Brain processing of visual sexual stimuli in healthy men: a functional magnetic resonance imaging study

The brain plays a central role in sexual motivation. To identify cerebral areas whose activation was correlated with sexual desire, eight healthy male volunteers were studied with functional magnetic resonance imaging (fMRI). Visual stimuli were sexually stimulating photographs (S condition) and emotionally neutral photographs (N condition). Subjective responses pertaining to sexual desire were recorded after each condition. To image the entire brain, separate runs focused on the upper and the lower parts of the brain. Statistical Parametric Mapping was used for data analysis. Subjective ratings confirmed that sexual pictures effectively induced sexual arousal. In the S condition compared to the N condition, a group analysis conducted on the upper part of the brain demonstrated an increased signal in the parietal lobes (superior parietal lobules, left intraparietal sulcus, left inferior parietal lobule, and right postcentral gyrus), the right parietooccipital sulcus, the left superior occipital gyrus, and the precentral gyri. In addition, a decreased signal was recorded in the right posterior cingulate gyrus and the left precuneus. In individual analyses conducted on the lower part of the brain, an increased signal was found in the right and/or left middle occipital gyrus in seven subjects, and in the right and/or left fusiform gyrus in six subjects. In conclusion, fMRI allows to identify brain responses to visual sexual stimuli. Among activated regions in the S condition, parietal areas are known to be involved in attentional processes directed toward motivationally relevant stimuli, while frontal premotor areas have been implicated in motor preparation and motor imagery. Further work is needed to identify those specific features of the neural responses that distinguish sexual desire from other emotional and motivational states.     

Gene expression profiling of peripheral blood cells for early detection of breast cancer

Introduction  

Early detection of breast cancer is key to successful treatment and patient survival. We have previously reported the potential use of gene expression profiling of peripheral blood cells for early detection of breast cancer. The aim of the present study was to refine these findings using a larger sample size and a commercially available microarray platform.     

Changes in staphylococcal cassette chromosome type and antibiotic resistance profile in methicillin-resistant Staphylococcus aureus isolates from a French hospital over an 11 year period

BACKGROUND: In this study, we investigated the relationship between changes in antibiotic resistance and distribution of staphylococcal cassette chromosome (SCC) types amongst methicillin-resistant Staphylococcus aureus (MRSA) isolates expressing the most frequently encountered profiles of antibiotic resistance over an 11 year period in the University Hospital of Rennes, France. METHODS: Antibiotic susceptibilities were determined by agar diffusion. SCC typing was performed using PCR. PFGE demonstrated that isolates were phylogenetically related. RESULTS: Fourteen profiles of antibiotic resistance were defined among MRSA isolates. For each resistance profile, only one SCC type was associated: four patterns corresponded to SCC type I or IA, nine to SCC type IV or IVA, and none to types II and III. One was not typed. PFGE indicated that isolates with SCC type I or IA belong to a single genetic lineage, which also includes most of the epidemic isolates, which carry SCC type IVA. In contrast to type I or IA, isolates with SCC type IV or IVA were found to be associated with several different PFGE clusters, although not all of these represent epidemic isolates. CONCLUSIONS: During the course of the study, the spectrum of antibiotic resistance in MRSA isolates decreased. This occurred due to the emergence of strains with SCC type IV or IVA, which are susceptible to more antibiotics than type I or IA strains. The greater prevalence of such isolates could not be linked conclusively to the presence of SCC type IV or IVA, or to one particular PFGE cluster.     

Distinct functional substrates along the right superior temporal sulcus for the processing of voices

The right superior temporal sulcus (STS) is involved in processing the human voice. In this paper, we report fMRI findings showing that segregated cortical regions along the STS are involved in distinct aspects of voice processing and that they functionally cooperate during speaker recognition. Subjects listened to identical sets of auditory sentences while recognizing either a target sentence irrespective of the speaking voice or a target voice irrespective of the sentence meaning. As the same stimulus material was used in both conditions, task-related activations were not confounded by differences in speech acoustic features. Half of the stimuli were voices of familiar persons and half of persons that were never encountered before. Recognizing voices activated the right anterior and posterior STS more than recognizing verbal content. While the right anterior STS responded equally to both voice categories, the right posterior STS displayed stronger responses to non-familiar than to familiar speakers' voices. It also responded to our baseline condition of amplitude modulated noises that required a detailed analysis of complex temporal patterns. Analyses of connectivity (psychophysiological interactions) revealed that during speaker recognition both anterior and posterior right STS interacted with a region in the mid/anterior part of the right STS, a region that has been implicated in processing the acoustic properties of voices. Moreover, the anterior and posterior STS displayed distinct connectivity patterns depending on familiarity. Our results thus distinguish three STS regions that process different properties of voices and interact in a specific manner depending on familiarity with the speaker.     

Cobalamin status and its biochemical markers methylmalonic acid and homocysteine in different age groups from 4 days to 19 years

BACKGROUND: Recent data indicate that cobalamin and folate status, including the metabolic markers methylmalonic acid (MMA) and total homocysteine (tHcy), undergo marked changes during childhood, particularly during the first year. METHODS: Serum cobalamin, serum and whole-blood folate, and plasma MMA and tHcy were determined in a cross-sectional study of 700 children, ages 4 days to 19 years. RESULTS: During the first 6 months, serum cobalamin was lower than and plasma MMA, tHcy, and serum folate were higher than the concentrations detected in the other age groups. In infants 6 weeks to 6 months of age, median MMA and tHcy concentrations were >0.78 and >75 micro mol/L, respectively. In older children (>6 months), serum cobalamin peaked at 3-7 years and then decreased, median plasma MMA remained low (<0.26 micro mol/L), median plasma tHcy was low (<6 micro mol/L) and increased from the age of 7 years on, and serum folate gradually decreased. Plasma MMA was inversely associated with cobalamin (r = -0.4) in both age groups, but across the whole range of cobalamin concentrations, MMA was markedly higher in infants (< or =6 months) than in older children. Plasma tHcy showed a strong negative correlation to cobalamin (r = -0.52) but not to serum folate in infants < or =6 months. In older children, tHcy showed the expected association with both cobalamin (r = -0.48) and folate (r = -0.51). CONCLUSIONS: In infants 6 weeks to 6 months, concentrations of the metabolic markers MMA and tHcy were higher than in the other age groups and strongly correlated to cobalamin, whereas in older children, both makers showed correlations to cobalamin and folate concentrations documented in adults. Whether this metabolic profile in infants is explained by impaired cobalamin status, which in turn may have long-term effects on psychomotor development, remains to be addressed in intervention studies.     

ERCC1 and RRM1 in the international adjuvant lung trial by automated quantitative in situ analysis

The excision repair cross completing group 1 gene product (ERCC1) and the regulatory subunit of ribonucleotide reductase (RRM1) have been reported as being prognostic of outcome and predictive of therapeutic efficacy in patients with non-small cell lung cancer. Routinely processed surgical specimens from 784 patients from the International Adjuvant Lung Trial were arrayed as tissue microarrays. In situ protein levels were scored with an automated, quantitative analysis system, dichotomized into high and low marker categories, and analyzed for associations with patients' characteristics, survival, and benefit from adjuvant chemotherapy. Scores for both markers were significantly associated with contributing center (P < 0.001) and skewed, with the bulk of scores being low. High scores were more frequent in women for ERCC1 and RRM1 and in older patients and those with adenocarcinoma for RRM1. Low ERCC1 scores indicated significant benefit from adjuvant chemotherapy [hazard ratio (HR) = 0.73 for chemotherapy versus control, P = 0.02]. Although all other survival associations were not statistically significant, low RRM1 scores trended to indicate benefit from adjuvant chemotherapy (HR = 0.84, P = 0.25), and ERCC1 scores were marginally prognostic of survival (HR = 0.77 for high versus low scores, P = 0.10). We conclude that contributing center and specimen quality substantially affect the levels of both markers. Future trials should incorporate the collection and processing of tumor specimens prospectively on standardized protocols to better reveal the impact of biomarkers on clinically relevant outcomes.     

CC2D2A mutations in Meckel and Joubert syndromes indicate a genotype–phenotype correlation

Meckel-Gruber syndrome (MKS) is a lethal fetal disorder characterized by diffuse renal cystic dysplasia, polydactyly, a brain malformation that is usually occipital encephalocele, and/or vermian agenesis, with intrahepatic biliary duct proliferation. Joubert syndrome (JBS) is a viable neurological disorder with a characteristic “molar tooth sign” (MTS) on axial images reflecting cerebellar vermian hypoplasia/dysplasia. Both conditions are classified as ciliopathies with an autosomal recessive mode of inheritance. Allelism of MKS and JBS has been reported for TMEM67/MKS3, CEP290/MKS4, and RPGRIP1L/MKS5. Recently, one homozygous splice mutation with a founder effect was reported in the CC2D2A gene in Finnish fetuses with MKS, defining the 6th locus for MKS. Shortly thereafter, CC2D2A mutations were also reported in JBS. The analysis of the CC2D2A gene in our series of MKS fetuses, identified 14 novel truncating mutations in 11 cases. These results confirm the involvement of CC2D2A in MKS and reveal a major contribution of CC2D2A to the disease. We also identified three missense CC2D2A mutations in two JBS cases. Therefore, and in accordance with the data reported regarding RPGRIP1L, our results indicate phenotype–genotype correlations, as missense and presumably hypomorphic mutations lead to JBS while all null alleles lead to MKS. Hum Mutat 30:1–9, 2009. © 2009 Wiley-Liss, Inc.