Bedtime Salivary Cortisol as a Screening Test for Cushing Syndrome in Children

Background Diagnosing Cushing syndrome (CS) can be challenging. The 24-hour urine free cortisol (UFC) measurement is considered gold standard. This is a laborious test, dependent on correct urine collection. Late-night salivary cortisol is easier and is used as a screening test for CS in adults, but has not been validated for use in children. Objective To define liquid chromatography tandem mass spectrometry (LC-MS/MS)-based cutoff values for bedtime and morning salivary cortisol and cortisone in children, and validate the results in children with and without CS. Methods Bedtime and morning salivary samples were collected from 320 healthy children aged 4 to 16 years. Fifty-four patients from the children’s outpatient obesity clinic and 3 children with pituitary CS were used for validation. Steroid hormones were assayed by LC-MS/MS. Cutoff levels for bedtime salivary cortisol and cortisone were defined by the 97.5% percentile in healthy subjects. Results Bedtime cutoff levels for cortisol and cortisone were 2.4 and 12.0 nmol/L, respectively. Applying these cutoff levels on the verification cohort, 1 child from the obesity clinic had bedtime salivary cortisol exceeding the defined cutoff level, but normal salivary cortisone. All 3 children with pituitary CS had salivary cortisol and cortisone far above the defined bedtime cutoff levels. Healthy subjects showed a significant decrease in salivary cortisol from early morning to bedtime. Conclusions We propose that bedtime salivary cortisol measured by LC-MS/MS with a diagnostic threshold above 2.4 nmol/L can be applied as a screening test for CS in children. Age- and gender-specific cutoff levels are not needed.publishedVersio

Obesity and COVID-19: The Two Sides of the Coin

The World Health Organization declared COVID-19, the infectious disease caused by the coronavirus SARS-CoV-2, a pandemic on March 12, 2020. COVID-19 is causing massive health problems and economic suffering around the world. The European Association for the Study of Obesity (EASO) promptly recognised the impact that the outbreak could have on people with obesity. On one side, emerging data suggest that obesity represents a risk factor for a more serious and complicated course of COVID-19 in adults. On the other side, the health emergency caused by the outbreak diverts attention from the prevention and care of non-communicable chronic diseases to communicable diseases. This might be particularly true for obesity, a chronic and relapsing disease frequently neglected and linked to significant bias and stigmatization. The Obesity Management Task Force (OMTF) of EASO contributes in this paper to highlighting the key aspects of these two sides of the coin and suggests some specific actions

European Association for the Study of Obesity Position Statement on the Global COVID-19 Pandemic

open18openFrühbeck, Gema; Baker, Jennifer Lyn; Busetto, Luca; Dicker, Dror; Goossens, Gijs H; Halford, Jason C G; Handjieva-Darlenska, Teodora; Hassapidou, Maria; Holm, Jens-Christian; Lehtinen-Jacks, Susanna; Mullerova, Dana; O'Malley, Grace; Sagen, Jørn V; Rutter, Harry; Salas, Ximena Ramos; Woodward, Euan; Yumuk, Volkan; Farpour-Lambert, Nathalie JFrühbeck, Gema; Baker, Jennifer Lyn; Busetto, Luca; Dicker, Dror; Goossens, Gijs H; Halford, Jason C G; Handjieva-Darlenska, Teodora; Hassapidou, Maria; Holm, Jens-Christian; Lehtinen-Jacks, Susanna; Mullerova, Dana; O'Malley, Grace; Sagen, Jørn V; Rutter, Harry; Salas, Ximena Ramos; Woodward, Euan; Yumuk, Volkan; Farpour-Lambert, Nathalie

Multipurpose acoustic networks in the integrated arctic ocean observing system

The dramatic reduction of sea ice in the Arctic Ocean will increase human activities in the coming years. This activity will be driven by increased demand for energy and the marine resources of an Arctic Ocean accessible to ships. Oil and gas exploration, fisheries, mineral extraction, marine transportation, research and development, tourism, and search and rescue will increase the pressure on the vulnerable Arctic environment. Technologies that allow synoptic in situ observations year-round are needed to monitor and forecast changes in the Arctic atmosphere-ice-ocean system at daily, seasonal, annual, and decadal scales. These data can inform and enable both sustainable development and enforcement of international Arctic agreements and treaties, while protecting this critical environment. In this paper, we discuss multipurpose acoustic networks, including subsea cable components, in the Arctic. These networks provide communication, power, underwater and under-ice navigation, passive monitoring of ambient sound (ice, seismic, biologic, and anthropogenic), and acoustic remote sensing (tomography and thermometry), supporting and complementing data collection from platforms, moorings, and vehicles. We support the development and implementation of regional to basin-wide acoustic networks as an integral component of a multidisciplinary in situ Arctic Ocean observatory

European association for the study of obesity position statement on the global COVID-19 pandemic

COVID-19, the infectious disease caused by the coronavirus SARS-CoV-2, was declared a pandemic by the World Health Organization on March 12, 2020. The European Association for the Study of Obesity (EASO), as a scientific and medical society dedicated to the promotion of health and well-being, is greatly concerned about this global health challenge and its significant impacts on individuals, families, communities, health systems, nations, and wider society

Mapping a beautiful voice : theoretical considerations

The prime purpose of this paper is to draw on a range of diverse literatures to clarify those elements thatare perceived to constitute a ‘beautiful’ sung performance. The text rehearses key findings from existingliteratures in order to determine the extent to which particular elements might appear the most salientfor an individual listener and also ‘quantifiable’ (in the sense of being open to empirical study). Thepaper concludes with a theoretical framework for the elements that are likely to construct and shape ourresponses to particular sung performances

DNA glycosylase Neil3 regulates vascular smooth muscle cell biology during atherosclerosis development.

BACKGROUND AND AIMS: Atherogenesis involves a complex interaction between immune cells and lipids, processes greatly influenced by the vascular smooth muscle cell (VSMC) phenotype. The DNA glycosylase NEIL3 has previously been shown to have a role in atherogenesis, though whether this is due to its ability to repair DNA damage or to other non-canonical functions is not yet clear. Hereby, we investigate the role of NEIL3 in atherogenesis, specifically in VSMC phenotypic modulation, which is critical in plaque formation and stability. METHODS: Chow diet-fed atherosclerosis-prone Apoe-/- mice deficient in Neil3, and NEIL3-abrogated human primary aortic VSMCs were characterized by qPCR, and immunohistochemical and enzymatic-based assays; moreover, single-cell RNA sequencing, mRNA sequencing, and proteomics were used to map the molecular effects of Neil3/NEIL3 deficiency in the aortic VSMC phenotype. Furthermore, BrdU-based proliferation assays and Western blot were performed to elucidate the involvement of the Akt signaling pathway in the transdifferentiation of aortic VSMCs lacking Neil3/NEIL3. RESULTS: We show that Neil3 deficiency increases atherosclerotic plaque development without affecting systemic lipids. This observation was associated with a shift in VSMC phenotype towards a proliferating, lipid-accumulating and secretory macrophage-like cell phenotype, without changes in DNA damage. VSMC transdifferentiation in Neil3-deficient mice encompassed increased activity of the Akt signaling pathway, supported by cell experiments showing Akt-dependent proliferation in NEIL3-abrogated human primary aortic VSMCs. CONCLUSIONS: Our findings show that Neil3 deficiency promotes atherosclerosis development through non-canonical mechanisms affecting VSMC phenotype involving activation of the Akt signaling pathway

Outcome prediction models in AQP4-IgG positive neuromyelitis optica spectrum disorders

Pathogenic antibodies targeting the aquaporin-4 water channel on astrocytes are associated with relapsing inflammatory neuromyelitis optica spectrum disorders. The clinical phenotype is characterized by recurrent episodes of optic neuritis, longitudinally extensive transverse myelitis, area postrema attacks and less common brainstem and cerebral events. Patients often develop major residual disability from these attacks, so early diagnosis and initiation of attackpreventing medications is important. Accurate prediction of relapse would assist physicians in counselling patients, planning treatment and designing clinical trials. We used a large multicentre dataset of 441 patients from the UK, USA, Japan and Martinique who collectively experienced 1976 attacks, and applied sophisticated mathematical modelling to predict likelihood of relapse and disability at different time points. We found that Japanese patients had a lower risk of subsequent attacks except for brainstem and cerebral events, with an overall relative relapse risk of 0.681 (P = 0.001) compared to Caucasians and African patients, who had a higher likelihood of cerebral attacks, with a relative relapse risk of 3.309 (P = 0.009) compared to Caucasians. Female patients had a higher chance of relapse than male patients (P = 0.009), and patients with younger age of onset were more likely to have optic neuritis relapses (P < 0.001). Immunosuppressant drugs reduced and multiple sclerosis disease-modifying agents increased the likelihood of relapse (P < 0.001). Patients with optic neuritis at onset were more likely to develop blindness (P < 0.001), and those with older age of onset were more likely to develop ambulatory disability. Only 25% of long-term disability was related to initial onset attack, indicating the importance of early attack prevention. With respect to selection of patients for clinical trial design, there would be no gain in power by selecting recent onset patients and only a small gain by selecting patients with recent high disease activity. We provide risk estimates of relapse and disability for patients diagnosed and treated with immunosuppressive treatments over the subsequent 2, 3, 5 and 10 years according to type of attack at onset or the first 2-year course, ethnicity, sex and onset age. This study supports significant effects of onset age, onset phenotype and ethnicity on neuromyelitis optica spectrum disorders outcomes. Our results suggest that powering clinical treatment trials based upon relapse activity in the preceding 2 years may offer little benefit in the way of attack risk yet severely hamper clinical trial success

Clinical reappraisal of SHORT syndrome with PIK3R1 mutations: towards recommendation for molecular testing and management

International audienceSHORT syndrome has historically been defined by its acronym: short stature (S), hyperextensibility of joints and/or inguinal hernia (H), ocular depression (O), Rieger abnormality (R) and teething delay (T). More recently several research groups have identified PIK3R1 mutations as responsible for SHORT syndrome. Knowledge of the molecular etiology of SHORT syndrome has permitted a reassessment of the clinical phenotype. The detailed phenotypes of 32 individuals with SHORT syndrome and PIK3R1 mutation, including eight newly ascertained individuals, were studied to fully define the syndrome and the indications for PIK3R1 testing. The major features described in the SHORT acronym were not universally seen and only half (52%) had 4 or more of the classic features. The commonly observed clinical features of SHORT syndrome seen in the cohort included IUGR \textless 10(th) percentile, postnatal growth restriction, lipoatrophy and the characteristic facial gestalt. Anterior chamber defects and insulin resistance or diabetes were also observed but were not as prevalent. The less specific, or minor features of SHORT syndrome include teething delay, thin wrinkled skin, speech delay, sensorineural deafness, hyperextensibility of joints and inguinal hernia. Given the high risk of diabetes mellitus, regular monitoring of glucose metabolism is warranted. An echocardiogram, ophthalmological and hearing assessments are also recommended