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Concentric and eccentric contractions show different patterns of neural activity at both peripheral and cortical levels, which are thought to influence the perception of action properties such as the weight of objects moved by others. The aim of this study was to investigate how the type of muscle contraction influences weight estimation during action observation. Forty‐eight volunteers completed the Main experiment and the Control experiment. In the Main experiment, they performed a weight discrimination video task in which they watched videos of an actor moving two objects, a comparison, and a reference box, executing concentric or eccentric contractions and they had to indicate which box was the heaviest. Sensitivity analysis and psychometric functions were used to analyse the data. In the Control experiment, observers judged the actor's effort in moving the boxes. The results of the Main experiment showed that the weight discrimination sensitivity was higher in the eccentric condition for the light boxes. Conversely, for the heaviest boxes, discrimination sensitivity was higher in the concentric condition. These results were confirmed by the psychometric function analysis. The control experiment showed that the perceived difference in effort between the comparison and reference stimuli was greater in the eccentric than in the concentric condition for light stimuli. These results showed that the ability to evaluate the weight of the object involved in the observed action was influenced by the type of contraction and the amount of weight. The effort attributed to the actor influenced the observer's perception. [ABSTRACT FROM AUTHOR]

Summary: Insomnia disorder is considered as a stress‐related disorder associated with hyperarousal, stress and emotion dysregulation and the instability of the 'flip‐flop' switch system. The orexinergic system is well known for its key role in sleep and arousal processes but also in the allostatic system regulating stress and emotions and may thus be of major interest for insomnia and its treatment. Accordingly, we discuss the potential role of orexins on sleep processes, brain systems modulating stress and emotions with potential implications for insomnia pathophysiology. We reviewed available data on the effect of dual orexin receptor antagonists (DORAs) on sleep and brain systems modulating stress/emotions with implications for insomnia treatment. We present our findings as a narrative review. Few data in animals and humans have reported that disrupted sleep and insomnia may be related to the overactivation of orexinergic system, while some more consistent data in humans and animals reported the overactivation of orexins in response to acute stress and in stress‐related disorders. Taken together these findings may let us hypothesise that an orexins overactivation may be associated with stress‐related hyperarousal and the hyperactivation of arousal‐promoting systems in insomnia. On the other hand, it is possible that by rebalancing orexins with DORAs we may regulate both sleep and allostatic systems, in turn, contributing to a 'switch off' of hyperarousal in insomnia. Nevertheless, more studies are needed to clarify the role of the orexin system in insomnia and to evaluate the effects of DORAs on sleep, stress and emotions regulating systems. [ABSTRACT FROM AUTHOR]

Introduction: Research shows there is a significant increase in gingival inflammation during pregnancy. This study was conducted to determine if an oral health intervention (OHI), including oral hygiene education delivered by nurse‐led staff and an advanced over‐the‐counter (OTC) oral home care regimen, improved gingival inflammation in pregnant women with moderate‐to‐severe gingivitis compared with a standard oral hygiene control group. Methods: This was a multicenter, randomized, controlled, single‐masked, parallel group clinical trial conducted in obstetrics clinics of 2 medical centers. A total of 750 pregnant women between 8 and 24 weeks of pregnancy with at least 20 natural teeth and moderate‐to‐severe gingivitis (>30 intraoral bleeding sites) were enrolled. Participants were randomized to either the OHI group, which included oral hygiene instructions supplemented with an educational video and advanced OTC antibacterial/mechanical oral hygiene products, or the control group receiving oral hygiene instructions and standard products. Both groups received oral hygiene instructions from nurse‐led staff. Experienced, masked examiners measured whole mouth gingival index (GI) and periodontal probing depths (PDs) at baseline and months 1, 2, and 3. Results: Participants enrolled in this study presented with moderate‐to‐severe gingivitis at baseline. Both the OHI and control groups exhibited significant reductions in GI (P <.001) and PD (P <.03) from baseline that persisted throughout the study period. The OHI group exhibited modest, yet statistically greater, reductions in GI (P ≤.044) compared with the control at all time points. The reduction in PD directionally favored the OHI group, but between‐group differences were small (<0.03 mm) and not statistically significant (P >.18). Discussion: Significant gingivitis was prevalent among participants in this study and identifies an opportunity to improve gingival health during pregnancy by providing oral health education during the course of prenatal care when coupled with an advanced OTC oral hygiene regimen. [ABSTRACT FROM AUTHOR]

Several formulations of artificial saliva have been used for corrosion studies. The present work focuses on the effect of different saliva formulations on the composition of the surface film formed on CuZn37 brass alloy by X‐ray photoelectron spectroscopy (XPS), in order to clarify the corrosion mechanism of historical brass wind instruments when used. Three different saliva solutions, Darvell (D), Carter‐Brugirard (C‐B) and SALMO, were selected. They differ for the content of the organic compounds. The XPS results show the presence of a film made of CuSCN and zinc‐phosphate on the brass exposed to C‐B and SALMO. In the case of samples exposed to D formulation, phosphorus is not revealed, a decrease in the zinc content in the film is detected and the S 2p shows the presence of a second component together with the one ascribed to CuSCN. A comparison with the results obtained on the pure metals in the presence of the organic compounds suggests that the formation of zinc and copper complexes may lead to thin and less protective surface film and thus to the observed high corrosion rates. [ABSTRACT FROM AUTHOR]

The composition of natural saliva is strongly variable and unstable outside the oral cavity, therefore corrosion tests are usually performed in artificial saliva solutions. In this study the effect of the composition of various saliva solutions on the corrosion behavior of a CuZn37 alloy, exposed for 1, 3, and 16 h to the solutions, is investigated by using electrochemical measurements, optical microscopy, and X‐ray photoelectron spectroscopy (XPS). The solutions investigated in this study are: Darvell, Carter‐Brugirard, and SALMO, selected for their composition that mainly differs in the organic compounds' content. Electrochemical measurements show that the open circuit potential and the polarization resistance increase with exposure time in the solutions, indicating a decrease in the corrosion rate. The corrosion rate (µm/year) in the Darvell solution is found to be two times higher than the other artificial saliva formulations and varies in the order: Darvell > Carter‐Brugirard > SALMO. These data suggest that the presence of different organic compounds might limit the formation of a stable protective surface film as confirmed by XPS surface analyses. [ABSTRACT FROM AUTHOR]

A 10‐year‐old cat was presented with a 3‐months history of recurrent episodes of circling to the right with increasing frequency. Physical and blood examination results were unremarkable. Neurological examination showed right circling and non‐measurable menace response; both eyes were absent since 2 months of age. A right forebrain disorder was suspected, possibly caused by vascular, neoplastic or infective/inflammatory disease. An MRI scan excluded brain lesions and revealed an incidental left middle ear infection. A functional lesion in a postictal phase following focal epileptic seizure was considered; however, the right circling behaviour worsened despite phenobarbital treatment. Aggression against owners and co‐habiting cats was also reported. Obsessive‐compulsive disorder was suspected after excluding other compulsive behaviours through a behavioural evaluation. Fluoxetine (0.5 mg/kg, every 24 hours) reduced the intensity and frequency of the circling behaviour by approximately 50% within 25 days. In cats showing compulsive lateralised circling, behavioural disorders are a key differential diagnosis. [ABSTRACT FROM AUTHOR]

Purpose: To explore Italian psychiatrists' attitudes toward the off‐label use of second generation antipsychotics (SGAs) in patients with substance use disorder and psychotic symptoms. Design and Methods: A sample of 300 Italian psychiatrists associated with the Italian Society of Neuropsychopharmacology was randomly selected to complete a survey about the off‐label prescription of SGAs. Findings: Oral aripiprazole (32.7%), olanzapine (30.2%), and quetiapine (25.2%) were considered "appropriate." Long‐acting antipsychoticss were generally considered "inappropriate." Practice Implications: Our findings reflect a substantial level of uncertainty and a lack of coherent clinical guidance within the realm of dual diagnosis treatment. Therefore, they emphasize the need to develop specific guidelines to improve the management of pharmacotherapy among this population. [ABSTRACT FROM AUTHOR]

Fetal growth restriction (FGR), broadly defined as a fetus not reaching its growth potential, is caused by maternal, fetal and placental conditions that contribute to suboptimal placental perfusion, fetal nutrition and, in some cases, oxygenation1,2. In an attempt to distinguish between FGR and constitutionally small fetuses, consensus-based definitions for both early- and late-onset FGR were established through a Delphi procedure12 and recently adopted by the ISUOG FGR guideline6. For instance, uterine artery Doppler was included in the Delphi definition as a contributory parameter for the diagnosis of early FGR despite its low sensitivity (25.8%) in predicting composite adverse pregnancy outcomes15. In view of these findings, we believe that the 10 SP th sp percentile EFW threshold seems to be the most suitable cut-off for the diagnosis of FGR and is currently the most commonly applied threshold for FGR diagnosis in several national guidelines11. [Extracted from the article]

Background and Aim: The health care and social assistance industry has one of the highest rates of non‐fatal occupational injuries and illnesses, both in California and nationally. In the coming years, the health care industry will face added pressure as both the population and workforce age. The aim of this study is to identify targeted populations that may benefit from interventions to prevent future injuries, keep the workforce healthy, and decrease injury‐related costs. Methods: This retrospective study analyzed California workers' compensation claims from 2009 to 2018 in the health care and social assistance industry. Results: Across the four industry sub‐groups, the highest number of claims came from hospitals (n = 243 605; 38.9%), followed by ambulatory care (n = 187 010; 29.9%), nursing/residential care (n = 133 206; 21.3%), and social assistance (n = 62 211; 9.9%). Nursing/residential care settings reported the highest proportion of both lifting injuries (15.8%) and low back injuries (16.9%) as compared to the other settings. Across all settings within California, nurses had the highest proportion of injuries (22.1%), followed by aides/assistants (20.4%), services staff (13.2%), administrative staff (11.0%), and technicians (10.3%). Thirty‐five of California's counties had an increasing rate of population‐adjusted claims during the study period. Conclusion: This study found that while hospitals have the highest number of injuries, ambulatory care employee injuries are increasing. Employees involved in non‐patient care tasks, such as those working in facility service roles, would likely benefit from additional injury prevention interventions. [ABSTRACT FROM AUTHOR]

Action observation combined with proprioceptive stimulation able to induce a kinesthetic illusion of movement (AO‐KI) was shown to elicit a plastic increase in primary motor cortex (M1) excitability, with promising applications in rehabilitative interventions. Nevertheless, the known individual variability in response to combined stimulation protocols limits its application. The aim of this study was to examine whether a relationship exists between changes in M1 excitability during AO‐KI and the long‐lasting changes in M1 induced by AO‐KI. Fifteen volunteers received a conditioning protocol consisting in watching a video showing a thumb‐opposition movement and a simultaneous proprioceptive stimulation that evoked an illusory kinesthetic experience of their thumbs closing. M1 excitability was evaluated by means of single‐pulse transcranial magnetic stimulation before, DURING the conditioning protocol, and up to 60 min AFTER it was administered. M1 excitability significantly increased during AO‐KI with respect to a rest condition. Furthermore, AO‐KI induced a long‐lasting increase in M1 excitability up to 60 min after administration. Finally, a significant positive correlation appeared between M1 excitability changes during and after AO‐KI; that is, participants who were more responsive during AO‐KI showed greater motor cortical activity changes after it. These findings suggest that M1 response during AO‐KI can be considered a neurophysiological marker of individual responsiveness to the combined stimulation since it was predictive of its efficacy in inducing long‐lasting M1 increase excitability. This information would allow knowing in advance whether an individual will be a responder to AO‐KI. [ABSTRACT FROM AUTHOR]

Key points: The combination of action observation (AO) and a peripheral nerve stimulation has been shown to induce plasticity in the primary motor cortex (M1). However, using peripheral nerve stimulation little is known about the specificity of the sensory inputs.The current study, using muscle tendon vibration to stimulate muscle spindles and transcranial magnetic stimulation to assess M1 excitability, investigated whether a proprioceptive stimulation leading to a kinaesthetic illusion of movement (KI) was able to evoke M1 plasticity when combined with AO.M1 excitability increased immediately and up to 60 min after AO‐KI stimulation as a function of the vividness of the perceived illusion, and only when the movement directions of AO and KI were congruent.Tactile stimulation coupled with AO and KI alone were not sufficient to induce M1 plasticity.This methodology might be proposed to subjects during a period of immobilization to promote M1 activity without requiring any voluntary movement. Physical practice is crucial to evoke cortical plasticity, but motor cognition techniques, such as action observation (AO), have shown their potentiality in promoting it when associated with peripheral afferent inputs, without the need of performing a movement. Here we investigated whether the combination of AO and a proprioceptive stimulation, able to evoke a kinaesthetic illusion of movement (KI), induced plasticity in the primary motor cortex (M1). In the main experiment, the role of congruency between the observed action and the illusory movement was explored together with the importance of the specificity of the sensory input modality (proprioceptive vs. tactile stimulation) to induce plasticity in M1. Further, a control experiment was carried out to assess the role of the mere kinaesthetic illusion on M1 excitability. Results showed that the combination of AO and KI evoked plasticity in M1, with an increase of the excitability immediately and up to 60 min after the conditioning protocol (P always <0.05). Notably, a significant increase in M1 excitability occurred only when the directions of the observed and illusory movements were congruent. Further, a significant positive linear relationship was found between the amount of M1 excitability increase and the vividness of the perceived illusion (P = 0.03). Finally, the tactile stimulation coupled with AO was not sufficient to induce changes in M1 excitability as well as the KI alone. All these findings indicate the importance of combining different sensory input signals to induce plasticity in M1, and that proprioception is the most suitable sensory modality to allow it. Key points: The combination of action observation (AO) and a peripheral nerve stimulation has been shown to induce plasticity in the primary motor cortex (M1). However, using peripheral nerve stimulation little is known about the specificity of the sensory inputs.The current study, using muscle tendon vibration to stimulate muscle spindles and transcranial magnetic stimulation to assess M1 excitability, investigated whether a proprioceptive stimulation leading to a kinaesthetic illusion of movement (KI) was able to evoke M1 plasticity when combined with AO.M1 excitability increased immediately and up to 60 min after AO‐KI stimulation as a function of the vividness of the perceived illusion, and only when the movement directions of AO and KI were congruent.Tactile stimulation coupled with AO and KI alone were not sufficient to induce M1 plasticity.This methodology might be proposed to subjects during a period of immobilization to promote M1 activity without requiring any voluntary movement. [ABSTRACT FROM AUTHOR]

Summary: Background: Cord blood adiponectin and leptin concentrations are associated with birth weight and adiposity. Birth size and rate of infant weight gain are associated with future obesity risk. However, it is unclear whether biomarkers reflecting the intrauterine environment are predictive of infant prospective body composition change. Objectives: To examine whether cord blood adiponectin and leptin are predictive of neonatal adiposity and fat mass (FM) accrual to 3 months of age. Methods: Participants (n = 36) were healthy African American infants. Leptin and adiponectin concentrations were measured in umbilical cord blood. At 2 weeks and 3 months, infant body composition was assessed via air displacement plethysmography. Weight‐for‐length z‐scores (WLZ) were calculated using World Health Organization standards. Multiple linear regression was used to examine associations of cord blood adiponectin and leptin with birth WLZ; WLZ, FM and fat‐free mass at 2 weeks, and the conditional change in these variables from 2 weeks to 3 months (body composition at 3 months adjusted for body composition at 2 weeks). Results: Adiponectin was positively associated with FM at 2 weeks (r = 0.45, P < 0.01), but inversely associated with conditional FM change from 2 weeks to 3 months of age (r = −0.38, P < 0.05). Leptin was not significantly associated with infant body composition. Conclusions: Adiponectin may be a marker for FM accrual in African American infants, a relatively understudied population with a high long‐term obesity risk. Mechanistic studies are needed to determine whether adiponectin directly influences infant growth or is simply a maker reflective of other ongoing biological changes after birth. [ABSTRACT FROM AUTHOR]

Summary: Post‐partum weight retention is relatively common and increases the risk for future obesity. Women who are overweight or obese prior to pregnancy, or who gain excessively during pregnancy, are more likely to retain weight post‐partum. Much of the existing research is limited by a single post‐partum body‐weight measure and therefore cannot distinguish post‐partum weight retention from post‐partum weight accrual. This study tested the hypothesis that early pregnancy body mass index (BMI) is positively associated with post‐partum weight change, independent of gestational weight gain (GWG) and breastfeeding (BF) among African–American women, a demographic group with greater risk for obesity. Healthy African–American women (n = 32) were weighed at 2 weeks and 3 months post‐partum to derive post‐partum weight change. Data from prenatal care records were retrieved to calculate BMI at the first prenatal care visit and GWG. BF status at 2 weeks post‐partum was self‐reported. Early pregnancy BMI was positively associated with post‐partum weight change (partial r = 0.53, P < 0.005), independent of GWG and BF status at 2 weeks post‐partum. These results extend the literature by suggesting that the association between early pregnancy BMI and post‐partum weight retention may be at least partially attributable to the accrual of new weight during the post‐partum period. Future research in a larger and more diverse cohort is warranted and should explore potential mechanisms contributing to post‐partum weight change. [ABSTRACT FROM AUTHOR]

Objective: To compare maternal genotypes between women with and without significant prolongation of pregnancy in the setting of 17-alpha hydroxyprogesterone caproate (17-P) administration for the prevention of recurrent preterm birth (PTB).Design: Case-control.Setting: Three tertiary-care centres across the USA.Population: Women (n = 99) with ≥ 1 prior singleton spontaneous PTB, receiving 17-P.Methods: Women were classified as having successful prolongation of pregnancy during the 17-P treated pregnancy, in two ways: (1) Definition A: success/non-success based on difference in gestational age at delivery between 17-P-treated and untreated pregnancies (success: delivered ≥ 3 weeks later with 17-P) and (2) Definition B: success/non-success based on reaching term (success: delivered at term with 17-P).Main Outcome Measures: To assess genetic variation, all women underwent whole exome sequencing. Between-group sequence variation was analysed with the Variant Annotation, Analysis, and Search Tool (VAAST). Genes scored by VAAST with P < 0.05 were then analysed with two online tools: (1) Protein ANalysis THrough Evolutionary Relationships (PANTHER) and (2) Database for Annotation, Visualization, and Integrated Discovery (DAVID).Results: Using Definition A, there were 70 women with successful prolongation and 29 without; 1375 genes scored by VAAST had P < 0.05. Using Definition B, 47 women had successful prolongation and 52 did not; 1039 genes scored by VAAST had P < 0.05. PANTHER revealed key differences in gene ontology pathways. Many genes from definition A were classified as prematurity genes (P = 0.026), and those from definition B as pharmacogenetic genes (P = 0.0018); (P, non-significant after Bonferroni correction).Conclusion: A novel analytic approach revealed several genetic differences among women delivering early vs later with 17-P.Tweetable Abstract: Several key genetic differences are present in women with recurrent preterm birth despite 17-P treatment. [ABSTRACT FROM AUTHOR]

The emphasis on research quality has taken great strides in recent years. Publication of clinical trial protocols (i.e. SPIRIT guideline), prospective registration (e.g. ClinicalTrials. gov, WHO registry), high standards in research conduct (i.e. ICH-Good Clinical Practice guidelines) and transparent reporting of the findings (i.e. CONSORT guideline) are all becoming features of clinical effectiveness research. However, many more gains are possible to improve the efficiency of clinical research and therefore reduction of waste in health research, a problem that is estimated to consume 85% of the global medical research budget each year. This article is protected by copyright. All rights reserved. [ABSTRACT FROM AUTHOR]

Neuronal plasticity is achieved by regulation of the expression of genes for neurotransmitter receptors such as the type A receptor (GABAAR) for γ-aminobutyric acid. We now show that two different rat neuronal populations in culture manifest distinct patterns of GABAAR plasticity in response to identical stimuli. Whereas prolonged exposure to ethanol had no effect on expression of the δ subunit of GABAARs at the mRNA or protein level in cerebellar granule neurons, it increased the abundance of δ subunit mRNA and protein in hippocampal neurons. Subsequent ethanol withdrawal transiently down-regulated δ subunit expression in cerebellar granule neurons and gradually normalized that in hippocampal neurons. These effects of ethanol exposure and withdrawal were accompanied by corresponding functional changes in GABAARs. GABAARs containing the δ subunit were also distributed differentially in the cerebellar and hippocampal neurons. These findings reveal complex and distinct mechanisms of regulation of the expression of GABAARs that contain the δ subunit in different neuronal types. [ABSTRACT FROM AUTHOR]

Obesity and late‐night food consumption are associated with impaired glucose tolerance. Late‐night carbohydrate consumption may be particularly detrimental during late pregnancy because insulin sensitivity declines as pregnancy progresses. Further, women who were obese (Ob) prior to pregnancy have lower insulin sensitivity than do women of normal weight (NW). The aim of this study is to test the hypothesis that night‐time carbohydrate consumption is associated with poorer glucose tolerance in late pregnancy and that this association would be exacerbated among Ob women. Forty non‐diabetic African American women were recruited based upon early pregnancy body mass index (NW, <25 kg m−2; Ob, ≥30 kg m−2). Third trimester free‐living dietary intake was assessed by food diary, and indices of glucose tolerance and insulin action were assessed during a 75‐g oral glucose tolerance test. Women in the Ob group reported greater average 24‐h energy intake (3055 kcal vs. 2415 kcal, P < 0.05). Across the whole cohort, night‐time, but not day‐time, carbohydrate intake was positively associated with glucose concentrations after the glucose load and inversely associated with early phase insulin secretion (P < 0.05). Multiple linear regression modelling within each weight group showed that the associations among late‐night carbohydrate intake, glucose concentrations and insulin secretion were present only in the Ob group. This is the first study to report an association of night‐time carbohydrate intake specifically on glucose tolerance and insulin action during pregnancy. If replicated, these results suggest that late‐night carbohydrate intake may be a potential target for intervention to improve metabolic health of Ob women in late pregnancy. [ABSTRACT FROM AUTHOR]

We conducted a survey-based study of the opinions, attitudes, and management practices of neonatologists across the United States regarding prenatally diagnosed Trisomy 18. The survey was designed based on previously validated surveys of severe fetal anomalies and collected demographic information on participants, as well as their attitudes, and management choices given a series of vignettes beginning in the prenatal period. The survey was sent to 3,143 American Academy of Pediatrics Section on Neonatal-Perinatal Medicine members of which 409 (13%) completed the survey. While the response rate was rather low, our respondent pool was representative of the national neonatologist population. Respondents were predominately white (81%), married (88%), Christian (54%), had children (86%), and were pro-choice in terms of abortion (68%). Eighty-three percent (83%) of respondents thought that trisomy 18 is a lethal condition and 60% thought that treatment is futile. Seventy-five percent (75%) expected that the best neurodevelopmental outcome in the case of infant survival would be profound intellectual disability. Regarding neonatal care, 95% stated that they would recommend palliative care only. Ninety-five percent (95%) would never recommend or recommend only if asked full code resuscitation for a neonate with full trisomy 18, yet, 44% would comply partially or in full with a full code request for resuscitation measures. The demographic features that correlated most significantly with these responses were clinician race and years in practice. The attitudes toward and management of infants affected with trisomy 18 seem to be largely driven by parental attitudes and wishes. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

We conducted a retrospective cohort study including all prenatal and postnatal diagnoses of trisomy 18 (T18) from 2004 to 2014 at a single tertiary referral center in the southern United States to evaluate the natural history and perinatal outcomes associated with T18 over the past decade. We analyzed pregnancy outcome, mode of delivery, and for live-births, the number and types of neonatal interventions, and characterized interventions as aggressive or non-aggressive. Survival analyses were conducted based on mode of delivery and aggressive compared to non-aggressive interventions. A total of 167 cases of T18 were identified, 150 with available records. There were 141 (94.0%) with full T18; the remainder had mosaicism (1.3%), a translocation (0.7%), or an isochromosome 18 (4.0%). Most diagnoses were prenatal (73.3%, n = 110). Of the 150 patients, there were 54 live births: 21 (38.9%) delivered vaginally, 32 (59.3%) delivered by cesarean, and mode of delivery could not be ascertained for one. Median duration of survival was 12 days (interquartile range 3-90 days). Over time, there were no changes toward increased intervention (obstetric or neonatal). For the 49 neonates who received some intervention, there was no significant difference in survival time between neonates receiving aggressive (n = 36, median survival 24 days, interquartile range 6-247) and non-aggressive (n = 13, median survival 30 days, interquartile range 8-148) intervention ( P = 0.90). There was similarly no difference in neonatal survival based on mode of delivery ( P = 0.79). Survival of infants with T18 is not improved with aggressive obstetric or neonatal care. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Introduction: Vaginal tenofovir (TFV) 1% gel may reduce incident HIV-1 and herpes simplex virus 2 infection. Pregnancy may increase risk of HIV acquisition, and incident HIV in pregnancy potentiates perinatal HIV transmission. Our objective was to investigate the safety and pharmacokinetics of seven days of TFV 1% vaginal gel in term and near-term pregnancy.Methods: Ninety-eight healthy pregnant women, stratified to a term cohort followed by a near-term cohort, were enrolled into a 2:1 randomized, double-blinded, placebo-controlled trial. Women received TFV or placebo gel for seven consecutive days with pharmacokinetic sampling on days 0 and 6. Maternal and cord blood were collected at delivery. Primary end points included laboratory and genital adverse events, adverse pregnancy and neonatal outcomes, and maternal TFV levels.Results: Most adverse events were grade 1 and none of the grade 3 or 4 adverse events were related to study product. There was no significant difference in safety end points between the two pregnancy cohorts (p=0.18); therefore, their data were combined. Primary safety end point rates were similar for mothers randomized to the TFV gel vs placebo arm (72.7 and 68.8%, p=0.81). The same was true for newborns in the TFV gel vs placebo arms (4.5% vs 6.3%, p=0.66). All women randomized to TFV had quantifiable serum levels within eight hours of dosing, with low overall median (interquartile range) day 0 and day 6 peak values (3.8 (2.0 to 7.0) and 5.8 (2.6 to 9.4) ng/mL, respectively).Conclusions: Daily TFV 1% vaginal gel use in term and near-term pregnancy appears to be safe and produces low serum drug levels. [ABSTRACT FROM AUTHOR]

A high number of differences exist in bone histological features depending on the species, breed, age and bone. Moreover, osteon distribution may vary in the different sides of a bone as a consequence of different biomechanical strains. The aim of this work was to study the distribution and morphology of osteons in different sides of the equine femoral diaphysis with the attempt to correlate them to the main strains operating on them. The following parameters of secondary osteons and Haversian canals were measured in the transverse sections of diaphyses: perimeter, area, minimum and maximum diameter, eccentricity and osteon population density. A typical Haversian tissue was observed with elliptic secondary osteons consisting in about 10 well-defined lamellae surrounding a circular Haversian canal. Quantitative analysis displays a different population density of secondary osteons depending on the side. The caudal and medial sides, where compression strains are higher, have more secondary osteons in comparison with the cranial and lateral sides, where tension strains are prevalent. These data suggest that secondary osteon population density may depend on the predominant strains. Even the elliptical shape of secondary osteons may be related to biomechanical strains, as their major axes are oriented cranio-caudally parallel to prevalent strains. [ABSTRACT FROM AUTHOR]

Pregnancy needs complex pathways that together play a role in proper growth and protection of the fetus preventing its premature loss. Changes during pregnancy and postpartum period include the manifold machinery of neuroactive steroids that plays a crucial role in neuronal excitability by local modulation of specific inhibitory receptors: the GABAA receptors. Marked fluctuations in both blood and brain concentration of neuroactive steroids strongly contribute to GABAA receptor function and plasticity. In this review, we listed several interesting results regarding the regulation and plasticity of GABAA receptor function during pregnancy and postpartum period in rats. The increase in brain levels of neuroactive steroids during pregnancy and their sudden decrease immediately before delivery are causally related to changes in the expression/function of specific GABAA receptor subunits in the hippocampus. These data suggest that alterations in GABAA receptor expression and function may be related to neurological and psychiatric disorders associated with crucial periods in women. These findings could help to provide potential new treatments for these women’s disabling syndromes. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective To determine the most cost-effective timing of delivery in pregnancies complicated by gastroschisis, using a decision-analytic model. Methods We created a decision-analytic model to compare planned delivery at 35, 36, 37, 38 and 39 weeks' gestation. Outcomes considered were stillbirth, death within 1 year of birth and respiratory distress syndrome ( RDS). Probability estimates of events (stillbirth, complex gastroschisis and RDS for each gestational age at delivery and risk of death with simple and complex gastroschisis), utilities and costs assigned to the outcomes were obtained from the published literature. Cost analysis was assessed from a societal perspective, using a willingness-to-pay threshold of $100 000 per surviving infant. Outcomes and costs were considered throughout 1 year of postnatal life. Multiway sensitivity analysis was performed to address uncertainties in baseline assumptions. Results In the base-case analysis, delivery at 38 weeks' gestation was the most cost-effective strategy. Planned delivery at 35 weeks was associated with the fewest stillbirths and deaths within 1 year of delivery, owing largely to a lower ongoing risk of stillbirth. In Monte Carlo simulation when every variable was varied over its entire range, delivery at 38 weeks was cost-effective compared to delivery at 39 weeks in 76% of trials and delivery at 37 weeks was cost-effective in 69% of trials. Delivery at 38 weeks resulted in three additional cases of RDS for every 100 stillbirths or deaths within 1 year that were prevented. Conclusions For pregnancies complicated by gastroschisis, the most cost-effective timing of delivery is at 38 weeks. Few additional cases of RDS are caused for every one stillbirth or death within 1 year that was prevented with delivery at 37-38 weeks compared with at 39 weeks. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

This paper proposes a numerical method for accurate time‐domain noise simulation of mixed analogue/digital electrical circuits that in principle do not admit a periodic steady‐state working condition, such as fractional ΔΣ phase‐locked loops (PLLs). By means of a tool known as saltation matrix, which allows dealing with non‐smooth vector fields, a variational approach is adopted. The power spectral density of a noisy electrical variable is computed by applying the Thomson's multitaper method (MTM) to the numerical solution of the stochastic variational model of the circuit. This allows to resort to a single transient simulation run, thus avoiding cpu time consuming Monte‐Carlo‐like approaches. The effectiveness of the proposed method is shown by comparing simulation results related to a commercial fractional ΔΣ PLL with experimental data. [ABSTRACT FROM AUTHOR]

This paper is focused on the transient dynamics of an adiabatic nano-electromechanical system (NEMS), consisting of a nano-mechanical oscillator coupled to a quantum dot. By numerically solving the nonlinear stochastic differential equation governing the oscillator, the time evolution of the oscillator position, of the dot occupation number and of the current are studied. Different parameter settings are studied where the system exhibits bi-stable, tri-stable or mono-stable behavior on a finite-time horizon. It is shown that, after a typically long transient, the system under investigation exhibits no hysteretic behavior and that a unique steady state is reached, independently of the initial conditions. The transient dynamics is marked out by one or two well separated characteristic times, depending on the considered case (i.e., mono- or multi-stable). These times are evaluated for a dot on-resonance or off-resonance. It turns out that the characteristic time scales are long in comparison to the period of the uncoupled oscillator, particularly at low bias, suggesting that the predicted transient dynamics may be observed in state-of-the-art experimental setups. [ABSTRACT FROM AUTHOR]

We study the spin ordering of a quantum dot defined via magnetic barriers in an interacting quantum spin Hall edge. The spin-resolved density-density correlation functions are computed. We show that strong electron interactions induce a ground state with a highly correlated spin pattern. The crossover from the liquid-type correlations at weak interactions to the ground state spin texture found at strong interactions parallels the formation of a one-dimensional Wigner molecule in an ordinary strongly interacting quantum dot. [ABSTRACT FROM AUTHOR]

Social isolation in male rats at weaning results in reduced basal levels of the neuroactive steroid 3α,5α-tetrahydroprogesterone (3α,5α- TH PROG) in the brain and plasma as well as increased anxiety-like behavior. We now show that socially isolated female rats also manifest a reduced basal cerebrocortical concentration of 3α,5α- TH PROG as well as an anxiety-like profile in the elevated plus-maze and Vogel conflict tests compared with group-housed controls. In contrast, despite the fact that they were raised under normal conditions, adult male offspring of male and female rats subjected to social isolation before mating exhibited an increased basal cerebrocortical level of 3α,5α- TH PROG but no difference in emotional reactivity compared with the offspring of group-housed parents. These animals also showed an increased basal activity of the hypothalamic-pituitary-adrenal axis as well as reduced abundance of corticotropin-releasing factor in the hypothalamus and of corticotropin-releasing factor receptor type 1 in the pituitary. Moreover, negative feedback regulation of hypothalamic-pituitary-adrenal axis activity by glucocorticoid was enhanced in association with up-regulation of glucocorticoid receptor expression in the hippocampus. There was also attenuation of corticosterone release induced by foot-shock stress in the offspring of socially isolated parents. The increase in the brain concentration of 3α,5α- TH PROG induced by acute stress was also blunted in these animals. Our results thus show that a stressful experience before mating can influence neuroendocrine signaling in the next generation. [ABSTRACT FROM AUTHOR]

Obstetrics has long been guided by the tenet, accurate or not, that if a complication occurred in a prior pregnancy, it is likely to recur in a subsequent pregnancy. Women with singleton, as well as twin, gestations who have had a prior singleton PTB are more likely to have a subsequent PTB, with increasing risks for earlier gestational ages of the prior PTB. As interventions to prevent PTB in twins are of limited proven efficacy, better methods of risk stratification may allow for heightened vigilance and more targeted interventions in those at highest risk. [Extracted from the article]

J. Neurochem. (2010) 113, 1285–1295. Gonadal steroids, in particular estradiol, exert important actions during pre- and perinatal periods in the regulation of sexual dimorphism and development of the nervous system. We have now examined the effects of neonatal estradiol administration in female rats on brain concentrations of the neuroactive steroids allopregnanolone and tetrahydrodeoxycorticosterone, expression of GABAA receptor subunits, and behavioral sensitivity to benzodiazepines and allopregnanolone. Administration of β-estradiol 3-benzoate on the day of birth resulted in marked decreases in the concentrations of progesterone and allopregnanolone in the cerebral cortex at 21, 60, and 180 days after birth. The concentrations of tetrahydrodeoxycorticosterone, 17β-estradiol, and dehydroepiandrosterone in the brain at 60 days were not affected by such treatment. Neonatal administration of β-estradiol 3-benzoate also increased the cerebrocortical abundance of α1, α2, and γ2 subunits of the GABAA receptor without affecting that of α3, α4, α5, or δ subunits. Diazepam induced a greater reduction in locomotor activity as well as a more pronounced anxiolytic-like effect in the elevated plus-maze test in rats subjected to neonatal treatment with β-estradiol 3-benzoate than in vehicle-treated controls, while allopregnanolone induced a similar effect in both groups. These effects of estradiol suggest that it plays a major role in regulation both of GABAergic transmission and of the abundance of endogenous modulators of such transmission during development of the central nervous system. [ABSTRACT FROM AUTHOR]

The article reports on the study that examines patients with acute myeloid leukemia (AML) who were treated on the Acute Leukemia French Association 9802 trial. It identifies wilms tumor 1 (WT1) mutations in 5% of patients, and no mutation was detected in patients who had favorable cytogenetics. It suggests that WT1 mutations represent an adverse prognostic factor in young adults with AML.

Seizure exacerbation in catamenial epilepsy (CE) is associated with the decrease in progesterone secretion and increase in estradiol secretion during the premenstrual period. Moreover, experimental evidence suggests that tetrahydrodeoxycorticosterone (THDOC), a positive modulator of the type A receptor for γ-aminobutyric acid (GABA), and dehydroepiandrosterone sulfate (DHEAS), a negative modulator of this receptor, might play a crucial role in modulating seizure frequency during the menstrual cycle. Following these studies it seems of interest to investigate possible variations, among other hormonal parameters, of THDOC and DHEAS in CE patients. The serum concentrations of progesterone (P4), pregnenolone, allopregnanolone (AP), THDOC, DHEAS, cortisol, and DHEAS/cortisol ratio were measured throughout the menstrual cycle at the 7th, 11th, 15th, 19th, 23rd, and 27th day from the onset of spontaneous menstrual blood loss in young premenopausal women with CE (n = 17) and age-matched controls (n = 13). At each time of the study, the serum concentration of THDOC and the DHEAS/cortisol ratio were lower (p < 0.05) in women with CE than in control women. The concentrations of P4, pregnenolone, and AP did not differ between the two groups of subjects. The reduced serum concentration of THDOC and the reduced DHEAS/cortisol ratio detected throughout the menstrual cycle in women with CE might play a role in CE. Moreover, the peculiar pattern of CE seizure exacerbation might suggest that these neuroendocrine variations are worth investigating in other epileptic syndromes, particularly in those characterized by relevant and uncontrolled variations in seizure frequency. [ABSTRACT FROM AUTHOR]

Previous studies have shown that GABAergic neuroactive steroids increase Y1 receptor (Y1R) gene expression in the amygdala of Y 1 R/ LacZ transgenic mice, harbouring the murine Y1R gene promoter linked to a LacZ reporter gene. As ethanol is known to increase GABAergic neuroactive steroids, we investigated the relationship between fluctuations in the brain content of neuroactive steroids induced by chronic voluntary ethanol consumption or ethanol discontinuation and both the level of neuropeptide Y (NPY) immunoreactivity and Y1R gene expression in the amygdala of Y 1 R/ LacZ transgenic mice. Ethanol discontinuation (48 h) after voluntary consumption of consecutive solutions of 3%, 6%, 10% and 20% (v/v) ethanol over 4 weeks produced an anxiety-like behaviour as measured by elevated plus maze. Voluntary ethanol intake increased the cerebrocortical concentration of the progesterone metabolite 3α-hydroxy-5α-pregnan-20-one (3α,5α-TH PROG) that returned to control level 48 h after discontinuation of ethanol intake. Ethanol discontinuation significantly decreased NPY immunoreactivity and concomitantly increased Y 1 R/ LacZ transgene expression in the amygdala, whereas chronic ethanol intake failed to affect these parameters. The 5α-reductase inhibitor finasteride prevented both the increase in the cerebrocortical concentration of 3α,5α-TH PROG apparent after 4 weeks of ethanol intake and the changes in NPY immunoreactivity and transgene expression induced by ethanol discontinuation. Data suggest that 3α,5α-TH PROG plays an important role in the changes in NPY–Y1R signalling in the amygdala during ethanol discontinuation. [ABSTRACT FROM AUTHOR]

The actions of ethanol on γ-aminobutyric acid type A (GABAA) receptors are still highly controversial issues but it appears that some of its pharmacological effects may depend on receptor subunit composition. Prolonged ethanol exposure produces tolerance and dependence and its withdrawal alters GABAA receptor subunit gene expression and function. Whereas benzodiazepines are clinically effective in ameliorating ethanol withdrawal symptoms, work in our laboratory showed that benzodiazepines also prevent, in vitro, some of the ethanol withdrawal-induced molecular and functional changes of the GABAA receptors. In the present work, we investigated the effects, on such changes, of the benzodiazepine receptor antagonist flumazenil that can positively modulate α4-containing receptors. We here report that flumazenil prevented both the ethanol withdrawal-induced up-regulation of the α4-subunit and the increase in its own modulatory action. In contrast, flumazenil did not inhibit ethanol withdrawal-induced decrease in α1- and δ-subunit expression as well as the corresponding decrease in the modulatory action on GABAA receptor function of both the α1-selective ligand zaleplon and the δ-containing receptor preferentially acting steroid allopregnanolone. These observations are the first molecular and functional evidence that show a selective inhibition by flumazenil of the up-regulation of α4-subunit expression elicited by ethanol withdrawal. [ABSTRACT FROM AUTHOR]

Type A receptors for GABA (GABAA receptors) that contain the δ subunit are located predominantly at extrasynaptic sites and are implicated in modulation of neuronal excitability through tonic inhibition. We have examined the effects of chronic exposure to and subsequent withdrawal of progesterone or the progesterone metabolite 3α-hydroxy-5α-pregnan-20-one (3α,5α-THPROG) on expression of the d subunit of GABAA receptors and on receptor function in cultured rat hippocampal neurons. Progesterone treatment for 1 day increased the amounts of both d subunit mRNA and protein, whereas such treatment for 6 days induced marked decreases in the abundance of both them RNA and protein. Subsequent progesterone withdrawal up-regulated expression of the d subunit, which was significantly increased at 9-12 h after withdrawal. These effects of progesterone were mimicked by 3α,5α-THPROG and blocked by the 5α-reductase inhibitor finasteride. They were also accompanied by parallel changes in the function of GABAA receptors in hippocampal neurons. These results show that chronic exposure to and withdrawal of progesterone induce differential effects on both expression of the d subunit of GABAA receptors and receptor function that are mediated by 3α,5α-THPROG. They are consistent with the notion that this progesterone metabolite plays a key physiological role in modulation of GABAergic synapses. [ABSTRACT FROM AUTHOR]

Previously we have demonstrated that social isolation of rats reduces both the cerebrocortical and plasma concentrations of 3α-hydroxy-5α-pregnan-20-one (3α,5α-TH PROG), and potentiates the positive effects of acute ethanol administration on the concentrations of this neurosteroid. We now show that the ethanol-induced increase in 3α,5α-TH PROG is more pronounced in the brain than in the plasma of isolated rats. The ability of ethanol to inhibit isoniazid-induced convulsions is greater in isolated rats than in group-housed animals and this effect is prevented by treatment with finasteride. Social isolation modified the effects of ethanol on the amounts of steroidogenic regulatory protein mRNA and protein in the brain. Moreover, ethanol increased the amplitude of GABAA receptor-mediated miniature inhibitory postsynaptic currents recorded from CA1 pyramidal neurones with greater potency in hippocampal slices prepared from socially isolated rats than in those from group-housed rats, an effect inhibited by finasteride. The amounts of the α4 and δ subunits of the GABAA receptor in the hippocampus were increased in isolated rats as were GABAA receptor-mediated tonic inhibitory currents in granule cells of the dentate gyrus. These results suggest that social isolation results in changes in GABAA receptor expression in the brain, and in an enhancement of the stimulatory effect of ethanol on brain steroidogenesis, GABAA receptor function and associated behaviour. [ABSTRACT FROM AUTHOR]

We determined the molecular haplotypes of the HLA-A, HLA-C and HLA-B loci and the MHC class I-B-related (MIB) microsatellite in 179 unrelated psoriatic patients (72 familial cases) and in 120 controls. The HLA-A*3002-Cw*0501-B*1801-MIB1 haplotype showed a strong negative association with psoriasis vulgaris (PV) and in particular with familial PV, revealing the presence of a PV-protective gene. Analysis of association and linkage disequilibrium of the single alleles and the various two-three-four-locus segments of this haplotype indicated the presence of a protective gene telomeric to the HLA-C locus. This finding was confirmed in 13 informative multiplex PV families, in which at least one parent carried the EH18.2 haplotype. In two families, an affected sibling presented HLA-A/C recombination on the EH18.2 haplotype. A study of 12 polymorphic microsatellites in all members of the informative families, 145 PV patients, 120 controls and 32 EH18.2 homozygous healthy individuals demonstrated that the protection conferred by the EH18.2 haplotype lies within a 170 kb interval between the C143 and C244 loci, most probably in a 60 kb segment between the C132 and C244 loci. [ABSTRACT FROM AUTHOR]

A sustained increase in the brain concentrations of neuroactive steroids was previously shown to induce Y1 receptor gene expression in the amygdala of Y1R/LacZ transgenic mice which harbour a construct comprising the murine Y1 receptor gene promoter and the lacZ reporter gene. We now investigated the effects of restraint stress on both the cere- brocortical concentrations of neuroactive steroids and Y1 receptor gene expression in the amygdala and hypothalamic paraventricular nucleus (PVN) of Y1R/LacZ transgenic mice. The cerebrocortical concentrations of allopregnanolone and allotetrahydrodeoxycorticosterone were significantly increased immediately after a 1-h exposure to restraint stress and had returned to control values within 30 min. Expression of Y1R/LacZ was increased in the amygdala and PVN 6 h after restraint. The 5α-reductase inhibitor finasteride, that prevented the increase in neuroactive steroid concentrations, did not block that in transgene expression induced by 1-h restraint. Daily exposure to restraint for 10 days also increased the cerebrocortical concentrations of neuroactive steroids but failed to affect transgene expression. Acute but not repeated restraint thus increases Y1 receptor gene expression in the amygdala and PVN, suggesting that tolerance develops towards this stressor. The effect of acute restraint is not mediated by the increase in the brain concentrations of neuroactive steroids but may rather reflect a ligand-induced increase in Y1 receptor gene transcription. Data support a role of Y1 receptors in the behavioural and neuroendocrine responses to stress. [ABSTRACT FROM AUTHOR]

Abstract Social isolation of rats for 30 days immediately after weaning results in marked decreases in the cerebrocortical and plasma concentrations of pregnenolone, progesterone, 3α-hydroxy-5α-pregnan-20-one (3α,5α-TH PROG), and 3α,5α-tetrahydrodeoxycorticosterone (3α,5α-TH DOC), as well as a moderate increase in the plasma concentration of corticosterone. This mildly stressful condition has now been shown to increase the sensitivity of rats to the effect of acute ethanol administration on the cerebrocortical and plasma concentrations of neuroactive steroids. The percentage increases in the brain and plasma concentrations of pregnenolone, progesterone, 3α,5α-TH PROG, and 3α,5α-TH DOC, apparent 20 min after a single intraperitoneal injection of ethanol (1 g/kg), were thus markedly greater in isolated rats than in group-housed animals. A subcutaneous injection of isoniazid (300 mg/kg) also induced greater percentage increases in the concentrations of these steroids in isolated rats than in group-housed animals. These results suggest that mild chronic stress, such as that induced by social isolation, enhances the steroidogenic effect of ethanol, a drug abused by humans under stress or affected by neuropsychiatric disorders. Social isolation also induced hyper-responsiveness of the hypothalamic–pituitary–adrenal (HPA) axis, as was apparent after reduction of GABA-mediated inhibitory tone by isoniazid administration. [ABSTRACT FROM AUTHOR]

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The effect of endogenous 3α-hydroxy-5α-pregnan-20-one (3α,5α-TH PROG) on the modulation of mesocortical dopamine extracellular concentration by ethanol was investigated by microdialysis in rats. Intraperitoneal injection of progesterone (5 mg/kg, once a day for 5 days) increased the cortical content of 3α,5α-TH PROG and potentiated the biphasic effect of acute intraperitoneal administration of ethanol on dopamine content. A dose of ethanol (0.25 g/kg) that was ineffective in naïve rats induced a 55% increase in dopamine extracellular concentration in rats pretreated with progesterone. This increase was similar to that induced by a higher dose (0.5 g/kg) of ethanol in naïve rats. Administration of ethanol at 0.5 g/kg to progesterone-pretreated rats inhibited dopamine content by an extent similar to that observed with an even higher dose (1 g/kg) in naïve rats. The administration of the 5α-reductase inhibitor finasteride (25 mg/kg, subcutaneous), together with progesterone, prevented the effects of the latter, both on the cortical concentration of 3α,5αTH PROG and on the modulation by ethanol of dopamine content. These data suggest that 3α,5α-TH PROG contributes to the action of ethanol on the mesocortical dopaminergic system. They also suggest that physiological fluctuations in the brain concentrations of neuroactive steroids associated with the oestrous cycle, menopause, pregnancy and stress may alter the response of mesocortical dopaminergic neurons to ethanol. [ABSTRACT FROM AUTHOR]

A psoriasis susceptibility locus has been mapped to the HLA region in the proximity of the HLA-C locus. This critical region also contains the CDSN gene coding for the corneodesmosin protein. In a case–control association study of psoriasis in the Sardinian population, we analyzed the allele distribution of eight intragenic SNPs (positions 619, 767, 1215, 1118, 1236, 1243, 1331, 1593) of the CDSN gene and the six haplotypes that are coded by these SNPs. Our study showed that these CDSN haplotypes are very stable and well-conserved in the Sardinian population. The CDSN2 haplotype was found to be associated with susceptibility to psoriasis. The association did not depend upon any one of the intragenic SNPs taken separately. At the HLA-C locus, the Cw6 and Cw7 alleles were dragged along by linkage disequilibrium with the CDSN2 haplotype and only revealed a trend towards association with the disease. Therefore, the intragenic SNPs of the CDSN gene and the HLA-Cw6 and Cw7 alleles are not directly involved in susceptibility to psoriasis. However, the strong association of the CDSN2 haplotype suggests a possible role for the CDSN gene and its chromosome region in susceptibility to psoriasis. [ABSTRACT FROM AUTHOR]

Long-term administration of progesterone or allopregnanolone was previously shown to increase Y[sub 1] receptor gene expression in the medial amygdala of Y[sub 1]R/LacZ transgenic mice, which harbor a construct comprising the murine Y[sub 1] receptor gene promoter and a lacZ reporter. We have now investigated the effects of physiological fluctuations in the cerebrocortical concentrations of neuroactive steroids during pregnancy on Y[sub 1]R/LacZ transgene expression by quantitative histochemical analysis of β-galactosidase activity. Cerebrocortical concentrations of progesterone and its metabolites allopregnanolone and allotetrahydrodeoxycorticosterone were increased on day 18 of pregnancy and had returned to control values 2 days after delivery. Transgene expression in the medial amygdala was also increased on day 18 of pregnancy and had returned to control values 2 days after delivery. Similar results were obtained after analysis of Y[sub 1]R mRNA levels in the medial amygdala of pregnant mice by in situ hybridization. Administration of the 5α-reductase inhibitor finasteride to pregnant mice prevented both the increase in the cerebrocortical concentrations of neuroactive steroids as well as the increase in transgene expression. These data suggest that fluctuations in the brain concentrations of endogenous neuroactive steroids during pregnancy are associated with changes in Y[sub 1] receptor gene expression in the medial amygdala, further supporting a functional interaction between the GABAergic and NPY–Y[sub 1] receptor systems. [ABSTRACT FROM AUTHOR]

Abstract Glycine acts as an inhibitory transmitter in the lower brain stem and spinal cord of vertebrate species, while very few data are yet available to support a similar role in invertebrate nervous systems. Here we report the identification and characterization of glycine receptors in the freshwater polyp Hydra vulgaris (Cnidaria, Hydrozoa) by biochemical and behavioural studies. Saturation experiments revealed the occurrence of one population of binding sites of nanomolar affinity (KD = 33 nm) and low capacity (Bmax = 79 fmol/mg protein) for [3H]strychnine. The addition of glycine or taurine (0.1 µm–1 mm) produced a dose-dependent inhibition of [3H]strychnine binding. β-alanine (0.1–1 mm) did not significantly affect [3H]strychnine binding. The pharmacological properties of these receptors compare with those of vertebrate glycine receptors. Stimulation of Hydra polyps by reduced glutathione resulted in a significant increase in the duration of mouth opening in the presence of glycine, taurine or β-alanine. The enhancement of the response was related both to amino acid (10–100 µm) and to glutathione concentration (1–10 µm). The effects of glycine or its agonists were suppressed by strychnine (1–10 µm). d-serine, a glycine agonist at the vertebrate NMDA receptor, produced opposite effects to those of glycine. The effects of d-serine were suppressed by 5,7-dichlorokynurenic acid but not by strychnine. In vitro, [3H]strychnine binding was not displaced by d-serine. These results indicate a dual action of glycine in Hydra tissues. The hypothesis that NMDA receptors may also be present in this elementary nervous system is proposed. [ABSTRACT FROM AUTHOR]

The neurosteroid allopregnanolone, a reduced metabolite of progesterone, induces anxiolytic effects by enhancing GABA[sub A] receptor function. Neuropeptide Y (NPY) and GABA are thought to interact functionally in the amygdala, and this interaction may be important in the regulation of anxiety. By using Y[sub 1]R/LacZ transgenic mice, which harbour a fusion construct comprising the promoter of the mouse gene for the Y[sub 1] receptor for NPY linked to the lacZ gene, we previously showed that long-term treatment with benzodiazepine receptor ligands modulates Y[sub 1] receptor gene expression in the medial amygdala. We have now investigated the effects of prolonged treatment with progesterone or allopregnanolone on Y[sub 1]R/LacZ transgene expression, as determined by quantitative histochemical analysis of β-galactosidase activity. Progesterone increased both the cerebrocortical concentration of allopregnanolone and β-galactosidase expression in the medial amygdala. Finasteride, a 5α-reductase inhibitor, prevented both of these effects. Long-term administration of allopregnanolone also increased both the cortical concentration of this neurosteroid and transgene expression in the medial amygdala. Treatment with neither progesterone nor allopregnanolone affected β-galactosidase activity in the medial habenula. These data suggest that allopregnanolone regulates Y[sub 1] receptor gene expression through modulation of GABA[sub A] receptor function, and they provide further support for a functional interaction between GABA and neuropeptide Y in the amygdala. [ABSTRACT FROM AUTHOR]