A New Brown Dwarf Desert? A Scarcity of Wide Ultracool Binaries

We present the results of a deep-imaging search for wide companions to low-mass stars and brown dwarfs using NSFCam on IRTF. We searched a sample of 132 M7-L8 dwarfs to magnitude limits of $J \sim 20.5$ and $K \sim 18.5$, corresponding to secondary-primary mass ratios of $\sim 0.5$. No companions were found with separations between 2{\arcsec} to 31{\arcsec} ($\sim$40 AU to $\sim$1000 AU). This null result implies a wide companion frequency below 2.3% at the 95% confidence level within the sensitivity limits of the survey. Preliminary modeling efforts indicate that we could have detected 85% of companions more massive than $0.05 M_{\odot}$ and 50% above $0.03 M_{\odot}$.Comment: 27 pages, 8 figures, 3 tables: accepted to the Astronomical Journa

Involvement of Purinergic P2X4 Receptors in Alcohol Intake of High-Alcohol-Drinking (HAD) Rats

Background: The P2X4 receptor is thought to be involved in regulating alcohol-consuming behaviors and ethanol (EtOH) has been reported to inhibit P2X4 receptors. Ivermectin is an anti-parasitic agent that acts as a positive allosteric modulator of the P2X4 receptor. The current study examined the effects of systemically- and centrally-administered ivermectin on alcohol drinking of replicate lines of high-alcohol-drinking (HAD-1/HAD-2) rats, and the effects of lentiviral-delivered short-hairpin RNAs (shRNAs) targeting P2rx4 on EtOH intake of female HAD2 rats. Method: For the 1st experiment, adult male HAD-1 & HAD-2 rats were given 24-hr free-choice access to 15% EtOH vs. water. Dose-response effects of ivermectin (1.5 to 7.5 mg/kg i.p.) on EtOH intake were determined; the effects of ivermectin were then examined for 2% w/v sucrose intake over 5 consecutive days. In the 2nd experiment, female HAD-2 rats were trained to consume 15% EtOH under 2-hr limited access conditions, and dose-response effects of intracerebroventricular (ICV) administration of ivermectin (0.5 to 2.0 μg) were determined over 5 consecutive days. The 3rd experiment determined the effects of microinfusion of a lentivirus expressing P2rx4 shRNAs into the posterior ventral tegmental area (VTA) on 24-hr EtOH free-choice drinking of female HAD-2 rats. Results: The highest i.p. dose of ivermectin reduced alcohol drinking (30-45%) in both rat lines, but did not alter sucrose intake. HAD-2 rats appeared to be more sensitive than HAD1 rats to the effects of ivermectin. ICV administration of ivermectin reduced 2-hr limited access intake (∼35%) of femal

FIGO good practice recommendations on reduction of preterm birth in pregnancies conceived by assisted reproductive technologies

Funding Information: This work has been supported by grants from March of Dimes to the FIGO Working Group for Preterm Birth. This document is endorsed by FIGO Committee for Reproductive Medicine, Endocrinology and Infertility, and was discussed at their committee meeting on March 11, 2021. Funding Information: Ben W. Mol reports an investigator grant from NHMRC; consultancy for ObsEva; and research funding from Guerbet, Ferring, and Merck KGaA. Bo Jacobbson reports Research grants from Swedish Research Council, Norwegian Research Council, March of Dimes, Burroughs Wellcome Fund and the US National Institute of Health; clinical diagnostic trials on NIPT with Ariosa (completed), Natera (ongoing), Vanadis (completed) and Hologic (ongoing) with expendidures reimbused per patient; clinical probiotic studies with product provided by FukoPharma (ongoing, no funding) and BioGaia (ongoing; also provided a research grant for the specific study); collaboration in IMPACT study where Roche, Perkin Elmer and Thermo Fisher provided reagents to PLGF analyses; coordination of scientific conferences and meetings with commercial partners as such as NNFM 2015, ESPBC 2016 and a Nordic educational meeting about NIPT and preeclampsia screening. Bo Jacobbson is also Chair of the FIGO Working Group for Preterm Birth and the European Association of Perinatal Medicine's special interest group of preterm delivery; steering group member of Genomic Medicine Sweden; chairs the Genomic Medicine Sweden complex diseases group; and is Swedish representative in the Nordic Society of Precision Medicine. William Grobman and Kelle Moley report no conflicts of interest.Peer reviewedPublisher PD

Ibudilast reduces alcohol drinking in multiple animal models of alcohol dependence

Neuroinflammatory signaling pathways in the central nervous system are of current interest as potential pharmacotherapy targets for alcohol dependence. In this study, we examined the ability of ibudilast, a non-selective phosphodiesterase inhibitor, to reduce alcohol drinking and relapse in alcohol-preferring P rats, high-alcohol drinking HAD1 rats, and in mice made dependent on alcohol through cycles of alcohol vapor exposure. When administered twice daily, ibudilast reduced alcohol drinking in rats by approximately 50% and reduced drinking by alcohol-dependent mice at doses which had no effect in non-dependent mice. These findings support the viability of ibudilast as a possible treatment for alcohol dependence

Reduction of alcohol drinking of alcohol-preferring (P) and high-alcohol drinking (HAD1) rats by targeting phosphodiesterase-4 (PDE4)

RATIONALE: Phosphodiesterase-4 (PDE4) and neuroimmune signaling have been posited to regulate alcohol drinking. OBJECTIVES: This study evaluated the involvement of PDE4 and Il22ra2 on ethanol (EtOH) intake by alcohol-preferring (P) and high-alcohol-drinking (HAD1) rats. METHODS: Exp 1 determined the dose-response effects of PDE4 inhibitors, rolipram, and Ro 20-1724, on 2 h/day free-choice EtOH intake by adult P and HAD1 rats. Exps 2-3 examined the effects of repeated administration with the PDE4 inhibitors on EtOH or sucrose intake and locomotor behavior. Exp 4 determined Pde4-associated gene expression differences in subregions of the extended amygdala, between high- and low-alcohol-consuming rat lines. Exp 5 evaluated the effects of infusing short hairpin RNA to knock down Il22ra2 in the nucleus accumbens (NAc) shell on a 24-h free-choice EtOH drinking by P rats. RESULTS: Administration of rolipram or Ro 20-1724 reduced EtOH intake by P rats; Ro 20-1724 reduced EtOH intake by HAD1 rats. Repeated rolipram or Ro 20-1724 exposure reduced EtOH intake by P and HAD1 rats. PDE4 inhibition induced motor impairment during the first hour of EtOH intake by P rats. Higher gene expression levels for PDE4A were found in the NAc shell of P vs NP rats. ShRNAs targeting Il22ra2 in the NAc shell significantly reduced chronic EtOH intake. CONCLUSIONS: PDE4 and neuroinflammatory/immune signaling pathways could represent molecular targets for the treatment of alcohol use disorders in genetically predisposed subjects. This study underscores the importance of testing compounds over multiple days and rat lines when determining efficacy to disrupt excessive alcohol intake