Low-temperature photoemission electron microscopy (PEEM) is used to image and compare the distribution of ferroelectric domains in multiferroic ErMnO3 above and below the magnetic ordering ...temperature (TN 80 K). Our temperature-dependent PEEM data demonstrate that the ferroelectric domain structure is robust against the onset of magnetic long- range order and the emergence of antiferromagnetic domains. The observed persistence indicates that antiferromagnetic domain walls adopt the position of ferroelectric walls – and not vice versa – developing a multiferroic domain-wall pattern congruent with the ferroelectric domain-wall distribution observed above TN.
Immunosuppressive therapy for cardiac sarcoidosis (CS) still largely consists of corticosteroid monotherapy. However, high relapse rates after tapering and insufficient efficacy are significant ...problems. The objective of this study was to investigate the efficacy and safety of non-biological and biological disease-modifying anti-rheumatic drugs (nb/bDMARDs) considering control of myocardial inflammation assessed by
F-fluorodeoxyglucose positron emission tomography/computed tomography (
F-FDG PET/CT) of the heart.
We conducted a retrospective analysis of treatment response to nb/bDMARDs of all CS patients seen in the sarcoidosis center of the University Hospital Zurich between January 2016 and December 2020.
We identified 50 patients with CS. Forty-five patients with at least one follow-up PET/CT scan were followed up for a mean of 20.5 ± 12.8 months. Most of the patients were treated with prednisone and concomitant nb/bDMARDs. At the first follow-up PET/CT scan after approximately 6.7 ± 3 months, only adalimumab showed a significant reduction in cardiac metabolic activity. Furthermore, comparing all serial follow-up PET/CT scans (143), tumor necrosis factor inhibitor (TNFi)-based therapies showed statistically significant better suppression of myocardial
F-FDG uptake compared to other treatment regimens. On the last follow-up, most adalimumab-treated patients were inactive (n = 15, 48%) or remitting (n = 11, 35%), and only five patients (16%) were progressive. TNFi was safe even in patients with severely reduced left ventricular ejection fraction (LVEF), and a significant improvement in LVEF under TNFi treatment was observed.
TNFi shows better control of myocardial inflammation compared to nbDMARDs and corticosteroid monotherapies in patients with CS. TNFi was efficient and safe even in patients with severely reduced LVEF.
Serotonin (5-HT) and the hormone leptin have been linked to the underlying neurobiology of appetite regulation with evidence coming from animal and cellular research, but direct evidence linking ...these two pathways in humans is lacking. We examined the effects of reduced brain 5-HT synthesis due to acute tryptophan depletion (ATD) on levels of soluble leptin receptor (sOb-R), the main high-affinity leptin binding protein, in healthy adults using an exploratory approach. Women, but not men, showed reduced sOb-R concentrations after ATD administration. With females showing reduced baseline levels of central 5-HT synthesis compared to males diminished brain 5-HT synthesis affected the leptin axis through the sOb-R in females, thereby potentially influencing their vulnerability to dysfunctional appetite regulation and co-morbid mood symptoms.
Hexagonal manganites are among the most intensively studied multiferroics, exhibit unusual geometrically driven ferroelectricity and magnetoelectric couplings, and form domains and domain walls with ...intriguing functional properties. In order to study these electronic correlation phenomena and develop a comprehensive understanding about the underlying physics, the availability of high-quality single-crystals is crucial. In particular, different members of the RMnO sub(3) (R = Sc, Y, In, Dy to Lu) family require different growth condition in order to achieve stoichiometric single-phase crystals. Here, we report on the growth of high-quality ErMnO sub(3) single crystals with dimensions of 5 mm in diameter and up to 60 mm in length using the pressurized floating-zone technique. We present Laue diffraction, piezo-response force microscopy, and conductive atomic force microscopy data, reflecting the quality of our single crystals regarding the structure, as well as electronic properties on the level of domains and domain walls.
Research has implicated that changes in zinc (Zn) metabolism may be associated with the biological underpinnings of eating disorders, in particular anorexia nervosa. However, to date research on the ...role of Zn in patients with bulimia nervosa (BN) is scarce.
We aimed to explore serum Zn concentrations in young patients with BN, with a focus on the stage of the disorder, comparing acutely ill and recovered patients with BN with healthy controls.
Serum Zn concentrations were obtained from healthy controls and from acutely ill and remitted young patients with BN. Mean duration of remission was 4.0±3.5 years.
Remitted patients showed elevated serum Zn concentrations when compared to controls (Cohen's d=2.022), but concentrations were still in the normal range. Acutely ill patients also had higher serum Zn levels when compared to controls (all values still being within the reference range, Cohen's d=0.882). There was no difference between acutely ill and remitted patients with BN in serum Zn concentrations. Of note, remitted patients had a significantly higher body weight when compared to the other two groups. Overall, there were no significant differences in dietary preferences with regard to Zn containing foods between the groups.
The present study provides preliminary evidence that the underlying factors for changes in Zn serum concentrations in young patients with BN do not vary with regard to the stage of illness (acute versus remitted BN). Further prospective research is needed in order to disentangle the possible interplay between serum Zn status and bulimic eating behaviors.
Aim
To assess the pharmacokinetics, pharmacodynamics, safety and tolerability of the 5‐lipoxygenase‐activating protein inhibitor, GSK2190915, after oral dosing in two independent phase I studies, one ...in Western European and one in Japanese subjects, utilizing different formulations.
Method
Western European subjects received single (50–1000 mg) or multiple (10–450 mg) oral doses of GSK2190915 or placebo in a dose‐escalating manner. Japanese subjects received three of four GSK2190915 doses (10–200 mg) plus placebo once in a four period crossover design. Blood samples were collected for GSK2190915 concentrations and blood and urine were collected to measure leukotriene B4 and leukotriene E4, respectively, as pharmacodynamic markers of drug activity.
Results
There was no clear difference in adverse events between placebo and active drug‐treated subjects in either study. Maximum plasma concentrations of GSK2190915 and area under the curve increased in a dose‐related manner and mean half‐life values ranged from 16–34 h. Dose‐dependent inhibition of blood leukotriene B4 production was observed and near complete inhibition of urinary leukotriene E4 excretion was shown at all doses except the lowest dose. The EC50 values for inhibition of LTB4 were 85 nm and 89 nm in the Western European and Japanese studies, respectively.
Conclusion
GSK2190915 is well‐tolerated with pharmacokinetics and pharmacodynamics in Western European and Japanese subjects that support once daily dosing for 24 h inhibition of leukotrienes. Doses of ≥50 mg show near complete inhibition of urinary leukotriene E4 at 24 h post‐dose, whereas doses of ≥150 mg are required for 24 h inhibition of blood LTB4.
Purpose of Review
Cryptococcal meningitis is the most common fungal infection of the central nervous system and the third most frequent neurological complication in AIDS patients. To understand the ...Argentinean epidemiology of cryptococcosis, several efforts have been made by the National Reference Laboratory in Clinical Mycology.
Recent Findings
In Argentina, reports of distribution and frequency of
Cryptococcus neoformans
and
Cryptococcus gattii
isolates are scarce and very little is known about its circulating genotypes and mating types. The National Mycology Laboratory Network and the National Reference Laboratory in Clinical Mycology joined forces to estimate the prevalence of cryptococcosis and to obtain and to analyse epidemiological data of this important fungal infection.
Summary
Data presented here were recovered from 1998 to 2016 and represents an approximation to the actual situation of cryptococcosis in Argentina. These results could be useful to design future investigations.
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