Trends in weight gain recorded in English primary care before and during the Coronavirus-19 pandemic: An observational cohort study using the OpenSAFELY platform.

BACKGROUND: Obesity and rapid weight gain are established risk factors for noncommunicable diseases and have emerged as independent risk factors for severe disease following Coronavirus Disease 2019 (COVID-19) infection. Restrictions imposed to reduce COVID-19 transmission resulted in profound societal changes that impacted many health behaviours, including physical activity and nutrition, associated with rate of weight gain. We investigated which clinical and sociodemographic characteristics were associated with rapid weight gain and the greatest acceleration in rate of weight gain during the pandemic among adults registered with an English National Health Service (NHS) general practitioner (GP) during the COVID-19 pandemic. METHODS AND FINDINGS: With the approval of NHS England, we used the OpenSAFELY platform inside TPP to conduct an observational cohort study of routinely collected electronic healthcare records. We investigated changes in body mass index (BMI) values recorded in English primary care between March 2015 and March 2022. We extracted data on 17,742,365 adults aged 18 to 90 years old (50.1% female, 76.1% white British) registered with an English primary care practice. We estimated individual rates of weight gain before (δ-prepandemic) and during (δ-pandemic) the pandemic and identified individuals with rapid weight gain (>0.5 kg/m2/year) in each period. We also estimated the change in rate of weight gain between the prepandemic and pandemic period (δ-change = δ-pandemic-δ-prepandemic) and defined extreme accelerators as the 10% of individuals with the greatest increase in their rate of weight gain (δ-change ≥1.84 kg/m2/year) between these periods. We estimated associations with these outcomes using multivariable logistic regression adjusted for age, sex, index of multiple deprivation (IMD), and ethnicity. P-values were generated in regression models. The median BMI of our study population was 27.8 kg/m2, interquartile range (IQR) [24.3, 32.1] in 2019 (March 2019 to February 2020) and 28.0 kg/m2, IQR [24.4, 32.6] in 2021. Rapid pandemic weight gain was associated with sex, age, and IMD. Male sex (male versus female: adjusted odds ratio (aOR) 0.76, 95% confidence interval (95% CI) [0.76, 0.76], p < 0.001), older age (e.g., 50 to 59 years versus 18 to 29 years: aOR 0.60, 95% CI [0.60, 0.61], p < 0.001]); and living in less deprived areas (least-deprived-IMD-quintile versus most-deprived: aOR 0.77, 95% CI [0.77, 0.78] p < 0.001) reduced the odds of rapid weight gain. Compared to white British individuals, all other ethnicities had lower odds of rapid pandemic weight gain (e.g., Indian versus white British: aOR 0.69, 95% CI [0.68, 0.70], p < 0.001). Long-term conditions (LTCs) increased the odds, with mental health conditions having the greatest effect (e.g., depression (aOR 1.18, 95% CI [1.17, 1.18], p < 0.001)). Similar characteristics increased odds of extreme acceleration in the rate of weight gain between the prepandemic and pandemic periods. However, changes in healthcare activity during the pandemic may have introduced new bias to the data. CONCLUSIONS: We found female sex, younger age, deprivation, white British ethnicity, and mental health conditions were associated with rapid pandemic weight gain and extreme acceleration in rate of weight gain between the prepandemic and pandemic periods. Our findings highlight the need to incorporate sociodemographic, physical, and mental health characteristics when formulating research, policies, and interventions targeting BMI in the period of post pandemic service restoration and in future pandemic planning

TESS Hunt for Young and Maturing Exoplanets (THYME) VII : Membership, rotation, and lithium in the young cluster Group-X and a new young exoplanet

The public, all-sky surveys Gaia and TESS provide the ability to identify new young associations and determine their ages. These associations enable study of planetary evolution by providing new opportunities to discover young exoplanets. A young association was recently identified by Tang et al. and F{\"u}rnkranz et al. using astrometry from Gaia (called "Group-X" by the former). In this work, we investigate the age and membership of this association; and we validate the exoplanet TOI 2048 b, which was identified to transit a young, late G dwarf in Group-X using photometry from TESS. We first identified new candidate members of Group-X using Gaia EDR3 data. To infer the age of the association, we measured rotation periods for candidate members using TESS data. The clear color--period sequence indicates that the association is the same age as the $300\pm50$ Myr-old NGC 3532. We obtained optical spectra for candidate members that show lithium absorption consistent with this young age. Further, we serendipitously identify a new, small association nearby Group-X, which we call MELANGE-2. Lastly, we statistically validate TOI 2048 b, which is $2.6\pm0.2$ \rearth\ radius planet on a 13.8-day orbit around its 300 Myr-old host star.Comment: Revised to correct error in reported planet radius (original: 2.1 Earth radii, corrected: 2.6 Earth radii) and units for planetary radius ratio entries in Table 8. All data tables available open-access with the AJ articl

TESS Hunt for Young and Maturing Exoplanets (THYME) IX: a 27 Myr extended population of Lower-Centaurus Crux with a transiting two-planet system

We report the discovery and characterization of a nearby (~ 85 pc), older (27 +/- 3 Myr), distributed stellar population near Lower-Centaurus-Crux (LCC), initially identified by searching for stars co-moving with a candidate transiting planet from TESS (HD 109833; TOI 1097). We determine the association membership using Gaia kinematics, color-magnitude information, and rotation periods of candidate members. We measure it's age using isochrones, gyrochronology, and Li depletion. While the association is near known populations of LCC, we find that it is older than any previously found LCC sub-group (10-16 Myr), and distinct in both position and velocity. In addition to the candidate planets around HD 109833 the association contains four directly-imaged planetary-mass companions around 3 stars, YSES-1, YSES-2, and HD 95086, all of which were previously assigned membership in the younger LCC. Using the Notch pipeline, we identify a second candidate transiting planet around HD 109833. We use a suite of ground-based follow-up observations to validate the two transit signals as planetary in nature. HD 109833 b and c join the small but growing population of <100 Myr transiting planets from TESS. HD 109833 has a rotation period and Li abundance indicative of a young age (< 100 Myr), but a position and velocity on the outskirts of the new population, lower Li levels than similar members, and a CMD position below model predictions for 27 Myr. So, we cannot reject the possibility that HD 109833 is a young field star coincidentally nearby the population.Comment: 23 pages, 15 figures, Accepted for publication in A

Extracellular matrix formation after transplantation of human embryonic stem cell-derived cardiomyocytes

Transplantation of human embryonic stem cell-derived cardiomyocytes (hESC-CM) for cardiac regeneration is hampered by the formation of fibrotic tissue around the grafts, preventing electrophysiological coupling. Investigating this process, we found that: (1) beating hESC-CM in vitro are embedded in collagens, laminin and fibronectin, which they bind via appropriate integrins; (2) after transplantation into the mouse heart, hESC-CM continue to secrete collagen IV, XVIII and fibronectin; (3) integrin expression on hESC-CM largely matches the matrix type they encounter or secrete in vivo; (4) co-transplantation of hESC-derived endothelial cells and/or cardiac progenitors with hESC-CM results in the formation of functional capillaries; and (5) transplanted hESC-CM survive and mature in vivo for at least 24 weeks. These results form the basis of future developments aiming to reduce the adverse fibrotic reaction that currently complicates cell-based therapies for cardiac disease, and to provide an additional clue towards successful engraftment of cardiomyocytes by co-transplanting endothelial cells

OpenSAFELY: The impact of COVID‐19 on azathioprine, leflunomide and methotrexate monitoring, and factors associated with change in monitoring rate

Aims The COVID-19 pandemic created unprecedented pressure on healthcare services. This study investigates whether disease-modifying antirheumatic drug (DMARD) safety monitoring was affected during the COVID-19 pandemic. Methods A population-based cohort study was conducted using the OpenSAFELY platform to access electronic health record data from 24.2 million patients registered at general practices using TPP's SystmOne software. Patients were included for further analysis if prescribed azathioprine, leflunomide or methotrexate between November 2019 and July 2022. Outcomes were assessed as monthly trends and variation between various sociodemographic and clinical groups for adherence with standard safety monitoring recommendations. Results An acute increase in the rate of missed monitoring occurred across the study population (+12.4 percentage points) when lockdown measures were implemented in March 2020. This increase was more pronounced for some patient groups (70–79 year-olds: +13.7 percentage points; females: +12.8 percentage points), regions (North West: +17.0 percentage points), medications (leflunomide: +20.7 percentage points) and monitoring tests (blood pressure: +24.5 percentage points). Missed monitoring rates decreased substantially for all groups by July 2022. Consistent differences were observed in overall missed monitoring rates between several groups throughout the study. Conclusion DMARD monitoring rates temporarily deteriorated during the COVID-19 pandemic. Deterioration coincided with the onset of lockdown measures, with monitoring rates recovering rapidly as lockdown measures were eased. Differences observed in monitoring rates between medications, tests, regions and patient groups highlight opportunities to tackle potential inequalities in the provision or uptake of monitoring services. Further research should evaluate the causes of the differences identified between groups

The primary cilium as a dual sensor of mechanochemical signals in chondrocytes

The primary cilium is an immotile, solitary, and microtubule-based structure that projects from cell surfaces into the extracellular environment. The primary cilium functions as a dual sensor, as mechanosensors and chemosensors. The primary cilia coordinate several essential cell signaling pathways that are mainly involved in cell division and differentiation. A primary cilium malfunction can result in several human diseases. Mechanical loading is sense by mechanosensitive cells in nearly all tissues and organs. With this sensation, the mechanical signal is further transduced into biochemical signals involving pathways such as Akt, PKA, FAK, ERK, and MAPK. In this review, we focus on the fundamental functional and structural features of primary cilia in chondrocytes and chondrogenic cells

TESS spots a mini-neptune interior to a hot saturn in the TOI-2000 system

Hot jupiters (P 60 $\mathrm{M}_\oplus$) are almost always found alone around their stars, but four out of hundreds known have inner companion planets. These rare companions allow us to constrain the hot jupiter's formation history by ruling out high-eccentricity tidal migration. Less is known about inner companions to hot Saturn-mass planets. We report here the discovery of the TOI-2000 system, which features a hot Saturn-mass planet with a smaller inner companion. The mini-neptune TOI-2000 b ($2.70 \pm 0.15 \,\mathrm{R}_\oplus$, $11.0 \pm 2.4 \,\mathrm{M}_\oplus$) is in a 3.10-day orbit, and the hot saturn TOI-2000 c ($8.14^{+0.31}_{-0.30} \,\mathrm{R}_\oplus$, $81.7^{+4.7}_{-4.6} \,\mathrm{M}_\oplus$) is in a 9.13-day orbit. Both planets transit their host star TOI-2000 (TIC 371188886, V = 10.98, TESS magnitude = 10.36), a metal-rich ([Fe/H] = $0.439^{+0.041}_{-0.043}$) G dwarf 174 pc away. TESS observed the two planets in sectors 9-11 and 36-38, and we followed up with ground-based photometry, spectroscopy, and speckle imaging. Radial velocities from CHIRON, FEROS, and HARPS allowed us to confirm both planets by direct mass measurement. In addition, we demonstrate constraining planetary and stellar parameters with MIST stellar evolutionary tracks through Hamiltonian Monte Carlo under the PyMC framework, achieving higher sampling efficiency and shorter run time compared to traditional Markov chain Monte Carlo. Having the brightest host star in the V band among similar systems, TOI-2000 b and c are superb candidates for atmospheric characterization by the JWST, which can potentially distinguish whether they formed together or TOI-2000 c swept along material during migration to form TOI-2000 b.Comment: v3 adds RV frequency analysis; 25 pages, 11 figures, 14 tables; revision submitted to MNRAS; machine-readable tables available as ancillary files; posterior samples available from Zenodo at https://doi.org/10.5281/zenodo.7683293 and source code at https://doi.org/10.5281/zenodo.798826

An experimental study of low-level laser therapy in rat Achilles tendon injury

The aim of this controlled animal study was to investigate the effect of low-level laser therapy (LLLT) administered 30 min after injury to the Achilles tendon. The study animals comprised 16 Sprague Dawley male rats divided in two groups. The right Achilles tendons were injured by blunt trauma using a mini guillotine, and were treated with LLLT or placebo LLLT 30 min later. The injury and LLLT procedures were then repeated 15 hours later on the same tendon. One group received active LLLT (λ = 904 nm, 60 mW mean output power, 0.158 W/cm2 for 50 s, energy 3 J) and the other group received placebo LLLT 23 hours after LLLT. Ultrasonographic images were taken to measure the thickness of the right and left Achilles tendons. Animals were then killed, and all Achilles tendons were tested for ultimate tensile strength (UTS). All analyses were performed by blinded observers. There was a significant increase in tendon thickness in the active LLLT group when compared with the placebo group (p < 0.05) and there were no significant differences between the placebo and uninjured left tendons. There were no significant differences in UTS between laser-treated, placebo-treated and uninjured tendons. Laser irradiation of the Achilles tendon at 0.158 W/cm2 for 50 s (3 J) administered within the first 30 min after blunt trauma, and repeated after 15 h, appears to lead to edema of the tendon measured 23 hours after LLLT. The guillotine blunt trauma model seems suitable for inflicting tendon injury and measuring the effects of treatment on edema by ultrasonography and UTS. More studies are needed to further refine this model