Detrimental effects of the 'bath salt' methylenedioxypyrovalerone on social play behavior in male rats

Methylenedioxypyrovalerone (MDPV) is the most popular synthetic cathinone found in products marketed as 'bath salts', widely abused among teenagers and young adults. Synthetic cathinones have pharmacological effects resembling those of psychostimulants, which are known to disrupt a variety of social behaviors. However, despite the popular use of MDPV by young people in social contexts, information about its effects on social behavior is scarce. To investigate the impact of MDPV on social behavior at young age, and the underlying neurobehavioral mechanisms, we focused on social play behavior. Social play behavior is the most characteristic social behavior displayed by young mammals and it is crucial for neurobehavioral development. Treatment with MDPV reduced social play behavior in both juvenile and young adult male rats, and its play-suppressant effect was subject to tolerance but not sensitization. As the behavioral effects of MDPV have been ascribed to dopaminergic and noradrenergic neurotransmission, and given the role of these neurotransmitters in social play, we investigated the involvement of dopamine and noradrenaline in the play-suppressant effects of MDPV. The effects of MDPV on social play were blocked by either the α2 adrenoceptor antagonist RX821002 or the dopamine receptor antagonist flupenthixol, given alone or together at sub-effective doses. In sum, MDPV selectively suppresses the most vigorous social behavior of developing rats through both noradrenergic and dopaminergic mechanisms. This study provides important preclinical evidence of the deleterious effects of MDPV on social behavior, and as such increases our understanding of the neurobehavioral effects of this popular cathinone

Regulation of oxytocin receptor gene expression in obsessive–compulsive disorder: a possible role for the microbiota-host epigenetic axis

Background: Obsessive–compulsive disorder (OCD) is a prevalent and severe clinical condition. Robust evidence suggests a gene-environment interplay in its etiopathogenesis, yet the underlying molecular clues remain only partially understood. In order to further deepen our understanding of OCD, it is essential to ascertain how genes interact with environmental risk factors, a cross-talk that is thought to be mediated by epigenetic mechanisms. The human microbiota may be a key player, because bacterial metabolites can act as epigenetic modulators. We analyzed, in the blood and saliva of OCD subjects and healthy controls, the transcriptional regulation of the oxytocin receptor gene and, in saliva, also the different levels of major phyla. We also investigated the same molecular mechanisms in specific brain regions of socially isolated rats showing stereotyped behaviors reminiscent of OCD as well as short chain fatty acid levels in the feces of rats. Results: Higher levels of oxytocin receptor gene DNA methylation, inversely correlated with gene expression, were observed in the blood as well as saliva of OCD subjects when compared to controls. Moreover, Actinobacteria also resulted higher in OCD and directly correlated with oxytocin receptor gene epigenetic alterations. The same pattern of changes was present in the prefrontal cortex of socially-isolated rats, where also altered levels of fecal butyrate were observed at the beginning of the isolation procedure. Conclusions: This is the first demonstration of an interplay between microbiota modulation and epigenetic regulation of gene expression in OCD, opening new avenues for the understanding of disease trajectories and for the development of new therapeutic strategies

HIPEC after Interval Debulking Surgery as Best Clinical Practice in Ovarian Cancer Patients: Case Series and Literature Review

Background: Hyperthermic intraperitoneal chemotherapy (HIPEC) combined with interval debulking surgery (IDS) constitutes an adjunctive treatment strategy in advanced ovarian cancer (AOC). This approach is based on the concept of perfusing chemotherapy targeting directly the site of residual tumor after optimal surgical debulking. It improves patients' outcome in terms of overall survival (OS) and disease free survival (DFS). The correct selection of patients eligible for IDS + HIPEC is crucial: in particular, they must have shown a good response to neoadjuvant chemotherapy (NACT) and have a good performance status (PS). The application of HIPEC at the end of debulking does not seem to increase neither the rate of intra/postoperative complications nor the time of hospitalization. Clinical Cases: After approving an internal protocol for the application of HIPEC in our hospital, we have submitted four patients to IDS + HIPEC in the past 12 months. One of these patients underwent a minimally invasive procedure. No intra- or postoperative complications were observed. Results: All patients underwent IDS + HIPEC after being assessed as eligible and after showing a good response to NACT. In the course of IDS in all cases complete debulking was achieved. No patient developed intra- or postoperative complications. Conclusions: The addition of HIPEC to interval debulking surgery should be offered to all eligible patients, considering that the association of HIPEC to IDS seems to improve patients' outcomes in terms of OS and DFS, without increasing post-operative morbidity

Nitrogen uptake and internal recycling in Zostera marina exposed to oyster farming: eelgrass potential as a natural biofilter

Oyster farming in estuaries and coastal lagoons frequently overlaps with the distribution of seagrass meadows, yet there are few studies on how this aquaculture practice affects seagrass physiology. We compared in situ nitrogen uptake and the productivity of Zostera marina shoots growing near off-bottom longlines and at a site not affected by oyster farming in San Quintin Bay, a coastal lagoon in Baja California, Mexico. We used benthic chambers to measure leaf NH4 (+) uptake capacities by pulse labeling with (NH4)-N-15 (+) and plant photosynthesis and respiration. The internal N-15 resorption/recycling was measured in shoots 2 weeks after incubations. The natural isotopic composition of eelgrass tissues and vegetative descriptors were also examined. Plants growing at the oyster farming site showed a higher leaf NH4 (+) uptake rate (33.1 mmol NH4 (+) m(-2) day(-1)) relative to those not exposed to oyster cultures (25.6 mmol NH4 (+) m(-2) day(-1)). We calculated that an eelgrass meadow of 15-16 ha (which represents only about 3-4 % of the subtidal eelgrass meadow cover in the western arm of the lagoon) can potentially incorporate the total amount of NH4 (+) excreted by oysters (similar to 5.2 x 10(6) mmol NH4 (+) day(-1)). This highlights the potential of eelgrass to act as a natural biofilter for the NH4 (+) produced by oyster farming. Shoots exposed to oysters were more efficient in re-utilizing the internal N-15 into the growth of new leaf tissues or to translocate it to belowground tissues. Photosynthetic rates were greater in shoots exposed to oysters, which is consistent with higher NH4 (+) uptake and less negative delta C-13 values. Vegetative production (shoot size, leaf growth) was also higher in these shoots. Aboveground/belowground biomass ratio was lower in eelgrass beds not directly influenced by oyster farms, likely related to the higher investment in belowground biomass to incorporate sedimentary nutrients

Strong Evidence of Anomalous Microwave Emission from the Flux Density Spectrum of M31

We have observed the Andromeda galaxy, Messier 31 (M31), at 6.7 GHz with the Sardinia Radio Telescope. We mapped the radio emission in the C-band, re-analyzed WMAP and Planck maps, as well as other ancillary data, and we have derived an overall integrated flux density spectrum from the radio to the infrared. This allowed us to estimate the emission budget from M31. Integrating over the whole galaxy, we found strong and highly significant evidence for anomalous microwave emission (AME), at the level of 1.45_(-0.19)^(+0.17) Jy at the peaking frequency of ≃ 25 GHz. Decomposing the spectrum into known emission mechanisms such as free–free, synchrotron, thermal dust, and AME arising from electric dipole emission from rapidly rotating dust grains, we found that the overall emission from M31 is dominated, at frequencies below 10 GHz, by synchrotron emission with a spectral index of -1.10_(-0.08)^(+0.10), with subdominant free–free emission. At frequencies ≳ 10 GHz, AME has a similar intensity to that of synchrotron and free–free emission, overtaking them between 20 and 50 GHz, whereas thermal dust emission dominates the emission budget at frequencies above 60 GHz, as expected

Pilot study of a randomized trial to evaluate a Web-based intervention targeting adolescents presenting to the emergency department with acute asthma

Abstract Background Low-income African-American adolescents use preventive medical services less frequently than their White counterparts, indicating a need for effective interventions targeting this group. Puff City is a Web-based, asthma management program for urban adolescents that has been evaluated in high school settings with promising results. The objective of this pilot was to assess the feasibility of initiating Puff City (treatment) in an emergency department setting, thereby informing the conduct of an individual randomized trial to evaluate its effectiveness compared to a generic, Web-based program (control) in preventing subsequent emergency department (ED) visits. Methods Teens aged 13–19 years presenting with acute asthma to two urban EDs within the study period were eligible. Subsequent ED visits were collected using the electronic medical record. A priori indication of a potential intervention effect was p < 0.20. Results Of the 121 teens randomized (65 treatment, 56 control), 86.0% were African-American and 44.6% male, with the mean age = 15.4 years. Computer ownership was reported by 76.8% of teens. Overall, 64.5% of teens completed >3 of 4 sessions and 90% completed the 12-month survey. At 12 months, the treatment group showed a trend toward fewer ED visits than controls (33.8 versus 46.4%), p = 0.15. Conclusions Results indicate the feasibility of enrolling at-risk adolescents in ED settings and set the stage for a large, pragmatic trial using a technology-based intervention to reduce the burden of pediatric asthma. Trial registration ClinicalTrials.gov, NCT01695031https://deepblue.lib.umich.edu/bitstream/2027.42/137647/1/40814_2017_Article_147.pd

QUBIC: The Q&U Bolometric Interferometer for Cosmology - A novel way to look at the polarized Cosmic Microwave Background

In this paper we describe QUBIC, an experiment that takes up the challenge posed by the detection of primordial gravitational waves with a novel approach, that combines the sensitivity of state-of-the art bolometric detectors with the systematic effects control typical of interferometers. The so-called "self-calibration" is a technique deeply rooted in the interferometric nature of the instrument and allows us to clean the measured data from instrumental effects. The first module of QUBIC is a dual band instrument (150 GHz and 220 GHz) that will be deployed in Argentina during the Fall 2018.Fil: Mennella, Aniello. University of Milan; ItaliaFil: Ade, P. A. R.. Cardiff University; Reino UnidoFil: Aumont, J.. Institut d'Astrophysique Spatiale; FranciaFil: Banfie, S.. Istituto Nazionale Di Fisica Nucleare; ItaliaFil: Battaglia, P.. Università degli Studi di Trieste; ItaliaFil: Battistelli, E. S.. Università degli Studi di Roma "La Sapienza"; ItaliaFil: Baùe, F.. Istituto Nazionale Di Fisica Nucleare; ItaliaFil: Buzi, D.. Università degli Studi di Roma "La Sapienza"; ItaliaFil: Columbro, F.. Università degli Studi di Roma "La Sapienza"; ItaliaFil: Bélie, B.. Institute of Fundamental Electronics; FranciaFil: Bennett, D.. Maynooth University; IrlandaFil: Bergé, L.. Centre de Sciences Nucléaires et de Sciences de la Matière; FranciaFil: Bernard, J. Ph.. Institut de Recherche en Astrophysique et Planétologie; FranciaFil: Bersanelli, M.. University of Milan; ItaliaFil: Bigot Sazy, M. A.. APC; FranciaFil: Bleurvacq, N.. APC; FranciaFil: Bordier, G.. APC; FranciaFil: Brossard, J.. APC; FranciaFil: Bunn, E. F.. Richmond University; Estados UnidosFil: Burke, D. P.. Maynooth University; IrlandaFil: Buzi, D.. Università degli Studi di Roma "La Sapienza"; ItaliaFil: Buzzelli, A.. Universita Tor Vergata; ItaliaFil: Cammilleri, D.. APC; FranciaFil: Cavaliere, F.. University of Milan; ItaliaFil: Chanial, P.. APC; FranciaFil: Etchegoyen, Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnología en Detección y Astropartículas. Comisión Nacional de Energía Atómica. Instituto de Tecnología en Detección y Astropartículas. Universidad Nacional de San Martín. Instituto de Tecnología en Detección y Astropartículas; ArgentinaFil: Harari, Diego Dario. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Medina, Maria Clementina. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Argentino de Radioastronomía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Argentino de Radioastronomía; ArgentinaFil: Romero, Gustavo Esteban. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Argentino de Radioastronomía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Argentino de Radioastronomía; ArgentinaFil: Suarez, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnología en Detección y Astropartículas. Comisión Nacional de Energía Atómica. Instituto de Tecnología en Detección y Astropartículas. Universidad Nacional de San Martín. Instituto de Tecnología en Detección y Astropartículas; ArgentinaThe European Physical Society Conference on High Energy PhysicsVeneciaItaliaEuropean Physical Societ

The geometry of the magnetic field in the central molecular zone measured by PILOT

We present the first far infrared (FIR) dust emission polarization map covering the full extent of Milky Way’s central molecular zone (CMZ). The data, obtained with the PILOT balloon-borne experiment, covers the Galactic center region − 2° < ℓ < 2°, − 4° < b < 3° at a wavelength of 240 μm and an angular resolution of 2.2′. From our measured dust polarization angles, we infer a magnetic field orientation projected onto the plane of the sky (POS) that is remarkably ordered over the full extent of the CMZ, with an average tilt angle of ≃22° clockwise with respect to the Galactic plane. Our results confirm previous claims that the field traced by dust polarized emission is oriented nearly orthogonally to the field traced by GHz radio synchrotron emission in the Galactic center region. The observed field structure is globally compatible with the latest Planck polarization data at 353 and 217 GHz. Upon subtraction of the extended emission in our data, the mean field orientation that we obtain shows good agreement with the mean field orientation measured at higher angular resolution by the JCMT within the 20 and 50 km s−1 molecular clouds. We find no evidence that the magnetic field orientation is related to the 100 pc twisted ring structure within the CMZ. The low polarization fraction in the Galactic center region measured with Planck at 353 GHz combined with a highly ordered projected field orientation is unusual. This feature actually extends to the whole inner Galactic plane. We propose that it could be caused by the increased number of turbulent cells for the long lines of sight towards the inner Galactic plane or to dust properties specific to the inner regions of the Galaxy. Assuming equipartition between magnetic pressure and ram pressure, we obtain magnetic field strength estimates of the order of 1 mG for several CMZ molecular clouds

Exploring Cosmic Origins with CORE: Cluster Science

We examine the cosmological constraints that can be achieved with a galaxycluster survey with the future CORE space mission. Using realistic simulationsof the millimeter sky, produced with the latest version of the Planck SkyModel, we characterize the CORE cluster catalogues as a function of the mainmission performance parameters. We pay particular attention to telescope size,key to improved angular resolution, and discuss the comparison and thecomplementarity of CORE with ambitious future ground-based CMB experiments thatcould be deployed in the next decade. A possible CORE mission concept with a150 cm diameter primary mirror can detect of the order of 50,000 clustersthrough the thermal Sunyaev-Zeldovich effect (SZE). The total yield increases(decreases) by 25% when increasing (decreasing) the mirror diameter by 30 cm.The 150 cm telescope configuration will detect the most massive clusters($>10^{14}\, M_\odot$) at redshift $z>1.5$ over the whole sky, although theexact number above this redshift is tied to the uncertain evolution of thecluster SZE flux-mass relation; assuming self-similar evolution, CORE willdetect $\sim 500$ clusters at redshift $z>1.5$. This changes to 800 (200) whenincreasing (decreasing) the mirror size by 30 cm. CORE will be able to measureindividual cluster halo masses through lensing of the cosmic microwavebackground anisotropies with a 1-$\sigma$ sensitivity of $4\times10^{14}M_\odot$, for a 120 cm aperture telescope, and $10^{14} M_\odot$ for a 180 cmone. [abridged