Glypican-4 serum levels are associated with cognitive dysfunction and vascular risk factors in Parkinson's disease.

Glypicans are biomarkers for various pathologies, including cardiovascular disease, cancer and diabetes. Increasing evidence suggests that glypicans also play a role in the context of neurodegenerative disorders. Initially described as supporting functionality of synapses via glutamate receptors during CNS development, Glypican 4 (GPC-4) also plays a role in the context of dementia via tau hyperphosphorylation in Alzheimer's disease, which is also a co-pathology in Parkinson's disease dementia. However, clinical evidence of circulating GPC-4 in Parkinson's disease (PD) is missing so far. We therefore investigated GPC-4 in biofluids of PD patients. We analyzed GPC-4 levels in cerebrospinal fluid (CSF, n = 140), serum (n = 80), and tear fluid samples (n = 70) of PD patients and control subjects in a similar age range by ELISA (serum, CSF) and western blot (tear fluid). Expression of circulating GPC-4 was confirmed in all three biofluids, with highest levels in serum. Interestingly, GPC-4 levels were age-dependent, and multiple regression analysis revealed a significant association between GPC-4 serum levels and MoCA score, suggesting an involvement of GPC-4 in PD-associated cognitive decline. Furthermore, stratification of PD patients for vascular risk factors revealed a significant increase of GPC-4 serum levels in PD patients with vascular risk factors. Our results suggest GPC-4 as a clinical biomarker for vascular risk stratification in order to identify PD patients with increased risk of developing dementia.

Advancing the Actionability of Mental Health Information: Identifying Online, Evidence-Based Mental Health Resources.

To improve the dissemination and actionability of mental health research, many mental health professionals have developed online informational resources to increase the general public's awareness of mental health difficulties and available treatments. Yet, limited information exists on the quality and scope of these resources. This study aimed to explore the scope and quantity of online, free, evidence-based mental health resources. Fifty-two mental health professionals nominated 178 resources, which predominantly consisted of homepages and links to more information. When reviewing the original nominations, our team identified an additional 290 resources (e.g., fact sheets linked from a nominated homepage). Of the 468 total nominated resources, 72 were screened out due to not meeting the inclusion criteria of being free (inter-screener reliability = 95%), evidence-based (inter-screener reliability = 94%), and online (inter-screener reliability = 96%). Nominated resources most commonly covered anxiety and obsessive-compulsive disorder (n = 67) and suicide (n = 60). Resources providing information about the mental health problem were most common (n = 210) and resources providing information about immediate help (e.g., hotline) were least common (n = 57). Our findings indicate many free, online, evidence-based resources are available and raise questions of whether efforts to disseminate mental health research are recreating the issue of information overload. Other considerations and future directions for improving the utilization and synthesizing of available resources are discussed.

Combining viral genomics and clinical data to assess risk factors for severe COVID-19 (mortality, ICU admission, or intubation) amongst hospital patients in a large acute UK NHS hospital Trust.

Throughout the COVID-19 pandemic, valuable datasets have been collected on the effects of the virus SARS-CoV-2. In this study, we combined whole genome sequencing data with clinical data (including clinical outcomes, demographics, comorbidity, treatment information) for 929 patient cases seen at a large UK hospital Trust between March 2020 and May 2021. We identified associations between acute physiological status and three measures of disease severity; admission to the intensive care unit (ICU), requirement for intubation, and mortality. Whilst the maximum National Early Warning Score (NEWS2) was moderately associated with severe COVID-19 (A = 0.48), the admission NEWS2 was only weakly associated (A = 0.17), suggesting it is ineffective as an early predictor of severity. Patient outcome was weakly associated with myriad factors linked to acute physiological status and human genetics, including age, sex and pre-existing conditions. Overall, we found no significant links between viral genomics and severe outcomes, but saw evidence that variant subtype may impact relative risk for certain sub-populations. Specific mutations of SARS-CoV-2 appear to have little impact on overall severity risk in these data, suggesting that emerging SARS-CoV-2 variants do not result in more severe patient outcomes. However, our results show that determining a causal relationship between mutations and severe COVID-19 in the viral genome is challenging. Whilst improved understanding of the evolution of SARS-CoV-2 has been achieved through genomics, few studies on how these evolutionary changes impact on clinical outcomes have been seen due to complexities associated with data linkage. By combining viral genomics with patient records in a large acute UK hospital, this study represents a significant resource for understanding risk factors associated with COVID-19 severity. However, further understanding will likely arise from studies of the role of host genetics on disease progression.

Prevalence and characteristics of resistant hypertensive patients in an Asian population.

BACKGROUND: Resistant hypertension is a well-recognized clinical challenge yet there are no reported data on its prevalence in Pakistan. These patients are subjected to a higher risk of developing hypertensive complications. The objective of our study was to evaluate the prevalence and determinants of resistant hypertension in an Asian cohort of hypertensive patients. METHODS: This cross-sectional study was carried out among hypertensive patients visiting a tertiary care hospital in Karachi from September-December 2015. Patient data and characteristics were recorded using a pre-coded questionnaire. Morisky and Berlin questionnaires were used to assess compliance to medications and determine the risk of developing obstructive sleep apnea, respectively. Pearson's chi-square test was used to analyze statistical differences between hypertensive patients and related factors. RESULTS: A total of 515 patients were included in the study. Overall, 12% of the total patients (n=62) were resistant hypertensives and 25% (n=129) had pseudo-resistant hypertension. Resistant patients were more often females, older and had a higher body mass index (all P<0.001). Use of painkillers and noncompliance to dietary recommendations were found to be significant determinants of resistant hypertension. Prevalence of comorbid conditions, including diabetes (p=0.33), hyperlipidemia (p=0.46), and chronic kidney disease (p=0.23), was not significantly higher in patients with resistant hypertension. CONCLUSION: Nearly one in ten hypertensive patients had true resistant hypertension, and twenty-five percent of patients had pseudo-resistance. Resistance hypertensions is significantly associated with female gender, older age, obesity, dietary noncompliance and increased use of NSAIDs.