There is some evidence that an adequate "anabolic hormonal milieu" is essential for mechanosensitivity/-transduction/-response of bone tissue.
To determine whether enhancing Hormone Therapy (HT) with ...exercise increases the isolated effect of HT on BMD at lumbar spine (LS) and femoral neck (FN).
A comprehensive search of six electronic databases according to the PRISMA statement up to April 28, 2021 included controlled trials longer than 6 months with three study arms: (a) HT, (b) exercise, (c) HT plus exercise (HT+E). Apart from HT, no pharmaceutic therapy or diseases with relevant osteo-anabolic or -catabolic effect on bone metabolism were included. The present analysis was conducted as a random-effects meta-analysis. Outcome measures were standardized mean differences (SMD) for BMD changes at the LS, and FN.
Our search identified six eligible studies (n=585). Although the effect of HT+E was more pronounced on LS (SMD: 0.19, 95%-CI: -0.15 to 0.53) and FN-BMD (0.18, -0.09 to 0.44) compared to the HT group, we did not observe significant differences between the two groups. We observed a low (I 2: 29%) or moderate (I 2: 49%) level of heterogeneity between the trials for FN or LS.
We do not observe a significant effect of HT+E vs. HT alone. We largely attribute this result to varying HT supplementation and hormonal status. Bearing in mind that synergistic/additive effects between HT and mechanical stimulation can only be expected in situations of hormonal insufficiency, further clinical studies should consider baseline endogenous estrogen production but also HT dosing more carefully.
Hintergrund:Es gibt Hinweise darauf, dass ein adäquates anaboles hormonel- les Milieu für die Mechanosensitivität/-transduktion/-reaktion des Knochengewe- bes von wesentlicher Bedeutung ...ist.Zielsetzung:Es sollte festgestellt werden, ob die Kombination einer Hormonthe- rapie (HT) mit körperlichem Training die isolierte Wirkung der HT auf die Kno- chenmineraldichte (BMD) der Lendenwirbelsäule (LWS) und des proximalen Femurs (FN) erhöht.Methoden:In einer umfassenden Literaturrecherche bis zum 28.04.2021 wurden Studien aus sechs Datenbanken eingeschlossen. Analog dem PRISMA-State- ment wurden kontrollierte Studien mit einer Dauer von mehr als sechs Monaten und drei Studienarmen eingeschlossen: (a) Hormontherapie (HT), (b) körperli- ches Training (E) und (c) die Kombination aus Hormontherapie und körperlichem Training (HT+E). Studien mit Medikamenten oder Krankheiten, welche auf die Knochenmineraldichte oder den Knochenstoffwechsel einen relevanten Einfluss haben, wurden ausgeschlossen. Die vorliegende Analyse wurde als Metaanalyse mit zufälligen Effekten durchgeführt. Ergebnismaße waren standardisierte Mittel- wertdifferenzen (SMD) für BMD-Änderungen an den LWS und FN.Ergebnisse: Unsere Suche ergab sechs geeignete Studien (n=585). Obwohl die Effekte der kombinierten Interventionsgruppen (HT+E) auf die Knochenmineral- dichte an LWS (SMD: 0,19, 95%-CI: -0,15 bis 0,53) und des FN (0,18, 95%-Cl: - 0,09 bis 0,44) im Vergleich zur isolierten HT-Gruppe ausgeprägter war, konnten keine signifikanten Unterschiede zwischen beiden Gruppen nachgewiesen wer- den. Wir beobachteten eine geringe (I2: 29%) oder mäßige (I2: 49%) Heterogeni- tät zwischen den Studien für FN oder LWS. Das Trichterdiagramm zeigte eine leichte (LWS) bis moderate (FN) Publikationsverzerrung.Schlussfolgerung:Wir konnten keinen signifikanten Effekt von HT+E im Ver- gleich zu HT allein feststellen. Wir führen dieses Ergebnis zu einem großen Teil auf die unterschiedliche HT-Supplementierung und den hormonellen Status zu- rück. In Anbetracht der Tatsache, dass synergistische/additive Effekte zwischen HT und mechanischer Stimulation nur bei Hormoninsuffizienz zu erwarten sind, sollten weitere klinische Studien die endogene Östrogenproduktion im Ausgangs- zustand, aber auch die HT-Dosierung sorgfältiger berücksichtigen.
Architekturmuseum der TU Berlin, Inv. Nr. SW-St 2010,02-02. Das Werk ist urheberrechtlich geschützt, eine Nutzung des Digitalisats darf nur nach Autorisierung erfolgen. (Creditline)
Architecture ...Museum of the TU Berlin, Inv. No. SW-St 2010.02-02. The work is protected by copyright, the digitalisate may only be used after authorization. (Creditline)
Architecture Museum of the TU Berlin, Inv. No. SW-St 2010.02-01. The work is protected by copyright, the digitalisate may only be used after authorization. (Creditline)
Architekturmuseum der TU ...Berlin, Inv. Nr. SW-St 2010,02-01. Das Werk ist urheberrechtlich geschützt, eine Nutzung des Digitalisats darf nur nach Autorisierung erfolgen. (Creditline)
Architecture Museum of the TU Berlin, Inv. No. SW-St 2010.02-03. The work is protected by copyright, a use of the digitalisat may only be made after authorization. (Creditline)
Architekturmuseum der ...TU Berlin, Inv. Nr. SW-St 2010,02-03. Das Werk ist urheberrechtlich geschützt, eine Nutzung des Digitalisats darf nur nach Autorisierung erfolgen. (Creditline)
Architecture Museum of the TU Berlin, Inv. No. SW-St 2010.02-04. The work is protected by copyright, the digitalisate may only be used after authorization. (Creditline)
Architekturmuseum der TU ...Berlin, Inv. Nr. SW-St 2010,02-04. Das Werk ist urheberrechtlich geschützt, eine Nutzung des Digitalisats darf nur nach Autorisierung erfolgen. (Creditline)
Recessive cytosolic aminoacyl-tRNA synthetase (ARS) deficiencies are severe multiorgan diseases, with limited treatment options. By loading transfer RNAs (tRNAs) with their cognate amino acids, ARS ...are essential for protein translation. However, it remains unknown why ARS deficiencies lead to specific symptoms, especially early life and during infections. We set out to increase pathophysiological insight and improve therapeutic possibilities.
In fibroblasts from patients with isoleucyl-RS (IARS), leucyl-RS (LARS), phenylalanyl-RS-beta-subunit (FARSB), and seryl-RS (SARS) deficiencies, we investigated aminoacylation activity, thermostability, and sensitivity to ARS-specific amino acid concentrations, and developed personalized treatments.
Aminoacylation activity was reduced in all patients, and further diminished at 38.5/40 °C (P
and P
), consistent with infectious deteriorations. With lower cognate amino acid concentrations, patient fibroblast growth was severely affected. To prevent local and/or temporal deficiencies, we treated patients with corresponding amino acids (follow-up: 1/2-2 2/3rd years), and intensified treatment during infections. All patients showed beneficial treatment effects, most strikingly in growth (without tube feeding), head circumference, development, coping with infections, and oxygen dependency.
For these four ARS deficiencies, we observed a common disease mechanism of episodic insufficient aminoacylation to meet translational demands and illustrate the power of amino acid supplementation for the expanding ARS patient group. Moreover, we provide a strategy for personalized preclinical functional evaluation.
Abstract Purpose Gyrate atrophy of the choroid and retina (GACR) is an autosomal recessive inherited metabolic disorder (IMD) characterised by progressive retinal degeneration, leading to severe ...visual impairment. The rapid developments in ophthalmic genetic therapies warrant knowledge on clinical phenotype of eligible diseases such as GACR to define future therapeutic parameters in clinical trials. Methods Retrospective chart analysis was performed in nineteen patients. Data were analysed using IBM SPSS Statistics version 28.0.1.1. Results Nineteen patients were included with a mean age of 32.6 years (range 8–58). Mean age at onset of ophthalmic symptoms was 7.9 years (range 3–16). Median logMAR of visual acuity at inclusion was 0.26 (range -0.18–3.00). Mean age at cataract surgery was 28.8 years ( n = 11 patients). Mean spherical equivalent of the refractive error was -8.96 (range -20.87 to -2.25). Cystoid maculopathy was present in 68% of patients, with a loss of integrity of the foveal ellipsoid zone (EZ) in 24/38 eyes. Of the 14 patients treated with dietary protein restriction, the four patients who started the diet before age 10 showed most benefit. Conclusion This study demonstrates the severe ophthalmic disease course associated with GACR, as well as possible benefit of early dietary treatment. In addition to visual loss, patients experience severe myopia, early-onset cataract, and CME. There is a loss of foveal EZ integrity at a young age, emphasising the need for early diagnosis enabling current and future therapeutic interventions.
How do we think beyond the dominant images and imaginaries of connectivity? Undoing Networks enables a different connectivity: “digital detox” is a luxury for stressed urbanites wishing to lead a ...mindful life. Self-help books advocate “digital minimalism” to recover authentic experiences of the offline. Artists envision a world without the internet. Activists mobilize against the expansion of the 5G network. If connectivity brought us virtual communities, information superhighways, and participatory culture, disconnection comes with privacy tools, Faraday shields, and figures of the shy. This book explores non-usage and the “right to disconnect” from work and from the excessive demands of digital capitalism.
Hyperglycemia and type 2 diabetes (T2D) are caused by failure of pancreatic beta cells. The role of the gut microbiota in T2D has been studied, but causal links remain enigmatic. Obese individuals ...with or without T2D were included from two independent Dutch cohorts. Human data were translated in vitro and in vivo by using pancreatic islets from C57BL6/J mice and by injecting flagellin into obese mice. Flagellin is part of the bacterial locomotor appendage flagellum, present in gut bacteria including Enterobacteriaceae, which we show to be more abundant in the gut of individuals with T2D. Subsequently, flagellin induces a pro-inflammatory response in pancreatic islets mediated by the Toll-like receptor (TLR)-5 expressed on resident islet macrophages. This inflammatory response is associated with beta-cell dysfunction, characterized by reduced insulin gene expression, impaired proinsulin processing and stress-induced insulin hypersecretion in vitro and in vivo in mice. We postulate that increased systemically disseminated flagellin in T2D is a contributing factor to beta-cell failure in time and represents a novel therapeutic target.
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