Developmental origins of cell heterogeneity in the human lung

The lung contains numerous specialized cell-types with distinct roles in tissue function and integrity. To clarify the origins and mechanisms generating cell heterogeneity, we created a first comprehensive topographic atlas of early human lung development. We report 83 cell states, several spatially-resolved developmental trajectories and predict cell interactions within defined tissue niches. We integrated scRNA-Seq and spatial transcriptomics into a web-based, open platform for interactive exploration. To illustrate the utility of our approach we show distinct states of secretory and neuroendocrine cells, largely overlapping with the programs activated either during lung fibrosis or small cell lung cancer progression. We define the origin of uncharacterized airway fibroblasts associated with airway smooth muscle in bronchovascular bundles, and describe a trajectory of Schwann cell progenitors to intrinsic parasympathetic neurons controlling bronchoconstriction. Our atlas provides a rich resource for further research and a reference for defining deviations from homeostatic and repair mechanisms leading to pulmonary diseases.

Vagus Nerve Cross-Sectional Area in Patients With Parkinson's Disease—An Ultrasound Case-Control Study

Background: Vagal parasympathetic neurons are prone to degeneration in Parkinson's disease (PD). High-resolution ultrasound can precisely estimate the cross-sectional (CSA) area of peripheral nerves. Here, we tested the hypothesis that vagus CSA is reduced in PD.Methods: We included 56 healthy controls (HCs) and 63 patients with PD. Using a high-end ultrasound system equipped with a high-frequency transducer, five images were obtained of each nerve. The hypoechoic neuronal tissue was delineated offline with dedicated software and the CSA extracted.Results: In the initial PD vs. HC comparison, no statistically significant differences were observed in mean left vagus CSA (HC: 1.97 mm2, PD: 1.89 mm2, P = 0.36) nor in mean right vagus CSA (HC: 2.37 mm2, PD: 2.23 mm2, P = 0.17). The right vagus CSA was significantly larger than the left vagus CSA in both groups (P < 0.0001). Females were overrepresented in the HC group and presented with generally smaller vagus CSAs. Consequently, sex-adjusted CSA was significantly smaller for the right vagus nerve of the PD group (P = 0.041), but not for the left.Conclusion: A small but significant reduction in sex-adjusted right vagus CSA was observed in patients with PD. The left vagus CSA was not significantly reduced in patients with PD. Ultrasound may not be a suitable method to detecting vagal axonal loss in individual patients.

Neural Mechanisms and Therapeutic Opportunities for Atrial Fibrillation

Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with an increased risk of all-cause mortality and complications. The autonomic nervous system (ANS) plays a central role in AF, with the heart regulated by both extrinsic and intrinsic properties. In the extrinsic ANS, the sympathetic fibers are derived from the major paravertebral ganglia, especially the stellate ganglion (SG), which is a source of cardiac sympathetic innervation since it connects with multiple intrathoracic nerves and structures. The major intrinsic ANS is a network of axons and ganglionated plexi that contains a variety of sympathetic and parasympathetic neurons, which communicate with the extrinsic ANS. Simultaneous sympathovagal activation contributes to the development of AF because it increases calcium entry and shortens the atrial action potential duration. In animal and human studies, neuromodulation methods such as electrical stimulation and renal denervation have indicated potential benefits in controlling AF in patients as they cause SG remodeling and reduce sympathetic outflow. This review focuses on the neural mechanisms relevant to AF and the recent developments of neuromodulation methods for AF control.

Vagus nerve cross-sectional area in patients with Parkinson’s Disease – an ultrasound case-control study

BackgroundVagal parasympathetic neurons are prone to degeneration in Parkinson’s disease (PD). High-resolution ultrasound can precisely estimate the cross-sectional area (CSA) of peripheral nerves. Here, we tested the hypothesis that vagus CSA is reduced in PD.MethodsWe included 56 healthy controls (HCs) and 63 patients with PD. Using a high-end ultrasound system equipped with a high-frequency transducer, five images were obtained of each nerve. The hypoechoic neuronal tissue was delineated offline with dedicated software and the CSA extracted.ResultsIn the initial PD vs. HC comparison, no statistically significant differences were observed in mean left vagus CSA (HC: 1.97mm2, PD: 1.89mm2, P=0.36) or in mean right vagus CSA (HC: 2.37mm2, PD: 2.23mm2, P=0.17). The right vagus CSA was significantly larger than the left vagus CSA in both groups (P<0.0001). Females were overrepresented in the HC group and presented with generally smaller vagus CSAs. Consequently, sex-adjusted CSA was significantly smaller for the right vagus nerve of the PD group (P=0.041), but not for the left.ConclusionA small but significant reduction in sex-adjusted right vagus CSA was observed in patients with PD. The left vagus CSA was not significantly reduced in patients with PD. Ultrasound may not be a suitable method to detecting vagal axonal loss in individual patients.

The prevention and management of Frey's syndrome and a step by step guide through the nonsurgical treatment with Botulinum toxin

Firstly described by Lucy Frey in 1923 the “Frey’s syndrome” is characterized by sweating and flushing in direct response to mastication. The mechanism is aberrant regeneration of postganglionic parasympathetic neurons from the auriculotemporal nerve and Acetylcholine secretion by a masticatory stimulus. This entity occurs in up to 65% following lateral parotid resections and less commonly after neck dissection or facelift procedures. This article aims to list possible surgical and non-surgical treatment options of this iatrogenic entity but should focus on the treatment with botulinum toxin A and provide a step by step guide from the Lugol-Iodine-Starch test to the botulinum toxin A (BoNTA-ONA) injection within the affected area.

The prevention and management of Frey's syndrome and a step by step guide through the nonsurgical treatment with Botulinum toxin

Firstly described by Lucy Frey in 1923 the “Frey’s syndrome” is characterized by sweating and flushing in direct response to mastication. The mechanism is aberrant regeneration of postganglionic parasympathetic neurons from the auriculotemporal nerve and Acetylcholine secretion by a masticatory stimulus. This entity occurs in up to 65% following lateral parotid resections and less commonly after neck dissection or facelift procedures. This article aims to list possible surgical and non-surgical treatment options of this iatrogenic entity but should focus on the treatment with botulinum toxin A and provide a step by step guide from the Lugol-Iodine-Starch test to the botulinum toxin A (BoNTA-ONA) injection within the affected area.

The diversity of neuronal phenotypes in rodent and human autonomic ganglia

Selective sympathetic and parasympathetic pathways that act on target organs represent the terminal actors in the neurobiology of homeostasis and often become compromised during a range of neurodegenerative and traumatic disorders. Here, we delineate several neurotransmitter and neuromodulator phenotypes found in diverse parasympathetic and sympathetic ganglia in humans and rodent species. The comparative approach reveals evolutionarily conserved and non-conserved phenotypic marker constellations. A developmental analysis examining the acquisition of selected neurotransmitter properties has provided a detailed, but still incomplete, understanding of the origins of a set of noradrenergic and cholinergic sympathetic neuron populations, found in the cervical and trunk region. A corresponding analysis examining cholinergic and nitrergic parasympathetic neurons in the head, and a range of pelvic neuron populations, with noradrenergic, cholinergic, nitrergic, and mixed transmitter phenotypes, remains open. Of particular interest are the molecular mechanisms and nuclear processes that are responsible for the correlated expression of the various genes required to achieve the noradrenergic phenotype, the segregation of cholinergic locus gene expression, and the regulation of genes that are necessary to generate a nitrergic phenotype. Unraveling the neuron population-specific expression of adhesion molecules, which are involved in axonal outgrowth, pathway selection, and synaptic organization, will advance the study of target-selective autonomic pathway generation.