Assessment of plasma chitotriosidase activity, CCL18/PARC concentration and NP-C suspicion index in the diagnosis of Niemann-Pick disease type C: A prospective observational study

Background: Niemann-Pick disease type C (NP-C) is a rare, autosomal recessive neurodegenerative disease caused by mutations in either the NPC1 or NPC2 genes. The diagnosis of NP-C remains challenging due to the non-specific, heterogeneous nature of signs/symptoms. This study assessed the utility of plasma chitotriosidase (ChT) and Chemokine (C-C motif) ligand 18 (CCL18)/pulmonary and activation-regulated chemokine (PARC) in conjunction with the NP-C suspicion index (NP-C SI) for guiding confirmatory laboratory testing in patients with suspected NP-C. Methods: In a prospective observational cohort study, incorporating a retrospective determination of NP-C SI scores, two different diagnostic approaches were applied in two separate groups of unrelated patients from 51 Spanish medical centers (n = 118 in both groups). From Jan 2010 to Apr 2012 (Period 1), patients with =2 clinical signs/symptoms of NP-C were considered ''suspected NP-C'' cases, and NPC1/NPC2 sequencing, plasma chitotriosidase (ChT), CCL18/PARC and sphingomyelinase levels were assessed. Based on findings in Period 1, plasma ChT and CCL18/PARC, and NP-C SI prediction scores were determined in a second group of patients between May 2012 and Apr 2014 (Period 2), and NPC1 and NPC2 were sequenced only in those with elevated ChT and/or elevated CCL18/PARC and/or NP-C SI =70. Filipin staining and 7-ketocholesterol (7-KC) measurements were performed in all patients with NP-C gene mutations, where possible. Results: In total across Periods 1 and 2, 10/236 (4%) patients had a confirmed diagnosis o NP-C based on gene sequencing (5/118 4.2%] in each Period): all of these patients had two causal NPC1 mutations. Single mutant NPC1 alleles were detected in 8/236 (3%) patients, overall. Positive filipin staining results comprised three classical and five variant biochemical phenotypes. No NPC2 mutations were detected. All patients with NPC1 mutations had high ChT activity, high CCL18/PARC concentrations and/or NP-C SI scores =70. Plasma 7-KC was higher than control cut-off values in all patients with two NPC1 mutations, and in the majority of patients with single mutations. Family studies identified three further NP-C patients. Conclusion: This approach may be very useful for laboratories that do not have mass spectrometry facilities and therefore, they cannot use other NP-C biomarkers for diagnosis

Ca2+ transport by the synaptosomal plasma membrane Ca2+-ATPase and the effect of thioridazine

Thioridazine inhibits the activity of the synaptic plasma membrane Ca2+-ATPase from pig brain and slightly decreases the rate of Ca2+ accumulation by synaptic plasma membrane vesicles in the absence of phosphate. However, in the presence of phosphate, thioridazine increases the rate of Ca2+ accumulation into synaptic plasma membrane vesicles. Phosphate anions diffuse through the membrane and form calcium phosphate crystals, reducing the free Ca2+ concentration inside the vesicles and the rate of Ca2+ leak. The higher levels of Ca2+ accumulation obtained in the presence of thioridazine could be explained by a reduction of the rate of slippage on the plasma membrane ATPase

Feasibility and Outcomes of Meta Salud Diabetes Behavioral Health Intervention: A Pilot Study of a Community Health Worker-Administered Educational Intervention to Prevent Cardiovascular Disease and Its Complications among Hispanic Patients with Type-2 Diabetes

Background: Hispanics in the United States experience a greater burden of type-2 diabetes (T2D), with a prevalence rate (17%) more than twice that of non-Hispanic whites (8%). Cardiovascular disease (CVD) is the leading cause of death among people with T2D. A culturally appropriate behavioral health intervention that addresses healthy lifestyle promotion is an impactful approach for health systems with scarce medical resources and a high prevalence of chronic conditions, including obesity and high blood pressure, which increase the likelihood of CVD mortality among type-2 diabetics. Purpose: To assess the feasibility and outcomes of a behavioral intervention to decrease CVD and complications in a Hispanic diabetic population. Methods: Meta Salud Diabetes (MSD), a behavioral intervention effective in a Mexican population, consists of a 13-week intervention addressing CVD and T2D knowledge and risk reduction. It was implemented in a sample of Hispanic diabetic patients from two federally qualified health centers (FQHCs). Clinical and behavioral variables were measured at baseline, postintervention, and 1-year follow-up. Results: The feasibility of MSD was rated as successful by all FQHC staff and well-received by both staff and study participants, with positive remarks about the culturally relevant components of the intervention. The sample size was n = 30 (baseline), n = 23 (postintervention), and n = 19 (1-year follow-up). Of note, quantitative results showed trending decreases in Hba1c (7.06; 6.80; 6.30), blood pressure (132/83; 126/80; 123/78), and total cholesterol (160; 159; 154). Conclusion: MSD is a feasible intervention and can address the need to improve health outcomes among Hispanic patients with T2D. © 2023 by the authors.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Inflation at Askja, Iceland. New and revisited relative microgravity data

In August 2021 Askja caldera in Iceland started to show uplift after decades of subsidence. The uplift signal is centered at the northwestern edge of lake Ӧskjuvatn and an order of magnitude larger than the subsidence in the last decade. In September 2021 a geodesy campaign was carried out at Askja, including relative microgravity measurements acquired with the use of two Scintrex CG-5 instruments. Relative microgravity campaigns at Askja are not straightforward due to the long walking distances between sites, which makes a “double loop” procedure impossible. We revisit existing Scintrex relative microgravity data sets (2015 onward) and analyse data using the same joint weighted least squares inversion routine. We define recommendations for future relative microgravity campaigns at Askja which will be important to establish the cause of the ongoing uplift. The density of subsurface magma is only identifiable with microgravity data. Knowledge of the type of magma accumulating under Askja is vital to assess possible hazard implications.Mathematical Geodesy and Positionin