsy

Journal of Neurology - Little is known about metabolic changes in progressive supranuclear palsy. Goals of the present study are to: (1) investigate whether early progressive supranuclear palsy is...     

The Frontal Assessment Battery 20 years later: normative data for a shortened version (FAB15)

Neurological Sciences - The Frontal Assessment Battery (FAB) is a neuropsychological tool largely used to assess executive functions. Prior studies found a marked ceiling effect for the prehension...     

Cerebral venous thrombosis without thrombocytopenia after a single dose of COVID-19 (Ad26.COV2.S) vaccine injection: a case report

Neurological Sciences - The coronavirus pandemic became the hard challenge for the modern global health system. To date, vaccination is the best strategy against Sars-Cov-2-related illness. About 3...     

Acute cellular rejection and HLA mismatch in heart transplantation: insights from a developing country

The notable evolution of heart transplant (HTX) has paralleled the capacity of diagnosing rejection and, consequently, initiating timely treatment. Acute cellular rejection, diagnosed by endomyocardial biopsy, is the most frequent in the first 6 months after HTX. HLA matching is not routinely performed in HTX due to the absence of consensus regarding its usefulness. However, the use of HLA typing might be underscored if it could predict an increased risk of rejection. Therefore, the aim of this study was to evaluate, at a public cardiology center in Brazil, the association between HLA mismatches and the incidence of acute cellular rejection in the first 6 months after HTX. Data were obtained from hospital records and from the National Transplant System. Overall, there was no association between the number of HLA mismatches and the frequency of acute cellular rejection, but there was a tendency toward a higher incidence of rejection with HLA‐DR incompatibility.     

Expression of nuclear insulin receptor substrate 1 in breast cancer

BACKGROUND: Insulin receptor substrate 1 (IRS-1), a cytoplasmic protein transmitting signals from the insulin and insulin-like growth factor 1 receptors, has been implicated in breast cancer. Previously, it was reported that IRS-1 can be translocated to the nucleus and modulate oestrogen receptor alpha (ERalpha) activity in vitro. However, the expression of nuclear IRS-1 in breast cancer biopsy specimens has never been examined. AIMS: To assess whether nuclear IRS-1 is present in breast cancer and non-cancer mammary epithelium, and whether it correlates with other markers, especially ERalpha. Parallel studies were carried out for the expression of cytoplasmatic IRS-1. METHODS: IRS-1 and ERalpha expression was assessed by immunohistochemical analysis. Data were evaluated using Pearson's correlation, linear regression and receiver operating characteristic analysis. RESULTS: Median nuclear IRS-1 expression was found to be low in normal mammary epithelial cells (1.6%) and high in benign tumours (20.5%), ductal grade 2 carcinoma (11.0%) and lobular carcinoma (approximately 30%). Median ERalpha expression in normal epithelium, benign tumours, ductal cancer grade 2 and 3, and lobular cancer grade 2 and 3 were 10.5, 20.5, 65.0, 0.0, 80 and 15%, respectively. Nuclear IRS-1 and ERalpha positively correlated in ductal cancer (p<0.001) and benign tumours (p<0.01), but were not associated in lobular cancer and normal mammary epithelium. In ductal carcinoma, both nuclear IRS-1 and ERalpha negatively correlated with tumour grade, size, mitotic index and lymph node involvement. Cytoplasmic IRS-1 was expressed in all specimens and positively correlated with ERalpha in ductal cancer. CONCLUSIONS: A positive association between nuclear IRS-1 and ERalpha is a characteristic for ductal breast cancer and marks a more differentiated, non-metastatic phenotype.     

Medial temporal lobe abnormalities in pediatric unipolar depression

In vivo anatomical magnetic resonance imaging (MRI) studies in adults with major depressive disorder (MDD) have implicated neurocircuitries involved in mood regulation in the pathophysiology of mood disorders. Specifically, abnormalities in the medial temporal lobe structures have been reported. This study examined a sample of children and adolescents with major depressive disorder to investigate anatomical abnormalities in these key medial temporal brain regions. Nineteen children and adolescents with DSM-IV major depression (mean age +/- S.D.=13.0 +/- 2.4 years; 10 unmedicated) and 24 healthy comparison subjects (mean age +/- S.D.=13.9 +/- 2.9 years) were studied using a 1.5T Philips MRI scanner. We measured hippocampus and amygdala gray matter volumes. MRI structural volumes were compared using analysis of covariance with age and total brain volumes as covariates. Pediatric depressed patients had significantly smaller left hippocampal gray matter volumes compared to healthy controls (1.89 +/- 0.16 cm(3) versus 1.99 +/- 0.18 cm(3), respectively; F=5.0, d.f.=1/39, p=0.03; effect size: eta2(p) =0.11). Unmedicated depressed patients showed a trend towards smaller left hippocampal volumes compared to medicated patients and healthy subjects (F=2.8, d.f.=2/38, p=0.07; effect size: eta2(p) =0.13). There were no statistically significant differences in mean volumes for left or right amygdala. Smaller left hippocampal volumes in children and adolescents with MDD are in agreement with findings from adult studies and suggest that such abnormalities are present early in the course of the illness. Amygdala volumes are not abnormal in this age group. Smaller hippocampal volumes may be related to an abnormal developmental process or HPA axis dysfunction.     

Anatomical measurements of the orbitofrontal cortex in child and adolescent patients with bipolar disorder

Imaging studies indicate smaller orbitofrontal cortex (OFC) volume in mood disorder patients compared with healthy subjects. We sought to determine whether child and adolescent patients with bipolar disorder have smaller OFC volumes than healthy controls. Fourteen children and adolescents meeting DSM-IV criteria for bipolar disorder (six males and eight females with a mean age+/-S.D.=15.5+/-3.2 years) and 20 healthy controls (11 males and nine females with mean age+/-S.D.=16.9+/-3.8 years) were studied. Orbitofrontal cortex volume was measured using magnetic resonance imaging. Male bipolar patients had smaller gray matter volumes in medial (p=0.044), right medial (0.037) and right (p=0.032) lateral OFC subdivisions compared to male controls. In contrast, female patients had larger gray matter volumes in left (p=0.03), lateral (p=0.012), left lateral (p=0.007), and trends for larger volumes in right lateral and left medial OFC subdivisions compared with female controls. Male patients exhibit smaller gray matter volumes, while female patients exhibit larger volumes in some OFC sub-regions. Gender differences in OFC abnormalities may be involved in illness pathophysiology among young bipolar patients.