Elastin point mutations cause an obstructive vascular disease, supravalvular aortic stenosis

Supravalvular aortic stenosis (SVAS) is an inherited obstructive vascular disease that affects the aorta, carotid, coronary and pulmonary arteries. Previous molecular genetic data have led to the hypothesis that SVAS results from mutations in the elastin gene, ELN. In these studies, the disease phenotype was linked to gross DNA rearrangements (35 and 85 kb deletions and a translocation) in three SVAS families. However, gross rearrangements of ELN have not been identified in most cases of autosomal dominant SVAS. To define the spectrum of ELN mutations responsible for this disorder, we refined the genomic structure of human ELN and used this information in mutational analyses. ELN point mutations co-segregate with the disease in four familial cases and are associated with SVAS in three sporadic cases. Two of the mutations are nonsense, one is a single base pair deletion and four are splice site mutations. In one sporadic case, the mutation arose de novo. These data demonstrate that point mutations of ELN cause autosomal dominant SVAS.      

Contextual modulation of synchronization to random dots in the cat visual cortex

Synchronization of neuronal activity has been proposed as a binding mechanism for integration of image properties into one coherent percept. In the present study, we investigated the contextual modulation of synchronization to random dot patterns. Coherent motion of random dots evoked well synchronized responses in area 17 of anaesthetized cats when the stimulus was presented in the compound receptive field of recorded sites. Gradually changing the directional coherence of random dots in the surround while maintaining fully coherent motion of the stimulus in the receptive field significantly suppressed synchronization of neuronal activity for some stimulus conditions. However, usually one or two peaks of increased synchronization were found in the surround coherence tuning curves with low (8–12%) and/or moderate (25–50%) coherence in the surround. At the population level, synchronization was significantly depressed with incoherent motion in the receptive field and when both the surround and the receptive field were jointly stimulated with 0% coherence. The intriguing finding was the discovery of two distinct groups of cells with opposite synchronization changes dependent on the presence or absence of significant synchronization in their spontaneous activity. The latter group of neurons showed peaks of increased synchronization with lower surround coherence, thus probably being more sensitive to the direction of the surround motion. Overall, our findings support the notion that binding of stimulus properties can be achieved by synchronized activity of cortical cells. However, our findings go further than the original hypothesis of feature binding by synchrony to show that synchronization of cortical activity may be directly related to the decision making processes, which in turn are related to the threshold of perception of coherent motion.     

Anxiety during pregnancy and fetal attachment after in-vitro fertilization conception

The aim of this study was to compare 70 couples who had conceived by in- vitro fertilization (IVF) with 63 matched controls for the prevalence of anxiety and quality of attachment to the baby during pregnancy. Results for mothers showed no group differences using a global measure of anxiety, the Spielberger State-Trait Anxiety Inventory. However, pregnancy-specific measures revealed significantly higher levels of anxiety in IVF mothers about the survival and normality of their unborn babies, about damage to their babies during childbirth and about separating from their babies after birth. When IVF mothers were differentiated according to the number of treatment cycles, more differences in anxiety level were revealed, with most increases occurring in mothers who had experienced two or more treatment cycles. IVF fathers did not differ from controls on the global anxiety measure. No data on pregnancy-specific anxiety were available for fathers. Neither IVF mothers nor IVF fathers differed from controls on measures of attachment to the baby during pregnancy. Results are discussed in the context of the need for researchers to employ differentiated and issue-specific measures to identify concerns that may be unique to IVF couples. Clinical implications regarding the need for psychological support during pregnancy are also discussed.      

Correlates of suicide risk in adolescent inpatients who report a history of childhood abuse

The study objective was to examine correlates of suicide risk in psychiatrically hospitalized adolescents with a reported history of childhood abuse. Predictors of suicide risk were examined in 74 subjects who reported a history of childhood abuse and 53 depressed subjects who did not report a history of childhood abuse. Subjects completed a battery of psychometrically well-established self-report instruments to assess childhood abuse, suicide risk, and internalizing and externalizing psychopathology. Correlational analyses showed that higher levels of depression, self-criticism, and hopelessness were significantly associated with suicide risk in both study groups and violence was significantly associated with suicide risk in the childhood abuse group. For the childhood abuse group, multiple regression analyses with seven predictor variables accounted for 54% of the variance in suicide risk; depression and alcohol problems made significant independent contributions, while violence and self-criticism were independent predictors at the trend level. For the depressed/nonabused group, multiple regression analyses with the seven predictor variables accounted for 60% of the variance in suicide risk; depression, hopelessness, and self-criticism were independent predictors. Our findings suggest that both internalizing (i.e., depression or self-criticism) and externalizing (i.e., violence or alcohol) factors predict suicide risk in adolescent inpatients who report childhood abuse. This profile appears different from the more internalizing pattern (i.e., depression, self-criticism, and hopelessness) observed for the depressed adolescent inpatients who reported no history of childhood abuse.     

Factor analysis of the DSM-III-R borderline personality disorder criteria in psychiatric inpatients

OBJECTIVE: The goal of this study was to examine the factor structure of the DSM-III-R criteria for borderline personality disorder in young adult psychiatric inpatients. METHOD: The authors assessed 141 acutely ill inpatients with the Personality Disorder Examination, a semistructured diagnostic interview for DSM-III-R personality disorders. They used correlational analyses to examine the associations among the different criteria for borderline personality disorder and performed an exploratory factor analysis. RESULTS: Cronbach's coefficient alpha for the borderline personality disorder criteria was 0.69. A principal components factor analysis with a varimax rotation accounted for 57.2% of the variance and revealed three homogeneous factors. These factors were disturbed relatedness (unstable relationships, identity disturbance, and chronic emptiness); behavioral dysregulation (impulsivity and suicidal/self-mutilative behavior); and affective dysregulation (affective instability, inappropriate anger, and efforts to avoid abandonment). CONCLUSIONS: Exploratory factor analysis revealed three homogeneous components of borderline personality disorder that may represent personality, behavioral, and affective features central to the disorder. Recognition of these components may inform treatment plans.     

Respiratory syncytial virus genotypes and disease severity among children in hospital

OBJECTIVES: To determine the spectrum of N and G genotypes of respiratory syncytial virus (RSV) causing respiratory tract infection and whether particular genotypes are associated with severity of infection. PATIENTS AND METHODS: Nasopharyngeal aspirates (NPAs) were obtained from 114 infants with acute respiratory tract infection due to RSV over two seasons. Viral mRNA was extracted from NPAs or cultured virus, reverse transcribed, and the cDNA amplified by the polymerase chain reaction using primers directed to parts of the N and G gene respectively. Amplicons were separately digested with four different restriction endonucleases for each gene. The fragments were separated by agarose gel, electrophoresis, and the electrophoretic patterns used to assign the various genotypes. Disease severity was assessed as very mild (upper respiratory tract signs only), mild (coryza and signs of lower respiratory tract infection), moderate (requiring nasogastric or intravenous fluids), and severe (requiring oxygen or ventilation). RESULTS: Five of the six known N genotypes were detected, but NP4 and NP2 were found most frequently. There was no association between N genotype and disease severity. Six G (SHL) genotypes were detected. Significantly (p = 0.04) more of the infants infected with the SHL2 genotype had severe or moderate disease. CONCLUSIONS: During the seasonal peaks of RSV respiratory tract infection at least 10 different RSV genotypes cocirculated. While there is no association between N genotypes and disease severity, infection with the SHL2 G genotype appears to result in moderate to severe disease.