Abnormalities in the processing of emotional prosody from single words in schizophrenia

Background: Abnormalities in emotional prosody processing have been consistently reported in schizophrenia and are related to poor social outcomes. However, the role of stimulus complexity in abnormal emotional prosody processing is still unclear. Method: We recorded event-related potentials in 16 patients with chronic schizophrenia and 16 healthy controls to investigate: 1) the temporal course of emotional prosody processing; and 2) the relative contribution of prosodic and semantic cues in emotional prosody processing. Stimuli were prosodic single words presented in two conditions: with intelligible (semantic content condition—SCC) and unintelligible semantic content (pure prosody condition—PPC). Results: Relative to healthy controls, schizophrenia patients showed reduced P50 for happy PPC words, and reduced N100 for both neutral and emotional SCC words and for neutral PPC stimuli. Also, increased P200 was observed in schizophrenia for happy prosody in SCC only. Behavioral results revealed higher error rates in schizophrenia for angry prosody in SCC and for happy prosody in PPC. Conclusions: Together, these data further demonstrate the interactions between abnormal sensory processes and higher-order processes in bringing about emotional prosody processing dysfunction in schizophrenia. They further suggest that impaired emotional prosody processing is dependent on stimulus complexity.

Inferior frontal gyrus white matter abnormalities in obsessive-compulsive disorder

The aim of the present study is to explore obsessive-compulsive disorder (OCD)-related abnormalities in white matter connectivity in OCD for a core region associated with inhibitory control [i.e. inferior frontal gyrus (IFG)]. Fifteen patients with OCD (11 men) and 15 healthy controls (nine men) underwent diffusion tensor imaging scanning to study four diffusivity indexes of white matter integrity [fractional anisotropy, mean diffusivity (MD), axial diffusivity and radial diffusivity (RD)]. The results showed that persons with OCD manifested significantly lower fractional anisotropy levels in the bilateral IFG as well as its parcellations in the pars opercularis, pars triangularis, and pars orbitalis. Significantly higher levels of MD, RD were evident for the OCD group in the IFG as a whole as well as in the bilateral subregions of the pars triangularis and pars opercularis (for MD and RD), the right side of the pars orbitalis (for RD), and the left side of the pars triangularis and right side pars opercularis (for axial diffusivity). Overall, the results suggest significant alterations in structural connectivity, probably associated with myelination and axonal abnormalities in the IFG of OCD patients.

Risk of multiple myeloma is associated with polymorphisms within telomerase genes and telomere length

Compelling biological and epidemiological evidences point to a key role of genetic variants of the TERT and TERC genes in cancer development. We analyzed the genetic variability of these two gene regions using samples of 2,267 multiple myeloma (MM) cases and 2,796 healthy controls. We found that a TERT variant, rs2242652, is associated with reduced MM susceptibility (OR?=?0.81; 95% CI: 0.72-0.92; p?=?0.001). In addition we measured the leukocyte telomere length (LTL) in a subgroup of 140 cases who were chemotherapy-free at the time of blood donation and 468 controls, and found that MM patients had longer telomeres compared to controls (OR?=?1.19; 95% CI: 0.63-2.24; ptrend ?=?0.01 comparing the quartile with the longest LTL versus the shortest LTL). Our data suggest the hypothesis of decreased disease risk by genetic variants that reduce the efficiency of the telomerase complex. This reduced efficiency leads to shorter telomere ends, which in turn may also be a marker of decreased MM risk.

Characterization of the oculomotor alterations in inicial phase of Multiple Sclerosis

Dissertação de mestrado em Advanced Optometry

Cerebral perfusion and automated individual analysis using SPECT among an obsessive-compulsive population

OBJECTIVE: To make individual assessments using automated quantification methodology in order to screen for perfusion abnormalities in cerebral SPECT examinations among a sample of subjects with OCD. METHODS: Statistical parametric mapping (SPM) was used to compare 26 brain SPECT images from patients with OCD individually with an image bank of 32 normal subjects, using the statistical threshold of p < 0.05 (corrected for multiple comparisons at the level of individual voxels or clusters). The maps were analyzed, and regions presenting voxels that remained above this threshold were sought. RESULTS: Six patients from a sample of 26 OCD images showed abnormalities at cluster or voxel level, considering the criteria described above, which represented 23.07%. However, seven images from the normal group of 32 were also indicated as cases of perfusional abnormality, representing 21.8% of the sample. CONCLUSION: The automated quantification method was not considered to be a useful tool for clinical practice, for analyses complementary to visual inspection.

Single line for assembly just-in-sequence multiple models

Programa Doutoral em Líderes para as Indústrias Tecnológicas

Type 2 diabetes-related variants influence the risk of developing multiple myeloma: results from the IMMEnSE consortium

Type 2 diabetes (T2D) has been suggested to be a risk factor for multiple myeloma (MM), but the relationship between the two traits is still not well understood. The aims of this study were to evaluate whether 58 genome-wide-association-studies (GWAS)-identified common variants for T2D influence the risk of developing MM and to determine whether predictive models built with these variants might help to predict the disease risk. We conducted a case–control study including 1420 MM patients and 1858 controls ascertained through the International Multiple Myeloma (IMMEnSE) consortium. Subjects carrying the KCNQ1rs2237892T allele or the CDKN2A-2Brs2383208G/G, IGF1rs35767T/T and MADDrs7944584T/T genotypes had a significantly increased risk of MM (odds ratio (OR)=1.32–2.13) whereas those carrying the KCNJ11rs5215C, KCNJ11rs5219T and THADArs7578597C alleles or the FTOrs8050136A/A and LTArs1041981C/C genotypes showed a significantly decreased risk of developing the disease (OR=0.76–0.85). Interestingly, a prediction model including those T2D-related variants associated with the risk of MM showed a significantly improved discriminatory ability to predict the disease when compared to a model without genetic information (area under the curve (AUC)=0.645 vs AUC=0.629; P=4.05×10-06). A gender-stratified analysis also revealed a significant gender effect modification for ADAM30rs2641348 and NOTCH2rs10923931 variants (Pinteraction=0.001 and 0.0004, respectively). Men carrying the ADAM30rs2641348C and NOTCH2rs10923931T alleles had a significantly decreased risk of MM whereas an opposite but not significant effect was observed in women (ORM=0.71 and ORM=0.66 vs ORW=1.22 and ORW=1.15, respectively). These results suggest that TD2-related variants may influence the risk of developing MM and their genotyping might help to improve MM risk prediction models.

Risk factors for suicide in multiple sclerosis: a case-control study

ABSTRACT Objective To evaluated the prevalence and the suicide risk in a Brazilian sample of patients with multiple sclerosis (MS) and to identify potential factors associated with the risk of suicide. A study was performed with outpatient with MS. The risk of suicide and the presence of psychiatric disorders were assessed by version 5.0 of the Mini-International Neuropsychiatric Interview (MINI). The sample of patients at risk for suicide was matched by sex and age to a control group of patients with MS. Results Eight point three percent of the patients had a past history of attempted suicide, and 8.3% had a current suicide risk, totaling 16.6%. The results of this study suggest that the risk factors associated with suicide in this population are depression, marital status single, widowed or divorced, and lower education level.

Cardiac abnormalities in the acquired immunodeficiency syndrome. A prospective study with a clinical-pathological correlation in twenty-one adult patients

OBJECTIVE - To evaluate the cardiac abnormalities and their evolution during the course of the acquired immunodeficiency syndrome, as well as to correlate clinical and pathological data. METHODS - Twenty-one patients, admitted to the hospital with the diagnosis of acquired immunodeficiency syndrome, were prospectively studied and followed until their death. Age ranged from 19 to 42 years (17 males). ECG and echocardiogram were also obtained every six months. After death, macro- and microscopic examinations were also performed. RESULTS - The most frequent causes of referral to the hospital were: diarrhea or repeated pneumonias, tuberculosis, toxoplasmosis or Kaposi sarcoma. The most frequent findings were acute or chronic pericarditis (42%) and dilated cardiomyopathy (19%). Four patients died of cardiac problems: infective endocarditis, pericarditis with pericardial effusion, bacterial myocarditis and infection by Toxoplasma gondii. CONCLUSION - Severe cardiac abnormalities were the cause of death in some patients. In the majority of the patients, a good correlation existed between clinical and anatomical-pathological data. Cardiac evaluation was important to detect early manifestations and treat them accordingly, even in asymptomatic patients.

Multiple recurrences of cardiac myxomas with acute tumoral pulmonary embolism

We report the case of a 42-year-old female with a second recurrence of cardiac myxoma. Her first diagnosis was at the age of 24 years, when cardiac tumors were withdrawn from her right ventricle and left atrium. Her first recurrence was at the age of 36 years, when tumors were removed from the left and right atria, and the right ventricle. Six years later, the patient was admitted to the Hospital das Clínicas de Porto Alegre complaining of sudden dyspnea, dry cough, and pain in the right hypochondrium, which bore no relation to breathing. The transesophageal echocardiography showed a small tumor in the interatrial septum, close to the superior vena cava, and 2 larger tumors in the right ventricle, 1 close to the outflow tract and the other almost completely obstructing the right branch of the pulmonary artery. The patient was referred to surgery, in which myxomas were removed from the right atrium and ventricle with extension to the right pulmonary artery. The postoperative period was uneventful.

Multiple Embolism in a Female Patient with Infective Endocarditis: Low Back Pain and Hematuria as the Initial Clinical Manifestations

A 59-year-old female patient with mitral valve prolapse and a previous history of lumbosacral spondyloarthrosis and lumbar disk hernia had an episode of infective endocarditis due to Streptococcus viridans, which evolved with peripheral embolism to the left kidney, spleen, and left iliac artery, and intraventricular cerebral hemorrhage. Her clinical manifestations were low back pain and hematuria, which were initially attributed to an osteoarticular condition. Infective endocarditis is a severe polymorphic disease with multiple clinical manifestations and it should always be included in the differential diagnosis by clinicians.

Development of a water-in-oil-in-water multiple emulsion system integrating biomimetic aqueous-core lipid nanodroplets for protein entity stabilization. Part I: experimental factorial design

Lipid nanoballoons integrating multiple emulsions of the type water-in-oil-in-water enclose, at least in theory, a biomimetic aqueous-core suitable for housing hydrophilic biomolecules such as proteins, peptides and bacteriophage particles. The research effort entertained in this paper reports a full statistical 23x31 factorial design study (three variables at two levels and one variable at three levels) to optimize biomimetic aqueous-core lipid nanoballoons for housing hydrophilic protein entities. The concentrations of protein, lipophilic and hydrophilic emulsifiers, and homogenization speed were set as the four independent variables, whereas the mean particle hydrodynamic size (HS), zeta potential (ZP) and polydispersity index (PI) were set as the dependent variables. The V23x31 factorial design constructed led to optimization of the higher (+1) and lower (-1) levels, with triplicate testing for the central (0) level, thus producing thirty three experiments and leading to selection of the optimized processing parameters as 0.015% (w/w) protein entity, 0.75% (w/w) lipophilic emulsifier (soybean lecithin) and 0.50% (w/w) hydrophilic emulsifier (poloxamer 188). In the present research effort, statistical optimization and production of protein derivatives encompassing full stabilization of their three-dimensional structure, has been attempted via housing said molecular entities within biomimetic aqueous-core lipid nanoballoons integrating a multiple (W/O/W) emulsion.

Echocardiographic Abnormalities and Antiphospholipid Antibodies in Patients with Systemic Lupus Erythematosus

OBJECTIVE: Lupus anticoagulant and anticardiolipin antibodies (aCL) have been associated with thrombosis, recurrent abortion, and thrombocytopenia in patients with systemic lupus erythematosus (SLE), but their relationship with cardiac disease is less clear. The purpose of this study was to evaluate the association between antiphospholipid antibodies (aPL) and echocardiographic abnormalities in patients with SLE. METHODS: A total of 70 consecutive patients and 42 control subjects underwent M-mode, 2-dimensional and Doppler echocardiography and tests for lupus anticoagulant, aCL IgG, IgM, and IgA. Lupus anticoagulant was assayed with the dilute Russell viper venom time, and aCL IgG, IgM, and IgA were measured by an enzyme-linked immunosorbent assay (ELISA). RESULTS: Lupus anticoagulant showed a prevalence of 10%. As a whole, aCL had a prevalence of 44.3% and aPL had a prevalence of 50%. Patients with echocardiographic abnormalities had a prevalence of 54.3% and showed a trend towards an association with aCL IgG (P=0.06). The presence of pulmonary hypertension (PH) was significantly associated with aCL IgG (p=0.02). CONCLUSION: aCL IgG was significantly associated with PH and showed a strong trend towards an association with echocardiographic abnormalities taken together. These findings suggest a role for aCL IgG in the development of lupus cardiovascular disease.

Electrocardiographic abnormalities in neurological diseases

OBJECTIVE: To evaluate electrocardiographic abnormalities in patients with neurologic diseases. METHODS: We studied 161 patients with neurologic disorders by analyzing the 12-lead electrocardiogram during the pathological process. An expert who did not know anything about the patients evaluated the traces. RESULTS: Neurological process included brain tumor (41%), stroke (27.3%), cerebral aneurysm (15.5%), subarachnoid hemorrhage (6.8%), subdural hemorrhage (5%), and head injury (4.4%). Electrocardiograms were normal in 61% of cases, and the most frequent abnormality was ventricular repolarization (23.7%). The presence of T waves (4.6%) and prolonged QT intervals (8.8%) was the most characteristic of brain injuries. CONCLUSION: We observed a lower incidence of electrocardiographic abnormalities than that described in the literature.

Williams-Beuren syndrome: cardiovascular abnormalities in 20 patients diagnosed with fluorescence in situ hybridization

OBJECTIVE: To evaluate the cardiovascular findings and clinical follow-up of patients with Williams-Beuren syndrome. METHODS: We studied 20 patients (11 males, mean age at diagnosis: 5.9 years old), assessed for cardiovascular abnormalities with electrocardiography and Doppler echocardiography. Fluorescence in situ hybridization (FISH) was used to confirm the diagnosis of the syndrome. RESULTS: Elastin gene locus microdeletion was detected in 17 patients (85%) (positive FISH), and in 3 patients deletion was not detected (negative FISH). Sixteen patients with a positive FISH (94%) had congenital cardiovascular disease (mean age at diagnosis: 2,3 years old). We observed isolated (2/16) supravalvular aortic stenosis and supravalvular aortic stenosis associated (11/16) with pulmonary artery stenosis (4/11); mitral valve prolapse (3/11); bicuspid aortic valve (3/11); aortic coarctation (2/11), thickened pulmonary valve (2/11); pulmonary valvular stenosis (1/11); supravalvular pulmonary stenosis (1/11); valvular aortic stenosis (1/11); fixed subaortic stenosis (1/11); pulmonary artery stenosis (2/16) associated with pulmonary valvar stenosis (1/2) and with mitral valve prolapse (1/2); and isolated mitral valve prolapse (1/16). Four patients with severe supravalvular aortic stenosis underwent surgery (mean age: 5.7 years old), and 2 patients had normal pressure gradients (mean follow-up: 8.4 years). CONCLUSION: A detailed cardiac evaluation must be performed in all patients with Williams-Beuren syndrome due to the high frequency of cardiovascular abnormalities.