The intervertebral disc during growth : Signal intensity changes on magnetic resonance imaging and their relevance to low back pain

Funding Information: This research (official recipient: DS) was supported by The Research Institute of the Invalid Foundation (later Research Institute Orton) through grants by the Ministry of Social Affairs and Health in Finland (Project Identification Number A2500/ 465), and by the Siviä Kosti Foundation of the Invalid Foundation in Helsinki, Finland. The funders did not play any role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: © 2022 Lund et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Life-time prevalence of low back pain (LBP) in children and adolescents varies from 7% to 72%. Disc changes on magnetic resonance imaging (MRI) have been reported in up to 44% of children with earliest observations around pre-puberty. In this longitudinal cohort study, our objective was to determine the natural history of disc changes from childhood to early adulthood, and the possible association of these changes to LBP. Healthy 8-year-old schoolchildren were recruited for this longitudinal study consisting of a semi-structured interview, a clinical examination, and an MRI investigation at the age of 8–9 (Y8), 11–12 (Y12) and 18–19 (Y19) years. The interview inquired about LBP without trauma. T2-weighted sagittal MRI of the lumbar spine was acquired. Life-long prevalence of LBP was determined, and the disc signal intensity (SI) at the three lowest lumbar levels was assessed both visually using the Schneiderman classification (Bright-Speckled-Dark), and digitally using the disc to cerebrospinal fluid -SI ratio. Possible associations between SI changes and LBP were analyzed. Ninety-four of 208 eligible children were included at Y8 in 1994, 13 and 23 participants were lost to follow-up at Y12 and Y19, respectively. Prevalence of LBP increased after the pubertal growth spurt reaching 54% at Y19. On MRI, 18%, 10% and 38% of participants had disc SI changes at Y8, Y12 and Y19, respectively. No significant associations between self-reported LBP and either qualitative or quantitative disc SI changes were observed at any age. Life-time prevalence of LBP reached 54% by early adulthood. Disc SI changes on MRI traditionally labeled as degenerative were seen earlier than previously reported. Changes in disc SI were not associated with the presence of LBP in childhood, adolescence or early adulthood.Peer reviewe

ISSLS prize in clinical science 2022 : accelerated disc degeneration after pubertal growth spurt differentiates adults with low back pain from their asymptomatic peers

Purpose In this prospective observational cohort study, the development of lumbar intervertebral discs (LIVD) on magnetic resonance imaging (MRI) was investigated from childhood to adulthood with emphasis on the possible association of disc degeneration (DD) to low back pain (LBP). Methods In 2021, 89 subjects who were enrolled in 1994 in a longitudinal study with lumbar spine MRI at ages 8, 11 and 18 were invited to participate in a long-term follow-up comprising a clinical examination, selected patient-reported outcome measures and a lumbar spine MRI. We assessed all MRIs (three lowest LIVDs) with the Pfirrmann summary score, and the ratio of signal intensity of nucleus pulposus to signal intensity of cerebrospinal fluid (SINDL). We further analyzed whether disc changes at any age were associated with self-reported LBP at age 34. Results Of the 48 subjects in the follow-up, 35 reported LBP at age 34. The Pfirrmann summary score significantly increased with age (p < 0.001). Subjects reporting LBP at age 34 demonstrated statistically significantly higher summary scores at age 18 and 34 compared to asymptomatic subjects (p = 0.004 at age 18, and p = 0.039 at age 34). SINDL significantly decreased with age (p < 0.001 for all levels separately), but no significant differences between subjects with or without LBP at age 34 were noticed. Conclusion Subjects with LBP at age 34 had more widespread or severe DD already at age 18 compared to those without LBP.Peer reviewe

Decorin Expression and Oncosuppression in Human Embryonic Carcinomas

Human embryonic stem cells in culture can transform into malignant, cancer-like cells exhibiting lesser differentiation. After transplantation, these transformed cells can form highly malignant germ cell tumors. In humans, germ cell tumors often appear at gonadal sites, like in the testis. In this study, we examined the expression of small leucine rich proteoglycans in normal and karyotypically abnormal human embryonic stem cells using a publicly available transcriptome data. We also examined the expression of the small leucine rich proteoglycans in healthy human testis and in different human testicular non-seminoma germ cell tumors using IST Online database. Furthermore, we localized the expression of decorin, the prototype member of the small leucine rich proteoglycans, in samples representing the above testicular tissues, using in situ hybridization and immunohistochemistry. The analysis revealed that the expression of two small leucine rich proteoglycans, namely decorin and lumican, was induced in normal but not in karyotypically abnormal human embryonic stem cells during early cell differentiation. Similarly, in IST Online database the expression of these two small leucine rich proteoglycans was markedly higher in differentiated teratoma tissue than in undifferentiated embryonal carcinoma tissue. In testicular germ cell tumors decorin expression was completely lacking in the areas of undifferentiated malignant cells. The above results collectively suggest that decorin and lumican have a role in human stem cell differentiation and testicular non-seminoma germ cell tumor formation.</p

TOI-2119: A transiting brown dwarf orbiting an active M-dwarf from NASA’s TESS mission

We report the discovery of TOI-2119b, a transiting brown dwarf (BD) that orbits and is completely eclipsed by an active M-dwarf star. Using light curve data from the Transiting Exoplanet Survey Satellite mission and follow-up high-resolution Doppler spectroscopic observations, we find the BD has a radius of $R_b = 1.08 \pm 0.03{\rm R_J}$, a mass of $M_b = 64.4 \pm 2.3{\rm M_J}$, an orbital period of $P = 7.200865 \pm 0.00002$ days, and an eccentricity of $e=0.337\pm 0.002$. The host star has a mass of $M_\star = 0.53 \pm 0.02{\rm M_\odot}$, a radius of $R_\star= 0.50 \pm 0.01{\rm R_\odot}$, an effective temperature of $T_{\rm eff} = 3621 \pm 48$K, and a metallicity of $\rm [Fe/H]=+0.06\pm 0.08$. TOI-2119b joins an emerging population of transiting BDs around M-dwarf host stars, with TOI-2119 being the ninth such system. These M-dwarf--brown dwarf systems typically occupy mass ratios near $q = M_b/M_\star \approx 0.1-0.2$, which separates them from the typical mass ratios for systems with transiting substellar objects and giant exoplanets that orbit more massive stars. The nature of the secondary eclipse of the BD by the star enables us to estimate the effective temperature of the substellar object to be $2030\pm 84$K, which is consistent with predictions by substellar evolutionary models.Comment: 14 pages, 13 figures, 4 tables, accepted in MNRA

Short interferon and ribavirin treatment for HCV genotype 2 or 3 infection: NORDynamIC trial and real-life experience

Peer reviewe

Affectus Hispaniae en la historiografía del Alto Imperio

This paper analyses texts written by Greek and Latin High Empire historians dealing with Hispania. Some of the authors have a very positive view (Florus, Iustinus, Appian) while others are clearly negative (Veleius Paterculus, Valerius Maximus) though most of them show little interest, indifference or variety of opinions. When there is interest in the region or praise, it is because the author comes from Hispania or he is trying to please an emperor born in Hispania, but it could also be due to a universal conception of history revealing a critical attitude towards Roman imperialism, as in Appian. The praise found in Iustinus’s epitome should be attributed to the author of the epitome rather than to Pompeius Trogus. This can be taken as evidence for situating Iustinus’s life and work in the 2nd century A.D. Loathing of Hispania seems to have its origins in conservative, ‘optimate’ nationalist circles, who perceive the province as the ‘popular’ region that acclaimed and welcomed ‘seditious’ individuals such as Tiberius Gracchus and Sertorius.Se estudian en este trabajo los textos de historiadores del Alto Imperio, latinos y griegos, que tratan sobre Hispania. En algunos autores encontramos una visión muy positiva (Floro, Justino, Apiano) y en otros claramente negativa (Veleyo Patérculo, Valerio Máximo), aunque en la mayoría de los casos hay escasa atención, indiferencia o diversidad de opiniones. El interés por la región y los elogios pueden estar motivados por el origen hispánico del autor o su voluntad de agradar a algún emperador oriundo de Hispania, pero también por una concepción universal de la historia que denota en ocasiones una posición crítica con el imperialismo romano, como es el caso de Apiano. La alabanza que hallamos en el epítome de Justino creemos que debe atribuirse más al epitomador que a Pompeyo Trogo, lo que apoyaría una datación temprana de la vida y la obra de Justino (s. II d.C.). La aversión hacia Hispania parece haber surgido en medios conservadores, “optimates” nacionalistas, que ven la provincia como el territorio “popular”, que encumbró y acogió a “sediciosos” como Tiberio Graco y Sertorio

Greening of the brown-dwarf desert EPIC 212036875b: a 51 M-J object in a 5-day orbit around an F7V star

Context. Although more than 2000 brown dwarfs have been detected to date, mainly from direct imaging, their characterisation is difficult due to their faintness and model-dependent results. In the case of transiting brown dwarfs, however, it is possible to make direct high-precision observations. Aims. Our aim is to investigate the nature and formation of brown dwarfs by adding a new well-characterised object, in terms of its mass, radius and bulk density, to the currently small sample of less than 20 transiting brown dwarfs. Methods. One brown dwarf candidate was found by the KESPRINT consortium when searching for exoplanets in the K2 space mission Campaign 16 field. We combined the K2 photometric data with a series of multicolour photometric observations, imaging, and radial velocity measurements to rule out false positive scenarios and to determine the fundamental properties of the system. Results. We report the discovery and characterisation of a transiting brown dwarf in a 5.17-day eccentric orbit around the slightly evolved F7V star EPIC 212036875. We find a stellar mass of 1.15 +/- 0.08 M-circle dot, a stellar radius of 1.41 +/- 0.05 R-circle dot, and an age of 5.1 +/- 0.9 Gyr. The mass and radius of the companion brown dwarf are 51 +/- 2 M-J and 0.83 +/- 0.03 R-J, respectively, corresponding to a mean density of 108(-13)(+15) g cm(-3). Conclusions. EPIC 212036875 b is a rare object that resides in the brown-dwarf desert. In the mass-density diagram for planets, brown dwarfs, and stars, we find that all giant planets and brown dwarfs follow the same trend from similar to 0.3 M-J to the turn-over to hydrogen burning stars at similar to 73 M-J. EPIC 212036875 b falls close to the theoretical model for mature H/He dominated objects in this diagram as determined by interior structure models. We argue that EPIC 212036875 b formed via gravitational disc instabilities in the outer part of the disc, followed by a quick migration. Orbital tidal circularisation may have started early in its history for a brief period when the brown dwarf\u27s radius was larger. The lack of spin-orbit synchronisation points to a weak stellar dissipation parameter (Q(star)\u27 greater than or similar to 10(8)), which implies a circularisation timescale of greater than or similar to 23 Gyr, or suggests an interaction between the magnetic and tidal forces of the star and the brown dwarf

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

Migration and Evolution of giant ExoPlanets (MEEP) I: Nine Newly Confirmed Hot Jupiters from the TESS Mission

Hot Jupiters were many of the first exoplanets discovered in the 1990s, but in the decades since their discovery, the mysteries surrounding their origins remain. Here, we present nine new hot Jupiters (TOI-1855 b, TOI-2107 b, TOI-2368 b, TOI-3321 b, TOI-3894 b, TOI-3919 b, TOI-4153 b, TOI-5232 b, and TOI-5301 b) discovered by NASA's TESS mission and confirmed using ground-based imaging and spectroscopy. These discoveries are the first in a series of papers named the Migration and Evolution of giant ExoPlanets (MEEP) survey and are part of an ongoing effort to build a complete sample of hot Jupiters orbiting FGK stars, with a limiting Gaia $G$-band magnitude of 12.5. This effort aims to use homogeneous detection and analysis techniques to generate a set of precisely measured stellar and planetary properties that is ripe for statistical analysis. The nine planets presented in this work occupy a range of masses (0.55 Jupiter masses (M$_{\rm{J}}$) $<$ M$_{\rm{P}}$ $<$ 3.88 M$_{\rm{J}}$) and sizes (0.967 Jupiter radii (R$_{\rm{J}}$) $<$ R$_{\rm{P}}$ $<$ 1.438 R$_{\rm{J}}$) and orbit stars that range in temperature from 5360 K $<$ Teff $<$ 6860 K with Gaia $G$-band magnitudes ranging from 11.1 to 12.7. Two of the planets in our sample have detectable orbital eccentricity: TOI-3919 b ($e = 0.259^{+0.033}_{-0.036}$) and TOI-5301 b ($e = 0.33^{+0.11}_{-0.10}$). These eccentric planets join a growing sample of eccentric hot Jupiters that are consistent with high-eccentricity tidal migration, one of the three most prominent theories explaining hot Jupiter formation and evolution.Comment: 35 pages, 7 tables, and 14 figures. Submitted to AAS Journals on 2023 Dec 2

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