The vertebral body growth plate in scoliosis: a primary disturbance of growth?

Study Design and Aims: This was an observational pilot study of the vertebral body growth plates in scoliosis involving high-resolution coronal plane magnetic resonance (MR) imaging and histological examination. One aim of this study was to determine whether vertebral body growth plates in scoliosis demonstrated abnormalities on MR imaging. A second aim was to determine if a relationship existed between MR and histological abnormalities in these vertebral body growth plates. Methods: MR imaging sequences of 18 patients demonstrated the vertebralbody growth plates well enough to detect gross abnormalities/ deficient areas/zones. Histological examination of ten vertebral body growth plates removed during routine scoliosis surgery was performed. Observational histological comparison with MR images was possible in four cases. Results: Four of the 18 MR images demonstrated spines with normal curvature and normal vertebral body growth plates. In 13 scoliotic spines, convex and concave side growth plate deficiencies were observed most frequently at or near the apex of the curve. One MR image demonstrated a 55° kyphosis and no convex or concave side deficiencies. The degree of vertebral body wedging was independent of the presence of vertebral body growth plate deficiency. Histological abnormalities of the vertebral body growth plates were demonstrated in four with MR imaging abnormalities. Conclusion: This study demonstrated MR image abnormalities of scoliotic vertebral body growth plates compared to controls. A qualitative relationship was demonstrated between MR imaging and histological abnormalities. The finding that vertebral body growth plate deficiencies occurred both on the convex and concave sides of the spine, closest to the apical vertebra of the scoliosis curve, implied that they are less likely to be the result of adaptive changes to the physical forces involved in the scoliotic deformity. One explanation is that they represent a primary disturbance of growth

Pathogenetics of alveolar capillary dysplasia with misalignment of pulmonary veins.

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a lethal lung developmental disorder caused by heterozygous point mutations or genomic deletion copy-number variants (CNVs) of FOXF1 or its upstream enhancer involving fetal lung-expressed long noncoding RNA genes LINC01081 and LINC01082. Using custom-designed array comparative genomic hybridization, Sanger sequencing, whole exome sequencing (WES), and bioinformatic analyses, we studied 22 new unrelated families (20 postnatal and two prenatal) with clinically diagnosed ACDMPV. We describe novel deletion CNVs at the FOXF1 locus in 13 unrelated ACDMPV patients. Together with the previously reported cases, all 31 genomic deletions in 16q24.1, pathogenic for ACDMPV, for which parental origin was determined, arose de novo with 30 of them occurring on the maternally inherited chromosome 16, strongly implicating genomic imprinting of the FOXF1 locus in human lungs. Surprisingly, we have also identified four ACDMPV families with the pathogenic variants in the FOXF1 locus that arose on paternal chromosome 16. Interestingly, a combination of the severe cardiac defects, including hypoplastic left heart, and single umbilical artery were observed only in children with deletion CNVs involving FOXF1 and its upstream enhancer. Our data demonstrate that genomic imprinting at 16q24.1 plays an important role in variable ACDMPV manifestation likely through long-range regulation of FOXF1 expression, and may be also responsible for key phenotypic features of maternal uniparental disomy 16. Moreover, in one family, WES revealed a de novo missense variant in ESRP1, potentially implicating FGF signaling in the etiology of ACDMPV

The JWST Early Release Science Program for the Direct Imaging and Spectroscopy of Exoplanetary Systems

The direct characterization of exoplanetary systems with high-contrast imaging is among the highest priorities for the broader exoplanet community. As large space missions will be necessary for detecting and characterizing exo-Earth twins, developing the techniques and technology for direct imaging of exoplanets is a driving focus for the community. For the first time, JWST will directly observe extrasolar planets at mid-infrared wavelengths beyond 5 μm, deliver detailed spectroscopy revealing much more precise chemical abundances and atmospheric conditions, and provide sensitivity to analogs of our solar system ice-giant planets at wide orbital separations, an entirely new class of exoplanet. However, in order to maximize the scientific output over the lifetime of the mission, an exquisite understanding of the instrumental performance of JWST is needed as early in the mission as possible. In this paper, we describe our 55 hr Early Release Science Program that will utilize all four JWST instruments to extend the characterization of planetary-mass companions to ∼15 μm as well as image a circumstellar disk in the mid-infrared with unprecedented sensitivity. Our program will also assess the performance of the observatory in the key modes expected to be commonly used for exoplanet direct imaging and spectroscopy, optimize data calibration and processing, and generate representative data sets that will enable a broad user base to effectively plan for general observing programs in future Cycles

The past, present, and future of the Brain Imaging Data Structure (BIDS)

The Brain Imaging Data Structure (BIDS) is a community-driven standard for the organization of data and metadata from a growing range of neuroscience modalities. This paper is meant as a history of how the standard has developed and grown over time. We outline the principles behind the project, the mechanisms by which it has been extended, and some of the challenges being addressed as it evolves. We also discuss the lessons learned through the project, with the aim of enabling researchers in other domains to learn from the success of BIDS

The Past, Present, and Future of the Brain Imaging Data Structure (BIDS)

The Brain Imaging Data Structure (BIDS) is a community-driven standard for the organization of data and metadata from a growing range of neuroscience modalities. This paper is meant as a history of how the standard has developed and grown over time. We outline the principles behind the project, the mechanisms by which it has been extended, and some of the challenges being addressed as it evolves. We also discuss the lessons learned through the project, with the aim of enabling researchers in other domains to learn from the success of BIDS.Development of the BIDS Standard has been supported by the International Neuroinformatics Coordinating Facility, Laura and John Arnold Foundation, National Institutes of Health (R24MH114705, R24MH117179, R01MH126699, R24MH117295, P41EB019936, ZIAMH002977, R01MH109682, RF1MH126700, R01EB020740), National Science Foundation (OAC-1760950, BCS-1734853, CRCNS-1429999, CRCNS-1912266), Novo Nordisk Fonden (NNF20OC0063277), French National Research Agency (ANR-19-DATA-0023, ANR 19-DATA-0021), Digital Europe TEF-Health (101100700), EU H2020 Virtual Brain Cloud (826421), Human Brain Project (SGA2 785907, SGA3 945539), European Research Council (Consolidator 683049), German Research Foundation (SFB 1436/425899996), SFB 1315/327654276, SFB 936/178316478, SFB-TRR 295/424778381), SPP Computational Connectomics (RI 2073/6-1, RI 2073/10-2, RI 2073/9-1), European Innovation Council PHRASE Horizon (101058240), Berlin Institute of Health & Foundation Charité, Johanna Quandt Excellence Initiative, ERAPerMed Pattern-Cog, and the Virtual Research Environment at the Charité Berlin – a node of EBRAINS Health Data Cloud.N

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

The life of Henry Jeanneret (1802–1886). Pioneer Australian dentist

Henry Jeanneret was a pioneer Australian dentist, perhaps the first in this country to promote the discipline of dentistry as distinct from medicine and general surgery. This profile describes his early life and training, his emigration to Australia, his clinical practice in Sydney and in Van Diemen's Land, and his contributions to natural history, particularly in the field of botany

Congenital cystic eye with optic nerve

Congenital cystic eye (CCE) is a rare condition caused by failure of invagination of the optic vesicle resulting in a persistent cyst replacing the eye. An associated optic nerve attached to the cyst is a rarely reported phenomenon that has been sparsely described histologically, with no immunohistochemistry reported previously. The authors present a case of CCE with optic nerve tissue inserting into the cyst, and present the histological and immunohistochemical findings

Surveillance culture utility and safety using low-volume blind bronchoalveolar lavage in the diagnosis of ventilator-associated pneumonia

Background and objectives: Surveillance cultures may improve the prediction of ventilator-associated pneumonia (VAP) and empirical antibiotic selection. This study examined the utility and patient safety of blind, non-protected, low-volume mini-bronchial lavage (BM-BAL) surveillance cultures in predicting VAP