Worldwide diagnostic reference levels for single-photon emission computed tomography myocardial perfusion imaging: findings from INCAPS.

OBJECTIVES: This study sought to establish worldwide and regional diagnostic reference levels (DRLs) and achievable administered activities (AAAs) for single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI). BACKGROUND: Reference levels serve as radiation dose benchmarks to compare individual laboratories against aggregated data, helping to identify sites in greatest need of dose reduction interventions. DRLs for SPECT MPI have previously been derived from national or regional registries. To date there have been no multiregional reports of DRLs for SPECT MPI from a single standardized dataset. METHODS: Data were submitted voluntarily to the INCAPS (International Atomic Energy Agency Nuclear Cardiology Protocols Study), a cross-sectional, multinational registry of MPI protocols. A total of 7,103 studies were included. DRLs and AAAs were calculated by protocol for each world region and for aggregated worldwide data. RESULTS: The aggregated worldwide DRLs for rest-stress or stress-rest studies employing technetium Tc 99m-labeled radiopharmaceuticals were 11.2 mCi (first dose) and 32.0 mCi (second dose) for 1-day protocols, and 23.0 mCi (first dose) and 24.0 mCi (second dose) for multiday protocols. Corresponding AAAs were 10.1 mCi (first dose) and 28.0 mCi (second dose) for 1-day protocols, and 17.8 mCi (first dose) and 18.7 mCi (second dose) for multiday protocols. For stress-only technetium Tc 99m studies, the worldwide DRL and AAA were 18.0 mCi and 12.5 mCi, respectively. Stress-first imaging was used in 26% to 92% of regional studies except in North America where it was used in just 7% of cases. Significant differences in DRLs and AAAs were observed between regions. CONCLUSIONS: This study reports reference levels for SPECT MPI for each major world region from one of the largest international registries of clinical MPI studies. Regional DRLs may be useful in establishing or revising guidelines or simply comparing individual laboratory protocols to regional trends. Organizations should continue to focus on establishing standardized reporting methods to improve the validity and comparability of regional DRLs

Women with Fibromyalgia Have Lower Levels of Calcium, Magnesium, Iron and Manganese in Hair Mineral Analysis

Little is known about hair mineral status in fibromyalgia patients. This study evaluated the characteristics of hair minerals in female patients with fibromyalgia compared with a healthy reference group. Forty-four female patients diagnosed with fibromyalgia according to the American College of Rheumatology criteria were enrolled as the case group. Ageand body mass index-matched data were obtained from 122 control subjects enrolled during visit for a regular health check-up. Hair minerals were analyzed and compared between the two groups. The mean age was 43.7 yr. General characteristics were not different between the two groups. Fibromyalgia patients showed a significantly lower level of calcium (775 µg/g vs 1,093 µg/g), magnesium (52 µg/g vs 72 µg/g), iron (5.9 µg/g vs 7.1 µg/g), copper (28.3 µg/g vs 40.2 µg/g) and manganese (140 ng/g vs 190 ng/g). Calcium, magnesium, iron, and manganese were loaded in the same factor using factor analysis; the mean of this factor was significantly lower in fibromyalgia group in multivariate analysis with adjustment for potential confounders. In conclusion, the concentrations of calcium, magnesium, iron, and manganese in the hair of female patients with fibromyalgia are lower than of controls, even after adjustment of potential confounders

Clonal evolution of CD8+ T cell responses against latent viruses: relationship among phenotype, localization, and function

Human cytomegalovirus (hCMV) infection is characterized by a vast expansion of resting effector-type virus-specific T cells in the circulation. In mice, interleukin-7 receptor α (IL-7Rα)-expressing cells contain the precursors for long-lived antigen-experienced CD8(+) T cells, but it is unclear if similar mechanisms operate to maintain these pools in humans. Here, we studied whether IL-7Rα-expressing cells obtained from peripheral blood (PB) or lymph nodes (LNs) sustain the circulating effector-type hCMV-specific pool. Using flow cytometry and functional assays, we found that the IL-7Rα(+) hCMV-specific T cell population comprises cells that have a memory phenotype and lack effector features. We used next-generation sequencing of the T cell receptor to compare the clonal repertoires of IL-7Rα(+) and IL-7Rα(-) subsets. We observed limited overlap of clones between these subsets during acute infection and after 1 year. When we compared the hCMV-specific repertoire between PB and paired LNs, we found many identical clones but also clones that were exclusively found in either compartment. New clones that were found in PB during antigenic recall were only rarely identical to the unique LN clones. Thus, although PB IL-7Rα-expressing and LN hCMV-specific CD8(+) T cells show typical traits of memory-type cells, these populations do not seem to contain the precursors for the novel hCMV-specific CD8(+) T cell pool during latency or upon antigen recall. IL-7Rα(+) PB and LN hCMV-specific memory cells form separate virus-specific compartments, and precursors for these novel PB hCMV-specific CD8(+) effector-type T cells are possibly located in other secondary lymphoid tissues or are being recruited from the naive CD8(+) T cell pool. IMPORTANCE: Insight into the self-renewal properties of long-lived memory CD8(+) T cells and their location is crucial for the development of both passive and active vaccination strategies. Human CMV infection is characterized by a vast expansion of resting effector-type cells. It is, however, not known how this population is maintained. We here investigated two possible compartments for effector-type cell precursors: circulating acute-phase IL-7Rα-expressing hCMV-specific CD8(+) T cells and lymph node (LN)-residing hCMV-specific (central) memory cells. We show that new clones that appear after primary hCMV infection or during hCMV reactivation seldom originate from either compartment. Thus, although identical clones may be maintained by either memory population, the precursors of the novel clones are probably located in other (secondary) lymphoid tissues or are recruited from the naive CD8(+) T cell pool

Current and prospective pharmacological targets in relation to antimigraine action

Migraine is a recurrent incapacitating neurovascular disorder characterized by unilateral and throbbing headaches associated with photophobia, phonophobia, nausea, and vomiting. Current specific drugs used in the acute treatment of migraine interact with vascular receptors, a fact that has raised concerns about their cardiovascular safety. In the past, α-adrenoceptor agonists (ergotamine, dihydroergotamine, isometheptene) were used. The last two decades have witnessed the advent of 5-HT1B/1D receptor agonists (sumatriptan and second-generation triptans), which have a well-established efficacy in the acute treatment of migraine. Moreover, current prophylactic treatments of migraine include 5-HT2 receptor antagonists, Ca2+ channel blockers, and β-adrenoceptor antagonists. Despite the progress in migraine research and in view of its complex etiology, this disease still remains underdiagnosed, and available therapies are underused. In this review, we have discussed pharmacological targets in migraine, with special emphasis on compounds acting on 5-HT (5-HT1-7), adrenergic (α1, α2, and β), calcitonin gene-related peptide (CGRP 1 and CGRP2), adenosine (A1, A2, and A3), glutamate (NMDA, AMPA, kainate, and metabotropic), dopamine, endothelin, and female hormone (estrogen and progesterone) receptors. In addition, we have considered some other targets, including gamma-aminobutyric acid, angiotensin, bradykinin, histamine, and ionotropic receptors, in relation to antimigraine therapy. Finally, the cardiovascular safety of current and prospective antimigraine therapies is touched upon

Erratum to: Scaling up strategies of the chronic respiratory disease programme of the European Innovation Partnership on Active and Healthy Ageing (Action Plan B3: Area 5).

[This corrects the article DOI: 10.1186/s13601-016-0116-9.]

Erratum to: Scaling up strategies of the chronic respiratory disease programme of the European Innovation Partnership on Active and Healthy Ageing (Action Plan B3: Area 5).

[This corrects the article DOI: 10.1186/s13601-016-0116-9.]

Positioning the principles of precision medicine in care pathways for allergic rhinitis and chronic rhinosinusitis - A EUFOREA-ARIA-EPOS-AIRWAYS ICP statement.

Precision medicine (PM) is increasingly recognized as the way forward for optimizing patient care. Introduced in the field of oncology, it is now considered of major interest in other medical domains like allergy and chronic airway diseases, which face an urgent need to improve the level of disease control, enhance patient satisfaction and increase effectiveness of preventive interventions. The combination of personalized care, prediction of treatment success, prevention of disease and patient participation in the elaboration of the treatment plan is expected to substantially improve the therapeutic approach for individuals suffering from chronic disabling conditions. Given the emerging data on the impact of patient stratification on treatment outcomes, European and American regulatory bodies support the principles of PM and its potential advantage over current treatment strategies. The aim of the current document was to propose a consensus on the position and gradual implementation of the principles of PM within existing adult treatment algorithms for allergic rhinitis (AR) and chronic rhinosinusitis (CRS). At the time of diagnosis, prediction of success of the initiated treatment and patient participation in the decision of the treatment plan can be implemented. The second-level approach ideally involves strategies to prevent progression of disease, in addition to prediction of success of therapy, and patient participation in the long-term therapeutic strategy. Endotype-driven treatment is part of a personalized approach and should be positioned at the tertiary level of care, given the efforts needed for its implementation and the high cost of molecular diagnosis and biological treatment

Genetics and not shared environment explains familial resemblance in adult metabolomics data

Metabolites are small molecules involved in cellular metabolism where they act as reaction substrates or products. The term 'metabolomics' refers to the comprehensive study of these molecules. The concentrations of metabolites in biological tissues are under genetic control, but this is limited by environmental factors such as diet. In adult mono- and dizygotic twin pairs, we estimated the contribution of genetic and shared environmental influences on metabolite levels by structural equation modeling and tested whether the familial resemblance for metabolite levels is mainly explained by genetic or by environmental factors that are shared by family members. Metabolites were measured across three platforms: two based on proton nuclear magnetic resonance techniques and one employing mass spectrometry. These three platforms comprised 237 single metabolic traits of several chemical classes. For the three platforms, metabolites were assessed in 1407, 1037 and 1116 twin pairs, respectively. We carried out power calculations to establish what percentage of shared environmental variance could be detected given these sample sizes. Our study did not find evidence for a systematic contribution of shared environment, defined as the influence of growing up together in the same household, on metabolites assessed in adulthood. Significant heritability was observed for nearly all 237 metabolites; significant contribution of the shared environment was limited to 6 metabolites. The top quartile of the heritability distribution was populated by 5 of the 11 investigated chemical classes. In this quartile, metabolites of the class lipoprotein were significantly overrepresented, whereas metabolites of classes glycerophospholipids and glycerolipids were significantly underrepresented.Analytical BioScience