Pulmonary hypertension due to left heart disease (PH-LHD; Group 2), especially in the setting of heart failure with preserved ejection fraction (HFpEF), is the most frequent cause of PH. Despite its prevalence, no effective therapies for PH-LHD are available at present. This is largely due to the lack of a concise definition for hemodynamic phenotyping, existence of significant gaps in the understanding of the underlying pathology and the impact of associated comorbidities, as well as the absence of specific biomarkers that can aid in the early diagnosis and management of this challenging syndrome. Currently, B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) are guideline-recommended biomarkers for the diagnosis and prognosis of heart failure (HF) and PH. Endothelin-1 (ET-1), vascular endothelial growth factor-D (VEGF-D), and microRNA-206 have also been recently identified as new potential circulating biomarkers for patients with PH-LHD. In this review, we aim to present the current state of knowledge of circulating biomarkers that can be used to guide future research toward diagnosis, refine specific patient phenotype, and develop therapeutic approaches for PH-LHD, with a particular focus on PH-HFpEF. Potential circulating biomarkers identified in pre-clinical models of PH-LHD are also summarized here.

Traxoprodil is a selective N-methyl-d-aspartate receptor subunit 2B (NR2B) receptor inhibitor with rapid and long-lasting antidepressant effects. However, the appropriate dosage, duration of administration, and underlying mechanism of traxoprodil’s antidepressant effects remain unclear. The purpose of this study is to compare the antidepressant effects of traxoprodil in different doses and different durations of administration and to explore whether traxoprodil exerts antidepressant effects via the brain-derived neurotrophic factor/extracellular signal-regulated kinase/cAMP-response element binding protein (BDNF/ERK/CREB) and protein kinase B/Forkhead box O/building information modelling (AKT/FOXO/Bim) signaling pathway. Mice were randomly divided into control group, chronic unpredictable mild stress (CUMS) + vehicle group, CUMS + traxoprodil (10 mg/kg, 20 mg/kg, and 40 mg/kg) groups, and CUMS + fluoxetine (5 mg/kg) group, followed by a forced swimming test, tail suspension test, and sucrose preference test. Western blotting and immunohistochemistry were used to measure the protein expression of BDNF, p-ERK1/2, p-CREB, NR2B, AKT, FOXO1, FOXO3a, and Bim. Compared with the control group, CUMS treatment increased immobility time; decreased sucrose preference; reduced expression of BDNF, p-ERK1/2, and p-CREB; and increased expression of AKT, FOXO, and Bim in the hippocampus. These alterations were ameliorated by administration of 20 mg/kg or 40 mg/kg of traxoprodil after 7 or 14 days of administration and with 10 mg/kg of traxoprodil or 5 mg/kg of fluoxetine after 21 days of administration. At the 7-day and 14-day timepoints, traxoprodil displayed dose-dependent antidepressant effects, with 20 and 40 mg/kg doses of traxoprodil producing rapid and strong antidepressant effects. However, at 21 days of administration, 10 and 20 mg/kg doses of traxoprodil exerted more pronounced antidepressant effects. The mechanism of traxoprodil’s antidepressant effects may be closely related to the BDNF/ERK/CREB and AKT/FOXO/Bim signaling pathway.

Background: Coronavirus disease (COVID-19) was declared a global pandemic by the World Health Organization (WHO) on March 11, 2020. Now a subset of individuals are experiencing post- acute sequelae of COVID-19, more colloquially known as Long-COVID. Research surrounding the long-term consequences of COVID-19 is now at the height of importance as approximately 5.8% of individuals will be diagnosed with new psychiatric illnesses. Mind long consequences of COVID-19 include brain fog, difficulties with memory, and focusing. Objective/Methods: While many of the symptoms associated with Long-COVID have been summarized, the cognitive impairment that takes place was quantified in this study using BrainCheck cognitive assessment. The aim of this study was to utilize a database of over 500 individuals suffering from Long-COVID symptoms and analyze differing levels of cognitive impairment to find correlations with different predispositions and demographics. The focused variables were age, gender, weight, (body mass index) BMI, and hospitalization status. A retrospective chart review was conducted on subjects’ data that was included in the Parkview Post-COVID Clinic (PPCC) registry database. Results: The data analysis showed that age was correlated with mental flexibility (p-value = <.001, correlation = 0.31), and executive functioning. The extremes of BMI were associated with impaired mental flexibility (chi-squared = 14.00, p-value = <.001). Finally, hospitalization status at the onset of COVID-19 infection had correlations with impaired short-term memory recognition (p-value = <.05, correlation = 0.17). Conclusion: This research project was undertaken to gain a better understanding of the cognitive deterioration that takes place because of COVID-19’s effect on the central nervous system. Furthermore, this research is intended to help predict the levels of cognitive impairment that clinicians can expect for their patients when presenting with Long-COVID symptoms, and spark future research on the neurological implications of COVID-19.

Objective: A retrospective study was conducted to examine the relationship between long-COVID peripheral neuropathy and patient demographics and comorbid medical conditions. Methods: Electronic health records of 543 patients from the Parkview Post-COVID Clinic were reviewed for their demographic information, past medical histories, and post-COVID clinic visit summaries. Based on whether patients had peripheral neuropathy as a post-COVID clinical visit diagnosis and whether they had had a history of neuropathy prior to COVID infection, the patients were assigned into the new-onset neuropathy group, progressing and non-progressing neuropathy groups, and non-neuropathy group. Age and BMI were compared among the four groups using two-sampled t test. Sex, prior COVID hospitalization status, and chronic comorbidities including hypertension, diabetes, and anemia were compared using chi-squared test. Results: 19 of 543 (3.5%) patients had new-onset neuropathy and 18 (3.3%) were found to have progressing neuropathy. The study’s incidence of new-onset peripheral neuropathy (3.5% over two years) in long-COVID patients is higher than the incidence of non-COVID-related neuropathy indicated in literature (0.76% each year, p = 0.025). Compared with patients with no neuropathy, patients with new-onset neuropathy were of older age (p = 0.042), more male (p = 0.022), and more frequently hospitalized for COVID (p = 0.003). Compared to patients with no neuropathy, patients with progressing neuropathy were of older age (p < 0.001), had more COVID hospitalization (p = 0.033), diabetes (0.014), hypertension (p < 0.001), and anemia (p = 0.02). Conclusion: Age and COVID hospitalization were found to be risk factors for both new-onset and progressing neuropathy. Being male was a risk factor for new-onset neuropathy only. Diabetes, anemia, and hypertensionwere risk factors for both progressing and non-progressing neuropathy but not for new-onset neuropathy. The results can prompt clinicians to assess peripheral neuropathy in long-COVID patients that have high demographic and medical risk factors.