Improving diagnosis of pulmonary hypertension
Researchers in Germany have devised a new technical approach for the diagnosis of pulmonary hypertension (PH), which may enhance treatment by distinguishing between different types of underlying conditions affecting pulmonary arteries and veins. PH is a serious health problem seen with several lung diseases that can lead to right ventricular dysfunction and death. Long-term treatment and prognosis depend on knowing whether the problem stems from the pulmonary arteries or veins, but in early stages it is often difficult to differentiate between pulmonary arterial hypertension (PAH) and the more rare subtype, pulmonary veno-occlusive disease (PVOD). The team looked at lung samples from patients with PAH, PVOD, idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease and healthy controls. Using deep-learning algorithms to analyze the molecular findings, the researchers differentiated PVOD from PAH samples with a sensitivity of 100% and a specificity of 92%. Further, various alterations were identified regarding the gene expression of explanted lungs with pulmonary vascular remodeling vs. controls. In particular, “the dysregulation of microtubule-associated serine/threonine kinase 2 and protein-o-mannose kinase SGK196 in all disease groups suggests a key role in pulmonary vasculopathy for the first time,” the authors wrote. The study is the first to offer a molecular model capable of differentiating between patients with PH due to predominantly precapillary pulmonary vascular remodeling PAH and PVOD lung explants with predominantly postcapillary pulmonary vascular remodeling. “Because lung biopsies, the gold standard for the diagnosis of PVOD, remain as high-risk interventions for patients with PH, and noninvasive approaches currently do not lead to high diagnostic accuracy, these findings may open a concept facilitating diagnostics of PVOD by molecular analysis, provided that these findings are reproducible in blood or urine samples,” the authors wrote. They said genetic signaling changes in various forms of PH might serve as novel pharmaceutical targets with the potential to address severe vascular remodeling and recommended further studies to investigate the diagnostic value of the identified markers in the clinical setting. They reported their analysis in the July 2020 issue of The American Journal of Pathology.
A web-based COVID-19 assessment tool
Most people who used a University of Southern California web-based COVID-19 self-assessment tool reported symptoms that could be managed at home. The tool was developed by a team of researchers from USK and Akido Labs Inc., a Los Angeles-based health data technology company, in partnership with Altamed Health Services. People with symptoms of COVID-19 could access the self-assessment tool, which was based on CDC information about the novel coronavirus, in either English or Spanish. Based on the user’s response to a series of questions, the tool recommends consulting a doctor vs. at-home self-care and provides advice on preventing the spread of infection. Of the 276,560 users who accessed the tool between March 17 and April 9, 80% reported mild to moderate symptoms. Only 20% reported severe symptoms for which the tool recommended immediate medical attention. “Of those with mild symptoms, 7.1% reported direct exposure to someone with confirmed COVID-19; for these users, our tool recommends consideration of telephone consultation with a healthcare professional to determine the need for testing,” the team wrote. The study was published online June 15, 2020, in the Journal of General Internal Medicine.
Discovering pharmacological enzyme activators
Although there are some examples of enzyme activators, most pharmacological research has focused on inhibition. Now, scientists at the Scripps Research Institute have adapted the screening method, activity-based protein profiling (ABPP), to identify activators rather than inhibitors of enzyme activity. They then used ABPP to identify an activator of the LYPLAL1, whose functions are poorly characterized, though it has been linked to multiple metabolic disorders in genomewide association studies. The researchers showed that the activator increased insulin sensitivity and glucose tolerance in insulin-dependent mice. The authors concluded that “these findings reveal a new model of pharmacological regulation for this enzyme family and suggest that ABPP may aid discovery of activators for additional enzyme classes.” Their work appeared in the June 8, 2020, online issue of Nature Chemical Biology.