Developmental beta-cell death orchestrates the islet's inflammatory milieu by regulating immune system crosstalk.

While pancreatic beta-cell proliferation has been extensively studied, the role of cell death during islet development remains incompletely understood. Using a genetic model of caspase inhibition in beta cells coupled with mathematical modeling, we here discover an onset of beta-cell death in juvenile zebrafish, which regulates beta-cell mass. Histologically, this beta-cell death is underestimated due to phagocytosis by resident macrophages.

Management of Vulnerable Patients Hospitalized for COVID-19 With Remdesivir: A Retrospective Comparative Effectiveness Study of Mortality in US Hospitals.

Background: Coronavirus disease 2019 (COVID-19) remains a major public health concern, with continued resurgences of cases and substantial risk of mortality for hospitalized patients. Remdesivir has become standard-of-care for hospitalized COVID-19 patients. Given the continued evolution of the disease, clinical management of COVID-19 relies on evidence from the current endemic period.

Air travel in patients suffering from pulmonary hypertension-A prospective, multicentre study.

The PEGASUS study is the first multicentric and prospective assessment of the safety of air travel flying in pulmonary hypertension (PH) (NCT03051763). Data of air travel from 60 patients with PH was available. No severe adverse events occurred.

Optogenetic β cell interrogation in vivo reveals a functional hierarchy directing the Ca response to glucose supported by vitamin B6.

Coordination of cellular activity through Ca enables β cells to secrete precise quantities of insulin. To explore how the Ca response is orchestrated in space and time, we implement optogenetic systems to probe the role of individual β cells in the glucose response. By targeted β cell activation/inactivation in zebrafish, we reveal a hierarchy of cells, each with a different level of influence over islet-wide Ca dynamics.

Phenotypes and treatment outcomes in idiopathic pulmonary arterial hypertension patients with comorbidities.

Idiopathic pulmonary arterial hypertension (IPAH) is often diagnosed in elderly patients with many comorbidities. Whereas a clear treatment strategy and risk assessment is recommended for patients with rare classical IPAH, monotherapy with phosphodiesterase type 5 inhibitors or endothelin receptor antagonists followed by regular follow-up and individualised therapy should be used for patients with many cardiopulmonary comorbidities. Here, we focus on these patients with IPAH and comorbidities, present a review of the literature with a focus on recently published work and summarise factors that may help to provide guidance for individualised treatment approaches in such patients.

Transplantation of porcine adrenal spheroids for the treatment of adrenal insufficiency.

Primary adrenal insufficiency is a life-threatening disorder, which requires lifelong hormone replacement therapy. Transplantation of xenogeneic adrenal cells is a potential alternative approach for the treatment of adrenal insufficiency. For a successful outcome of this replacement therapy, transplanted cells should provide adequate hormone secretion and respond to adrenal physiological stimuli.

Early post-discharge mortality in CAP: frequency, risk factors and a prediction tool.

There are few data on mortality after discharge with community-acquired pneumonia (CAP). Therefore, we evaluated risk factors for 30-day post-discharge mortality after CAP. We included all patients of the prospective multi-national CAPNETZ study between 2002 and 2018 with (1) hospitalized CAP, (2) survival until discharge, and (3) complete follow-up data.

Simultaneous Calcium Imaging and Glucose Stimulation in Living Zebrafish to Investigate In Vivo β-Cell Function.

The pancreatic β-cells sustain systemic glucose homeostasis by producing and secreting insulin according to the blood glucose levels. Defects in β-cell function are associated with hyperglycemia that can lead to diabetes. During the process of insulin secretion, β-cells experience an influx of Ca.

Leader β-cells coordinate Ca dynamics across pancreatic islets in vivo.

Pancreatic β-cells form highly connected networks within isolated islets. Whether this behaviour pertains to the situation in vivo, after innervation and during continuous perfusion with blood, is unclear. In the present study, we used the recombinant Ca sensor GCaMP6 to assess glucose-regulated connectivity in living zebrafish Danio rerio, and in murine or human islets transplanted into the anterior eye chamber.

Mutually reinforcing effects of genetic variants and interferon-β 1a therapy for pulmonary arterial hypertension development in multiple sclerosis patients.

Based on a small number of cases, interferon beta (IFN-β) has been added to the list of drugs that might induce pulmonary arterial hypertension (PAH) in the current European guidelines for the diagnosis and treatment of pulmonary hypertension. Here, we propose that multiple sclerosis patients who are genetically predisposed to PAH may be at higher risk to develop disease when treated with IFN-β. We included two patients with multiple sclerosis who developed a manifest PAH after five amd eight years on IFN-β 1a therapy, respectively (without confirmed right heart catheterization).

Extreme biomimetics: Preservation of molecular detail in centimeter-scale samples of biological meshes laid down by sponges.

Fabrication of biomimetic materials and scaffolds is usually a micro- or even nanoscale process; however, most testing and all manufacturing require larger-scale synthesis of nanoscale features. Here, we propose the utilization of naturally prefabricated three-dimensional (3D) spongin scaffolds that preserve molecular detail across centimeter-scale samples. The fine-scale structure of this collagenous resource is stable at temperatures of up to 1200°C and can produce up to 4 × 10-cm-large 3D microfibrous and nanoporous turbostratic graphite.

Modelling pancreatic β-cell inflammation in zebrafish identifies the natural product wedelolactone for human islet protection.

Islet inflammation and cytokine production are implicated in pancreatic β-cell dysfunction and diabetes pathogenesis. However, we lack therapeutics to protect the insulin-producing β-cells from inflammatory damage. Closing this clinical gap requires the establishment of new disease models of islet inflammation to facilitate screening efforts aimed at identifying new protective agents.

Machine learning based classification of cells into chronological stages using single-cell transcriptomics.

Age-associated deterioration of cellular physiology leads to pathological conditions. The ability to detect premature aging could provide a window for preventive therapies against age-related diseases. However, the techniques for determining cellular age are limited, as they rely on a limited set of histological markers and lack predictive power.

Analysis of Beta-cell Function Using Single-cell Resolution Calcium Imaging in Zebrafish Islets.

Pancreatic beta-cells respond to increasing blood glucose concentrations by secreting the hormone insulin. The dysfunction of beta-cells leads to hyperglycemia and severe, life-threatening consequences. Understanding how the beta-cells operate under physiological conditions and what genetic and environmental factors might cause their dysfunction could lead to better treatment options for diabetic patients.

Ambrisentan improves exercise capacity and symptoms in patients with portopulmonary hypertension.

Introduction: Ambrisentan, a selective endothelin receptor antagonist has been approved in several countries for pulmonary arterial hypertension. No data have been published on the efficacy of ambrisentan on improvement of exercise capacity in patients with portopulmonary hypertension (PoPH).

Patients And Methods: We retrospectively analyzed the safety and efficacy of ambrisentan in patients with PoPH in four German university hospitals.