Empirical evidence concerning the psychosocial health outcomes after puberty suppression and gender-affirming (GA) medical interventions of adolescents with gender dysphoria (GD) is scarce. The aim ...of the present study was to describe how dimensions of psychosocial health were distributed among different intervention groups of adolescents with a GD diagnosis from the Hamburg Gender Identity Service before and after treatment. Participants included
n
= 75 adolescents and young adults from a clinical cohort sample, measured at their initial intake and on average 2 years later (
M
treatment duration = 21.4 months). All cases were divided into four different intervention groups, three of which received medical interventions. At baseline, both psychological functioning and quality of life scores were significantly below the norm mean for all intervention groups. At follow-up, adolescents in the gender-affirming hormone (GAH) and surgery (GAS) group reported emotional and behavioral problems and physical quality of life scores similar to the German norm mean. However, some of the psychosocial health outcome scores were still significantly different from the norm. Because this study did not test for statistically significant differences between the four intervention groups or before and after treatment, the findings cannot be generalized to other samples of transgender adolescents. However, GA interventions may help to improve psychosocial health outcomes in this sample of German adolescents. Long-term treatment decisions during adolescence warrant careful evaluation and informed, participatory decision-making by a multidisciplinary team and should include both medical interventions and psychosocial support. The present study highlights the urgent need for further ongoing longitudinal research.
The electrical discharge characteristics of a large‐area experimental dielectric barrier discharge in argon–hexamethyldisiloxane mixtures containing up to about 1,600 ppm of the monomer is analysed ...by means of electrical measurements and numerical modelling. A time‐dependent, spatially one‐dimensional fluid model is employed, taking into account the spatial variation of the discharge plasma between the two plane‐parallel dielectrics covering the electrodes. Reasonable agreement between electrical measurements and modelling results is generally found for the gap voltages and discharge currents. Remaining differences between the measured and calculated electrical energy dissipated in the plasma per period are discussed.
Experimental results of the electrical characteristics obtained in a large‐area dielectric barrier discharge in argon–hexamethyldisiloxane mixtures at atmospheric pressure are compared with a corresponding modelling study. Measured and calculated results agree reasonably well, and certain differences in the electrical energy dissipated in the discharge per period are discussed from different viewpoints.
Abstract Merkel cell carcinoma (MCC) is a rare tumour of the skin of neuro-endocrine origin probably developing from neuronal mechanoreceptors. A collaborative group of multidisciplinary experts form ...the European Dermatology Forum (EDF), The European Association of Dermato-Oncology (EADO) and the European Organization of Research and Treatment of Cancer (EORTC) was formed to make recommendations on MCC diagnosis and management, based on a critical review of the literature, existing guidelines and expert’s experience. Clinical features of the cutaneous/subcutaneous nodules hardly contribute to the diagnosis of MCC. The diagnosis is made by histopathology, and an incisional or excisional biopsy is mandatory. Immunohistochemical staining contributes to clarification of the diagnosis. Initial work-up comprises ultrasound of the loco-regional lymph nodes and total body scanning examinations. The primary tumour should be excised with 1–2 cm margins. In patients without clinical evidence of regional lymph node involvement, sentinel node biopsy is recommended, if possible, and will be taken into account in a new version of the AJCC classification. In patients with regional lymph node involvement radical lymphadenectomy is recommended. Adjuvant radiotherapy might be considered in patients with multiple affected lymph nodes of extracapsular extension. In unresectable metastatic MCC mono- or poly-chemotherapy achieve high remission rates. However, responses are usually short lived. Treatment within clinical trials is regarded as a standard of care in disseminated MCC.
In this study the prevalence of Methicillin-resistant
Staphylococcus pseudintermedius (MRSP) in clinical specimens of different animal species was defined by investigating a total of 16,103 clinical ...samples originating from veterinary facilities of five German federal states in 2007. Of all samples examined, 72 were positive for MRSP, giving an overall prevalence of 0.45%. In clinical specimens originating from small animals the prevalence was 0.58% (
n
=
67; dogs
n
=
61 and cats
n
=
6), while samples from equidaes revealed a prevalence of 0.10% (
n
=
5; horses
n
=
4, donkey
n
=
1). Forty-six representative phenotypically identified MRSP were further differentiated by DNA-based species assignment, PCR detection of
mecA, SCC
mec-typing and MIC determination. As expected, all 46 isolates were unambiguously proven to be MRSP by sequencing of housekeeping genes
pta and
cpn60 and being positive for
mecA. Furthermore, all isolates harboured the mobile staphylococcal cassette chromosome
mec (SCC
mec) SCC
mecIII. Antibiotic susceptibility testing for 20 different conventional antimicrobial agents disclosed a high rate of multidrug-resistant isolates (45 of 46) displaying an identical or at least similar resistance pattern for non-β-lactam antimicrobials. The recognized prevalence of MRSP, which have already been shown to be potential zoonotic agents, reflects the recently emerging development of these serious and often multidrug-resistant pathogens in Germany.
Background & Aims Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder in industrialized countries. Mouse models of NAFLD have been used in studies of pathogenesis and ...treatment, and have certain features of the human disease. We performed a systematic transcriptome-wide analysis of liver tissues from patients at different stages of NAFLD progression (ranging from healthy obese individuals to those with steatosis), as well as rodent models of NAFLD, to identify those that most closely resemble human disease progression in terms of gene expression patterns. Methods We performed a systematic evaluation of genome-wide messenger RNA expression using liver tissues collected from mice fed a standard chow diet (controls) and 9 mouse models of NAFLD: mice on a high-fat diet (with or without fructose), mice on a Western-type diet, mice on a methionine- and choline-deficient diet, mice on a high-fat diet given streptozotocin, and mice with disruption of Pten in hepatocytes. We compared gene expression patterns with those of liver tissues from 25 patients with nonalcoholic steatohepatitis (NASH), 27 patients with NAFLD, 15 healthy obese individuals, and 39 healthy nonobese individuals (controls). Liver samples were obtained from patients undergoing liver biopsy for suspected NAFLD or NASH, or during liver or bariatric surgeries. Data sets were analyzed using the limma R-package. Overlap of functional profiles was analyzed by gene set enrichment analysis profiles. Results We found differences between human and mouse transcriptomes to be significantly larger than differences between disease stages or models. Of the 65 genes with significantly altered expression in patients with NASH and 177 genes with significantly altered expression in patients with NAFLD, compared with controls, only 1–18 of these genes also differed significantly in expression between mouse models of NAFLD and control mice. However, expression of genes that regulate pathways associated with the development of NAFLD were altered in some mouse models (such as pathways associated with lipid metabolism). On a pathway level, gene expression patterns in livers of mice on the high-fat diet were associated more closely with human fatty liver disease than other models. Conclusions In comparing gene expression profiles between liver tissues from different mouse models of NAFLD and patients with different stages of NAFLD, we found very little overlap. Our data set is available for studies of pathways that contribute to the development of NASH and NAFLD and selection of the most applicable mouse models ( http://www.nash-profiler.com ).
Noninvasive imaging at the molecular level is an emerging field in biomedical research. This paper introduces a new technology synergizing two leading imaging methodologies: positron emission ...tomography (PET) and magnetic resonance imaging (MRI). Although the value of PET lies in its high-sensitivity tracking of biomarkers in vivo, it lacks resolving morphology. MRI has lower sensitivity, but produces high soft-tissue contrast and provides spectroscopic information and functional MRI (fMRI). We have developed a three-dimensional animal PET scanner that is built into a 7-T MRI. Our evaluations show that both modalities preserve their functionality, even when operated isochronously. With this combined imaging system, we simultaneously acquired functional and morphological PET-MRI data from living mice. PET-MRI provides a powerful tool for studying biology and pathology in preclinical research and has great potential for clinical applications. Combining fMRI and spectroscopy with PET paves the way for a new perspective in molecular imaging.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Cardiac implantable electronic device infection is a major complication that usually requires device removal. PADIT (Prevention of Arrhythmia Device Infection Trial) was a large cluster crossover ...trial of conventional versus incremental antibiotics.
This study sought to investigate independent predictors of device infection in PADIT and develop a novel infection risk score.
In brief, over 4 6-month periods, 28 centers used either conventional or incremental prophylactic antibiotic treatment in all patients. The primary outcome was hospitalization for device infection within 1 year (blinded endpoint adjudication). Multivariable logistic prediction modeling was used to identify the independent predictors and develop a risk score for device infection. The prediction models were internally validated with bootstrap methods.
Device procedures were performed in 19,603 patients, and hospitalization for infection occurred in 177 (0.90%) within 1 year of follow-up. The final prediction model identified 5 independent predictors of device infection (prior procedures P, age A, depressed renal function D, immunocompromised I, and procedure type T) with an optimism-corrected C-statistic of 0.704 (95% confidence interval: 0.660 to 0.744). A PADIT risk score ranging from 0 to 15 points classified patients into low (0 to 4), intermediate (5 to 6) and high (≥7) risk groups with rates of hospitalization for infection of 0.51%, 1.42%, and 3.41%, respectively.
This study identified 5 independent predictors of device infection and developed a novel infection risk score in the largest cardiac implantable electronic device trial to date, warranting validation in an independent cohort. The 5 independent predictors in the PADIT score are readily adopted into clinical practice. (Prevention of Arrhythmia Device Infection Trial PADIT Pilot; NCT01002911)
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Upon interaction of the CD95 receptor with its ligand, sequential association of the adaptor molecule FADD (MORT1), pro-forms of caspases-8/10, and the caspase-8/10 regulator c-FLIP leads to the ...formation of a death-inducing signaling complex. Here, we identify polo-like kinase (Plk) 3 as a new interaction partner of the death receptor CD95. The enzymatic activity of Plk3 increases following interaction of the CD95 receptor with its ligand. Knockout (KO) or knockdown of caspase-8, CD95 or FADD prevents activation of Plk3 upon CD95 stimulation, suggesting a requirement of a functional DISC for Plk3 activation. Furthermore, we identify caspase-8 as a new substrate for Plk3. Phosphorylation occurs on T273 and results in stimulation of caspase-8 proapoptotic function. Stimulation of CD95 in cells expressing a non-phosphorylatable caspase-8-T273A mutant in a rescue experiment or in Plk3-KO cells generated by CRISPR/Cas9 reduces the processing of caspase-8 prominently. Low T273 phosphorylation correlates significantly with low Plk3 expression in a cohort of 95 anal tumor patients. Our data suggest a novel mechanism of kinase activation within the Plk family and propose a new model for the stimulation of the extrinsic death pathway in tumors with high Plk3 expression.
It has been proposed that CD4 T-cell responses to Staphylococcus aureus (SA) can inadvertently enhance neoplastic progression in models of skin cancer and cutaneous T-cell lymphoma (CTCL). In this ...prospective study, we explored the effect of transient antibiotic treatment on tumor cells and disease activity in 8 patients with advanced-stage CTCL. All patients experienced significant decrease in clinical symptoms in response to aggressive, transient antibiotic treatment. In some patients, clinical improvements lasted for more than 8 months. In 6 of 8 patients, a malignant T-cell clone could be identified in lesional skin, and a significant decrease in the fraction of malignant T cells was observed following antibiotics but an otherwise unchanged treatment regimen. Immunohistochemistry, global messenger RNA expression, and cell-signaling pathway analysis indicated that transient aggressive antibiotic therapy was associated with decreased expression of interleukin-2 high-affinity receptors (CD25), STAT3 signaling, and cell proliferation in lesional skin. In conclusion, this study provides novel evidence suggesting that aggressive antibiotic treatment inhibits malignant T cells in lesional skin. Thus, we provide a novel rationale for treatment of SA in advanced CTCL.
•Antibiotic treatment of CTCL inhibits disease activity and lymphocyte proliferation in lesional skin.•We provide a novel rationale for aggressive antibiotic treatment as an important adjuvant therapy in patients with advanced stage CTCL.
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A time-dependent, spatially one-dimensional fluid-Poisson model is applied to analyze the impact of small amounts of tetramethylsilane (TMS) as precursor on the discharge characteristics of an ...atmospheric-pressure dielectric barrier discharge (DBD) in argon. Based on an established reaction kinetics for argon, it includes a plasma chemistry for TMS, which is validated by measurements of the ignition voltage at the frequency
f
=
86.2
kHz
for TMS amounts of up to 200 ppm. Details of both a reduced Ar-TMS reaction kinetics scheme and an extended plasma-chemistry model involving about 60 species and 580 reactions related to TMS are given. It is found that good agreement between measured and calculated data can be obtained, when assuming that 25% of the reactions of TMS with excited argon atoms with a rate coefficient of
3.0
×
10
-
16
m
3
/
s
lead to the production of electrons due to Penning ionization. Modeling results for an applied voltage
U
a
,
0
=
4
kV
show that TMS is depleted during the residence time of the plasma in the DBD, where the percentage consumption of TMS decreases with increasing TMS fraction because only a finite number of excited argon species is available to dissociate and/or ionize the precursor via energy transfer. Main species resulting from that TMS depletion are presented and discussed. In particular, the analysis clearly indicates that trimethylsilyl cations can be considered to be mainly responsible for the film formation.
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