Accelerated cortical thinning and volume reduction over time in young people at high genetic risk for bipolar disorder.

BACKGROUND: Bipolar disorder (BD) is a familial psychiatric disorder associated with frontotemporal and subcortical brain abnormalities. It is unclear whether such abnormalities are present in relatives without BD, and little is known about structural brain trajectories in those at risk. METHOD: Neuroimaging was conducted at baseline and at 2-year follow-up interval in 90 high-risk individuals with a first-degree BD relative (HR), and 56 participants with no family history of mental illness who could have non-BD diagnoses. All 146 subjects were aged 12-30 years at baseline. We examined longitudinal change in gray and white matter volume, cortical thickness, and surface area in the frontotemporal cortex and subcortical regions. RESULTS: Compared to controls, HR participants showed accelerated cortical thinning and volume reduction in right lateralised frontal regions, including the inferior frontal gyrus, lateral orbitofrontal cortex, frontal pole and rostral middle frontal gyrus. Independent of time, the HR group had greater cortical thickness in the left caudal anterior cingulate cortex, larger volume in the right medial orbitofrontal cortex and greater area of right accumbens, compared to controls. This pattern was evident even in those without the new onset of psychopathology during the inter-scan interval. CONCLUSIONS: This study suggests that differences previously observed in BD are developing prior to the onset of the disorder. The pattern of pathological acceleration of cortical thinning is likely consistent with a disturbance of molecular mechanisms responsible for normal cortical thinning. We also demonstrate that neuroanatomical differences in HR individuals may be progressive in some regions and stable in others.

Dam parity and calf sex affect maternal and neonatal behaviors during the first week postpartum in stabled Maghrebi dairy camels.

Currently, a trend toward the commercialization of dromedary milk associated with recent intensive rearing systems has starting worldwide which impose constraints on animals affecting their behavioral repertoires and welfare status. The aim of this study was to investigate the effects of dam parity and calf sex on parturition, neonatal, and maternal behaviors in stabled Maghrebi dairy camels (Camelus dromedarius). Thirty-six (primiparas N = 10; multiparas N = 26) periparturient females were kept under video surveillance using a digital IR camera and 24-h sessions were chosen to assess calving, maternal, and neonatal behaviors in calving pens. Duration of restlessness, process of giving birth, and expulsion of fetal membranes were assessed. After first suckling, dams and their calves were moved into an individual enclosure to assess maternal behavior at 12 h, 24 h, 48 h, 72 h, and 7d postpartum. Behavior was assessed using a camcorder for 30 min after 1 h of young separation in an adjacent enclosure. Results showed an effect of parity on the duration of the birth process which was longer for primiparous than multiparous camels (P = 0.034). During this stage, primiparous females tended to raise their tails more often (P = 0.054) and spent more time standing (P = 0.001) than multiparous camels. Neonatal behavior was affected by calf sex. Female newborns took less time to raise their heads (P = 0.041) and to stand up (P = 0.048) for the first time and were the earliest to suckle their dams (P = 0.032). Multiparous dams stood up sooner (P = 0.019) after calving and suckled their calves earlier (P = 0.043) than primiparous dams. They emitted more bleats and exhibited more sniffing during the first week postpartum than primiparas. During the first postpartum week, both primiparas and multiparas showed a decrease in the total number of bleats (P < 0.001), low-pitch bleats (P < 0.001), and high-pitch bleats (P < 0.001), in sniffing frequency (P < 0.001) and sniffing duration (P < 0.001). This is the first study to describe in detail the calving, maternal, and neonatal behaviors of dromedary camels and to show the influence of parity and calf sex. Maternal care toward the newborn calf exhibited by a high level of bleating and sniffing activities in the first 2 days suggest that they play an important role in the establishment of mother-young relationship.

Artificial milk preference of newborn lambs is prenatally influenced by transfer of the flavor from the maternal diet to the amniotic fluid.

The present study examined in lambs whether exposure to flavors derived from pregnant mother's diet and transferred to amniotic fluid (AF) could induce a preference for artificial milk containing one of these flavors. To test this hypothesis, cumin was added to the maternal diet in the last month of gestation. Preference for artificial milk containing p-cymene, one of the chemosensory compounds of cumin, was tested within the first two days after birth in maternally deprived lambs born from mothers fed a cumin-flavored diet (Cumin group), or an unflavored diet (Control group). Aromatic profile of AF from cumin-fed mothers was analyzed by GC-MS/MS to determine whether p-cymene could be detected. While the control group avoided the flavored artificial milk on day 1, the Cumin group did not and showed a preference for the cumin-scented formula on day 2. GC-MS/MS profile of AF revealed that four of the main volatile cumin compounds, p-cymene, p-cymenene, ß-pinene and γ-terpinene were present in variable amounts in all samples, p-cymene being the most frequently detected. These findings indicate that newborn lambs can memorize flavors from the mother's diet present in AF and that prenatal experience influences their preference for an artificial milk containing one specific flavor.

Does lambing season affect mother-young relationships and lamb vigor in D'man sheep reared in oases?

Although sheep are known to be seasonal breeders and give birth in winter, not all of them follow this trend. A few breeds can be mated and give birth all year round, meaning that mothers and neonates will have to face contrasting climatic conditions. The aim of this study was to test whether lambing season affects maternal and neonatal behaviors in D'man sheep. During four different lambing seasons (winter, autumn, summer and spring), periparturient ewes (n = 111) and their lambs (n = 213) were kept under 24-h-video surveillance in order to record postpartum behaviors. Mother-young preference was tested around 48 h after parturition. Lamb vigor was studied by the determination of birth weight, early postnatal behavior and rectal temperature at birth and 48 h later. Litter expulsion time was not affected by lambing season, but birth weight was biased against summer and winter born lambs. Ewes provided a higher intensity of care to their offspring in winter: latency for grooming was shorter and time spent grooming was longer compared to lambing in spring and summer (P = 0.01 in all cases). On the other hand, lambs were the most active in spring as they were faster to extend their hind legs (P = 0.01), stand up (P = 0.04) and reach the udder (P = 0.04). Rectal temperature at 48 h was affected by season of birth (P < 0.001) with higher values observed in summer. Glycemia variation between birth and 48 h was the lowest in spring born lambs and plasma levels increased less in spring born lambs than in winter (P < 0.0001), autumn (P < 0.0001) and summer born lambs (P < 0.0001). In the choice test, mothers clearly preferred their own young and no season effect was detected except that in the first minute of the test they spent less time near their own young in winter than in the other seasons (P = 0.04). Lambs also chose their mother successfully without any major effect of the season however, but winter born lambs were the least vocal (P = 0.01). Overall, this study show that maternal care, lamb behavior and vigor vary lightly according to seasons, albeit not in a consistent manner. In conclusion, a season is no more detrimental than another for the onset of mother-young relationships.

Differential effects of oxytocin on olfactory, hippocampal and hypothalamic neurogenesis in adult sheep.

New neurons are continuously added in the dentate gyrus of the hippocampus, the olfactory bulb and the hypothalamus of mammalian brain. In sheep, while the control of adult neurogenesis by the social environment or the photoperiod has been the subject of several studies, its regulation by intrinsic factors, like hormones or neurotransmitters is less documented. We addressed this question by investigating the effects of central oxytocin administration on hippocampal, olfactory and hypothalamic neurogenesis. Endogenous markers, Ki67, Sox2 and DCX were used to assess cell proliferation, progenitor cells density and cell survival respectively in non-gestant ewes receiving a steroid treatment followed by intracerebroventricular injections of either oxytocin or saline. The results showed that oxytocin treatment significantly decreases the density of neuroblasts in the olfactory bulb, increases the density of neuroblasts in the ventromedian nucleus of the hypothalamus while no change is observed in both ventral and dorsal dentate gyrus. In addition, no change in the density of progenitor cells is found in the three neurogenic niches. These findings show for the first time that in females, oxytocin can regulate adult neurogenesis by acting on neuroblasts but not on progenitor cells and that this regulation is region specific.

Disruption of adult olfactory neurogenesis induces deficits in maternal behavior in sheep.

Profound behavioral changes occur in the mother at parturition, a time when the maternal brain undergoes extensive remodeling of neural circuits, especially in olfactory structures. Adult neurogenesis, a form of brain plasticity, could constitute an adaptive response to motherhood. The present study hypothesized that chemical disruption of olfactory neurogenesis would impair the establishment of maternal behavior in sheep. In addition, because ewes are able to learn the olfactory signature of their offspring, we also examined whether disruption of olfactory neurogenesis altered recognition of the familiar lamb. At one month of gestation, ewes received either infusion of the antimitotic drug Ara-C or saline into the lateral ventricles via one-month-long osmotic minipumps. Ara-C infusion dramatically decreased olfactory neurogenesis but spared hippocampal neurogenesis. Mothers exhibiting more than a 70% reduction in olfactory neurogenesis emitted fewer maternal bleats during the first hours after parturition. Reduction of olfactory neurogenesis also negatively affected discrimination of the familiar lamb. Differences in ewes' aggressive behavior toward familiar and alien lambs were observed in sham mothers, but not in mothers with reduced olfactory neurogenesis. In addition, when ewes were given the choice between familiar and unfamiliar anesthetized lambs, so that only olfactory cues were available, mothers with a reduction in neurogenesis greater than 70% were not able to discriminate their own lamb from an alien lamb. These results indicate that adult-born olfactory neurons are to some extent involved in the establishment of maternal behavior in sheep by contributing to the processing of offspring odors.

Structural dysconnectivity of key cognitive and emotional hubs in young people at high genetic risk for bipolar disorder.

Emerging evidence suggests that psychiatric disorders are associated with disturbances in structural brain networks. Little is known, however, about brain networks in those at high risk (HR) of bipolar disorder (BD), with such disturbances carrying substantial predictive and etiological value. Whole-brain tractography was performed on diffusion-weighted images acquired from 84 unaffected HR individuals with at least one first-degree relative with BD, 38 young patients with BD and 96 matched controls (CNs) with no family history of mental illness. We studied structural connectivity differences between these groups, with a focus on highly connected hubs and networks involving emotional centres. HR participants showed lower structural connectivity in two lateralised sub-networks centred on bilateral inferior frontal gyri and left insular cortex, as well as increased connectivity in a right lateralised limbic sub-network compared with CN subjects. BD was associated with weaker connectivity in a small right-sided sub-network involving connections between fronto-temporal and temporal areas. Although these sub-networks preferentially involved structural hubs, the integrity of the highly connected structural backbone was preserved in both groups. Weaker structural brain networks involving key emotional centres occur in young people at genetic risk of BD and those with established BD. In contrast to other psychiatric disorders such as schizophrenia, the structural core of the brain remains intact, despite the local involvement of network hubs. These results add to our understanding of the neurobiological correlates of BD and provide predictions for outcomes in young people at high genetic risk for BD.

Rare DNA variants in the brain-derived neurotrophic factor gene increase risk for attention-deficit hyperactivity disorder: a next-generation sequencing study.

Attention-deficit hyperactivity disorder (ADHD) is a prevalent and highly heritable disorder of childhood with negative lifetime outcomes. Although candidate gene and genome-wide association studies have identified promising common variant signals, these explain only a fraction of the heritability of ADHD. The observation that rare structural variants confer substantial risk to psychiatric disorders suggests that rare variants might explain a portion of the missing heritability for ADHD. Here we believe we performed the first large-scale next-generation targeted sequencing study of ADHD in 152 child and adolescent cases and 188 controls across an a priori set of 117 genes. A multi-marker gene-level analysis of rare (<1% frequency) single-nucleotide variants (SNVs) revealed that the gene encoding brain-derived neurotrophic factor (BDNF) was associated with ADHD at Bonferroni corrected levels. Sanger sequencing confirmed the existence of all novel rare BDNF variants. Our results implicate BDNF as a genetic risk factor for ADHD, potentially by virtue of its critical role in neurodevelopment and synaptic plasticity.

[Pathophysiology of hemorragic shock]. / Physiopathologie du choc hémorragique.

This review addresses the pathophysiology of hemorrhagic shock, a condition produced by rapid and significant loss of intravascular volume, which may lead to hemodynamic instability, decreases in oxygen delivery, decreased tissue perfusion, cellular hypoxia, organ damage, and death. The initial neuroendocrine response is mainly a sympathetic activation. Haemorrhagic shock is associated altered microcirculatory permeability and visceral injury. It is also responsible for a complex inflammatory response associated with hemostasis alteration.

Interhemispheric white matter integrity in young people with bipolar disorder and at high genetic risk.

BACKGROUND: White matter (WM) impairments have been reported in patients with bipolar disorder (BD) and those at high familial risk of developing BD. However, the distribution of these impairments has not been well characterized. Few studies have examined WM integrity in young people early in the course of illness and in individuals at familial risk who have not yet passed the peak age of onset. METHOD: WM integrity was examined in 63 BD subjects, 150 high-risk (HR) individuals and 111 participants with no family history of mental illness (CON). All subjects were aged 12 to 30 years. RESULTS: This young BD group had significantly lower fractional anisotropy within the genu of the corpus callosum (CC) compared with the CON and HR groups. Moreover, the abnormality in the genu of the CC was also present in HR participants with recurrent major depressive disorder (MDD) (n = 16) compared with CON participants. CONCLUSIONS: Our findings provide important validation of interhemispheric abnormalities in BD patients. The novel finding in HR subjects with recurrent MDD - a group at particular risk of future hypo/manic episodes - suggests that this may potentially represent a trait marker for BD, though this will need to be confirmed in longitudinal follow-up studies.

Abnormalities in left inferior frontal gyral thickness and parahippocampal gyral volume in young people at high genetic risk for bipolar disorder.

BACKGROUND: Fronto-limbic structural brain abnormalities have been reported in patients with bipolar disorder (BD), but findings in individuals at increased genetic risk of developing BD have been inconsistent. We conducted a study in adolescents and young adults (12-30 years) comparing measures of fronto-limbic cortical and subcortical brain structure between individuals at increased familial risk of BD (at risk; AR), subjects with BD and controls (CON). We separately examined cortical volume, thickness and surface area as these have distinct neurodevelopmental origins and thus may reflect differential effects of genetic risk. METHOD: We compared fronto-limbic measures of grey and white matter volume, cortical thickness and surface area in 72 unaffected-risk individuals with at least one first-degree relative with bipolar disorder (AR), 38 BD subjects and 72 participants with no family history of mental illness (CON). RESULTS: The AR group had significantly reduced cortical thickness in the left pars orbitalis of the inferior frontal gyrus (IFG) compared with the CON group, and significantly increased left parahippocampal gyral volume compared with those with BD. CONCLUSIONS: The finding of reduced cortical thickness of the left pars orbitalis in AR subjects is consistent with other evidence supporting the IFG as a key region associated with genetic liability for BD. The greater volume of the left parahippocampal gyrus in those at high risk is in line with some prior reports of regional increases in grey matter volume in at-risk subjects. Assessing multiple complementary morphometric measures may assist in the better understanding of abnormal developmental processes in BD.

Neuropsychological and social cognitive function in young people at genetic risk of bipolar disorder.

BACKGROUND: Impairments in key neuropsychological domains (e.g. working memory, attention) and social cognitive deficits have been implicated as intermediate (endo) phenotypes for bipolar disorder (BD), and should therefore be evident in unaffected relatives. METHOD: Neurocognitive and social cognitive ability was examined in 99 young people (age range 16-30 years) with a biological parent or sibling diagnosed with the disorder [thus deemed to be at risk (AR) of developing BD], compared with 78 healthy control (HC) subjects, and 52 people with a confirmed diagnosis of BD. RESULTS: Only verbal intelligence and affective response inhibition were significantly impaired in AR relative to HC participants; the BD participants showed significant deficits in attention tasks compared with HCs. Neither AR nor BD patients showed impairments in general intellectual ability, working memory, visuospatial or language ability, relative to HC participants. Analysis of BD-I and BD-II cases separately revealed deficits in attention and immediate memory in BD-I patients (only), relative to HCs. Only the BD (but not AR) participants showed impaired emotion recognition, relative to HCs. CONCLUSIONS: Selective cognitive deficits in the capacity to inhibit negative affective information, and general verbal ability may be intermediate markers of risk for BD; however, the extent and severity of impairment in this sample was less pronounced than has been reported in previous studies of older family members and BD cases. These findings highlight distinctions in the cognitive profiles of AR and BD participants, and provide limited support for progressive cognitive decline in association with illness development in BD.

The atypical antipsychotics clozapine and olanzapine promote down-regulation and display functional selectivity at human 5-HT7 receptors.

BACKGROUND AND PURPOSE: Classically, ligands of GPCRs have been classified primarily upon their affinity and efficacy to activate a signal transduction pathway. Recent reports indicate that the efficacy of a particular ligand can vary depending on the receptor-mediated response measured (e.g. activating G proteins, other downstream responses, internalization). Previously, we reported that inverse agonists induce both homo- and heterologous desensitization, similar to agonist stimulation, at the Gs -coupled 5-HT7 receptor. The primary objective of this study was to determine whether different inverse agonists at the 5-HT7 receptor also induce internalization and/or degradation of 5-HT7 receptors. EXPERIMENTAL APPROACH: HEK293 cells expressing 5-HT7(a, b or d) receptors were pre-incubated with 5-HT, clozapine, olanzapine, mesulergine or SB269970 and their effects upon receptor density, AC activity, internalization, recruitment of ß-arrestins and lysosomal trafficking were measured. KEY RESULTS: The agonist 5-HT and three out of four inverse agonists tested increased internalization independently of ß-arrestin recruitment. Among these, only the atypical antipsychotics clozapine and olanzapine promoted lysosomal sorting and reduced 5-HT7 receptor density (∼60% reduction within 24 h). Inhibition of lysosomal degradation with chloroquine blocked the clozapine- and olanzapine-induced down-regulation of 5-HT7 receptors. Incubation with SB269970 decreased both 5-HT7(b) constitutive internalization and receptor density but increased 5-HT7(d) receptor density, indicating differential ligand regulation among the 5-HT7 splice variants. CONCLUSIONS AND IMPLICATIONS: Taken together, we found that various ligands differentially activate regulatory processes governing receptor internalization and degradation in addition to signal transduction. Thus, these data extend our understanding of functional selectivity at the 5-HT7 receptor.

Chronic delivery of α-melanocyte-stimulating hormone in rat hypothalamus using albumin-alginate microparticles: effects on food intake and body weight.

Chronic delivery of neuropeptides in the brain is a useful experimental approach to study their long-term effects on various biological parameters. In this work, we tested albumin-alginate microparticles, as a potential delivery system, to study if continuous release in the hypothalamus of α-melanocyte-stimulating hormone (α-MSH), an anorexigenic neuropeptide, may result in a long-term decrease in food intake and body weight. The 2-week release of α-MSH from peptide-loaded particles was confirmed by an in vitro assay. Then, daily food intake and body weight were studied for 18 days in rats injected bilaterally into the paraventricular hypothalamic nucleus with particles loaded or not with α-MSH. A decrease in body weight gain, persisting throughout the study, was found in rats injected with α-MSH-charged particles as compared with rats receiving non-charged particles and with rats injected with the same dose of α-MSH in solution. Food intake was significantly decreased for 3 days in rats receiving α-MSH-loaded particles and it was not followed by the feeding rebound effect which appears after food restriction. The presence of α-MSH-loaded particles in the hypothalamus was confirmed by immunohistochemistry. In conclusion, our study validates albumin-alginate microparticles as a new carrier system for long-term delivery of neuropeptides in the brain and demonstrates that chronic delivery of α-MSH in the hypothalamus results in a prolonged suppression of food intake and a decrease of body weight gain in rats.

Dentifrice pH but not consistency may affect fluoride uptake in plaque.

OBJECTIVE: Test the ability of acidic fluoridated solutions to enhance fluoride (F) bound on bacteria (1) and the effect of dentifrice consistency on plaque fluid F uptake (2). METHODS: (1) Streptococcus mutans isolates were grown in BHI medium (37°C/18h). Bacteria were washed either with EDTA or CaCl2 both at 1mM to remove or add calcium, respectively. Pellets were incubated with 12 mM NaF at pH 4.5 or 7 for 1 min and F was quantified in the lysates and supernatants with the electrode, after HMDS-facilitated diffusion. (2) A randomized, double-blind, crossover clinical trial was performed in three phases with nineteen adults (20-35 years) that used one of the dentifrices: commercial toothpaste (1100 ppm F, pH7.0 and conventional viscosity (Sorriso Fresh(®))); experimental liquid dentifrice (ELD) (1100 ppm F, pH7.0 and low viscosity [1.1% carboxymethylcellulose (CMC)]) and ELD (1100 ppm F and high viscosity pH7.0 (2.2% CMC)). F concentration in plaque fluid was analyzed using an inverted F electrode. RESULTS: (1) Significantly higher F amounts were detected in the lysates of bacteria incubated with NaF solution at pH4.5 compared to the supernatant, which was not seen at pH7.0, being this effect calcium-dependent. (2) Significantly higher F concentrations in plaque fluid were found 1h after toothbrushing compared to 12h, but no significant differences were seen among the toothpastes. CONCLUSIONS: F at low pH binds more efficiently to S. mutans than at neutral pH and dentifrice viscosity does not interfere in plaque fluid fluoride incorporation. CLINICAL SIGNIFICANCE: pH of the dentifrice but not consistency may be important to F uptake in plaque.

Direct imaging of p-n junction in core-shell GaN wires.

While core-shell wire-based devices offer a promising path toward improved optoelectronic applications, their development is hampered by the present uncertainty about essential semiconductor properties along the three-dimensional (3D) buried p-n junction. Thanks to a cross-sectional approach, scanning electron beam probing techniques were employed here to obtain a nanoscale spatially resolved analysis of GaN core-shell wire p-n junctions grown by catalyst-free metal-organic vapor phase epitaxy on GaN and Si substrates. Both electron beam induced current (EBIC) and secondary electron voltage constrast (VC) were demonstrated to delineate the radial and axial junction existing in the 3D structure. The Mg dopant activation process in p-GaN shell was dynamically controlled by the ebeam exposure conditions and visualized thanks to EBIC mapping. EBIC measurements were shown to yield local minority carrier/exciton diffusion lengths on the p-side (∼57 nm) and the n-side (∼15 nm) as well as depletion width in the range 40-50 nm. Under reverse bias conditions, VC imaging provided electrostatic potential maps in the vicinity of the 3D junction from which acceptor Na and donor Nd doping levels were locally determined to be Na = 3 × 10(18) cm(-3) and Nd = 3.5 × 10(18) cm(-3) in both the axial and the radial junction. Results from EBIC and VC are in good agreement. This nanoscale approach provides essential guidance to the further development of core-shell wire devices.

Inhibition of phosphodiesterase-3 by levosimendan is sufficient to account for its inotropic effect in failing human heart.

BACKGROUND AND PURPOSE: Levosimendan is known as a calcium sensitizer, although it is also known to inhibit PDE3. We aimed to isolate each component and estimate their contribution to the increased cardiac contractility induced by levosimendan. EXPERIMENTAL APPROACH: Contractile force was measured in electrically stimulated ventricular strips from explanted failing human hearts and left ventricular strips from normal male Wistar rats. PDE activity was measured in a two-step PDE activity assay on failing human ventricle. KEY RESULTS: Levosimendan exerted a positive inotropic effect (PIE) reaching maximum at 10(-5) M in ventricular strips from failing human hearts. In the presence of the selective PDE3 inhibitor cilostamide, the PIE of levosimendan was abolished. During treatment with a PDE4 inhibitor and a supra-threshold concentration of isoprenaline, levosimendan generated an amplified inotropic response. This effect was reversed by ß-adrenoceptor blockade and undetectable in strips pretreated with cilostamide. Levosimendan (10(-6) M) increased the potency of ß-adrenoceptor agonists by 0.5 log units in failing human myocardium, but not in the presence of cilostamide. Every inotropic response to levosimendan was associated with a lusitropic response. Levosimendan did not affect the concentration-response curve to calcium in rat ventricular strips, in contrast to the effects of a known calcium sensitizer, EMD57033 [5-(1-(3,4-dimethoxybenzoyl)-1,2,3,4-tetrahydroquinolin-6-yl)-6-methyl-3,6-dihydro-2H-1,3,4-thiadiazin-2-one]. PDE activity assays confirmed that levosimendan inhibited PDE3 as effectively as cilostamide. CONCLUSIONS AND IMPLICATIONS: Our results indicate that the PDE3-inhibitory property of levosimendan was enough to account for its inotropic effect, leaving a minor, if any, effect to a calcium-sensitizing component.

[Etiopathogeny of the delusion of pregnancy using a literature review: Role of hyperprolactinemia and application of the theory of abductive inference]. / Étiopathogénie des délires de grossesse à partir d'une revue de la littérature : rôle de l'hyperprolactinémie et application de la théorie de l'inférence abductive.

INTRODUCTION: Delusions of pregnancy are not well known. The delusion of pregnancy is defined as the belief of being pregnant despite factual evidence to the contrary. The clinical picture is heterogeneous (duration, mechanisms, topics and pre-existing psychiatric disorders). Several causes have been proposed to explain the occurrence of the delusions of pregnancy: cenesthetic theory, hyperprolactinemia, polydipsia and psychodynamic conflicts. Hyperprolactinemia is an interesting hypothesis (physiologic increase during pregnancy and similar manifestations in the course of gestation). The abductive inference theory is a probabilistic model that can clarify the role of hyperprolactinemia in the delusions of pregnancy. The purpose of this paper is to study the role of hyperprolactinemia in the delusions of pregnancy using a literature review. The abductive inference model is used to specify the etiopathogeny of this pathology. METHODS: A research in Medline, Sudoc, BIUM and PSYLINK using the following key words "delusional pregnancy" or "delusion of pregnancy" and "hyperprolactinemia" was conducted. RESULTS: Three articles (case reports) about delusions of pregnancy associated with hyperprolactinemia were found. The cases have some similitudes. First of all, they have similar chronology: delusion appears at the same time as hyperprolactinemia and resolves with biological normalization. Secondly, hyperprolactinemia is always caused by a neuroleptic (haloperidol, olanzapine, risperidone). Concerning pre-existing disorders, a psychiatric pathology for each case was found (schizophrenia, schizo-affective disorder and bipolar disorder). Chronology, reproductivity and reversibility are strong arguments to involve hyperprolactinemia in the delusions of pregnancy (Bradford Hill criteria). Furthermore, this association is biologically plausible: physiologic increase during pregnancy (gestational signal), similar symptoms to those during pregnancy and the role in parental behavior (parental signal). Nevertheless, not everyone with hyperprolactinemia will develop a delusion of pregnancy; the interaction is more complex (non linear); the theory of abductive inference clarifies this relationship. THEORY OF ABDUCTIVE INFERENCE: Abductive inference is a probabilistic model whose goal is to explain the occurrence of delusional beliefs. The first factor is the abnormal data. The second factor is the cognitive process (abductive inference), which uses Bayes' theorem to select the most likely hypothesis to explain the abnormal data. In the delusion of pregnancy, abnormal data is the hyperprolactinemia, signal of gestation without pregnancy. Hypotheses in order to explain this signal are then produced (pregnancy or no pregnancy). In the second part, probabilities associated with each hypothesis, given the hyperprolactinemia, are compared. Since hyperprolactinemia is a gestational signal, the pregnancy hypothesis is most likely. Probabilities associated with each hypothesis without taking hyperprolactinemia into account are compared (prior probability). Since any element of reality indicates a pregnancy, the absence of pregnancy is most likely. In the last step, the posterior probability is calculated using the first two comparisons. The probability associated with the pregnancy hypothesis (taking into account hyperprolactinemia) is relatively higher than the probability associated with the no-pregnancy hypothesis (without taking into account hyperprolactinemia). So, the posterior probability associated with the pregnancy hypothesis is more likely than the posterior probability associated with the no-pregnancy hypothesis. Thus, the subject believes in a pregnancy. CONCLUSION: The research and the treatment of hyperprolactinemia must be conducted when faced with a delusion of pregnancy.

Inhibition of tooth erosion by milk containing different fluoride concentrations: an in vitro study.

OBJECTIVES: This in vitro study assessed the effect of milk containing different fluoride concentrations on tooth erosion. METHODS: Bovine enamel and root dentine specimens were treated with: (1) bovine whole milk with 0ppm F; (2) 2.5ppm F; (3) 5ppm F; (4) 10ppm F (all after erosion); (5) whole milk with 0ppm F (before erosion); (6) NaF (0.05% F, positive control, after erosion) or (7) 0.9% NaCl (negative control, after erosion). The specimens were submitted to pH cycles (4× 90s in soft drink) and treatments for 5 days. The specimens were immersed in the treatment solutions for 1min (only at the first cycle each day) with further exposition to 1:1 milk:saliva slurry for 10min. The tooth loss was measured using a contact profilometer and statistically analysed (p<0.05). RESULTS: Rinsing with milk before erosive challenge significantly reduced tooth loss compared to negative control (67% and 24% reduction in dentine and enamel loss, respectively) and to milk after erosive challenge, only for dentine. The addition of fluoride to milk also reduced tooth loss compared to negative control, but with no significant differences among fluoride concentrations for enamel and dentine (µm), respectively: 0ppm (3.63±0.04 and 2.51±0.53), 2.5ppm F (2.86±0.42 and 1.96±0.47), 5ppm F (2.81±0.27 and 1.77±0.44), 10ppm F (2.03±0.49 and 1.68±0.59). There was a negative and significant correlation between [F] and the tooth loss. CONCLUSIONS: Daily rinse with milk containing F is able to reduce both enamel and dentine erosion in vitro. CLINICAL SIGNIFICANCE: Since the prevalence of dental erosion is steadily increasing, rinse with milk or its derivate might be an important strategy to reduce the progression of tooth erosion.

Total fluoride intake and excretion in children up to 4 years of age living in fluoridated and non-fluoridated areas.

Fractional fluoride retention is important during the early years of life when considering the risk of development of dental fluorosis. This study aimed to measure fractional fluoride retention in young children. The objectives were to investigate the relationships between fractional fluoride retention and total daily fluoride intake, age, and body mass index (BMI). Twenty-nine healthy children, up to 4 yr of age, participated; 14 lived in a fluoridated area (0.64 µg ml(-1) of fluoride in drinking water) and 15 lived in a non-fluoridated area (0.04 µg ml(-1) of fluoride in drinking water). The total daily fluoride intake of each child was calculated from the daily dietary fluoride intake and toothpaste ingestion (if fluoride toothpaste was used). Total daily fluoride excretion was measured by collecting voided urine and faeces over a 24-h period, and fractional fluoride retention was calculated by dividing the amount of fluoride retained in the body (total daily fluoride intake minus total daily fluoride excretion) by the total daily fluoride intake. Nine children were excluded from data analysis because of suspected invalid samples. Mean (range) fractional fluoride retention for the remaining 20 children was 0.61 (0.06-0.98). There were no statistically significant correlations between fractional fluoride retention and either age or BMI. However, fractional fluoride retention was correlated with total daily fluoride intake: fractional fluoride retention = 1 - exp (-C × total daily fluoride intake), where C = 28.75 (95% CI = 19.75-37.75). The wide variation in fluoride retention in young children could have important implications when recommendations for fluoride use are being considered.