Abnormal thyroid function is common in takotsubo syndrome and depends on two distinct mechanisms: results of a multicentre observational study.

BACKGROUND: Several reports have described Takotsubo syndrome (TTS) secondary to thyrotoxicosis. A complex interaction of central and peripheral catecholamines with thyroid homeostasis has been suggested. In this study, we analysed sequential thyroid hormone profiles during the acute phase of TTS. METHODS: Thyrotropin (TSH), free T4 (FT4) and free T3 (FT3) concentrations were analysed at predefined time points in 32 patients presenting with TTS or acute coronary syndrome (ACS, n = 16 in each group) in a 2-year period in two German university hospitals. Data were compared to age- and sex-matched controls (10 samples, each of 16 subjects), and an unsupervised machine learning (ML) algorithm identified patterns in the hormone signature. Subjects with thyroid disease and patients receiving amiodarone were excluded from follow-up. RESULTS: Among patients with TTS, FT4 concentrations were significantly higher when compared to controls or ACS. Four subjects (25%) suffered from subclinical or overt thyrotoxicosis. Two additional patients developed subclinical or overt thyrotoxicosis during stay in hospital. In four subjects (25%), FT4 concentrations were increased, despite nonsuppressed TSH concentration, representing an elevated set point of thyroid homeostasis. The thyroid hormone profile was normal in only six patients (38%) presenting with TTS. CONCLUSION: Abnormal thyroid function is frequent in patients with TTS. Primary hyperthyroidism and an elevated set point of thyroid homeostasis are common in TTS, suggesting a stress-dependent endocrine response or type 2 thyroid allostasis. Thyroid function may be a worthwhile target in treating or preventing TTS.

Cortical fast-spiking parvalbumin interneurons enwrapped in the perineuronal net express the metallopeptidases Adamts8, Adamts15 and Neprilysin.

The in situ hybridization Allen Mouse Brain Atlas was mined for proteases expressed in the somatosensory cerebral cortex. Among the 480 genes coding for protease/peptidases, only four were found enriched in cortical interneurons: Reln coding for reelin; Adamts8 and Adamts15 belonging to the class of metzincin proteases involved in reshaping the perineuronal net (PNN) and Mme encoding for Neprilysin, the enzyme degrading amyloid ß-peptides. The pattern of expression of metalloproteases (MPs) was analyzed by single-cell reverse transcriptase multiplex PCR after patch clamp and was compared with the expression of 10 canonical interneurons markers and 12 additional genes from the Allen Atlas. Clustering of these genes by K-means algorithm displays five distinct clusters. Among these five clusters, two fast-spiking interneuron clusters expressing the calcium-binding protein Pvalb were identified, one co-expressing Pvalb with Sst (PV-Sst) and another co-expressing Pvalb with three metallopeptidases Adamts8, Adamts15 and Mme (PV-MP). By using Wisteria floribunda agglutinin, a specific marker for PNN, PV-MP interneurons were found surrounded by PNN, whereas the ones expressing Sst, PV-Sst, were not.

Optical Emission of Individual GaN Nanocolumns Analyzed with High Spatial Resolution.

Selective area growth has been applied to fabricate a homogeneous array of GaN nanocolumns (NC) with high crystal quality. The structural and optical properties of single NCs have been investigated at the nanometer-scale by transmission electron microscopy (TEM) and highly spatially resolved cathodoluminescence (CL) spectroscopy performed in a scanning transmission electron microscope (STEM) at liquid helium temperatures. TEM cross-section analysis reveals excellent structural properties of the GaN NCs. Sporadically, isolated basal plane stacking faults (BSF) can be found resulting in a remarkably low BSF density in the almost entire NC ensemble. Both, defect-free NCs and NCs with few BSFs have been investigated. The low defect density within the NCs allows the characterization of individual BSFs, which is of high interest for studying their optical properties. Direct nanometer-scale correlation of the CL and STEM data clearly exhibits a spatial correlation of the emission at 360.6 nm (3.438 eV) with the location of basal plane stacking faults of type I1.

Type I interferon signaling genes in recurrent major depression: increased expression detected by whole-blood RNA sequencing.

A study of genome-wide gene expression in major depressive disorder (MDD) was undertaken in a large population-based sample to determine whether altered expression levels of genes and pathways could provide insights into biological mechanisms that are relevant to this disorder. Gene expression studies have the potential to detect changes that may be because of differences in common or rare genomic sequence variation, environmental factors or their interaction. We recruited a European ancestry sample of 463 individuals with recurrent MDD and 459 controls, obtained self-report and semi-structured interview data about psychiatric and medical history and other environmental variables, sequenced RNA from whole blood and genotyped a genome-wide panel of common single-nucleotide polymorphisms. We used analytical methods to identify MDD-related genes and pathways using all of these sources of information. In analyses of association between MDD and expression levels of 13 857 single autosomal genes, accounting for multiple technical, physiological and environmental covariates, a significant excess of low P-values was observed, but there was no significant single-gene association after genome-wide correction. Pathway-based analyses of expression data detected significant association of MDD with increased expression of genes in the interferon α/ß signaling pathway. This finding could not be explained by potentially confounding diseases and medications (including antidepressants) or by computationally estimated proportions of white blood cell types. Although cause-effect relationships cannot be determined from these data, the results support the hypothesis that altered immune signaling has a role in the pathogenesis, manifestation, and/or the persistence and progression of MDD.

[Preparation of Transmembrane Fragments Growth Hormone Receptor GHR in a Cell-Free Expression System for Structural Studies].

Growth hormone somatotropin and its membrane receptor GHR, belonging to a superfamily of the type I receptors possessing tyrosine kinase activity, are involved in the intercellular signal transduction cascade and regulate a number of important physiological and pathological processes in humans. Binding with somatotropin triggers a transition of GHR between two alternative dimer states, resulting in an allosteric activation of JAK2 tyrosine kinase in the cell cytoplasm. Transmembrane domain of GHR directly involved in this complex conformational transition. It has presumably two dimerization interfaces corresponding to the "unliganded" and the active state of GHR. In order to study the molecular basis of biochemical signal transduction mechanism across the cell membrane, we have developed an efficient cell-free production system of a TM fragment of GHR, which contains its TM domain flanked by functionally important juxtamembrane regions (GHRtm residues 254-298). The developed system allows to obtain -1 mg per 1 ml of reaction mixture of 13C- and 15N-isotope-labeled protein for structural and dynamic studies of the GHR TM domain dimerization in the membrane-mimicking medium by high-resolution heteronuclear NMR spectroscopy.

An automated, high-throughput method for targeted quantification of intact insulin and its therapeutic analogs in human serum or plasma coupling mass spectrometric immunoassay with high resolution and accurate mass detection (MSIA-HR/AM).

The detection and quantification of insulin and its therapeutic analogs is important for medical, sports doping, and forensic applications. Synthetic variants contain slight sequence variations to affect bioavailability. To reduce sample handling bias, a universal extraction method is required for simultaneous extraction of endogenous and variant insulins with subsequent targeted quantification by LC-MS. A mass spectrometric immunoassay (MSIA), a multiplexed assay for intact insulin and its analogues that couples immunoenrichment with high resolution and accurate mass (HR/AM) spectrometric detection across the clinical range is presented in this report. The assay is sensitive, selective, semi-automated and can potentially be applied to detect new insulin isoforms allowing their further incorporation into second or third generation assays.

Plasma retinol-binding protein 4 (RBP4) levels and risk of coronary heart disease: a prospective analysis among women in the nurses' health study.

BACKGROUND: Retinol-binding protein 4 (RBP4) may play an important role in the origin of insulin resistance and metabolic syndrome. Few prospective data are available on the relationship between RBP4 and coronary heart disease (CHD). Furthermore, previous studies did not distinguish among full-length and truncated forms of RBP4 that might have various biological activities. METHODS AND RESULTS: We measured plasma levels of full-length and several C-terminally truncated subfractions of RBP4 among 468 women who developed CHD and 472 matched controls in the Nurses' Health Study cohort during 16 years of follow-up (1990-2006). We observed a temporal variation in the association of full-length RBP4 levels with CHD risk (P=0.04 for testing proportional hazard assumption). In the first 8 years of follow-up, after multivariate adjustment for covariates, the odds ratio of CHD risk comparing extreme quartiles of full-length RBP4 levels was 3.56 (95% confidence interval, 1.21-10.51; Ptrend=0.003), whereas this association was 0.77 (95% confidence interval, 0.38-1.56; Ptrend=0.44) in the follow-up period of 9 to 16 years. Results were similar for total RBP4 levels (summed levels of all RBP4 isoforms). Levels of the primary truncated isoform, RBP4-L, were not associated with CHD risk in any follow-up period; the odds ratios for extreme quartiles were 1.29 (95% confidence interval, 0.50-3.32) and 1.20 (95% confidence interval, 0.64-2.26) in the first and second 8 years of follow-up, respectively. CONCLUSIONS: In this cohort of women, higher circulating full-length and total RBP4 levels were associated with increased risk of CHD in a time-dependent fashion. Additional data are warranted to confirm the present findings.

Prevalence and factors associated with professional burnout in Polish oncologists-results of a nationwide survey.

BACKGROUND: High rates of burnout are observed among health care professionals worldwide, which could have negative consequences on personal and organizational levels. We aimed to evaluate the burnout prevalence and factors associated with burnout among oncologists in Poland. MATERIALS AND METHODS: An online survey was conducted using the validated Maslach Burnout Inventory-Human Services Survey (MBI-HSS) and additional work/lifestyle questions. Descriptive statistics, parametric and nonparametric tests, and multivariate logistic regression were used to identify factors associated with burnout. RESULTS: A total of 228 physicians participated in the survey, including 168 medical oncologists, 43 radiation oncologists, and 17 from other specialties. Data collected from 211 medical and radiation oncologists were included in the final analyses. Most participants were female (71.6%) and ≤40 years of age (70.1%). A self-reported feeling of burnout was present in 65.9% of participants. Based on the MBI-HSS, 74.9% showed evidence of burnout with burnout subdomains as follows: depersonalization 37.0%; emotional exhaustion 64.5%; low accomplishment 43.1%. There were no differences in burnout rates based on specialization (oncology/haematology-75.6%, radiotherapy-72.1%), career stage, gender, or age groups. Lack of work-life balance was the only significant factor associated with the risk of burnout in the logistic regression (relative risk 2.6, 95% confidence interval 1.3-5.4). Only 20.9% of physicians had access to psychological support in their workplace; however, 70.1% desired such support. Three main factors impacting burnout in cancer care workers were: bureaucracy and administrative duties overload, admissions of many patients, and poor work culture. CONCLUSIONS: Burnout is common among medical and radiation oncologists in Poland. There is a high demand for psychological support and organizational changes in the workplace to reduce risk and mitigate the adverse effects of burnout among health care professionals.

Bacterial and cell-free production of APP671-726 containing amyloid precursor protein transmembrane and metal-binding domains.

More than half of the mutations associated with familiar Alzheimer's disease have been found in the transmembrane domain of amyloid precursor protein (APP). These pathogenic mutations presumably influence the APP transmembrane domain structural and dynamic properties and result in its conformational change or/and lateral dimerization. Despite much data about the pathogenesis of Alzheimer's disease, the initial steps of the pathogenesis remain unclear so far. For the investigation of the molecular basis of Alzheimer's disease, we selected amyloid precursor protein fragment APP671-726 containing the transmembrane and metal-binding domains. This fragment is the substrate of the γ-secretase complex whose abnormal activity leads to the formation of amyloidogenic Aß42 peptides. This work for the first time describes a highly effective cell-free APP671-726 production method and improved method of bacterial synthesis. Both methods yield milligram quantities of isotope-labeled protein for structural study by high resolution NMR spectroscopy in membrane mimicking milieus.

Models of Care - End of Life Pathways.

Resuscitation status and Advance Care Plans need to be discussed and clearly documented The Liverpool Care Pathway is a recognized model of EOL care in, and has been adapted for patients with end stage renal disease Recognition of a dying patient allows initiation of a multidisciplinary EOL pathway such as the Liverpool Care Pathway for hospital inpatients, and for support for families if a home death is planned. A fall in performance status is an indicator of decline.

Structure and elemental distribution of (Ga,Mn)N nanowires.

(Ga,Mn)N nanowires were grown by plasma-assisted molecular beam epitaxy on p-type Si(111) substrates. Chemical composition and elemental distribution of single nanowires were analyzed by energy dispersive X-ray spectroscopy revealing an inhomogeneous Mn distribution decreasing from the surface of the nanowires toward the inner core region. The average Mn concentration within the nanowires is found to be below 1%. High-resolution transmission electron microscopy shows the presence of planar defects perpendicular to the growth direction in undoped and Mn-doped GaN nanowires. The density of planar defects dramatically increases under Mn supply.

[Workplace injury prevention in airport: intervention model]. / La prevenzione degli infortuni in ambito aeroportuale: modello d'intervento.

Since 2008, in order to create a collaboration directed to improve safety and consequently to reduce work injuries, we have introduced a new work methodological approach between SPRESAL (Service of Workplace Prevention and Safety) ASL 8 of Cagliari and Gruppo Sogaer, responsible for Airport Services in Cagliari. The study shows that the interaction between both parties produced encouraging results: significant decrease in injuries among operating and administrative areas employees. Accidents rate decreased from 5 to 1.8 during the observation period 2008-2010. Measures taken had increased the safety culture, a better worker behavior analisys, adherence to procedures, PPE use, more training.

Cross Determination of Exciton Coherence Length in J-Aggregates.

The coherence length of the Frenkel excitons (Ncoh) is one of the most critical parameters governing many key features of supramolecular J-aggregates. Determining experimentally the value of Ncoh is a nontrivial task since it is sensitive to the technique/method applied, causing discrepancies in the literature data even for the same chemical compound and aggregation conditions. By using a combination of different experimental techniques including UV-vis-NIR, fluorescence emission, time-resolved photoluminescence, and transient absorption spectroscopies, we determined Ncoh values for J-aggregates of a cyanine dye. We found that the absorption spectroscopy alone - a widely used technique- fails in determining right value for Ncoh. The correct approach is based on the modification of photoluminescence lifetime and nonlinear response upon aggregation and careful analysis of the Stokes shift and electron-phonon coupling strength. This approach revealed that Ncoh of JC-1 J-aggregates ranges from 3 to 6.

Reduction in generation of reactive oxygen species and endothelial dysfunction during postprandial state.

BACKGROUND AND AIMS: To characterise changes in generation of cellular reactive oxygen species (ROS) in healthy males during the postprandial state, and to analyse the influence of the postprandial state on endothelial ROS generation and endothelial dysfunction. METHODS AND RESULTS: Seventeen healthy subjects were recruited. Blood samples were collected in the fasting state and 2, 4, 6 and 8h after liquid-meal intake (composition: 25% fat, 55% dextromaltose and 14% protein), providing 40 gfat m(-2) body surface. Plasma lipids, apolipoproteins, glucose and insulin were measured during this period. Peripheral blood mononuclear cells (PBMCs) were isolated by density-gradient centrifugation. The influence of postprandial state on intracellular ROS generation was measured by two different methods in PBMCs and in a human immortalised endothelial cell line (ECV 304). Artery flow-mediated vasodilation (FMD) was used to evaluate the endothelial function, and oxygen consumption by PBMCs was measured. Reduced ROS generation was observed in all methods and cells during the postprandial period. FMD was impaired 8h after meal intake (23±6 vs. 13±2, P<0.05 vs. baseline). The consumption of oxygen was reduced in PBMCs (-14% into 2h, P<0.05 vs. baseline and -27% after 4h, P<0.01 vs. baseline). ROS generation was correlated with plasma lipids, insulin, apolipoproteins and oxygen consumption. CONCLUSIONS: In contrast to the previously reported elevation of postprandial oxidative stress, this study shows reduced ROS generation in PBMCs and in ECV 304. Data obtained in both cellular models suggest the existence of a protective response against plasma postprandial oxidative stress.

First spatially resolved measurements of the D-3He α-particle source with the upgraded JET gamma-ray camera.

The Joint European Torus (JET) gamma-ray camera has been recently upgraded with the installation of new gamma-ray detectors, based on LaBr3(Ce) scintillation crystals, which add spectroscopic capability to the existing system allowing measurements with good energy resolution (5% at 0.622 MeV), a dynamic range from hundreds of keV up to about 30 MeV, and high counting rate capabilities of MCps. First gamma-ray measurements during the C38 campaign of the JET have been successfully carried out, in particular, in D-3He plasmas from three-ion ion cyclotron resonance heating experiments, where the detection of 16.4 MeV γ-rays from D + 3He → γ + 5Li reactions with the gamma-ray camera upgrade allowed determining the spatial profile of alpha particles born in D + 3He fusion reactions.

The burden of heat-related mortality attributable to recent human-induced climate change.

Climate change affects human health; however, there have been no large-scale, systematic efforts to quantify the heat-related human health impacts that have already occurred due to climate change. Here, we use empirical data from 732 locations in 43 countries to estimate the mortality burdens associated with the additional heat exposure that has resulted from recent human-induced warming, during the period 1991-2018. Across all study countries, we find that 37.0% (range 20.5-76.3%) of warm-season heat-related deaths can be attributed to anthropogenic climate change and that increased mortality is evident on every continent. Burdens varied geographically but were of the order of dozens to hundreds of deaths per year in many locations. Our findings support the urgent need for more ambitious mitigation and adaptation strategies to minimize the public health impacts of climate change.

Controlled nanometric phase transitions of phospholipid membranes by plasmonic heating of single gold nanoparticles.

The development of remotely controlled nanoscopic sources of heat is essential for investigating and manipulating temperature sensitive processes at the nanoscale. Here, we use single gold nanoparticles to rapidly deposit controlled amounts of heat in nanoscopic regions of defined size. This allows us to induce and control nanoscale reversible gel-fluid phase transitions in phospholipid membranes. We exploit the optical control over the phase transition to determine the velocity of the fluid phase front into the gel phase membrane and to guide the nanoparticles to specific locations. These results illustrate how single gold nanoparticles enable local thermodynamic investigation and manipulation on nanoscale (bio-) systems.

Report: New reliable method for the measurement of chlorine in refuse-derived fuels through combustion experiments in a pilot plant.

The calorific values and the chlorine contents of refuse-derived fuels were measured in the pilot combustion plant (PCP) by means of combustion experiments followed by mass and energy balancing. This plant reaches an increased precision by measuring the integrated values throughout the whole experimental period of three hours, based on a fuel capacity of 10 kg per test, allowing a more reliable measurement of pollutants than for experimental analysis of only a few grams of the sample. The combustion experiments are shown for the verification of the quality of the chlorine balancing in the PCP. The test evaluation was carried out by balancing the inputs and outputs of chlorine in the mass streams, and the recovery rates for chlorine were determined. An emission pattern for the chlorine is described by the transfer coefficients and via the temporal fluctuation of the hydrogen chloride concentration in the flue gas. The results of the combustion experiments prove that the balancing via combustion experiments in the PCP provides reliable data on the chlorine concentrations in the fuels, and is a new and reliable method for measuring polluting chlorine in refuse-derived fuels.

[Evaluation of metabolites levels in feces of patients with inflammatory bowel diseases]. / Otsenka urovnia metabolitov v fekaliiakh patsientov s vospalitel'nymi zabolevaniiami kishechnika.

Inflammatory bowel diseases (IBD), which include ulcerative colitis (UC) and Crohn's disease (CD), are chronic intestinal inflammatory disorders with an unknown etiology. They are characterized by chronic recurrent inflammation of the intestinal mucosa and lead to a significant decrease in the quality of life and death of patients. IBD are associated with suppression of normal intestinal microflora, including a decrease in bacteria, producers of short chain fatty acids (SCFAs), exhibiting anti-inflammatory and protective properties. Among the various methods of intestinal microflora correction, fecal microbiota transplantation (FMT), which engrafts the fecal microbiota from a healthy donor into a patient recipient, is of a particular interest. As a result, a positive therapeutic effect is observed, accompanied by the restoration of the normal intestinal microflora of the patient. A significant drawback of the method is the lack of standardization. Metabolites produced by intestinal microflora, namely SCFAs, allow objective assessment of the functional state of the intestinal microbiota and, consequently, the success of the FMT procedure. Using gas chromatography and nuclear magnetic resonance spectroscopy techniques, we have analyzed concentrations and molar ratios of SCFAs in fecal samples of 60 healthy donors. Results were in good accord when comparing two methods as well as with published data. Analysis of SCFAs in feces of patients with UC (19 patients) and CD (17 patients) revealed a general decrease in the concentration of fatty acids in the experimental groups with significant fluctuations in the values in experimental groups compared to control group of healthy donors. On the limited group of IBD patients (6 patients with UC and 5 patients with CD) concentration of SCFAs before and within 30 days of observation after FMT was determined. It was shown that FMT had a significant impact on the SCFAs levels within 1 month term; tendency to reach characteristics of healthy donors is unambiguously traced for both diseases.

Boot camps in neonatal-perinatal medicine fellowship programs: A national survey.

BACKGROUND: Simulation is widely used in graduate medical education. A prior survey showed that 80% of Neonatal-Perinatal Medicine (NPM) fellowship programs in the U.S. use simulation. There are multiple ways to provide simulation-based education. One such method is through intensive simulation-based education sessions held at the beginning of a training program, common called 'boot camps'. The aim of this study was to describe the use of simulation-based boot camps in NPM fellowship programs. METHODS: Survey study of Accreditation Council for Graduate Medical Education (ACGME) accredited NPM fellowships in the U.S. RESULTS: Fifty-nine of 98 programs (60%) responded. Thirty six (61%) participated in 1st year fellow boot camps, which focused on procedural skills and newborn resuscitation. Nearly half of programs participated in regional boot camps. Most boot camps were one or two days long. Eleven programs (19%) held 2nd or 3rd year fellow boot camps, which focused on advanced resuscitation and communication. Barriers included lack of faculty protected time (57%), funding (39%), and lack of faculty experience (31%). CONCLUSIONS: A majority of ACGME accredited NPM fellowships participate in 1st year fellows' boot camps. Many participate in regional boot camps. A few programs have 2nd or 3rd year fellow boot camps. Lack of time, funding, and faculty experience were common barriers.