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Introduction: The German PID-NET registry was founded in 2009, serving as the first national registry of patients with primary immunodeficiencies (PID) in Germany. It is part of the European Society for Immunodeficiencies (ESID) registry. The primary purpose of the registry is to gather data on the epidemiology, diagnostic delay, diagnosis, and treatment of PIDs.
Methods: Clinical and laboratory data was collected from 2,453 patients from 36 German PID centres in an online registry. Data was analysed with the software Stata® and Excel.
Results: The minimum prevalence of PID in Germany is 2.72 per 100,000 inhabitants. Among patients aged 1–25, there was a clear predominance of males. The median age of living patients ranged between 7 and 40 years, depending on the respective PID. Predominantly antibody disorders were the most prevalent group with 57% of all 2,453 PID patients (including 728 CVID patients). A gene defect was identified in 36% of patients. Familial cases were observed in 21% of patients. The age of onset for presenting symptoms ranged from birth to late adulthood (range 0–88 years). Presenting symptoms comprised infections (74%) and immune dysregulation (22%). Ninety-three patients were diagnosed without prior clinical symptoms. Regarding the general and clinical diagnostic delay, no PID had undergone a slight decrease within the last decade. However, both, SCID and hyper IgE- syndrome showed a substantial improvement in shortening the time between onset of symptoms and genetic diagnosis. Regarding treatment, 49% of all patients received immunoglobulin G (IgG) substitution (70%—subcutaneous; 29%—intravenous; 1%—unknown). Three-hundred patients underwent at least one hematopoietic stem cell transplantation (HSCT). Five patients had gene therapy.
Conclusion: The German PID-NET registry is a precious tool for physicians, researchers, the pharmaceutical industry, politicians, and ultimately the patients, for whom the outcomes will eventually lead to a more timely diagnosis and better treatment.
BACKGROUND: Mutations in the chromodomain helicase DNA binding protein 7 gene (CHD7) lead to CHARGE syndrome, an autosomal dominant multiple malformation disorder. Proteins involved in chromatin remodeling typically act in multiprotein complexes. We previously demonstrated that a part of human CHD7 interacts with a part of human CHD8, another chromodomain helicase DNA binding protein presumably being involved in the pathogenesis of neurodevelopmental (NDD) and autism spectrum disorders (ASD). Because identification of novel CHD7 and CHD8 interacting partners will provide further insights into the pathogenesis of CHARGE syndrome and ASD/NDD, we searched for additional associated polypeptides using the method of stable isotope labeling by amino acids in cell culture (SILAC) in combination with mass spectrometry.
PRINCIPLE FINDINGS: The hitherto uncharacterized FAM124B (Family with sequence similarity 124B) was identified as a potential interaction partner of both CHD7 and CHD8. We confirmed the result by co-immunoprecipitation studies and showed a direct binding to the CHD8 part by direct yeast two hybrid experiments. Furthermore, we characterized FAM124B as a mainly nuclear localized protein with a widespread expression in embryonic and adult mouse tissues.
CONCLUSION: Our results demonstrate that FAM124B is a potential interacting partner of a CHD7 and CHD8 containing complex. From the overlapping expression pattern between Chd7 and Fam124B at murine embryonic day E12.5 and the high expression of Fam124B in the developing mouse brain, we conclude that Fam124B is a novel protein possibly involved in the pathogenesis of CHARGE syndrome and neurodevelopmental disorders.
Hepatic lipid deposition and inflammation represent risk factors for hepatocellular carcinoma (HCC). The mRNA-binding protein tristetraprolin (TTP, gene name ZFP36) has been suggested as a tumor suppressor in several malignancies, but it increases insulin resistance. The aim of this study was to elucidate the role of TTP in hepatocarcinogenesis and HCC progression. Employing liver-specific TTP-knockout (lsTtp-KO) mice in the diethylnitrosamine (DEN) hepatocarcinogenesis model, we observed a significantly reduced tumor burden compared to wild-type animals. Upon short-term DEN treatment, modelling early inflammatory processes in hepatocarcinogenesis, lsTtp-KO mice exhibited a reduced monocyte/macrophage ratio as compared to wild-type mice. While short-term DEN strongly induced an abundance of saturated and poly-unsaturated hepatic fatty acids, lsTtp-KO mice did not show these changes. These findings suggested anti-carcinogenic actions of TTP deletion due to effects on inflammation and metabolism. Interestingly, though, investigating effects of TTP on different hallmarks of cancer suggested tumor-suppressing actions: TTP inhibited proliferation, attenuated migration, and slightly increased chemosensitivity. In line with a tumor-suppressing activity, we observed a reduced expression of several oncogenes in TTP-overexpressing cells. Accordingly, ZFP36 expression was downregulated in tumor tissues in three large human data sets. Taken together, this study suggests that hepatocytic TTP promotes hepatocarcinogenesis, while it shows tumor-suppressive actions during hepatic tumor progression.
Background/Aims: Hepatocellular carcinoma (HCC) represents the second most common cause of cancer-related deaths worldwide, not least due to its high chemoresistance. The long non-coding RNA nuclear paraspeckle assembly transcript 1 (NEAT1), localised in nuclear paraspeckles, has been shown to enhance chemoresistance in several cancer types. Since data on NEAT1 in HCC chemosensitivity are completely lacking and chemoresistance is linked to poor prognosis, we aimed to study NEAT1 expression in HCC chemoresistance and its link to HCC prognosis.
Methods: NEAT1 expression was determined in either sensitive, or sorafenib, or doxorubicin resistant HepG2, PLC/PRF/5, and Huh7 cells by qPCR. Paraspeckles were detected by immunostaining of paraspeckle component 1 (PSPC1) in cell culture and in a cohort of HCC patients. PSPC1 expression was correlated with clinical data. The expression of transcript variants of NEAT1 and transcripts encoding the paraspeckle-associated proteins was analysed in the TCGA liver cancer data set.
Results: NEAT1 was overexpressed in all three sorafenib and doxorubicin resistant cell lines. Paraspeckles were present in all chemoresistant cells, whereas no signal was detected in the sensitive cells. Expression of NEAT1 transcripts as well as transcripts encoding PSPC1, NONO, and RBM14 was increased in tumour tissue. Expression of PSPC1, NONO, and RBM14 transcripts was significantly associated with poor survival, whereas NEAT1 expression was not. Immunohistochemical analysis revealed that nuclear and cytoplasmic PSPC1-positivity was significantly associated with shorter overall survival of HCC patients.
Conclusion: Our data show an induction of NEAT1 in HCC chemoresistance and a high correlation of transcripts encoding paraspeckle-associated proteins with poor survival in HCC. Therefore, NEAT1, PSPC1, NONO, and RBM14 might be promising targets for novel HCC therapies, and the paraspeckle-associated proteins might be clinical markers and predictors for poor survival in HCC.
Objective: To investigate the accuracy, efficiency and radiation dose of a novel laser navigation system (LNS) compared to those of free-handed punctures on computed tomography (CT).
Materials and methods: Sixty punctures were performed using a phantom body to compare accuracy, timely effort, and radiation dose of the conventional free-handed procedure to those of the LNS-guided method. An additional 20 LNS-guided interventions were performed on another phantom to confirm accuracy. Ten patients subsequently underwent LNS-guided punctures.
Results: The phantom 1-LNS group showed a target point accuracy of 4.0 ± 2.7 mm (freehand, 6.3 ± 3.6 mm; p = 0.008), entrance point accuracy of 0.8 ± 0.6 mm (freehand, 6.1 ± 4.7 mm), needle angulation accuracy of 1.3 ± 0.9° (freehand, 3.4 ± 3.1°; p < 0.001), intervention time of 7.03 ± 5.18 minutes (freehand, 8.38 ± 4.09 minutes; p = 0.006), and 4.2 ± 3.6 CT images (freehand, 7.9 ± 5.1; p < 0.001). These results show significant improvement in 60 punctures compared to freehand. The phantom 2-LNS group showed a target point accuracy of 3.6 ± 2.5 mm, entrance point accuracy of 1.4 ± 2.0 mm, needle angulation accuracy of 1.0 ± 1.2°, intervention time of 1.44 ± 0.22 minutes, and 3.4 ± 1.7 CT images. The LNS group achieved target point accuracy of 5.0 ± 1.2 mm, entrance point accuracy of 2.0 ± 1.5 mm, needle angulation accuracy of 1.5 ± 0.3°, intervention time of 12.08 ± 3.07 minutes, and used 5.7 ± 1.6 CT-images for the first experience with patients.
Conclusion: Laser navigation system improved accuracy, duration of intervention, and radiation dose of CT-guided interventions.
Attractiveness ratings for musicians and non-musicians: An evolutionary-psychology perspective
(2019)
From an evolutionary perspective, musical behavior such as playing an instrument can be considered as part of an individual’s courting behavior. Playing a musical instrument or singing might fulfill a function similar to that of a bird’s colored feathers: attracting attention. Therefore, musicians may be rated as more attractive than non-musicians. In an online survey, 137 volunteers (95 female) with ages ranging from 16 to 39 years rated the attractiveness of fictitious persons of the opposite sex described in short verbal profiles. These profiles differed with respect to whether the described person made music or not. Additionally, the musicians’ profiles varied with regard to whether the described person played music or sang in public or in private only. Results show that musicians’ profiles were not generally rated as more attractive than non-musicians’, but attractiveness did vary according to setting: private musicians were rated as most attractive, followed by non-musicians and public musicians. Furthermore, results indicate that participants who played a musical instrument or sang themselves gave higher ratings to profiles of musicians. But for participants who do not make music themselves, higher attractiveness ratings for musicians playing instruments or sing in private settings were found. These results indicate that the impression of sharing a common interest (making music) and furthermore making music in private instrumental settings seems to make people attractive to other people. No additional support for the sexual selection hypotheses for the evolution of music was provided by the current results. The musical status of the rater affected his or her judgements, with musicians rating other people as more attractive if they share the common interest in making music. Not the display of being a musician seems to be critical for attractiveness ratings but the perceived or imagined similarity by the rater created by information on musicality, fostering the theoretical significance of the communication aspect of music.
[MesnacnacZn(μ-H)]2 (1) was synthesized by reaction of MesnacnacZnI with either an equimolar amount of KNH(iPr)BH3 or an excess of NaH and characterized by multinuclear NMR and IR spectroscopy as well as X-ray diffraction. Two polymorphs of 1 were found and their structures determined on single crystals.