The economic burden of obesity in 4 south-eastern European countries associated with obesity-related co-morbidities.

OBJECTIVE: To provide an assessment of the cost burden of obesity across a spectrum of obesity-related comorbidities (ORCs) for four countries in South-Eastern Europe (SEE). METHODS: A micro-costing analysis from the public payer perspective was conducted to estimate direct healthcare costs associated with ten obesity-related comorbidities (ORCs) in Czech Republic, Greece, Hungary, and Romania. A survey was administered to obtain healthcare resource use and unit cost data. Cost estimates were validated by local steering committees which comprised at least one public sector clinician and a panel of independent industry experts. RESULTS: Chronic kidney disease and cardiovascular diseases were the costliest ORCs across all 4 countries, where annual cost burden per ORC exceeded 1,500 USD per patient per year. In general, costs were driven by the tertiary care resources allocated to address treatment-related adverse events, disease complications, and associated inpatient procedures. CONCLUSIONS: Our findings confirm that the high prevalence of obesity and its comorbidities result in substantial financial burden to all 4 SEE public payers. By quantifying the burden of obesity from a public healthcare perspective, our study aims to support policy efforts that promote health education and promotion in combating obesity in the region.

Innate immune activation by conditioned medium of cancer cells following combined phototherapy with photosensitizer-loaded gold nanorods.

Nanoparticle-based phototherapy has evolved to include immunotherapy as an effective treatment combination for cancers through inducing anti-cancer immune activation leading to downstream adaptive responses and immune protection. However, most cancer phototherapy studies that claimed anti-cancer immunogenic effects often included exogenous immunostimulants to potentiate immune responses and did not clearly establish their effects on immune cells. In this study, we showed that combined photodynamic (PDT) and photothermal therapy (PTT) using gold nanorods (NRs) loaded with the photosensitizer chlorin e6 (Ce6) on endogenously formed mouse serum (MS) protein coronas (i.e., NR-MS-Ce6) on EMT6 murine mammary carcinoma cells could potentiate the activation of both J774A.1 macrophages and DC2.4 dendritic cells. The activation of these innate immune cells by the conditioned media from cancer cells treated with combined PDT + PTT was cell-type and number dependent. While treated B16-OVA murine melanoma cells induced lower activation levels for both immune cell types compared to EMT6, they caused higher pro-inflammatory cytokine secretion levels. Our study suggests the importance of immunological investigations to complement any nanoparticle-based therapeutic interventions to better evaluate their efficacy. This could be achieved through a simple approach to screen for the first line of immune responses arising from these therapies prior to in vivo studies.

Quantitative and Label-Free Detection of Protein Kinase A Activity Based on Surface-Enhanced Raman Spectroscopy with Gold Nanostars.

The activity of extracellular protein kinase A (PKA) is known to be a biomarker for cancer. However, conventional PKA assays based on colorimetric, radioactive, and fluorometric techniques suffer from intensive labeling-related preparations, background interference, photobleaching, and safety concerns. While surface-enhanced Raman spectroscopy (SERS)-based assays have been developed for various enzymes to address these limitations, their use in probing PKA activity is limited due to subtle changes in the Raman spectrum with phosphorylation. Here, we developed a robust colloidal SERS-based scheme for label-free quantitative measurement of PKA activity using gold nanostars (AuNS) as a SERS substrate functionalized with bovine serum albumin (BSA)-kemptide (Kem) bioconjugate (AuNS-BSA-Kem), where BSA conferred colloidal stability and Kem is a high-affinity peptide substrate for PKA. By performing principle component analysis (PCA) on the SERS spectrum, we identified two Raman peaks at 725 and 1395 cm-1, whose ratiometric intensity change provided a quantitative measure of Kem phosphorylation by PKA in vitro and allowed us to distinguish MDA-MB-231 and MCF-7 breast cancer cells known to overexpress extracellular PKA catalytic subunits from noncancerous human umbilical vein endothelial cells (HUVEC) based on their PKA activity in cell culture supernatant. The outcome demonstrated potential application of AuNS-BSA-Kem as a SERS probe for cancer screening based on PKA activity.