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History and Admission Findings:  A 76-year old man was admitted with a globus sensation and weight loss for further investigations to our geriatric ward. A gastroscopic evaluation executed before had been unremarkable., Investigations:  Physical examination was unremarkable, including a neurological examination., Treatment and Course:  All radiological findings (computer tomography of chest, abdomen and neck) were unremarkable. In a FEES investigation we found retentions and a reduction of frequency of swallowing after a while. During the investigation the patient complained about a muscular weakness in his neck. The assumed diagnosis of a myasthenia gravis was confirmed by antibodies against acetylcholine receptors and a decrement in repetitive irritation of the orbicularis and trapezius muscle., Conclusion:  FEES can be a valid diagnosis tool for a pharyngeal type of a myasthenia gravis., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune-mediated neuromuscular disease thought to be caused by autoantibodies against P/Q-type voltage-gated calcium channels (VGCCs), which attack and reduce the number of VGCCs within transmitter release sites (active zones; AZs) at the neuromuscular junction (NMJ), resulting in neuromuscular weakness. However, patients with LEMS also have antibodies to other neuronal proteins, and about 15% of patients with LEMS are seronegative for antibodies against VGCCs. We hypothesized that a reduction in the number of P/Q-type VGCCs alone is not sufficient to explain LEMS effects on transmitter release. Here, we used a computational model to study a variety of LEMS-mediated effects on AZ organization and transmitter release constrained by electron microscopic, pharmacological, immunohistochemical, voltage imaging, and electrophysiological observations. We show that models of healthy AZs can be modified to predict the transmitter release and short-term facilitation characteristics of LEMS and that in addition to a decrease in the number of AZ VGCCs, disruption in the organization of AZ proteins, a reduction in AZ number, a reduction in the amount of synaptotagmin, and the compensatory expression of L-type channels outside the remaining AZs are important contributors to LEMS-mediated effects on transmitter release. Furthermore, our models predict that antibody-mediated removal of synaptotagmin in combination with disruption in AZ organization alone could mimic LEMS effects without the removal of VGCCs (a seronegative model). Overall, our results suggest that LEMS pathophysiology may be caused by a collection of pathological alterations to AZs at the NMJ, rather than by a simple loss of VGCCs. NEW & NOTEWORTHY We used a computational model of the active zone (AZ) in the mammalian neuromuscular junction to investigate Lambert-Eaton myasthenic syndrome (LEMS) pathophysiology. This model suggests that disruptions in presynaptic active zone organization and protein content (particularly synaptotagmin), beyond the simple removal of presynaptic calcium channels, play an important role in LEMS pathophysiology.

Large-animal models for Duchenne muscular dystrophy (DMD) are crucial for the evaluation of diagnostic procedures and treatment strategies. Pigs cloned from male cells lacking DMD exon 52 (DMDΔ52) exhibit molecular, clinical and pathological hallmarks of DMD, but die before sexual maturity and cannot be propagated by breeding. Therefore, we generated female DMD+/- carriers. A single founder animal had 11 litters with 29 DMDY/-, 34 DMD+/- as well as 36 male and 29 female wild-type offspring. Breeding with F1 and F2 DMD+/- carriers resulted in an additional 114 DMDY/- piglets. With intensive neonatal management, the majority survived for 3-4 months, providing statistically relevant cohorts for experimental studies. Pathological investigations and proteome studies of skeletal muscles and myocardium confirmed the resemblance to human disease mechanisms. Importantly, DMDY/- pigs displayed progressive myocardial fibrosis and increased expression of connexin-43, associated with significantly reduced left ventricular ejection fraction, at 3 months. Furthermore, behavioral tests provided evidence for impaired cognitive ability. Our breeding cohort of DMDΔ52 pigs and standardized tissue repositories provide important resources for studying DMD disease mechanisms and for testing novel treatment strategies., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2021. Published by The Company of Biologists Ltd.)

The discussion on the development of public health affairs was invigorated anew by the report on public health in Germany of Leopoldina/Acatech/Union of the German Academies of Sciences and Humanities of the year 2015. The report urges strengthening of public health and global health in Germany and addresses explicitly the Public Health Service (PHS). This indispensable inclusion of the PHS in further strategic planning offers for the first time an opportunity for a comprehensive and sustainable practice/policy transfer on the federal, state and community level, and also a chance for a sustainable network with modern academic public health institutions together with representation of medical specialization in public health at universities, that has been absent so far. A Johann-Peter Frank model for cooperation and stepwise modelling of this transition with the inclusion of the Academies for Public Health Service is presented., (© Georg Thieme Verlag KG Stuttgart · New York.)