Body composition in anorexia nervosa: Meta-analysis and meta-regression of cross-sectional and longitudinal studies

Objective: Clinically, anorexia nervosa (AN) presents with altered body composition. We quantified these alterations and evaluated their relationships with metabolites and hormones in patients with AN longitudinally. Method: In accordance with PRISMA guidelines, we conducted 94 meta-analyses on 62 samples published during 1996–2019, comparing up to 2,319 pretreatment, posttreatment, and weight-recovered female patients with AN with up to 1,879 controls. Primary outcomes were fat mass, fat-free mass, body fat percentage, and their regional distribution. Secondary outcomes were bone mineral density, metabolites, and hormones. Meta-regressions examined relationships among those measures and moderators. Results: Pretreatment female patients with AN evidenced 50% lower fat mass (mean difference [MD]: −8.80 kg, 95% CI: −9.81, −7.79, Q = 1.01 × 10−63) and 4.98 kg (95% CI: −5.85, −4.12, Q = 1.99 × 10−28) lower fat-free mass, with fat mass preferentially stored in the trunk region during early weight restoration (4.2%, 95% CI: −2.1, −6.2, Q = 2.30 × 10−4). While the majority of traits returned to levels seen in healthy controls after weight restoration, fat-free mass (MD: −1.27 kg, 95% CI: −1.79, −0.75, Q = 5.49 × 10−6) and bone mineral density (MD: −0.10 kg, 95% CI: −0.18, −0.03, Q = 0.01) remained significantly altered. Discussion: Body composition is markedly altered in AN, warranting research into these phenotypes as clinical risk or relapse predictors. Notably, the long-term altered levels of fat-free mass and bone mineral density suggest that these parameters should be investigated as potential AN trait markers

An in-vivo study exploring correlations between early-to-moderate disc degeneration and flexion mobility in the lumbar spine

Purpose: Early disc degeneration (DD) has been thought to be associated with loss of spine 6 stability. However, before this can be understood in relation to back pain, it is necessary to 7 know the relationship between DD and intervertebral motion in people without pain. This 8 study aimed to find out if early to moderate DD is associated with intervertebral motion in 9 people without back pain. 10 Methods: Ten pain free adults, aged 51-71 received recumbent and weight bearing MRI 11 scans and quantitative fluoroscopy (QF) screenings during recumbent and upright lumbar 12 flexion. Forty individual level and 10 composite (L2-S1) radiographic and MRI DD gradings 13 were recorded and correlated with intervertebral flexion ROM, translation, laxity, and 14 motion sharing inequality and variability for both positions. 15 Results: Kinematic values were similar to previous control studies. DD was evidenced up to 16 moderate levels by both radiographic and MRI grading. Disc height loss correlated slightly, 17 but negatively with flexion during weight bearing flexion (R=-0.356, p=0.0.025). Composite 18 MRI DD and T2 signal loss evidenced similar relationships (R= -0.305, R= -0.267) but did not 19 reach statistical significance (p=0.056, p=0.096). No significant relationships between any 20 other kinematic variables and DD were found. 21 Conclusion: This study found only small, indefinite associations between early-to-moderate 22 DD and intervertebral motion in healthy controls. Motion sharing in the absence of pain 23 was also not related to early DD, consistent with previous control studies. Further research 24 is needed to investigate these relationships in patients. 25 Key words: back pain, disc degeneration, instability, imagin

Lack of Support for the Genes by Early Environment Interaction Hypothesis in the Pathogenesis of Schizophrenia

Ursini et al reported recently that the liability of schizophrenia explained by a polygenic risk score (PRS) derived from the variants most associated with schizophrenia was increased 5-fold in individuals who experienced complications during pregnancy or birth. Follow-up gene expression analysis showed that the genes mapping to the most associated genetic variants are highly expressed in placental tissues. If confirmed, these findings will have major implications in our understanding of the joint effect of genes and environment in the pathogenesis of schizophrenia. We examined the interplay between PRS and obstetric complications (OCs) in 5 independent samples (effective N = 2110). OCs were assessed with the full or modified Lewis-Murray scale, or with birth weight < 2.5 kg as a proxy. In a large cohort we tested whether the pathways from placenta-relevant variants in the original report were associated with case-control status. Unlike in the original study, we did not find significant effect of PRS on the presence of OCs in cases, nor a substantial difference in the association of PRS with case-control status in samples stratified by the presence of OCs. Furthermore, none of the PRS by OCs interactions were significant, nor were any of the biological pathways, examined in the Swedish cohort. Our study could not support the hypothesis of a mediating effect of placenta biology in the pathway from genes to schizophrenia. Methodology differences, in particular the different scales measuring OCs, as well as power constraints for interaction analyses in both studies, may explain this discrepancy

An objective spinal motion imaging assessment (OSMIA): reliability, accuracy and exposure data

BACKGROUND: Minimally-invasive measurement of continuous inter-vertebral motion in clinical settings is difficult to achieve. This paper describes the reliability, validity and radiation exposure levels in a new Objective Spinal Motion Imaging Assessment system (OSMIA) based on low-dose fluoroscopy and image processing. METHODS: Fluoroscopic sequences in coronal and sagittal planes were obtained from 2 calibration models using dry lumbar vertebrae, plus the lumbar spines of 30 asymptomatic volunteers. Calibration model 1 (mobile) was screened upright, in 7 inter-vertebral positions. The volunteers and calibration model 2 (fixed) were screened on a motorised table comprising 2 horizontal sections, one of which moved through 80 degrees. Model 2 was screened during motion 5 times and the L2-S1 levels of the volunteers twice. Images were digitised at 5fps. Inter-vertebral motion from model 1 was compared to its pre-settings to investigate accuracy. For volunteers and model 2, the first digitised image in each sequence was marked with templates. Vertebrae were tracked throughout the motion using automated frame-to-frame registration. For each frame, vertebral angles were subtracted giving inter-vertebral motion graphs. Volunteer data were acquired twice on the same day and analysed by two blinded observers. The root-mean-square (RMS) differences between paired data were used as the measure of reliability. RESULTS: RMS difference between reference and computed inter-vertebral angles in model 1 was 0.32 degrees for side-bending and 0.52 degrees for flexion-extension. For model 2, X-ray positioning contributed more to the variance of range measurement than did automated registration. For volunteer image sequences, RMS inter-observer variation in intervertebral motion range in the coronal plane was 1.86 degreesand intra-subject biological variation was between 2.75 degrees and 2.91 degrees. RMS inter-observer variation in the sagittal plane was 1.94 degrees. Radiation dosages in each view were below the levels recommended for a plain film. CONCLUSION: OSMIA can measure inter-vertebral angular motion patterns in routine clinical settings if modern image intensifier systems are used. It requires skilful radiography to achieve optimal positioning and dose limitation. Reliability in individual subjects can be judged from the variance of their averaged inter-vertebral angles and by observing automated image registration

The continuing use of complementary and alternative medicine in South Australia: costs and beliefs in 2004

The document attached has been archived with permission from the editor of the Medical Journal of Australia. An external link to the publisher’s copy is included.Objective: To survey the use, cost, beliefs and quality of life of users of complementary and alternative medicine (CAM). Design: A representative population survey conducted in 2004 with longitudinal comparison to similar 1993 and 2000 surveys. Participants: 3015 South Australian respondents over the age of 15 years (71.7% participation). Results: In 2004, CAMs were used by 52.2% of the population. Greatest use was in women aged 25–34 years, with higher income and education levels. CAM therapists had been visited by 26.5% of the population. In those with children, 29.9% administered CAMs to them and 17.5% of the children had visited CAM therapists. The total extrapolated cost in Australia of CAMs and CAM therapists in 2004 was AUD$1.8 billion, which was a decrease from AUD$2.3 billion in 2000. CAMs were used mostly to maintain general health. The users of CAM had lower quality-of-life scores than non-users. Among CAM users, 49.7% used conventional medicines on the same day and 57.2% did not report the use of CAMs to their doctor. About half of the respondents assumed that CAMs were independently tested by a government agency; of these, 74.8% believed they were tested for quality and safety, 21.8% for what they claimed, and 17.9% for efficacy. Conclusions: Australians continue to use high levels of CAMs and CAM therapists. The public is often unaware that CAMs are not tested by the Therapeutic Goods Administration for efficacy or safety.Alastair H MacLennan, Stephen P Myers and Anne W Taylo

Cholesterol Depletion in Adipocytes Causes Caveolae Collapse Concomitant with Proteosomal Degradation of Cavin-2 in a Switch-Like Fashion

Caveolae, little caves of cell surfaces, are enriched in cholesterol, a certain level of which is required for their structural integrity. Here we show in adipocytes that cavin-2, a peripheral membrane protein and one of 3 cavin isoforms present in caveolae from non-muscle tissue, is degraded upon cholesterol depletion in a rapid fashion resulting in collapse of caveolae. We exposed 3T3-L1 adipocytes to the cholesterol depleting agent methyl-β-cyclodextrin, which results in a sudden and extensive degradation of cavin-2 by the proteasome and a concomitant movement of cavin-1 from the plasma membrane to the cytosol along with loss of caveolae. The recovery of cavin-2 at the plasma membrane is cholesterol-dependent and is required for the return of cavin-1 from the cytosol to the cell surface and caveolae restoration. Expression of shRNA directed against cavin-2 also results in a cytosolic distribution of cavin-1 and loss of caveolae. Taken together, these data demonstrate that cavin-2 functions as a cholesterol responsive component of caveolae that is required for cavin-1 localization to the plasma membrane, and caveolae structural integrity

Large-scale remote fear conditioning: demonstration of associations with anxiety using the FLARe smartphone app

Objectives We aimed to examine differences in fear conditioning between anxious and nonanxious participants in a single large sample. Materials and methods We employed a remote fear conditioning task (FLARe) to collect data from participants from the Twins Early Development Study (n = 1,146; 41% anxious vs. 59% nonanxious). Differences between groups were estimated for their expectancy of an aversive outcome towards a reinforced conditional stimulus (CS+) and an unreinforced conditional stimulus (CS−) during acquisition and extinction phases. Results During acquisition, the anxious group (vs. nonanxious group) showed greater expectancy towards the CS−. During extinction, the anxious group (vs. nonanxious group) showed greater expectancy to both CSs. These comparisons yielded effect size estimates (d = 0.26–0.34) similar to those identified in previous meta‐analyses. Conclusion The current study demonstrates that remote fear conditioning can be used to detect differences between groups of anxious and nonanxious individuals, which appear to be consistent with previous meta‐analyses including in‐person studies

Genetic identification of brain cell types underlying schizophrenia

With few exceptions, the marked advances in knowledge about the genetic basis of schizophrenia have not converged on findings that can be confidently used for precise experimental modeling. By applying knowledge of the cellular taxonomy of the brain from single-cell RNA sequencing, we evaluated whether the genomic loci implicated in schizophrenia map onto specific brain cell types. We found that the common-variant genomic results consistently mapped to pyramidal cells, medium spiny neurons (MSNs) and certain interneurons, but far less consistently to embryonic, progenitor or glial cells. These enrichments were due to sets of genes that were specifically expressed in each of these cell types. We also found that many of the diverse gene sets previously associated with schizophrenia (genes involved in synaptic function, those encoding mRNAs that interact with FMRP, antipsychotic targets, etc.) generally implicated the same brain cell types. Our results suggest a parsimonious explanation: the common-variant genetic results for schizophrenia point at a limited set of neurons, and the gene sets point to the same cells. The genetic risk associated with MSNs did not overlap with that of glutamatergic pyramidal cells and interneurons, suggesting that different cell types have biologically distinct roles in schizophrenia