Neural origins of the P300

A review of the literature investigating the neural origins of detection behavior in humans reveals two event-related potential components, P3a and P3b, each with a distinct neural organization and cognitive function.The P3a is involved in automatic novelty detection and characterized by a more anterior cortical distribution, whereas the P3b is concerned with volitional target detection and has a more posterior cortical distribution. Intracranial investigation, studies with patients with focal brain lesions, and functional neuroimaging (fMRI) studies converge with scalp-recorded event-related potential (ERP) data in suggesting that a widespread cortical network gives rise to both automatic and controlled detection behavior. The main regions consistently attributed to generating detection-related brain activation include the temporal-parietal junction, medial temporal complex, and the lateral prefrontal cortex. The extant human and animal literature addressing the neural networks, neuropharmacological underpinnings, and behavioral significance of the P300 potential will be reviewed.     

Mutations in the human melanocortin-4 receptor gene associated with severe familial obesity disrupts receptor function through multiple molecular mechanisms

Mutations in the melanocortin-4 receptor gene (MC4R) represent the commonest monogenic cause of human obesity. However, information regarding the precise effects of such mutations on receptor function is very limited. We examined the functional properties of 12 different mutations in human MC4R that result in severe, familial, early-onset obesity. Of the nine missense mutants studied, four were completely unable to generate cAMP in response to ligand and five were partially impaired. Four showed evidence of impaired cell surface expression and six of reduced binding affinity for ligand. One mutation in the C-terminal tail, I316S, showed reduced affinity for alpha-MSH but retained normal affinity for the antagonist AgRP. None of the mutations inhibited signaling through co-transfected wild-type receptors. Thus, in the most comprehensive study to date of the functional properties of naturally occurring MC4R mutations we have (1) established that defective expression on the cell surface is a common mechanism impairing receptor function, (2) identified mutations which specifically affect ligand binding affinity thus aiding the definition of receptor structure-function relationships, (3) provided evidence against the notion that these receptor mutants act as dominant-negatives, and (4) identified a potentially novel molecular mechanism of receptor dysfunction whereby a mutation alters the relative affinities of a receptor for its natural agonist versus antagonist.     

A de novo mutation affecting human TrkB associated with severe obesity and developmental delay

An 8-year-old male with a complex developmental syndrome and severe obesity was heterozygous for a de novo missense mutation resulting in a Y722C substitution in the neurotrophin receptor TrkB. This mutation markedly impaired receptor autophosphorylation and signaling to MAP kinase. Mutation of NTRK2, which encodes TrkB, seems to result in a unique human syndrome of hyperphagic obesity. The associated impairment in memory, learning and nociception seen in the proband reflects the crucial role of TrkB in the human nervous system.     

Bone mineral density is related to blood pressure in men

The aim of this study was to determine the relationships between bone mineral density (BMD) and blood pressure in 214 men, age 20–76. BMD measurements were done by dual X‐ray absorptiometry using a Lunar DPXMD densitometer at the lumbar spine (L2–L4) and different femoral regions. Systolic (SBP) and diastolic (DBP) blood pressure were measured using an MPC‐350 sphygmomanometer. Physicians gathered demographic data and participants' dietary intake of calcium were determined by using food frequency questionnaires. After adjusting for age, body mass index, dietary calcium, and exercise history, multiple linear regression models showed that DBP was negatively related to femoral neck BMD (β = ?0.145, P = 0.032) and just shy of significant association with femoral neck BMC (β = ?0.114, P = 0.079). SBP was correlated with femoral neck (r = ?0.171, P = 0.012) and Ward's (r = ?0.186, P = 0.006) BMD but not after adjusting for possible confounders. Further studies are needed to determine whether elevated blood pressure is causally related to the development of low bone mass. Am. J. Hum. Biol. 16:168–171, 2004. © 2004 Wiley‐Liss, Inc.     

Maffucci syndrome: Case report and review of diagnostic signs of the rare disease

Maffucci syndrome is a non-hereditary congenital condition that affects the skin and skeleton. Enchondromas (benign cartilage enlargements), bone abnormalities, and venous anomalies (hemangiomas) are all symptoms. Enchondromas occur as a result of mesodermal dysplasia and have the potential to become cancerous. They are most commonly found on the phalanges and long bones. Venous abnormalities commonly manifest themselves as soft lumps or tumors on the distal extremities. A 19-year-old boy presented with swellings on his fingers and left foot since the age of 5, along with a few bluish soft tissue swellings on his left heel. Multiple expansile lytic lesions and soft tissue swellings with phleboliths were seen on X-ray. Histology confirmed the diagnosis of hemangiomas and enchondromas. Soft tissue swellings were found to have hyper echoic areas, as well as modest marginal blood flow on Doppler, which could indicate hemangiomas. Maffucci syndrome was identified, and treatment with a multidisciplinary approach was initiated. Maffucci syndrome is a rare genetic illness reported in the literature less than 200 times. The enchondromas and hemangiomas have a strong link to malignant changes, with chondrosarcomas accounting for 30% of the associated malignancies. On X-ray, enchondromas are easily identified as osteolytic lesions with cortex thinning and endosteal scalloping while color Doppler ultrasound detects the presence of hemangiomas. Phleboliths are easily identified as small calcifications on X-rays. Radiographic examinations should be considered in patients presenting with bone or soft tissue swellings for an early diagnosis of Maffucci syndrome.     

Association between epstein barr virus and tongue squamous cell carcinoma in iranian patients

Detection of Epstein-Barr virus in oral squamous cell carcinoma suggests its involvement in the carcinogenesis of oral cavity. But, there are few studies on the incidence of EBV genome in squamous cell carcinomas at specific locations in the oral cavity like tongue and with different tumor progression. In this study the presence of EBV genome in tongue Squamous Cell Carcinoma (TSCC) in Iranian patients were investigated. Accordingly, a total of 94 cases with TSCC were firstly analyzed for the presence of viral genome through Nested PCR. Patients were divided into different groups based on their gender and the size, nodal involvement, grade and stage of their tumor. Results showed the presence of EBV genome in 72.3% of TSCCs with no significant difference between two genders, although slightly higher in females. Interestingly, PCR products of EBV genome showed a statistically significant higher distribution in TSCCs at IVa stage (p = 0.04), while a considerable low involvement of EBV genome was seen in T1-sized tumors. The result of this study further emphasizes the role of EBV in oral SCCs – mainly at tongue. This is the first investigation to clarify the association between EBV genome and different tumor size and stage in TSCCs; however, more studies in different regions and larger populations should be performed to be able to draw a firmed conclusion.     

High gamma activity in response to deviant auditory stimuli recorded directly from human cortex

We recorded electrophysiological responses from the left frontal and temporal cortex of awake neurosurgical patients to both repetitive background and rare deviant auditory stimuli. Prominent sensory event-related potentials (ERPs) were recorded from auditory association cortex of the temporal lobe and adjacent regions surrounding the posterior Sylvian fissure. Deviant stimuli generated an additional longer latency mismatch response, maximal at more anterior temporal lobe sites. We found low gamma (30-60 Hz) in auditory association cortex, and we also show the existence of high-frequency oscillations above the traditional gamma range (high gamma, 60-250 Hz). Sensory and mismatch potentials were not reliably observed at frontal recording sites. We suggest that the high gamma oscillations are sensory-induced neocortical ripples, similar in physiological origin to the well-studied ripples of the hippocampus.     

Carvacrol and human health: A comprehensive review

Carvacrol (CV) is a phenolic monoterpenoid found in essential oils of oregano (Origanum vulgare), thyme (Thymus vulgaris), pepperwort (Lepidium flavum), wild bergamot (Citrus aurantium bergamia), and other plants. Carvacrol possesses a wide range of bioactivities putatively useful for clinical applications such antimicrobial, antioxidant, and anticancer activities. Carvacrol antimicrobial activity is higher than that of other volatile compounds present in essential oils due to the presence of the free hydroxyl group, hydrophobicity, and the phenol moiety. The present review illustrates the state‐of‐the‐art studies on the antimicrobial, antioxidant, and anticancer properties of CV. It is particularly effective against food‐borne pathogens, including Escherichia coli, Salmonella, and Bacillus cereus. Carvacrol has high antioxidant activity and has been successfully used, mainly associated with thymol, as dietary phytoadditive to improve animal antioxidant status. The anticancer properties of CV have been reported in preclinical models of breast, liver, and lung carcinomas, acting on proapoptotic processes. Besides the interesting properties of CV and the toxicological profile becoming definite, to date, human trials on CV are still lacking, and this largely impedes any conclusions of clinical relevance.