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The increasing use of mobile digital technologies in our daily life is also affecting the healthcare sector. Digital health applications have the potential to improve disease monitoring and management, avoid hospitalizations, and more. A main task for the health care system is to create a framework that facilitates the identification of safe and effective apps for health care professionals and patients to generate the most health benefit as well as guide payer coverage decisions. Currently some European countries have already developed a national framework for market access approval, nevertheless only Belgium and Germany have additionally created a reimbursement system. The aim of this investigation is to compare the two different approaches of Belgium and Germany, based on the framework itself, the access requirements, and the experience so far. The overall approach seems to be similar, but scrutinizing the details, there are several significant differences. The evaluation procedure in Belgium consists of a 3-level validation pyramid while in Germany there is a normal procedure as well as a DiGA-Fast- Track. Only applications in stage 3 are reimbursable in Belgium whereas in Germany applications from provisional and permanent listing are reimbursable. The comparative overview shows that the two forerunners, Belgium, and Germany, use similar but not identical approaches, with partly relevant differences such as the evaluation procedure reimbursement and the formulation of the target group. The current situation (status 11.04.22) shows that the focus of the app indications differs between both countries. Furthermore, not a single app is listed in Belgium and Germany at the same time. From our perspective it should be a goal for manufacturers of CE marked medical devices to achieve reimbursement in as many member states as possible.

The determination of critical closing pressure (Pcrit) is the diagnostic gold standard for assessing the severity of pharyngeal instability. Pcrit measurements are typically performed during natural nocturnal sleep (NREM Stage 2) in combination with polysomnography. However, determining Pcrit during sleep is time-consuming and impractical for routine use. Alternatively, Pcrit measurements can also be done during drug-induced sleep. A disadvantage of this method is the varying doses of propofol needed to induce sleep, which can affect muscle tone differently. As an alternative to these methods, the application of negative pressure during wakefulness (NEP test) has proven effective. In this test, the patient is administered a subatmospheric pressure of -5 or -10 cmH 2 O via mask at the beginning of expiration, and the change in expiratory airflow in the pharynx is measured. NEP test can be performed in both sitting and lying position. According to current knowledge, the NEP test appears to be a diagnostic procedure comparable to critical closing pressure (Pcrit) for assessing upper airway collapsibility., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

The article provides a historical overview of developments in the understanding of respiratory rhythm and its control mechanisms over the last two centuries. In the 19 th century, a structure in the medulla oblongata was first described as the "node of life". In 1743, Taube discovered the carotid body, and in 1927 the Spaniard de Castro described its morphology and innervation. It was only with the work of father and son Heymans that the physiological and pharmacological significance of the carotid and aortic body was recognized. Today we understand that the generation and control of respiration are mediated by a complex neuronal network in the brainstem. Chemo-, mechano- and proprioreceptos convey information from blood, airways and muscles to the control centre. The respiratory centre integrates the afferent input from the receptors, the autonomic nervous system, the cardiovascular system, and voluntary input from the cerebral cortex to modulate the degree of respiratory activation of motoneurons and respiratory muscles., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Obstructive sleep apnea (OSA) is characterized by partial or complete obstruction of the pharyngeal airway. Anatomical factors can be distinguished from non-anatomical factors. Age and obesity are the main risk factors for OSA; however, approximately 50% of patients are not obese. In older patients (>60 years), the importance of obesity decreases. There is an increased prevalence of OSA among patients with normal weight. The effects of chronic intermittent hypoxemia, low-grade inflammation, increased sympathetic tone and mechanical stress contribute to a transformation of muscle fibers in the upper airway, resulting in reduced muscle mass and strength. Less frequently encountered non-anatomical factors include decreased muscle tone, increased arousal threshold, and altered sensitivity of CO 2 chemoreceptors., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Franciscus Sylvius, latinized from Franz de le Boë (*15 March 1614 in Hanau; † 14 November 1672 in Leiden), was a Hessian-Dutch physician, anatomist, and natural scientist of Flemish descent. He was an important clinician and iatrochemist, and is considered the founder of scientifically oriented medicine and clinical chemistry. Sylvius introduced the concept of affinity and dealt with digestive processes and body fluids. He was one of the leading exponents of the concept of blood circulation developed by William Harvey. As the person responsible for practical medicine in Leiden, Sylvius established bedside teaching as part of the medical curriculum, and he introduced his students to clinical medicine in an experimental way, both contrary to the rules of the time. He was also interested in pharmacology, herbalism and botany. For heartburn and digestive disorders, Sylvius mixed juniper berries, herbs and alcohol to create a medicine. According to legend, Sylvius marketed this medicine as Genever, for which the name Gin was later adopted in the British Isles, but not only used for medical purposes. Accordingly, the city of birth of Sylvius today calls itself a "birthplace of gin"., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Maurice Raynaud first described color changes and symptoms of the fingers due to cold-induced vasospasm and restricted blood flow in his medical school thesis in 1862. Raynaud's phenomenon is common and exists as an uncomplicated primary Raynaud phenomenon and a Raynaud phenomenon secondary to underlying diseases and medication. Mechanisms contributing to altered vasoconstrictor activity are endothelial and not-endothelial. Cold-induced vasospasm is probably a thermoregulatory problem and effects are mediated by sympathetic activity and selective stimulation of alpha 2c -adrenoreceptors., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (© Georg Thieme Verlag KG Stuttgart · New York.)

In multiple sclerosis (MS) and its animal model, experimental allergic encephalomyelitis (EAE), clinical disease is associated with infiltration of the central nervous system (CNS) by immune cells. Subsequent remission with remyelination has been linked to an increased occurrence of oligodendrocyte progenitor (O2A) cells. Platelet-derived growth factor (PDGF) and fibroblast growth factor-2 (FGF-2) are key growth factors for O2A cells, yet little is known about their relevance in EAE and MS. We analyzed the expression of PDGF, FGF-2, and their receptors by peripheral-blood leukocytes (PBLs) and lymphocyte subsets during MBP-induced EAE. Strong up-regulation of PDGF, but not FGF-2, was observed in PBLs, with the highest expression after the disease maximum. T, NK, and NKT cells expressed PDGF, which is a novel observation because thus far only monocytes/macrophages have been reported to express PDGF. These results extend the idea that growth factors may contribute to improved CNS tissue repair, including PDGF, which is secreted by lesion-homing immune cells. The production of PDGF by lymphocytes may have potential therapeutic value when activating or modulating T-cell responses in demyelinating diseases., ((c) 2007 Wiley-Liss, Inc.)

We have utilized a computational structure-based approach to identify nonpeptidic small organic compounds that bind to a human leukocyte antigen (HLA) DR1301 molecule (HLA-DR1301 or DR1301) and block the presentation of myelin basic protein peptide 152-165 (MBP 152-165) to T cells. A three-dimensional (3D) structure of DR1301 was derived by homology modeling followed by extensive molecular dynamics simulation for structural refinement. Computational structure-based database searching was performed to identify nonpeptidic small-molecule candidates from the National Cancer Institute (NCI) database containing over 150 000 compounds that can effectively interact with the peptide-binding groove of the HLA molecule. By in vitro testing of 106 candidate small molecules, two lead compounds were confirmed to specifically block IL-2 secretion by DR1301-restricted T cells in a dose-dependent and reversible manner. The specificity of blocking DR1301-restricted MBP presentation was further validated in a binding assay using an analogue of the most potent lead compound. Computational docking was performed to predict the three-dimensional binding model of these confirmed small molecule blockers to the DR1301 molecule and to gain structural insight into their interactions. Our results suggest that computational structure-based searching is an effective approach to discover nonpeptidic small organic compounds to block the interaction between DR1301 and T cells. The nonpeptidic small organic compounds identified in this study are useful pharmacological tools to study the interactions between HLA molecules and T cells and a starting point for the development of a novel therapeutic strategy for the treatment of multiple sclerosis (MS) or other immune-related disorders.