Parents\u27 Goals: An Analysis of Therapist Reasoning

Purpose: Illustrate the use of DDDM to develop parent-identified goals for occupational therapy and to identify underlying sensory integration factors hypothesized to be impacting participation

Caspase 3 cleavage of Pax7 inhibits self-renewal of satellite cells

Compensatory growth and regeneration of skeletal muscle is dependent on the resident stem cell population, satellite cells (SCs). Self-renewal and maintenance of the SC niche is coordinated by the paired-box transcription factor Pax7, and yet continued expression of this protein inhibits the myoblast differentiation program. As such, the reduction or removal of Pax7 may denote a key prerequisite for SCs to abandon self-renewal and acquire differentiation competence. Here, we identify caspase 3 cleavage inactivation of Pax7 as a crucial step for terminating the self-renewal process. Inhibition of caspase 3 results in elevated Pax7 protein and SC self-renewal, whereas caspase activation leads to Pax7 cleavage and initiation of the myogenic differentiation program. Moreover, in vivo inhibition of caspase 3 activity leads to a profound disruption in skeletal muscle regeneration with an accumulation of SCs within the niche. We have also noted that casein kinase 2 (CK2)-directed phosphorylation of Pax7 attenuates caspase-directed cleavage. Together, these results demonstrate that SC fate is dependent on opposing posttranslational modifications of the Pax7 protein

A Giant Planet Undergoing Extreme-Ultraviolet Irradiation By Its Hot Massive-Star Host

The amount of ultraviolet irradiation and ablation experienced by a planet depends strongly on the temperature of its host star. Of the thousands of extrasolar planets now known, only six have been found that transit hot, A-type stars (with temperatures of 7,300–10,000 kelvin), and no planets are known to transit the even hotter B-type stars. For example, WASP-33 is an A-type star with a temperature of about 7,430 kelvin, which hosts the hottest known transiting planet, WASP-33b (ref. 1); the planet is itself as hot as a red dwarf star of type M (ref. 2). WASP-33b displays a large heat differential between its dayside and nightside2, and is highly inflated–traits that have been linked to high insolation3,4. However, even at the temperature of its dayside, its atmosphere probably resembles the molecule-dominated atmospheres of other planets and, given the level of ultraviolet irradiation it experiences, its atmosphere is unlikely to be substantially ablated over the lifetime of its star. Here we report observations of the bright star HD 195689 (also known as KELT-9), which reveal a close-in (orbital period of about 1.48 days) transiting giant planet, KELT-9b. At approximately 10,170 kelvin, the host star is at the dividing line between stars of type A and B, and we measure the dayside temperature of KELT-9b to be about 4,600 kelvin. This is as hot as stars of stellar type K4 (ref. 5). The molecules in K stars are entirely dissociated, and so the primary sources of opacity in the dayside atmosphere of KELT-9b are probably atomic metals. Furthermore, KELT-9b receives 700 times more extreme-ultraviolet radiation (that is, with wavelengths shorter than 91.2 nanometres) than WASP-33b, leading to a predicted range of mass-loss rates that could leave the planet largely stripped of its envelope during the main-sequence lifetime of the host star (ref. 6)

An Interprofessional, Tailored Behavioral Intervention for Sleep Problems in Autism: Use of Sensory Data to Inform Intervention

Purpose: The purpose of this poster is to demonstrate how Sensory Profile data informed occupational therapy sleep interventions for two participants as part of an Interprofessional Tailored Behavioral Intervention study

Evaluation of the association of heterozygous germline variants in NTHL1 with breast cancer predisposition: an international multi-center study of 47,180 subjects.

Bi-allelic loss-of-function (LoF) variants in the base excision repair (BER) gene NTHL1 cause a high-risk hereditary multi-tumor syndrome that includes breast cancer, but the contribution of heterozygous variants to hereditary breast cancer is unknown. An analysis of 4985 women with breast cancer, enriched for familial features, and 4786 cancer-free women revealed significant enrichment for NTHL1 LoF variants. Immunohistochemistry confirmed reduced NTHL1 expression in tumors from heterozygous carriers but the NTHL1 bi-allelic loss characteristic mutational signature (SBS 30) was not present. The analysis was extended to 27,421 breast cancer cases and 19,759 controls from 10 international studies revealing 138 cases and 93 controls with a heterozygous LoF variant (OR 1.06, 95% CI: 0.82-1.39) and 316 cases and 179 controls with a missense variant (OR 1.31, 95% CI: 1.09-1.57). Missense variants selected for deleterious features by a number of in silico bioinformatic prediction tools or located within the endonuclease III functional domain showed a stronger association with breast cancer. Somatic sequencing of breast cancers from carriers indicated that the risk associated with NTHL1 appears to operate through haploinsufficiency, consistent with other described low-penetrance breast cancer genes. Data from this very large international multicenter study suggests that heterozygous pathogenic germline coding variants in NTHL1 may be associated with low- to moderate- increased risk of breast cancer

GDF15 promotes weight loss by enhancing energy expenditure in muscle

Funding Information: We thank R. Seeley for sharing GFRAL-null mice; B. Lowell for sharing β-less mice; and J. Wu for shipping β-less mice to us. G.R.S. was supported by a Diabetes Canada Investigator Award (DI-5-17-5302-GS), a Canadian Institutes of Health Research Foundation Grant (201709FDN-CEBA-116200), a Tier 1 Canada Research Chair in Metabolic Diseases and a J. Bruce Duncan Endowed Chair in Metabolic Diseases; D.W. by Fellowship Grants from the McMaster Institute for Research on Aging (MIRA) at McMaster University; S.R. by a postdoctoral fellowship supported by MITACS and Novo Nordisk; L.K.T. by a CIHR Post-Doctoral Fellowship Award and Michael DeGroote Fellowship Award in Basic Biomedical Science; E.M.D. by a Vanier Canada Graduate Scholarship; G.P.H. by the Natural Sciences and Engineering Research Council of Canada (NSERC: 400362); G.J.D. and S.M.F. by NSERC-CGSM scholarships; L.D. by the Fonds de Recherche du Québec-Santé doctoral training award; D.P.B. by the GSK Chair in Diabetes of Université de Sherbrooke and a FRQS J1 salary award. The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health, and by the NCI, NHGRI, NHLBI, NIDA, NIMH and NINDS. Funding Information: S.B.J. and R.E.K. are employees of Novo Nordisk, a pharmaceutical company producing and selling medicine for the treatment of diabetes and obesity. G.R.S. is a co-founder and shareholder of Espervita Therapeutics. McMaster University has received funding from Espervita Therapeutics, Esperion Therapeutics, Poxel Pharmaceuticals and Nestle for research conducted in the laboratory of G.R.S. S.R. is supported by a MITACS postdoctoral fellowship sponsored by Novo Nordisk. H.C.G. holds the McMaster-Sanofi Population Health Institute Chair in Diabetes Research and Care. G.R.S., G.P. and H.C.G. are inventors listed on a patent for identifying GDF15 as a biomarker for metformin. G.R.S. has received consulting/speaking fees from Astra Zeneca, Eli Lilly, Esperion Therapeutics, Merck, Poxel Pharmaceuticals and Cambrian Biosciences. The other authors declare no competing interests. Publisher Copyright: © 2023, The Author(s).Peer reviewedPublisher PD

KELT-16b: A Highly Irradiated, Ultra-short Period Hot Jupiter Nearing Tidal Disruption

We announce the discovery of KELT-16b, a highly irradiated, ultra-short period hot Jupiter transiting the relatively bright (V = 11.7) star TYC 2688-1839-1/KELT-16. A global analysis of the system shows KELT-16 to be an F7V star with ${T}_{\mathrm{eff}}=6236\pm 54$ K, $\mathrm{log}{g}_{\star }={4.253}_{-0.036}^{+0.031}$, $[\mathrm{Fe}/{\rm{H}}]=-{0.002}_{-0.085}^{+0.086}$, ${M}_{\star }={1.211}_{-0.046}^{+0.043}\,{M}_{\odot }$, and ${R}_{\star }\,={1.360}_{-0.053}^{+0.064}{R}_{\odot }$. The planet is a relatively high-mass inflated gas giant with ${M}_{{\rm{P}}}={2.75}_{-0.15}^{+0.16}{M}_{{\rm{J}}}$, ${R}_{{\rm{P}}}={1.415}_{-0.067}^{+0.084}{R}_{{\rm{J}}}$, density ${\rho }_{{\rm{P}}}=1.20\pm 0.18$ g cm−3, surface gravity $\mathrm{log}\,{g}_{{\rm{P}}}={3.530}_{-0.049}^{+0.042}$, and ${T}_{\mathrm{eq}}={2453}_{-47}^{+55}$ K. The best-fitting linear ephemeris is ${T}_{{\rm{C}}}=2457247.24791\pm 0.00019$ ${\mathrm{BJD}}_{\mathrm{TDB}}\$and $P=0.9689951\pm 0.0000024$ day. KELT-16b joins WASP-18b, −19b, −43b, −103b, and HATS-18b as the only giant transiting planets with P \u3c 1 day. Its ultra-short period and high irradiation make it a benchmark target for atmospheric studies by the Hubble Space Telescope, Spitzer, and eventually the James Webb Space Telescope. For example, as a hotter, higher-mass analog of WASP-43b, KELT-16b may feature an atmospheric temperature–pressure inversion and day-to-night temperature swing extreme enough for TiO to rain out at the terminator. KELT-16b could also join WASP-43b in extending tests of the observed mass–metallicity relation of the solar system gas giants to higher masses. KELT-16b currently orbits at a mere ~1.7 Roche radii from its host star, and could be tidally disrupted in as little as a few ×105 years (for a stellar tidal quality factor of ${Q}_{* }^{\prime }={10}^{5}$). Finally, the likely existence of a widely separated bound stellar companion in the KELT-16 system makes it possible that Kozai–Lidov (KL) oscillations played a role in driving KELT-16b inward to its current precarious orbit

Interhospital Transfer Before Thrombectomy Is Associated With Delayed Treatment and Worse Outcome in the STRATIS Registry (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke).

BACKGROUND: Endovascular treatment with mechanical thrombectomy (MT) is beneficial for patients with acute stroke suffering a large-vessel occlusion, although treatment efficacy is highly time-dependent. We hypothesized that interhospital transfer to endovascular-capable centers would result in treatment delays and worse clinical outcomes compared with direct presentation. METHODS: STRATIS (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) was a prospective, multicenter, observational, single-arm study of real-world MT for acute stroke because of anterior-circulation large-vessel occlusion performed at 55 sites over 2 years, including 1000 patients with severe stroke and treated within 8 hours. Patients underwent MT with or without intravenous tissue plasminogen activator and were admitted to endovascular-capable centers via either interhospital transfer or direct presentation. The primary clinical outcome was functional independence (modified Rankin Score 0-2) at 90 days. We assessed (1) real-world time metrics of stroke care delivery, (2) outcome differences between direct and transfer patients undergoing MT, and (3) the potential impact of local hospital bypass. RESULTS: A total of 984 patients were analyzed. Median onset-to-revascularization time was 202.0 minutes for direct versus 311.5 minutes for transfer patients ( CONCLUSIONS: In this large, real-world study, interhospital transfer was associated with significant treatment delays and lower chance of good outcome. Strategies to facilitate more rapid identification of large-vessel occlusion and direct routing to endovascular-capable centers for patients with severe stroke may improve outcomes. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02239640