P1 latency as a biomarker for central auditory development in children with hearing impairment

We used the latency of the P1 cortical auditory-evoked potential (CAEP) as a biomarker for the development of central auditory pathways in three children who received intervention through hearing aids and/or cochlear implants. Our goal was to examine the clinical feasibility of using the latency of the P1 CAEP as an objective tool to evaluate whether acoustic amplification for hearing-impaired children has provided sufficient stimulation for normal development of central auditory pathways. If clinicians have such a marker, then they can more confidently make a decision about whether to provide a child with a cochlear implant following an appropriate hearing-aid trial. Using the same marker, clinicians will also be able to monitor the maturation of central auditory pathways once electrical stimulation is initiated.     

Processing of highly novel auditory events in children and adults: an event-related potential study

In this study, the neural mechanisms of novelty detection in children and adults were examined by means of novelty-elicited event-related potentials. The gross morphology of the event-related potentials elicited by complex, novel stimuli was similar in children and adults, suggesting that processing of novel acoustic information is essentially similar across the age groups. The more frontally distributed P3 components and the larger late frontal negativities in children than in adults suggest an age-related change in activity in the frontal part of the brain. This is consistent with the findings showing that the structural maturation of the frontal cortex does not appear to be completed until late adolescence.     

No difference in platelet activation or inflammation markers after diets rich or poor in vegetables,berries and apple in healthy subjects

Summary.Background: High intake of vegetables and fruits is associated with decreased risk of coronary heart disease. Part of these cardioprotective effects may be mediated via the antithrombotic effects of compounds found in vegetables and fruits, such as flavonoids.Aim of the study: To study the effects of high and low intake of vegetables, berries and apple on platelet function and inflammatory markers.Methods: The study was a randomised, controlled parallel human dietary intervention with healthy female and male volunteers (n = 77, 19–52 y). Nineteen healthy volunteers served as controls. The volunteers consumed one of four strictly controlled isocaloric 6-week diets containing either 810 or 196 g/10 MJ of vegetables, berries and apple and rich either in linoleic acid (11% of energy, en%) or oleic acid (12 en%). Blood and three 24-hour urine samples were collected at the beginning and at the end of the study period for analyses of various markers of platelet function and inflammation.Results: No differences between the treatment groups were seen in platelet count or volume, markers of platelet activation (ex vivo aggregation to ADP and thrombin receptor activating peptide, protein kinase C activity, urinary 2,3-dinor-thromboxane B₂ excretion, plasma P-selectin), plasma intercellular adhesion molecule-1, sensitive C-reactive protein, or antiphospholipid antibodies.Conclusions: The results indicate that in healthy volunteers 6-week diets differing markedly in the amounts of vegetables, berries and apple do not differ in their effects on platelets or inflammation.     

Developmental toxicity of dioxin to mouse embryonic teeth in vitro: arrest of tooth morphogenesis involves stimulation of apoptotic program in the dental epithelium

Previous studies have shown that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) can arrest molar tooth development in rats after in utero and lactational exposure, and that the sensitive stage is temporally restricted. To define the stage in which TCDD is able to arrest tooth development and the cellular background of the effect, mouse embryonic molar tooth explants including various early developmental stages from initiation to late cap stage were exposed to TCDD in organ culture. TCDD did not inhibit morphogenesis of the first molar teeth including the early bud-staged E12 first molars, but the teeth were smaller than in control cultures. Accordingly, the second molars underwent morphogenesis in the presence of TCDD when explanted at E15 when they were at the bud stage. TCDD arrested their development when explanted at E14 when they had not yet reached the early bud stage. Immunohistochemical localization of incorporated bromodeoxyuridine in cultured E14 teeth showed that TCDD did not affect cell proliferation. Localization of apoptosis by terminal deoxynucleotidyl transferase (TdT)-mediated nick end labeling (TUNEL) method revealed that TCDD enhanced apoptosis of dental epithelial cells, especially in the dental lamina of both the first and second molars, and in the inner dental epithelium at the cusp tips of the first molars. Thus, TCDD can arrest tooth development in vitro if the exposure starts at the initiation stage, whereas exposure at later stages leads to smaller tooth size and deformation of cuspal morphology. TCDD interferes with tooth development by stimulating apoptosis in those cells of the dental epithelium, which are predetermined to undergo apoptosis during normal development.     

Citalopram challenge in social anxiety disorder

The aim of the present study was to evaluate neuroendocrine and behavioural responses to a challenge with the selective serotonin (5-HT) reuptake inhibitor citalopram (Cit) in patients with social anxiety disorder (SAD). Cit was given intravenously (20 mg over 30 min) to 18 patients with SAD and 18 matched healthy subjects in a double-blind, placebo-controlled cross-over design. Cit challenge resulted in the increased plasma concentrations of cortisol and prolactin relatively to placebo without significant differences between the patients and controls. The patients had higher ratings of anxiety that were not affected by Cit, and more headaches than controls after Cit. Thus, the neuroendocrine sensitivity to 5-HT stimulation with Cit in patients with SAD was not different from the response in controls indicating lack of major alterations in the function of 5-HT receptors. The increased headache in patients may suggest hypersensitivity of some subtypes of 5-HT receptors in SAD.     

Human CTLs to wild-type and enhanced epitopes of a novel prostate and breast tumor-associated protein, TARP, lyse human breast cancer cells

Vaccine therapy for prostate and breast cancer may have potential for treating these major causes of death in males and females, respectively. Critical to the development of tumor-specific vaccines is finding and characterizing novel antigens to be recognized by CD8(+) T cells. To define new CD8(+) T-cell tumor antigens, we determined two wild-type HLA-A2 epitopes from a recently found tumor-associated protein, TARP (T-cell receptor gamma alternate reading frame protein), expressed in prostate and breast cancer cells. We were also able to engineer epitope-enhanced peptides by sequence modifications. Both wild-type and enhanced epitopes induced peptide-specific CD8(+) T-cell responses in A2K(b) transgenic mice. In vitro restimulation of human CD8(+) T cells from a prostate cancer patient resulted in CD8(+) T cells reactive to the peptide epitopes that could lyse HLA-A2(+) human breast cancer cells (MCF-7) expressing TARP. Epitope-specific human CD8(+) T cells were also enumerated in patients' peripheral blood by tetramer staining. Our data suggest that HLA-A2-binding TARP epitopes and enhanced epitopes discovered in this study could be incorporated into a potential vaccine for both breast and prostate cancer.     

Nicotine reduces antisaccade errors in task impaired schizophrenic subjects

Nicotine and/or smoking have been shown to reduce various cognitive deficits associated with schizophrenia. Here, we examine the effects of nicotine gum on repeated performance on a simple eye movement task. Eight schizophrenic subjects and eight controls participated in three days of testing on saccade (S) and antisaccade (AS) tasks. On each testing day, subjects participated in four testing sessions and received both of two nicotine gum treatments (4 and 6 mg) and both of two control conditions (placebo gum and no gum), each followed by a recovery period. Overall, schizophrenics showed significant impairments on the AS task. However, upon individual examination only four schizophrenics showed significant differences in AS errors or reaction times (RTs) when compared to controls. The other four schizophrenic subjects showed control level performance. All schizophrenic subjects showed normal and better than control level performance on the simple S task. Furthermore, no effects of nicotine were seen on the simple S task. There were significant treatment effects on the AS task. Nicotine treatment significantly decreased errors in the task impaired schizophrenic group and this effect was most pronounced at the 6 mg level. No nicotine effects were demonstrated for non-impaired schizophrenic subjects or controls. This study demonstrates a benefit of short exposure to nicotine in cognitively impaired schizophrenic subjects. These results support previous findings of cognitive benefits of nicotine in schizophrenics.     

Activation in the anterior left auditory cortex associated with phonological analysis of speech input: localization of the phonological mismatch negativity response with MEG

The spatio-temporal dynamics of cortical activation underlying auditory word recognition, particularly its phonological stage, was studied with whole-head magnetoencephalography (MEG). Subjects performed a visuo-auditory priming task known to evoke the phonological mismatch negativity (PMN) response that is elicited by violations of phonological expectancies. Words and non-words were presented in separate conditions. In each of the 318 trials, the subjects first saw a word/non-word (e.g., 'cat') that was soon followed by a prime letter (e.g., 'h'). Their task was to replace mentally the sound of the first letter of the word/non-word with the prime letter, thus resulting in a new word/non-word (e.g., 'hat'). Finally, an auditory word/non-word either matching or mismatching with the anticipated item was presented. In most subjects, a PMNm followed by a later, N400m-like negativity was obtained in the left hemisphere to the mismatching auditory stimuli. A similar response pattern was obtained in the right hemisphere only in a few subjects. Source localization of the N1m, an index of acoustic analysis, and the PMNm and N400m-like responses was performed using L1 minimum-norm estimation. In the left hemisphere, the PMNm source for the words was significantly more anterior than the source of the N400m-like response; for the non-words, the PMNm source was significantly more anterior than the sources of the N1m and the N400m-like response. These results suggest that the left-hemisphere neuronal networks involved in sub-lexical phonological analysis are at least partly different from those responsible for the earlier (acoustic) and later (whole item) processing of speech input.     

Distal spinal muscular atrophy of upper limb (Hirayama disease) associated with high serum lead levels

Hirayama disease causes unilateral or asymmetrical bilateral distal weakness and atrophy of upper limbs. We report a 6 1/2-year-old female with Hirayama disease and associated high serum lead levels. This report highlights the occurrence of this condition in younger children and the need to further study the role of lead in its pathophysiology.