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Sonstige beteiligte Institutionen
- Agricultural Center, BASF SE, 67117 Limburgerhof, Germany (1)
- Center of Excellence for Science and Technology - Integration of Mediterranean region (STIM), Faculty of Science, University of Split, Poljička cesta 35, 2100 Split, Croatia (1)
- Departamento de Química, Facultad de Ciencias, Universidad Autónoma de Madrid, 28049 Madrid, Spain (1)
- Department of Chemistry, Humboldt Universität zu Berlin, Brook-Taylor-Strasse 2, 12489 Berlin, Germany (1)
- Institute of Organic Chemistry and Center for Molecular Biosciences Innsbruck, CMBI, Leopold-Franzens University Innsbruck, Austria (1)
- Istituto di Chimica dei Composti Organometallici (ICCOM–CNR), Area della Ricerca del CNR, Via Moruzzi 1, I-56124 Pisa, Italy. (1)
Context
Primary aldosteronism (PA) is the most frequent form of endocrine hypertension. Besides its deleterious impact on cardiovascular target organ damage, PA is considered to cause osteoporosis.
Patients and methods
We assessed bone turnover in a subset of 36 postmenopausal women with PA. 18 patients had unilateral PA and were treated by adrenalectomy, whereas 18 patients had bilateral PA and received mineralocorticoid receptor antagonist (MRA) therapy respectively. 18 age- and BMI-matched females served as controls. To estimate bone remodeling, we measured the bone turnover markers intact procollagen 1 N-terminal propeptide, bone alkaline phosphatase, osteocalcin and tartrate resistant acid phosphatase 5b in plasma by chemiluminescent immunoassays at time of diagnosis and one year after initiation of treatment.
Study design
Observational longitudinal cohort study.
Setting
Tertiary care hospital.
Results
Compared with controls, patients with PA had mildly elevated osteocalcin at baseline (p = 0.013), while the other bone markers were comparable between both groups. There were no differences between the unilateral and the bilateral PA subgroup. One year after initiation of MRA treatment with spironolactone bone resorption and bone formation markers had significantly decreased in patients with bilateral PA. In contrast, patients adrenalectomized because of unilateral PA showed no significant change of bone turnover markers.
Conclusion
This study shows that aldosterone excess in postmenopausal women with PA is not associated with a relevant increase of bone turnover markers at baseline. However, we observed a significant decrease of bone markers in patients treated with spironolactone, but not in patients treated by adrenalectomy.
Background: Intestinal infections remain a major public health burden in developing countries. Due to social, ecological, environmental, and cultural conditions, Indigenous peoples in Colombia are at particularly high risk. Materials: 137 stool samples were analyzed by microscopy and real-time-Polymerase Chain Reaction (RT-PCR), targeting protozoan parasites (Giardia intestinalis, Entamoeba histolytica, Cryptosporidium spp., and Cyclospora cayetanensis), bacteria (Campylobacter jejuni, Salmonella spp., Shigella ssp./enteroinvasive E. coli (EIEC), Yersinia spp., enterohemorrhagic E. coli (EHEC), enteropathogenic E. coli (EPEC), enterotoxin-producing E. coli (ETEC), enteroaggregative E. coli (EAEC), and Tropheryma whipplei), and helminths (Necator americanus, Strongyloides stercoralis, Ascaris lumbricoides, Ancylostoma spp., Trichuris. trichiura, Taenia spp., Hymenolepis nana, Enterobius vermicularis, and Schistosoma spp.). Microscopy found additional cases of helminth infections. Results: At least one pathogen was detected in 93% of the samples. The overall results revealed protozoa in 79%, helminths in 69%, and bacteria in 41%. G. intestinalis (48%), Necator/hookworm (27%), and EAEC (68%) were the most common in each group. Noteworthy, T. whipplei was positive in 7% and T. trichirua in 23% of the samples. A significant association of one infection promoting the other was determined for G. intestinalis and C. jejuni, helminth infections, and EIEC. Conclusions: The results illustrate the high burden of gastrointestinal pathogens among Indigenous peoples compared to other developing countries. Countermeasures are urgently required.
The main goal of the present study was the identification of cellular phenotypes in attention-deficit-/hyperactivity disorder (ADHD) patient-derived cellular models from carriers of rare copy number variants (CNVs) in the PARK2 locus that have been previously associated with ADHD. Human-derived fibroblasts (HDF) were cultured and human-induced pluripotent stem cells (hiPSC) were reprogrammed and differentiated into dopaminergic neuronal cells (mDANs). A series of assays in baseline condition and in different stress paradigms (nutrient deprivation, carbonyl cyanide m-chlorophenyl hydrazine (CCCP)) focusing on mitochondrial function and energy metabolism (ATP production, basal oxygen consumption rates, reactive oxygen species (ROS) abundance) were performed and changes in mitochondrial network morphology evaluated. We found changes in PARK2 CNV deletion and duplication carriers with ADHD in PARK2 gene and protein expression, ATP production and basal oxygen consumption rates compared to healthy and ADHD wildtype control cell lines, partly differing between HDF and mDANs and to some extent enhanced in stress paradigms. The generation of ROS was not influenced by the genotype. Our preliminary work suggests an energy impairment in HDF and mDAN cells of PARK2 CNV deletion and duplication carriers with ADHD. The energy impairment could be associated with the role of PARK2 dysregulation in mitochondrial dynamics.
Here, we assessed whether 36 single nucleotide polymorphisms (SNPs) within the TNFSF4 and MAPKAPK2 loci influence the risk of developing invasive aspergillosis (IA). We conducted a two-stage case control study including 911 high-risk patients diagnosed with hematological malignancies that were ascertained through the aspBIOmics consortium. The meta-analysis of the discovery and replication populations revealed that carriers of the TNFSF4\(_{rs7526628T/T}\) genotype had a significantly increased risk of developing IA (p = 0.00022). We also found that carriers of the TNFSF4\(_{rs7526628T}\) allele showed decreased serum levels of TNFSF14 protein (p = 0.0027), and that their macrophages had a decreased fungicidal activity (p = 0.048). In addition, we observed that each copy of the MAPKAPK2\(_{rs12137965G}\) allele increased the risk of IA by 60% (p = 0.0017), whereas each copy of the MAPKAPK2\(_{rs17013271T}\) allele was estimated to decrease the risk of developing the disease (p = 0.0029). Mechanistically, we found that carriers of the risk MAPKAPK2\(_{rs12137965G}\) allele showed increased numbers of CD38+IgM-IgD- plasmablasts in blood (p = 0.00086), whereas those harboring two copies of the allele had decreased serum concentrations of thymic stromal lymphopoietin (p = 0.00097). Finally, we also found that carriers of the protective MAPKAPK2\(_{rs17013271T}\) allele had decreased numbers of CD27-IgM-IgD- B cells (p = 0.00087) and significantly lower numbers of CD14+ and CD14+CD16- cells (p = 0.00018 and 0.00023). Altogether, these results suggest a role of the TNFSF4 and MAPKAPK2 genes in determining IA risk.
In the last decade there has been tremendous effort in offering better therapeutic management strategies to patients with hematologic malignancies. These efforts have ranged from biological to clinical approaches and resulted in the rapid development of new approaches. The main “problem” that comes with the high influx of newly approved drugs, which not only influences hematologists that frequently work with these drugs but also affects other healthcare professionals that work with hematologists in patient management, including intensive care unit (ICU) physicians, is they have to keep up within their specialty and, in addition, with the side-effects that can occur when encountering hematology-specific therapies. Nonetheless, there are few people that have an in-depth understanding of a specialty outside theirs. Thus, this manuscript offers an overview of the most common side-effects caused by therapies used in hematology nowadays, or that are currently being investigated in clinical trials, with the purpose to serve as an aid to other specialties. Nevertheless, because of the high amount of information on this subject, each chapter will offer an overview of the side-effects of a drug class with each reference of the section being intended as further reading.
Background: Infections are a leading cause of refugee morbidity. Recent data on the rate of airway infections and factors influencing their spread in refugee reception centers is scarce. Methods: A retrospective, cross-sectional study of de-identified medical records with a focus on respiratory infections in underage refugees was conducted at two large German refugee reception centers. Results: In total, medical data from n = 10,431 refugees over an observational period of n = 819 days was analyzed. Among pediatric patients (n = 4289), 55.3% presented at least once to the on-site medical ward with an acute respiratory infection or signs thereof. In 38.4% of pediatric consultations, acute airway infections or signs thereof were present. Airway infections spiked during colder months and were significantly more prevalent amongst preschool and resettled children. Their frequency displayed a positive correlation with the number of refugees housed at the reception centers. Conclusions: We show that respiratory infections are a leading cause for morbidity in young refugees and that their rate is influenced age, season, status, and residential density. This illustrates the need to protect refugee children from contracting airway infections which may also reduce the spread of coronavirus disease 2019 (COVID-19) during the current pandemic.
The effect of non-personalised tips on the continued use of self-monitoring mHealth applications
(2020)
Chronic tinnitus, the perception of a phantom sound in the absence of corresponding stimulus, is a condition known to affect patients' quality of life. Recent advances in mHealth have enabled patients to maintain a ‘disease journal’ of ecologically-valid momentary assessments, improving patients' own awareness of their disease while also providing clinicians valuable data for research. In this study, we investigate the effect of non-personalised tips on patients' perception of tinnitus, and on their continued use of the application. The data collected from the study involved three groups of patients that used the app for 16 weeks. Groups A & Y were exposed to feedback from the start of the study, while group B only received tips for the second half of the study. Groups A and Y were run by different supervisors and also differed in the number of hospital visits during the study. Users of Group A and B underwent assessment at baseline, mid-study, post-study and follow-up, while users of group Y were only assessed at baseline and post-study. It is seen that the users in group B use the app for longer, and also more often during the day. The answers of the users to the Ecological Momentary Assessments are seen to form clusters where the degree to which the tinnitus distress depends on tinnitus loudness varies. Additionally, cluster-level models were able to predict new unseen data with better accuracy than a single global model. This strengthens the argument that the discovered clusters really do reflect underlying patterns in disease expression.
New innovative neuropsychological tests in attention deficit hyperactivity disorder ADHD have been proposed as objective measures for diagnosis and therapy. The current study aims to investigate two different commercial continuous performance tests (CPT) in a head-to-head comparison regarding their comparability and their link with clinical parameters. The CPTs were evaluated in a clinical sample of 29 adult patients presenting in an ADHD outpatient clinic. Correlational analyses were performed between neuropsychological data, clinical rating scales, and a personality-based measure. Though inattention was found to positively correlate between the two tests (r = 0.49, p = 0.01), no association with clinical measures and inattention was found for both tests. While hyperactivity did not correlate between both tests, current ADHD symptoms were positively associated with Nesplora Aquarium's motor activity (r = 0.52 to 0.61, p < 0.05) and the Qb-Test's hyperactivity (r = 0.52 to 0.71, p < 0.05). Conclusively, the overall comparability of the tests was limited and correlation with clinical parameters was low. While our study shows some interesting correlation between clinical symptoms and sub-scales of these tests, usage in clinical practice is not recommended.
Tinnitus is a complex and heterogeneous psycho-physiological disorder responsible for causing a phantom ringing or buzzing sound albeit the absence of an external sound source. It has a direct influence on affecting the quality of life of its sufferers. Despite being around for a while, there has not been a cure for tinnitus, and the usual course of action for its treatment involves use of tinnitus retaining and sound therapy, or Cognitive Behavioral Therapy (CBT). One positive aspect about these therapies is that they can be administered face-to-face as well as delivered via internet or smartphone. Smartphones are especially helpful as they are highly personalized devices, and offer a well-established ecosystem of apps, accessible via respective marketplaces of differing mobile platforms. Note that current therapeutic treatments such as CBT have shown to be effective in suppressing the tinnitus symptoms when administered face-to-face, their effectiveness when being delivered using smartphones is not known so far. A quick search on the prominent market places of popular mobile platforms (Android and iOS) yielded roughly 250 smartphone apps offering tinnitus-related therapies and tinnitus management. As this number is expected to steadily increase due to high interest in smartphone app development, a contemporary review of such apps is crucial. In this paper, we aim to review scientific studies validating the smartphone apps, particularly to test their effectiveness in tinnitus management and treatment. We use the PRISMA guidelines for identification of studies on major scientific literature sources and delineate the outcomes of identified studies.
Muscle and bone interact via physical forces and secreted osteokines and myokines. Physical forces are generated through gravity, locomotion, exercise, and external devices. Cells sense mechanical strain via adhesion molecules and translate it into biochemical responses, modulating the basic mechanisms of cellular biology such as lineage commitment, tissue formation, and maturation. This may result in the initiation of bone formation, muscle hypertrophy, and the enhanced production of extracellular matrix constituents, adhesion molecules, and cytoskeletal elements. Bone and muscle mass, resistance to strain, and the stiffness of matrix, cells, and tissues are enhanced, influencing fracture resistance and muscle power. This propagates a dynamic and continuous reciprocity of physicochemical interaction. Secreted growth and differentiation factors are important effectors of mutual interaction. The acute effects of exercise induce the secretion of exosomes with cargo molecules that are capable of mediating the endocrine effects between muscle, bone, and the organism. Long-term changes induce adaptations of the respective tissue secretome that maintain adequate homeostatic conditions. Lessons from unloading, microgravity, and disuse teach us that gratuitous tissue is removed or reorganized while immobility and inflammation trigger muscle and bone marrow fatty infiltration and propagate degenerative diseases such as sarcopenia and osteoporosis. Ongoing research will certainly find new therapeutic targets for prevention and treatment.