Rx for addiction and medication safety: An evaluation of teen education for opioid misuse prevention

Background: Rhode Island (RI) ninth graders report lifetime nonmedical use of prescription opioids (NMUPO) of 8.9%. NMUPO is associated with transition to heroin use, opioid overdose, and death. Objectives: Measure changes in 9th grade students\u27 knowledge, confidence, perceptions of opioid use disorder prevention, overdose response with naloxone, treatment, and recovery, following the delivery of an interactive substance use disorder curriculum. Methods: Eight RI public high schools were recruited to participate. Freshman in each school were administered identical surveys that collected demographic data, substance use and misuse knowledge, students\u27 perceptions of substance misuse harm, reported drug use, and risk and protective behaviors before and after the curriculum. Results: Among 969 pre-intervention survey respondents, 19% reported use of marijuana, 3% heroin use, and 21% nonmedical use of prescription opioids. Between the pre-intervention to the post-intervention survey, significantly more students identified that addiction is a chronic brain disease (79%–83%, p = 0.05), drug users are not responsible for their addiction (81%–88%, p = 0.001), and that non-medical use of a prescription medication is use without a prescription (81%–88%, p = 0.001). Improved confidence was also reported in identifying opioid withdrawal symptoms (26%–45%, p \u3c 0.0001), identifying signs of an opioid overdose from 29% to 46% (p \u3c 0.0001), and knowing when to administer naloxone (17%–45%, p \u3c 0.0001). Confidence to refer someone to treatment improved from 31% to 45% (p \u3c 0.0001). Logistic regression showed associations between mental health, peer use, parental affection, and academic performance factors as related to NMUPO. Conclusions: Students reported significant NMUPO prevalence. Ninth grade students\u27 knowledge and confidence of opioid misuse, overdose response, and recovery resources increased following the delivery of a multi-modal interactive substance use disorder curriculum. Community, school, and student-level interventions are needed to reduce NMUPO

Egg activation events are regulated by the duration of a sustained [Ca2+]cyt signal in the mouse

AbstractAlthough the dynamics of oscillations of cytosolic Ca2+ concentration ([Ca2+]cyt) play important roles in early mammalian development, the impact of the duration when [Ca2+]cyt is elevated is not known. To determine the sensitivity of fertilization-associated responses [i.e., cortical granule exocytosis, resumption of the cell cycle, Ca2+/calmodulin-dependent protein kinase II (CaMKII) activity, recruitment of maternal mRNAs] and developmental competence of the parthenotes to the duration of a [Ca2+]cyt transient, unfertilized mouse eggs were subjected to a prolonged [Ca2+]cyt change for 15, 25, or 50 min by means of repetitive Ca2+ electropermeabilization at 2-min intervals. The initiation and completion of fertilization-associated responses are correlated with the duration of time in which the [Ca2+]cyt is elevated, with the exception that autonomous CaMKII activity is down-regulated with prolonged elevated [Ca2+]cyt. Activated eggs from 25- or 50-min treatments readily develop to the blastocyst stage with no sign of apoptosis or necrosis and some implant. Ca2+ influx into unfertilized eggs causes neither Ca2+ release from intracellular stores nor rapid removal of cytosolic Ca2+. Thus, the total Ca2+ signal input appears to be an important regulatory parameter that ensures completion of fertilization-associated events and oocytes have a surprising degree of tolerance for a prolonged change in [Ca2+]cyt

Bacterial Indole as a Multifunctional Regulator of Klebsiella oxytoca Complex Enterotoxicity.

Gastrointestinal microbes respond to biochemical metabolites that coordinate their behaviors. Here, we demonstrate that bacterial indole functions as a multifactorial mitigator of Klebsiella grimontii and Klebsiella oxytoca pathogenicity. These closely related microbes produce the enterotoxins tilimycin and tilivalline; cytotoxin-producing strains are the causative agent of antibiotic-associated hemorrhagic colitis and have been associated with necrotizing enterocolitis of premature infants. We demonstrate that carbohydrates induce cytotoxin synthesis while concurrently repressing indole biosynthesis. Conversely, indole represses cytotoxin production. In both cases, the alterations stemmed from differ- ential transcription of npsA and npsB, key genes involved in tilimycin biosynthesis. Indole also enhances conversion of tilimycin to tilivalline, an indole analog with reduced cytotox- icity. In this context, we established that tilivalline, but not tilimycin, is a strong agonist of pregnane X receptor (PXR), a master regulator of xenobiotic detoxification and intestinal inflammation. Tilivalline binding upregulated PXR-responsive detoxifying genes and inhib- ited tubulin-directed toxicity. Bacterial indole, therefore, acts in a multifunctional manner to mitigate cytotoxicity by Klebsiella spp.: suppression of toxin production, enhanced con- version of tilimycin to tilivalline, and activation of PXR

TOI-332 b: a super dense Neptune found deep within the Neptunian desert

To date, thousands of planets have been discovered, but there are regions of the orbital parameter space that are still bare. An example is the short period and intermediate mass/radius space known as the ‘Neptunian desert’, where planets should be easy to find but discoveries remain few. This suggests unusual formation and evolution processes are responsible for the planets residing here. We present the discovery of TOI-332 b, a planet with an ultra-short period of 0.78 d that sits firmly within the desert. It orbits a K0 dwarf with an effective temperature of 5251 ± 71 K. TOI-332 b has a radius of $3.20^{+0.16}_{-0.12}$ R⊕, smaller than that of Neptune, but an unusually large mass of 57.2 ± 1.6 M⊕. It has one of the highest densities of any Neptune-sized planet discovered thus far at $9.6^{+1.1}_{-1.3}$ g cm−3. A 4-layer internal structure model indicates it likely has a negligible hydrogen-helium envelope, something only found for a small handful of planets this massive, and so TOI-332 b presents an interesting challenge to planetary formation theories. We find that photoevaporation cannot account for the mass-loss required to strip this planet of the Jupiter-like envelope it would have been expected to accrete. We need to look towards other scenarios, such as high-eccentricity migration, giant impacts, or gap opening in the protoplanetary disc, to try and explain this unusual discovery

TKS X: Confirmation of TOI-1444b and a Comparative Analysis of the Ultra-short-period Planets with Hot Neptunes

We report the discovery of TOI-1444b, a 1.4-$R_\oplus$ super-Earth on a 0.47-day orbit around a Sun-like star discovered by {\it TESS}. Precise radial velocities from Keck/HIRES confirmed the planet and constrained the mass to be $3.87 \pm 0.71 M_\oplus$. The RV dataset also indicates a possible non-transiting, 16-day planet ($11.8\pm2.9M_\oplus$). We report a tentative detection of phase curve variation and secondary eclipse of TOI-1444b in the {\it TESS} bandpass. TOI-1444b joins the growing sample of 17 ultra-short-period planets with well-measured masses and sizes, most of which are compatible with an Earth-like composition. We take this opportunity to examine the expanding sample of ultra-short-period planets ($<2R_\oplus$) and contrast them with the newly discovered sub-day ultra-hot Neptunes ($>3R_\oplus$, $>2000F_\oplus$ TOI-849 b, LTT9779 b and K2-100). We find that 1) USPs have predominately Earth-like compositions with inferred iron core mass fractions of 0.32$\pm$0.04; and have masses below the threshold of runaway accretion ($\sim 10M_\oplus$), while ultra-hot Neptunes are above the threshold and have H/He or other volatile envelope. 2) USPs are almost always found in multi-planet system consistent with a secular interaction formation scenario; ultra-hot Neptunes ($P_{\rm orb} \lesssim$1 day) tend to be ``lonely' similar to longer-period hot Neptunes($P_{\rm orb}$1-10 days) and hot Jupiters. 3) USPs occur around solar-metallicity stars while hot Neptunes prefer higher metallicity hosts. 4) In all these respects, the ultra-hot Neptunes show more resemblance to hot Jupiters than the smaller USP planets, although ultra-hot Neptunes are rarer than both USP and hot Jupiters by 1-2 orders of magnitude.Comment: Accepted too AJ. 12 Figures, 4 table

The TESS-Keck Survey II: An Ultra-Short Period Rocky Planet and its Siblings Transiting the Galactic Thick-Disk Star TOI-561

We report the discovery of TOI-561, a multi-planet system in the galactic thick disk that contains a rocky, ultra-short period planet (USP). This bright ($V=10.2$) star hosts three small transiting planets identified in photometry from the NASA TESS mission: TOI-561 b (TOI-561.02, P=0.44 days, $R_b = 1.45\pm0.11\,R_\oplus$), c (TOI-561.01, P=10.8 days, $R_c=2.90\pm0.13\,R_\oplus$), and d (TOI-561.03, P=16.3 days, $R_d=2.32\pm0.16\,R_\oplus$). The star is chemically ([Fe/H]$=-0.41\pm0.05$, [$\alpha$/H]$=+0.23\pm0.05$) and kinematically consistent with the galactic thick disk population, making TOI-561 one of the oldest ($10\pm3\,$Gyr) and most metal-poor planetary systems discovered yet. We dynamically confirm planets b and c with radial velocities from the W. M. Keck Observatory High Resolution Echelle Spectrometer. Planet b has a mass and density of $3.2\pm0.8\,M_\oplus$ and $5.5^{+2.0}_{-1.6}\,$g$\,$cm$^{-3}$, consistent with a rocky composition. Its lower-than-average density is consistent with an iron-poor composition, although an Earth-like iron-to-silicates ratio is not ruled out. Planet c is $7.0\pm2.3\,M_\oplus$ and $1.6\pm0.6\,$g$\,$cm$^{-3}$, consistent with an interior rocky core overlaid with a low-mass volatile envelope. Several attributes of the photometry for planet d (which we did not detect dynamically) complicate the analysis, but we vet the planet with high-contrast imaging, ground-based photometric follow-up and radial velocities. TOI-561 b is the first rocky world around a galactic thick-disk star confirmed with radial velocities and one of the best rocky planets for thermal emission studies.Comment: Accepted at The Astronomical Journal; 25 pages, 10 figure

The discovery and follow-up of four transiting short-period sub-Neptunes orbiting M dwarfs

Sub-Neptunes with radii of 2–3 R⊕ are intermediate in size between rocky planets and Neptune-sized planets. The orbital properties and bulk compositions of transiting sub-Neptunes provide clues to the formation and evolution of close-in small planets. In this paper, we present the discovery and follow-up of four sub-Neptunes orbiting M dwarfs (TOI-782, TOI-1448, TOI-2120, and TOI-2406), three of which were newly validated by ground-based follow-up observations and statistical analyses. TOI-782 b, TOI-1448 b, TOI-2120 b, and TOI-2406 b have radii of Rp = 2.740 +0.082-0.079 R⊕, 2.769+0.073-0.068 R⊕, 2.120 ± 0.067 R⊕, and 2.830+0.068-0.066 R⊕ and orbital periods of P = 8.02, 8.11, 5.80, and 3.08 days, respectively. Doppler monitoring with the Subaru/InfraRed Doppler instrument led to 2σ upper limits on the masses of <19.1 M⊕, <19.5 M⊕, <6.8 M⊕, and <15.6 M⊕ for TOI-782 b, TOI-1448 b, TOI-2120 b, and TOI-2406 b, respectively. The mass–radius relationship of these four sub-Neptunes testifies to the existence of volatile material in their interiors. These four sub-Neptunes, which are located above the so-called "radius valley," are likely to retain a significant atmosphere and/or an icy mantle on the core, such as a water world. We find that at least three of the four sub-Neptunes (TOI-782 b, TOI-2120 b, and TOI-2406 b), orbiting M dwarfs older than 1 Gyr, are likely to have eccentricities of e ∼ 0.2–0.3. The fact that tidal circularization of their orbits is not achieved over 1 Gyr suggests inefficient tidal dissipation in their interiors.Peer reviewe

A pair of TESS planets spanning the radius valley around the nearby mid-M dwarf LTT 3780

We present the confirmation of two new planets transiting the nearby mid-M dwarf LTT 3780 (TIC 36724087, TOI-732, $V=13.07$, $K_s=8.204$, $R_s$=0.374 R$_{\odot}$, $M_s$=0.401 M$_{\odot}$, d=22 pc). The two planet candidates are identified in a single TESS sector and are validated with reconnaissance spectroscopy, ground-based photometric follow-up, and high-resolution imaging. With measured orbital periods of $P_b=0.77$ days, $P_c=12.25$ days and sizes $r_{p,b}=1.33\pm 0.07$ R$_{\oplus}$, $r_{p,c}=2.30\pm 0.16$ R$_{\oplus}$, the two planets span the radius valley in period-radius space around low mass stars thus making the system a laboratory to test competing theories of the emergence of the radius valley in that stellar mass regime. By combining 63 precise radial-velocity measurements from HARPS and HARPS-N, we measure planet masses of $m_{p,b}=2.62^{+0.48}_{-0.46}$ M$_{\oplus}$ and $m_{p,c}=8.6^{+1.6}_{-1.3}$ M$_{\oplus}$, which indicates that LTT 3780b has a bulk composition consistent with being Earth-like, while LTT 3780c likely hosts an extended H/He envelope. We show that the recovered planetary masses are consistent with predictions from both photoevaporation and from core-powered mass loss models. The brightness and small size of LTT 3780, along with the measured planetary parameters, render LTT 3780b and c as accessible targets for atmospheric characterization of planets within the same planetary system and spanning the radius valley.Comment: Accepted to AJ. 8 figures, 6 tables. CSV file of the RV measurements (i.e. Table 2) are included in the source cod

The L 98-59 System: Three Transiting, Terrestrial-size Planets Orbiting a Nearby M Dwarf

We report the Transiting Exoplanet Survey Satellite (TESS) discovery of three terrestrial-size planets transiting L 98-59 (TOI-175, TIC 307210830)—a bright M dwarf at a distance of 10.6 pc. Using the Gaia-measured distance and broadband photometry, we find that the host star is an M3 dwarf. Combined with the TESS transits from three sectors, the corresponding stellar parameters yield planet radii ranging from 0.8 R ⊕ to 1.6 R ⊕. All three planets have short orbital periods, ranging from 2.25 to 7.45 days with the outer pair just wide of a 2:1 period resonance. Diagnostic tests produced by the TESS Data Validation Report and the vetting package DAVE rule out common false-positive sources. These analyses, along with dedicated follow-up and the multiplicity of the system, lend confidence that the observed signals are caused by planets transiting L 98-59 and are not associated with other sources in the field. The L 98-59 system is interesting for a number of reasons: the host star is bright (V = 11.7 mag, K = 7.1 mag) and the planets are prime targets for further follow-up observations including precision radial-velocity mass measurements and future transit spectroscopy with the James Webb Space Telescope; the near-resonant configuration makes the system a laboratory to study planetary system dynamical evolution; and three planets of relatively similar size in the same system present an opportunity to study terrestrial planets where other variables (age, metallicity, etc.) can be held constant. L 98-59 will be observed in four more TESS sectors, which will provide a wealth of information on the three currently known planets and have the potential to reveal additional planets in the system