Investigation of decision-making under uncertainty in healthy subjects: a multi-centric fMRI study.

Decision-making is an everyday routine that entails several subprocesses. Decisions under uncertainty occur when either prior information is incomplete or the outcomes of the decision are unclear. The aim of the present study was to disentangle the neural correlates of information gathering as well as reaching a decision and to explore effects of uncertainty acceptance or avoidance in a large sample of healthy subjects. Sixty-four healthy volunteers performed a decision-making under uncertainty task in a multi-center approach while BOLD signal was measured with fMRI. Subjects either had to indicate via button press from which of two bottles red or blue balls were drawn (decision-making under uncertainty condition), or they had to indicate whether 8 red balls had been presented (baseline condition). During the information gathering phase (contrasted against the counting phase) a widespread network was found encompassing (pre-)frontal, inferior temporal and inferior parietal cortices. Reaching a decision was correlated with activations in the medial frontal cortex as well as the posterior cingulate and the precuneus. Effects of uncertainty acceptance were found within a network comprising of the superior frontal cortex as well as the insula and precuneus while uncertainty avoidance was correlated with activations in the right middle frontal cortex. The results depict two distinct networks for information gathering and the indication of having made a decision. While information-gathering networks are modulated by uncertainty avoidance and - acceptance, underlying networks of the decision itself are independent of these factors.

Attenuated prefrontal activation during decision-making under uncertainty in schizophrenia: a multi-center fMRI study.

Decisions are called decisions under uncertainty when either prior information is incomplete or the outcomes of the decision are unclear. Alterations in these processes related to decisions under uncertainty have been linked to delusions. In patients with schizophrenia, the underlying neural networks have only rarely been studied. We aimed to disentangle the neural correlates of decision-making and relate them to neuropsychological and psychopathological parameters in a large sample of patients with schizophrenia and healthy subjects. Fifty-seven patients and fifty-seven healthy volunteers from six centers had to either indicate via button-press from which of two bottles red or blue balls were drawn (decision-making under uncertainty condition), or indicate whether eight red balls had been presented (baseline condition) while BOLD signal was measured with fMRI. Patients based their decisions on less conclusive evidence and had decreased activations in the underlying neural network, comprising of medial and lateral frontal as well as parietal areas, as compared to healthy subjects. While current psychopathology was not correlated with brain activation, positive symptoms led to longer decision latencies in patients. These results suggest that decision-making under uncertainty in schizophrenia is affected by a complex interplay of aberrant neural activation. Furthermore, reduced neuropsychological functioning in patients was related to impaired decision-making and task performance was modulated by distinct positive symptoms.

Essentializing the binary self: individualism and collectivism in cultural neuroscience.

Within the emerging field of cultural neuroscience (CN) one branch of research focuses on the neural underpinnings of "individualistic/Western" vs. "collectivistic/Eastern" self-views. These studies uncritically adopt essentialist assumptions from classic cross-cultural research, mainly following the tradition of Markus and Kitayama (1991), into the domain of functional neuroimaging. In this perspective article we analyze recent publications and conference proceedings of the 18th Annual Meeting of the Organization for Human Brain Mapping (2012) and problematize the essentialist and simplistic understanding of "culture" in these studies. Further, we argue against the binary structure of the drawn "cultural" comparisons and their underlying Eurocentrism. Finally we scrutinize whether valuations within the constructed binarities bear the risk of constructing and reproducing a postcolonial, orientalist argumentation pattern.

["Sonorous man"--an approach to the singing voice through the process of Psychophony]. / "L'Homme sonore"--approche de la voix chantée par la Psychophonie.

Dealing with the voice requires total management, not only of the voice itself, but also of the bodily and psychological status. In fact, the patient who presents with vocal cord pathology is usually unaware of what has caused abuse of his voice. It is therefore our task to restore comfort, but also well-being. Here we cover the way in which we intend to guide him towards a new way of voice behaviour so that he now concentrates not only on the acoustic qualities of the sound he makes, but also on the quality of resonance as well as of posture and movement. To achieve this, we must embark on areas often related to play and to rich mental imagery in order to support his efforts. The patient or pupil must refine his perception of vibration and touch in order to enhance his proprioceptive skills.

WT1 splicing alterations in Wilms' tumors.

Hereditary and sporadic forms of tumors are generally related to germ-line and somatic mutations of the same tumor suppressor gene. Unexpectedly, in Wilms' tumor, somatic mutations of the WT1 gene were found only occasionally in sporadic cases, although constitutional mutations of this gene are clearly associated with predisposition. It has been suggested that abnormal splicing may be another mode of somatic WT1 alteration. However, this idea was based on the analysis of a small series of tumors, precluding accurate evaluation of the frequency of such changes. To investigate WT1 changes at the somatic level in more detail, we analyzed the levels of the four isoform transcripts produced by alternative splicing events in a large series of 50 tumors, normal mature kidneys, and fetal kidneys. We characterized splicing alterations in 63% of sporadic Wilms' tumors. Moreover, taking into account the decreased and increased overall levels of WT1 mRNA, the percentage of sporadic tumors with changes in WT1 expression reached 90%. Whether and how these alterations of expression play a role in the tumorigenic process remain to be evaluated.

Vestibular semicircular canal epithelium of the rat in culture on filter support: polarity and barrier properties.

The inner ear of mammals contains the vestibular apparatus which is involved in the maintenance of posture and balance. The tubular structure of the apparatus is bathed by the potassium-rich endolymph and sodium-rich perilymph in the luminal and abluminal compartments, respectively. The luminal compartment is lined by a continuous epithelium with islets of receptor organs, which separates the luminal from the abluminal compartment. The present work focuses on the epithelium, without the receptor organs, and shows that it can be reconstituted in culture. The epithelium from 4-day-old Wistar rats was grown on microporous membranes. High transepithelial electrical resistances (4000-6000 Omega.cm2) were achieved after 4-8 days in culture. The epithelium was characterized by the presence of cytokeratin, ZO-1 protein, occludin, and the presence of tight junctions and kinocilia. The transepithelial resistance of the cell monolayer withstood endolymph/perilymph dual bathing when the apical pole of the cells was in contact with endolymph, but collapsed in the reverse configuration. Weak but statistically highly significant basal to apical rubidium (86Rb) transport was observed. These findings show that this epithelium maintains its in vivo polarity and could enhance the potassium composition of endolymph up to maturity. This new culture model, in which dual bathing is possible, should enable further in vitro studies of the sensory vestibular epithelia.

Identification of constitutional WT1 mutations, in patients with isolated diffuse mesangial sclerosis, and analysis of genotype/phenotype correlations by use of a computerized mutation database.

Constitutional mutations of the WT1 gene, encoding a zinc-finger transcription factor involved in renal and gonadal development, are found in most patients with Denys-Drash syndrome (DDS), or diffuse mesangial sclerosis (DMS) associated with pseudohermaphroditism and/or Wilms tumor (WT). Most mutations in DDS patients lie in exon 8 or exon 9, encoding zinc finger 2 or zinc finger 3, respectively, with a hot spot (R394W) in exon 9. We analyzed a series of 24 patients, 10 with isolated DMS (IDMS), 10 with DDS, and 4 with urogenital abnormalities and/or WT. We report WT1 heterozygous mutations in 16 patients, 4 of whom presented with IDMS. One male and two female IDMS patients with WT1 mutations underwent normal puberty. Two mutations associated with IDMS are different from those described in DDS patients. No WT1 mutations were detected in the six other IDMS patients, suggesting genetic heterogeneity of this disease. We analyzed genotype/phenotype correlations, on the basis of the constitution of a WT1 mutation database of 84 germ-line mutations, to compare the distribution and type of mutations, according to the different symptoms. This demonstrated (1) the association between mutations in exons 8 and 9 and DMS; (2) among patients with DMS, a higher frequency of exon 8 mutations among 46, XY patients with female phenotype than among 46,XY patients with sexual ambiguity or male phenotype; and (3) statistically significant evidence that mutations in exons 8 and 9 preferentially affect amino acids with different functions.

Determination of platinum in wine by graphite furnace atomic absorption spectrometry.

A method based on graphite furnace atomic absorption spectrometry (GFAAS) was developed for determining platinum in wine. Wine samples were prepared by microwave acid digestion or dry mineralization. The method of standard addition was used for Pt determination in untreated wine samples and mineralized samples. Analyte modifiers and furnace conditions were optimized. Effects of cations (Mg2+, Ca2+, K+, Na+, and NH4+) and anions (PO4(3)-, SO4(2)-) were tested separately and in combination. Analytical characteristics of the method were optimized for analyte recovery and signal enhancement. Recoveries ranged from 92.5 to 102%, and precision reproducibility relative standard deviation varied from 7.5 to 10%. Red, rosé, and white wines from France were analyzed. Platinum levels found in most wines were very low (< 10 micrograms/L).

Inhibition of histamine-induced skin wheal and flare after 5 days of mizolastine.

Mizolastine is a new, nonsedating antihistamine providing satisfactory symptomatic relief in allergic rhinitis and urticaria. The purpose of this study was to use inhibition of wheal and flare formation after 2-mu g intradermal histamine injections as a measure of the antihistamine effect of repeated doses of mizolastine. Eight volunteers were enrolled in this four-arm, double-blind, cross-over, randomized study. Three dose levels of once-daily mizolastine (5 mg, 10 mg, and 15 mg) were compared with placebo during 5-day dose periods. Histamine tests were performed before drug intake on days 1 and 5, and then 2, 3, 4, 6, 8, 10, 12, 14, and 24 hours after drug intake on day 5. All 3 doses of mizolastine were more effective than placebo in suppressing wheal and flare reactions, and the antihistamine activity was highest at both the 10- and 15-mg dose levels. The effect on the flare reaction appeared within 1 hour, reached a maximum effect 4 hours after administration, and persisted for as long as 24 hours. The relative changes in wheal and flare areas were correlated with mizolastine trough plasma levels on day 5. Safety was satisfactory in all groups. This study confirms that mizolastine is a rapid and potent antihistamine; and its long-lasting effectiveness indicates that a once-daily regimen is acceptable for clinical use.

Comparative wheal and flare study of mizolastine vs terfenadine, cetirizine, loratadine and placebo in healthy volunteers.

1. Mizolastine, a new benzimidazole derivative with potent selective, non-sedative H1-histamine antagonist activity was compared with terfenadine, cetirizine and loratadine using the histamine-induced wheal and flare model in healthy volunteers. 2. Study design was a five way double-blind crossover design using a single dose of mizolastine 10 mg, terfenadine 120 mg, cetirizine 10 mg, loratadine 10 mg and placebo. 3. Histamine tests were performed on 10 occasions up to +24 h after dosing using an intradermal injection of histamine 2 micrograms with concommittant contralateral injection of a saline control. 4. Mizolastine, terfenadine, cetirizine and loratadine significantly (P < 0.001 vs placebo) inhibited the wheal and flare formation starting 1 to 2 h after dosing up to 24 h after dosing. 5. Mizolastine was significantly more active than loratadine on the wheal (P < 0.01) and flare (P < 0.05) inhibition from 3 up to 6 and 8 h respectively, as active as terfenadine on both parameters and as active as cetirizine on wheal inhibition while less active (P < 0.01) than cetirizine on flare inhibition at 2 and 12 h post-dosing.

The effects of lintopride, a 5HT-4 antagonist, on oesophageal motility.

AIM: To evaluate the effects of various doses of lintopride, a new 5HT-4 antagonist with moderate 5HT-3 antagonist properties, on oesophageal body and lower oesophageal sphincter (LOS) motility in humans. METHODS: Eight healthy male volunteers, mean age 22 (19-28) years, without any history of digestive disease or chest pain, were randomized to three doses of lintopride (0.1, 0.3 and 0.5 mg/kg i.v.) and a placebo at 1-week intervals in a double-blind, crossover study. Oesophageal motility was recorded continuously for 4 h after each dose, using perfused catheters inserted at the level of the LOS and in the body of the oesophagus, at 5, 10 and 15 cm from the LOS. Peristalsis was studied during 10 wet swallows, at 30-min intervals (T0-T240 min). RESULTS: The LOS basal pressure (23.3 +/- 2.0 cmH2O; mean +/- s.d.) remained stable after dosing with placebo to T240. After lintopride, LOS basal pressure increased significantly vs. placebo (AUC comparison: 0.1 mg/kg, P = 0.036; 0.3 mg/kg, P = 0.027; 0.5 mg/kg, P = 0.052). In contrast, the duration and extent of LOS relaxation after swallowing was not affected by any of the three doses of lintopride. The amplitude of peristaltic waves in the oesophagus increased significantly at T30 after lintopride 0.3 mg/kg (34.5 cmH2O, P = 0.020) and 0.5 mg/kg (32.5 cmH2O, P = 0.027), at T60 after 0.3 mg/kg (48.8 cmH2O, P = 0.0009) and 0.5 mg/kg (29.1 cmH2O, P = 0.029) and at T90 after 0.3 mg/kg (34.5 cmH2O, P = 0.0018). CONCLUSIONS: Lintopride significantly increased the LOS basal tone without affecting LOS physiological relaxation after swallowing. Peristaltic waves were also enhanced by lintopride.

Effects of mizolastine, a new antihistamine, on psychomotor performance and memory in elderly subjects.

The effects of a single 10 mg dose of the new H1 antihistamine mizolastine on psychomotor performance and memory in the elderly were assessed in a double-blind, cross-over, placebo-controlled study in 15 elderly female volunteers aged 66-77 years, using clemastine 2 mg as a positive control. Objective (critical flicker fusion, choice reaction time, digit symbol substitution, immediate and delayed free recall) and subjective (linear analogue rating scales) assessments were done on each test day before the dose, then 4 and 8 h post-dose. Plasma samples were also collected. A single oral dose of mizolastine within the range of recommended daily therapeutic dosages (10 mg) failed to induce subjective drowsiness and produced no detrimental effects on psychomotor performance or on short-term and long-term memory in the elderly subjects. In contrast, 2 mg clemastine induced significant impairments (decrease in critical flicker fusion, increase in recognition reaction time) in comparison with placebo and mizolastine, although it did not impair memory. The pharmacokinetic profile of mizolastine in the elderly study subjects was similar to that observed in healthy young volunteers. Therefore, it can be concluded that mizolastine 10 mg could be used safely in elderly out-patients as it preserves functions involved in activities of daily living.

Interstitial deletion of the proximal region of the long arm of chromosome 18, del(18q12) a distinct clinical entity? A report of two new cases.

Two unrelated mentally retarded patients were found to have an interstitial deletion of 18q12. They were a 2-year-old, short, macrocephalic and autistic girl, and a 5-year-old boy. Six other liveborn patients with comparable deletion have been so far identified. The common findings are mild dysmorphic features (telecanthus, epicanthal folds, flaring eyebrows, small mouth with thin upper lip), hypotonia, behavioural disorders, mental retardation with speech delay and lack of major malformation.

X-linked hypohidrotic ectodermal dysplasia and t(X;12) in a female.

A female patient with features of hypohidrotic ectodermal dysplasia (HED) was found to be a carrier of a de novo t(X;12) with a breakpoint in Xq13.1. This is the second instance of an X/autosome translocation, with apparently the same X breakpoint, reported in HED.

Multibranched chromosomes in the ICF syndrome: immunodeficiency, centromeric instability, and facial anomalies.

A new patient with the rare ICF syndrome (immunodeficiency, centromeric heterochromatin instability, and facial anomalies) is reported. The six patients previously reported in the literature are reviewed. The main clinical and cytogenetic characteristics of the syndrome are discussed.

Comparison of four methods for digesting food samples for determination of trace levels of cadmium by flameless atomic absorption spectrophotometry.

We compared 4 digestion procedures, namely, sulfuric-nitric acid in an open flask, nitric acid under pressure, sulfuric-nitric acid with refluxing, and nitric-hydrochloric-peroxide with refluxing, for the determination of cadmium by flameless atomic absorption spectrophotometry in 3 foodstuffs: rice, beef, and cream cheese. The foodstuffs were homogenized and divided into several batches for analysis. The results were evaluated using a 2-way cross analysis of variance. The study revealed that the digestion procedure was a highly significant factor (P less than 10(-4] in the analysis of the 3 foods; whereas the nature of the foodstuffs was not significant for rice and meat and only slightly significant (P less than 10(-2] for cream cheese. When the foodstuffs were spiked with a known amount of cadmium, we observed a loss of the metal when the sulfuric-nitric acid procedure in an open flask and the nitric-hydrochloric-peroxide digestion procedure were used. Taken together, the results of the present study indicate that the choice of the reagents used for digestion of foodstuffs is a crucial factor for cadmium determination by flameless atomic absorption spectrophotometry.

6q1 monosomy: a distinctive syndrome.

A female infant with a de novo del 6q14q16.2 and five other patients with del 6q1 reported in the literature allow the delineation of a characteristic syndrome, the main features of which are: severe mental retardation, a round face with full cheeks, upslanting palpebral fissures, a short neck, umbilical hernia, malpositioned feet with syndactyly II-III, and typical dermatoglyphics with an excess of whorls and clinodactyly of the Vth finger.

[Interstitial deletion in the long arm of chromosome 7]. / Délétion interstitielle du bras long du chromosome 7.

An interstitial deletion of 7q (q31.2-q32.3) is reported. Main features of this boy included facial dysmorphy, psychomotor retardation and absence of language.

Maternal origin of a de novo balanced t(21q21q) identified by ets-2 polymorphism.

Molecular investigations were done in a woman with a de novo balanced t(21q21q) discovered because of the birth of a trisomic 21 baby. Polymorphisms detected with probe ets-2 after Msp I digestion showed that both chromosomes 21 involved in the rearrangement were of maternal origin. The most likely hypothesis is that of a disomic 21 oocyte fertilized by a nullisomic 21 sperm.