Translation calibration of inverse-kappa goniometers in macromolecular crystallography

A rapid, easy-to-perform translation calibration procedure has been developed for use with the EMBL/ESRF mini-κ goniometer head and for other inverse-kappa goniometers designed for macromolecular crystallography. Regular calibration ensures the precision of experiments that rely on many degrees of freedom in crystal reorientation

Versatile Cross-Dehydrogenative Coupling of Heteroaromatics and Hydrogen Donors via Decatungstate Photocatalysis

A facile sunlight-induced derivatization of heteroaromatics via photocatalyzed C-H functionalization in amides, ethers, alkanes and aldehydes is described. Tetrabutylammonium decatungstate (TBADT) was used as the photocatalyst and allowed to carry out the process under mild conditions

18F-choline PET/CT and PET/MRI in primary and recurrent hyperparathyroidism: a systematic review of the literature

The aims of the present systematic review were to: (1) assess the role of 18F-fluorocholine (FCH) positron emission tomography (PET) with computed tomography (CT) and PET with magnetic resonance imaging (MRI) in patients with biochemically known hyperparathyroidism; (2) compare the diagnostic performance of FCH PET/CT or PET/MRI with conventional morphological and functional imaging. A literature search until December 2019 was performed in the PubMed, Scopus and Web of Science databases, using the terms “choline” AND “PET” AND “hyperparathyroidism”. The search was conducted with and without the addition of filters (e.g., language: English only; type of article: original article; subjects: humans only) and selecting only articles published in the last 5 years. Twenty-three articles and 1112 patients were considered. Different FCH PET/CT acquisition protocols were adopted across the studies, using dynamic, early or delayed scans. FCH PET/CT proved more accurate than ultrasonography (US) or 99mTc-sestamibi single-photon emission tomography (SPET). PET/MRI also seemed to be more accurate than MRI alone in detecting benign parathyroid lesions. FCH PET/CT is more accurate than conventional morphological and functional imaging modalities (US or SPET) for the detection of benign parathyroid lesions. It could, therefore, be a reliable tool in both primary and recurrent hyperparathyroidism

Simultaneous identification and quantitative determination in urine of the more significant metabolites of synthetic cannabinoids JWH-018, JWH-073, JWH-122 and JWH-250 using authentic references and deuterated isotopologues as internal standards

Introduction Synthetic cannabinoids (SC) are substances displaying a high affinity for cannabinoid receptor CB1 and represent the psychoactive agents in herbal mixtures called \u201cSpice\u201d or \u201cK2\u201d which are sold as an incense or smoking material mainly through the Internet. Because of its great abusive potential, several SC are banned in many countries, but despite this, the widespread use of herbal smoking mixtures containing SC may be partially explained by the fact that post-ingestion urines are known to produce negative results in standard toxicological screening methods for cannabis. As a consequence, an increasing number of analytical methods have been developed in forensic and doping control laboratories to enable the detection of illegal intake of these psychoactive substances in human fluids originating from psychiatric patients, emergency units or assessment of fitness to drive. Due to rapid metabolic transformation, the native SC are not usually detectable in urine samples and then the analytical methods must be based on the identification and quantization of their metabolites. Aims The aim of our study is to set-up, using synthesized reference standards, a LC-MS/MS method for routine screening procedures to assess the assumption of JWH-018, JWH-073, JWH 122 and JWH-250, the SC included in Table 1 of narcotic and psychotropic substances banned in Italy. The method gives the simultaneous identification of the three more significant metabolites of each cannabinoid and adequate sensitivity, precision and accuracy are assured by the use of deuterated internal standards. Methods For each of the four cannabinoids were synthesized the three more significant metabolites, the \u3c9- and (\u3c9-1)-hydroxyl and the \u3c9-carboxyl derivatives (\u3c9 position represent the terminal carbon of the N-alkyl side chain) while as internal standards were synthesized the (\u3c9-1)-hydroxyl metabolites trideuterated on the terminal methyl of the side chain. Urine samples were subjected to deconjugation using 30% hydrochloric acid at 90-95\ub0C for 60 min, followed by a solvent extraction procedure with n-hexane-ethyl acetate (9/1 v/v). The LC-MS/MS analysis was performed in positive mode on an API 4000 Triple Quadrupole Mass Spectrometer (AB Sciex) equipped with a 1,8\ub5m Acquity C-18 HSS T3 100 x 2 mm HPLC column (Waters) with isocratic elution (55 % of 10 mM HCOONH4 in water containing 0.1% HCOOH and 45 % of acetonitrile) at 45 \ub0C and at flow rate of 0.4 mL/min. Two transitions in \u2018multiple reaction monitoring\u2019 mode and the retention time have permitted the unambiguous identification of each metabolite which, through the presence of a suitable internal standard, was quantified. Result and discussion All the synthesized compounds were fully characterized with regard to the structure and purity, by 1H,13C NMR and GC-MS (after esterification with CH2N2 for the \u3c9-carboxylic metabolites). For sample treatment, the recovery of the metabolites was evaluated at different pH (1, 3, 5, 9 and 10). The validation of the method was performed testing linearity (0.5-100 ng/mL), reproducibility and accuracy (ranged between -15% and + 15%) at three levels. The method developed was applied to the analysis of urine samples from individuals who have taken SC. This LC-MS/MS method can be used for routine screening of urine specimens from subjects suspected of using \u201cherbal incense\u201d or \u201cSpice\u201d products spiked with the synthetic cannabinoids JWH-018, JWH-073, JWH 122 or JWH-250

Size-Dependent Transition to High-Dimensional Chaotic Dynamics in a Two-Dimensional Excitable Medium

The spatiotemporal dynamics of an excitable medium with multiple spiral defects is shown to vary smoothly with system size from short-lived transients for small systems to extensive chaos for large systems. A comparison of the Lyapunov dimension density with the average spiral defect density suggests an average dimension per spiral defect varying between three and seven. We discuss some implications of these results for experimental studies of excitable media.Comment: 5 pages, Latex, 4 figure

The challenge of early diagnosis of autoimmune lymphoproliferative syndrome in children with suspected autoinflammatory/autoimmune disorders

OBJECTIVES: To test the usefulness of an extended panel of lymphocyte subsets in combination with Oliveira's diagnostic criteria for the identification of autoimmune lymphoproliferative syndrome (ALPS) in children referred to a paediatric rheumatology centre. METHODS: Patients referred from 2015 to 2018 to our rheumatology unit for an autoimmune or autoinflammatory condition were retrospectively analysed. Oliveira's required criteria [chronic lymphoproliferation and elevated double-negative T (DNT)] were applied as first screening. Flow cytometry study included double-negative CD4-CD8-TCR\u3b1\u3b2+ T lymphocytes (DNT), CD25+CD3+, HLA-DR+CD3+ T cells, B220+ T cells and CD27+ B cells. Data were analysed with a univariate logistic regression analysis, followed by a multivariate analysis. Sensitivity and specificity of the Oliveira's required criteria were calculated. RESULTS: A total of 264 patients were included in the study and classified as: (i) autoimmune diseases (n\u2009=\u200926); (ii) juvenile idiopathic arthritis (JIA) (35); (iii) monogenic systemic autoinflammatory disease (27); (iv) periodic fever, aphthous stomatitis, pharyngitis and adenitis syndrome (100); (v) systemic undefined recurrent fever (45); (vi) undetermined-systemic autoinflammatory disease (14); or (vii) ALPS (17). Oliveira's required criteria displayed a sensitivity of 100% and specificity of 79%. When compared with other diseases the TCR\u3b1\u3b2+B220+ lymphocytes were significantly increased in ALPS patients. The multivariate analysis revealed five clinical/laboratory parameters positively associated to ALPS: splenomegaly, female gender, arthralgia, elevated DNT and TCR\u3b1\u3b2+B220+ lymphocytes. CONCLUSIONS: Oliveira's required criteria are useful for the early suspicion of ALPS. TCR\u3b1\u3b2+B220+ lymphocytes should be added in the diagnostic work-up of patients referred to the paediatric rheumatology unit for a suspected autoimmune or autoinflammatory condition, providing a relevant support in the early diagnosis of ALPS