Bone Marrow Edema: Overview of Etiology and Treatment Strategies

➤: Bone marrow edema (BME) is a nonspecific but relevant finding, usually indicating the presence of an underlying pathology. ➤: The gold standard technique for detecting BME is magnetic resonance imaging (MRI), as it allows for a correct diagnosis to be made, which is extremely important given the heterogeneity of BME-related diseases. ➤: Depending on the severity of painful symptomatology and the MRI evidence, different treatment strategies can be followed: physical modalities, pharmacological options, and surgical therapy

Observation of channeling for 6500 GeV/c protons in the crystal assisted collimation setup for LHC

Two high-accuracy goniometers equipped with two bent silicon crystals were installed in the betatron cleaning insertion of the CERN Large Hadron Collider (LHC) during its long shutdown. First beam tests were recently performed at the LHC with 450 GeV/c and 6500 GeV/c stored proton beams to investigate the feasibility of beam halo collimation assisted by bent crystals. For the first time channeling of 6500 GeV/c protons was observed in a particle accelerator. A strong reduction of beam losses due to nuclear inelastic interactions in the aligned crystal in comparison with its amorphous orientation was detected. The loss reduction value was about 24. Thus, the results show that deflection of particles by a bent crystal due to channeling is effective for this record particle energy.peer-reviewe

Large-scale analysis of association between LRP5 and LRP6 variants and osteoporosis

CONTEXT: Mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) gene cause rare syndromes characterized by altered bone mineral density (BMD). More common LRP5 variants may affect osteoporosis risk in the general population.OBJECTIVE: To generate large-scale evidence on whether 2 common variants of LRP5 (Val667Met, Ala1330Val) and 1 variant of LRP6 (Ile1062Val) are associated with BMD and fracture risk.DESIGN AND SETTING: Prospective, multicenter, collaborative study of individual-level data on 37,534 individuals from 18 participating teams in Europe and North America. Data were collected between September 2004 and January 2007; analysis of the collected data was performed between February and May 2007. Bone mineral density was assessed by dual-energy x-ray absorptiometry. Fractures were identified via questionnaire, medical records, or radiographic documentation; incident fracture data were available for some cohorts, ascertained via routine surveillance methods, including radiographic examination for vertebral fractures.MAIN OUTCOME MEASURES: Bone mineral density of the lumbar spine and femoral neck; prevalence of all fractures and vertebral fractures.RESULTS: The Met667 allele of LRP5 was associated with reduced lumbar spine BMD (n = 25,052 [number of participants with available data]; 20-mg/cm2 lower BMD per Met667 allele copy; P = 3.3 x 10(-8)), as was the Val1330 allele (n = 24,812; 14-mg/cm2 lower BMD per Val1330 copy; P = 2.6 x 10(-9)). Similar effects were observed for femoral neck BMD, with a decrease of 11 mg/cm2 (P = 3.8 x 10(-5)) and 8 mg/cm2 (P = 5.0 x 10(-6)) for the Met667 and Val1330 alleles, respectively (n = 25 193). Findings were consistent across studies for both LRP5 alleles. Both alleles were associated with vertebral fractures (odds ratio [OR], 1.26; 95% confidence interval [CI], 1.08-1.47 for Met667 [2001 fractures among 20 488 individuals] and OR, 1.12; 95% CI, 1.01-1.24 for Val1330 [1988 fractures among 20,096 individuals]). Risk of all fractures was also increased with Met667 (OR, 1.14; 95% CI, 1.05-1.24 per allele [7876 fractures among 31,435 individuals)]) and Val1330 (OR, 1.06; 95% CI, 1.01-1.12 per allele [7802 fractures among 31 199 individuals]). Effects were similar when adjustments were made for age, weight, height, menopausal status, and use of hormone therapy. Fracture risks were partly attenuated by adjustment for BMD. Haplotype analysis indicated that Met667 and Val1330 variants both independently affected BMD. The LRP6 Ile1062Val polymorphism was not associated with any osteoporosis phenotype. All aforementioned associations except that between Val1330 and all fractures and vertebral fractures remained significant after multiple-comparison adjustments.CONCLUSIONS: Common LRP5 variants are consistently associated with BMD and fracture risk across different white populations. The magnitude of the effect is modest. LRP5 may be the first gene to reach a genome-wide significance level (a conservative level of significance [herein, unadjusted P < 10(-7)] that accounts for the many possible comparisons in the human genome) for a phenotype related to osteoporosis

Identification of a novel locus on chromosome 2q13, which predisposes to clinical vertebral fractures independently of bone density.

OBJECTIVES: To identify genetic determinants of susceptibility to clinical vertebral fractures, which is an important complication of osteoporosis. METHODS: Here we conduct a genome-wide association study in 1553 postmenopausal women with clinical vertebral fractures and 4340 controls, with a two-stage replication involving 1028 cases and 3762 controls. Potentially causal variants were identified using expression quantitative trait loci (eQTL) data from transiliac bone biopsies and bioinformatic studies. RESULTS: A locus tagged by rs10190845 was identified on chromosome 2q13, which was significantly associated with clinical vertebral fracture (P=1.04×10-9) with a large effect size (OR 1.74, 95% CI 1.06 to 2.6). Bioinformatic analysis of this locus identified several potentially functional SNPs that are associated with expression of the positional candidate genes TTL (tubulin tyrosine ligase) and SLC20A1 (solute carrier family 20 member 1). Three other suggestive loci were identified on chromosomes 1p31, 11q12 and 15q11. All these loci were novel and had not previously been associated with bone mineral density or clinical fractures. CONCLUSION: We have identified a novel genetic variant that is associated with clinical vertebral fractures by mechanisms that are independent of BMD. Further studies are now in progress to validate this association and evaluate the underlying mechanism

Assessment of gene-by-sex interaction effect on bone mineral density

To access publisher's full text version of this article. Please click on the hyperlink in Additional Links field.Sexual dimorphism in various bone phenotypes, including bone mineral density (BMD), is widely observed; however, the extent to which genes explain these sex differences is unclear. To identify variants with different effects by sex, we examined gene-by-sex autosomal interactions genome-wide, and performed expression quantitative trait loci (eQTL) analysis and bioinformatics network analysis. We conducted an autosomal genome-wide meta-analysis of gene-by-sex interaction on lumbar spine (LS) and femoral neck (FN) BMD in 25,353 individuals from 8 cohorts. In a second stage, we followed up the 12 top single-nucleotide polymorphisms (SNPs; p < 1 × 10(-5) ) in an additional set of 24,763 individuals. Gene-by-sex interaction and sex-specific effects were examined in these 12 SNPs. We detected one novel genome-wide significant interaction associated with LS-BMD at the Chr3p26.1-p25.1 locus, near the GRM7 gene (male effect = 0.02 and p = 3.0 × 10(-5) ; female effect = -0.007 and p = 3.3 × 10(-2) ), and 11 suggestive loci associated with either FN- or LS-BMD in discovery cohorts. However, there was no evidence for genome-wide significant (p < 5 × 10(-8) ) gene-by-sex interaction in the joint analysis of discovery and replication cohorts. Despite the large collaborative effort, no genome-wide significant evidence for gene-by-sex interaction was found to influence BMD variation in this screen of autosomal markers. If they exist, gene-by-sex interactions for BMD probably have weak effects, accounting for less than 0.08% of the variation in these traits per implicated SNP. © 2012 American Society for Bone and Mineral Research.Medtronic NIH R01 AG18728 R01HL088119 R01AR046838 U01 HL084756 R01 AR43351 P01-HL45522 R01-MH-078111 R01-MH-083824 Nutrition and Obesity Research Center of Maryland P30DK072488 NIAMS/NIH F32AR059469 Instituto de Salud Carlos III-FIS (Spanish Health Ministry) PI 06/0034 PI08/0183 Canadian Institutes of Health Research (CIHR) NHLBI HHSN268201200036C N01-HC-85239 N01-HC-85079 N01-HC-85086 N01-HC-35129 N01 HC15103 N01 HC-55222 N01-HC-75150 N01-HC-45133 HL080295 HL087652 HL105756 NIA AG-023629 AG-15928 AG-20098 AG-027058 N01AG62101 N01AG62103 N01AG62106 1R01AG032098-01A1 National Center of Advancing Translational Technologies CTSI UL1TR000124 National Institute of Diabetes and Digestive and Kidney Diseases DK063491 EUROSPAN (European Special Populations Research Network) European Commission FP6 STRP grant 018947 LSHG-CT-2006-01947 Netherlands Organisation for Scientific Research Erasmus MC Centre for Medical Systems Biology (CMSB) Netherlands Brain Foundation (HersenStichting Nederland) US National Institute for Arthritis, Musculoskeletal and Skin Diseases National Institute on Aging R01 AR/AG41398 R01 AR050066 R21 AR056405 National Heart, Lung, and Blood Institute's Framingham Heart Study N01-HC-25195 Affymetrix, Inc. N02-HL-6-4278 Canadian Institutes of Health Research from Institute of Aging 165446 Institute of Genetics 179433 Institute of Musculoskeletal health 221765 Intramural Research Program of the NIH, National Institute on Aging National Institutes of Health HHSN268200782096C Hong Kong Research Grant Council HKU 768610M Bone Health Fund of HKU Foundation KC Wong Education Foundation Small Project Funding 201007176237 Matching Grant CRCG Grant Osteoporosis and Endocrine Research Fund Genomics Strategic Research Theme of The University of Hong Kong Netherlands Organisation of Scientific Research NWO Investments 175.010.2005.011 911-03-012 Research Institute for Diseases in the Elderly 014-93-015 Netherlands Genomics Initiative (NGI)/Netherlands Consortium for Healthy Aging (NCHA) 050-060-810 Erasmus Medical Center and Erasmus University, Rotterdam Netherlands Organization for the Health Research and Development (ZonMw) Research Institute for Diseases in the Elderly (RIDE) Ministry of Education, Culture and Science Ministry for Health, Welfare and Sports European Commission (DG XII) Municipality of Rotterdam German Bundesministerium fur Forschung und Technology 01 AK 803 A-H 01 IG 07015

The characteristics and activities of child and adolescent mental health services in Italy: a regional survey

<p>Abstract</p> <p>Background</p> <p>To date, no studies have assessed in detail the characteristics, organisation, and functioning of Child and Adolescent Mental Health Services (CAMHS). This information gap represents a major limitation for researchers and clinicians because most mental disorders have their onset in childhood or adolescence, and effective interventions can therefore represent a major factor in avoiding chronicity. Interventions and mental health care are delivered by and through services, and not by individual, private clinicians, and drawbacks or limitations of services generally translate in inappropriateness and ineffectiveness of treatments and interventions: therefore information about services is essential to improve the quality of care and ultimately the course and outcome of mental disorders in childhood and adolescence.</p> <p>The present paper reports the results of the first study aimed at providing detailed, updated and comprehensive data on CAMHS of a densely populated Italian region (over 4 million inhabitants) with a target population of 633,725 subjects aged 0-17 years.</p> <p>Methods</p> <p>Unit Chiefs of all the CAMHS filled in a structured 'Facility Form', with activity data referring to 2008 (data for inpatient facilities referred to 2009), which were then analysed in detail.</p> <p>Results</p> <p>Eleven CAMHS were operative, including 110 outpatient units, with a ratio of approximately 20 child psychiatrists and 23 psychologists per 100,000 inhabitants aged 0-17 years. All outpatient units were well equipped and organized and all granted free service access. In 2008, approximately 6% of the target population was in contact with outpatient CAMHS, showing substantial homogeneity across the eleven areas thereby. Most patients in contact in 2008 received a language disorder- or learning disability diagnosis (41%). First-ever contacts accounted for 30% of annual visits across all units. Hospital bed availability was 5 per 100,000 inhabitants aged 0-17 years.</p> <p>Conclusion</p> <p>The percentage of young people in contact with CAMHS for mental disorders is in line with those observed in previous epidemiological studies. The overall number of child psychiatrists per 100,000 inhabitants is one of the highest in Europe and it is comparable with the most well equipped areas in the US. This comparison should be interpreted with caution, however, because in Italy, child psychiatrists also treat neurological disorders. Critical areas requiring improvement are: the uneven utilisation of standardised assessment procedures and the limited availability of dedicated emergency services during non-office hours (e.g., nights and holidays).</p

Mediterranean winter rainfall in phase with African monsoons during the past 1.36 million years

Mediterranean climates are characterized by strong seasonal contrasts between dry summers and wet winters. Changes in winter rainfall are critical for regional socioeconomic development, but are difficult to simulate accurately1 and reconstruct on Quaternary timescales. This is partly because regional hydroclimate records that cover multiple glacial–interglacial cycles2,3 with different orbital geometries, global ice volume and atmospheric greenhouse gas concentrations are scarce. Moreover, the underlying mechanisms of change and their persistence remain unexplored. Here we show that, over the past 1.36 million years, wet winters in the northcentral Mediterranean tend to occur with high contrasts in local, seasonal insolation and a vigorous African summer monsoon. Our proxy time series from Lake Ohrid on the Balkan Peninsula, together with a 784,000-year transient climate model hindcast, suggest that increased sea surface temperatures amplify local cyclone development and refuel North Atlantic low-pressure systems that enter the Mediterranean during phases of low continental ice volume and high concentrations of atmospheric greenhouse gases. A comparison with modern reanalysis data shows that current drivers of the amount of rainfall in the Mediterranean share some similarities to those that drive the reconstructed increases in precipitation. Our data cover multiple insolation maxima and are therefore an important benchmark for testing climate model performance