Health Savings Accounts: Participation Increased and Was More Common among Individuals with Higher Incomes

[Excerpt] he number of individuals participating in HSA-eligible health plans and HSAs increased significantly between 2004 and 2007; however, in all years, many HSA-eligible plan enrollees did not open an HSA. The number of individuals covered by HSA-eligible plans increased significantly between September 2004 and January 2007 from about 438,000 to approximately 4.5 million, according to industry estimates. Despite the growth, these plans represented a small share of individuals with private health coverage about 2 percent in 2006. The number of tax filers reporting HSA activity also increased, nearly tripling between 2004 and 2005, from about 120,000 to about 355,000. Industry estimates suggest continued growth in HSA participation in 2006 and 2007. Despite the growth in HSA participation, nationally representative survey estimates from 2005, 2006, and 2007 found that more than 40 percent of HSA-eligible health plan enrollees did not open an HSA. Tax filers who reported HSA activity in 2005 had higher incomes on average than other tax filers. Among tax filers between the ages of 19 and 64, the average AGI for filers reporting HSA activity was about $139,000 compared with about$57,000 for all other filers. The income differences existed across all age groups. The total value of all HSA contributions reported to IRS in 2005 was about twice that of withdrawals$754 million compared with$366 million. Among all filers reporting HSA activity in 2005, average contributions were about $2,100, compared to average withdrawals of about$1,000. Survey estimates of the contributions employers made to employees\u27 HSAs in 2007 varied. One employer survey reported average contributions for single coverage of $626 among large employers, while another employer survey reported average contributions for single coverage of$806 among small and large employers. More than a third of surveyed employers that offered HSA-eligible plans made no HSA contributions

Identification of MS-specific serum miRNAs in an international multicenter study.

ObjectiveTo identify circulating microRNAs (miRNAs) linked to disease, disease stage, and disability in MS across cohorts.MethodsSamples were obtained from the Comprehensive Longitudinal Investigation of Multiple Sclerosis (CLIMB, Boston, MA), EPIC (San Francisco, CA), AMIR (Beirut, Lebanon) as part of the SUMMIT consortium, and Stockholm Prospective Assessment of Multiple Sclerosis (Stockholm, Sweden) cohorts. Serum miRNA expression was measured using locked nucleic acid-based quantitative PCR. Four groups were compared: (1) MS vs healthy control (HC), (2) relapsing-remitting (RR) vs HC, (3) secondary progressive (SP) vs HC, and (4) RR vs SP. A Wilcoxon rank-sum test was used for the comparisons. The association between each miRNA and the Expanded Disability Status Scale (EDSS) score was assessed using the Spearman correlation coefficient. For each comparison, the p values were corrected for multiple comparisons using the approach of Benjamini and Hochberg to control the false discovery rate.ResultsIn the CLIMB cohort, 5 miRNAs (hsa-miR-484, hsa-miR-140-5p, hsa-miR-320a, hsa-miR-486-5p, and hsa-miR-320c) showed a significant difference between patients with MS and healthy individuals; among these, miR-484 remained significant after accounting for multiple comparisons (p = 0.01). When comparing RRMS with HCs, hsa-miR-484 showed a significant difference (p = 0.004) between the groups after accounting for multiple group comparisons. When SP and HC were compared, 6 miRNAs (hsa-miR-484, hsa-miR-140-5p, hsa-miR-142-5p, hsa-miR-320a, hsa-miR-320b, and hsa-miR-320c) remained significantly different after accounting for multiple comparisons. Disability correlation analysis with miRNA provided 4 miRNAs (hsa-miR-320a, hsa-miR-337-3p, hsa-miR-199a-5p, and hsa-miR-142-5p) that correlated with the EDSS during the internal reproducibility phase. Among these, hsa-miR-337-3p was the most statistically significant miRNA that negatively correlated with the EDSS in three of the MS cohorts tested.ConclusionsThese findings further confirm the use of circulating serum miRNAs as biomarkers to diagnose and monitor disease status in MS.Classification of evidenceThis study provides Class III evidence that levels of circulating miRNAs identify patients with MS

The feasibility of radiolabeling for human serum albumin (HSA) adsorption studies

Human serum albumin (HSA) was labeled in various ways and with different radioactive labels (Technetium-99m and Iodine-125). Characterization with electrophoresis on polyacryl gel and immunoelectrophoresis did not reveal differences between labeled and nonlabeled HSA. The release of the label from labeled proteins in phosphate buffer (pH 7.4) was studied as a function of time. 125I-labeled proteins were stable and 99mTc-labeled proteins showed different stabilities depending on the labeling method which was used. The adsorption behavior of labeled HSA and HSA onto polystyrene (PS) and silicon rubber (SR) was studied by using two methods. It appeared that all labeled HSA compounds showed a preferential adsorption onto PS (and SR) substrates. The 99mTc-labeled HSA showed a high value of the preferential adsorption factor (φ 1). The φ value for 125I-labeled HSA was about 1.4. It was also shown that φ was dependent on the kind of substrate used. The methods developed to determine preferential adsorption of labeled proteins compared to their nonlabeled analogs are also generally applicable for different types of compounds

Interactions of Poly(amidoamine) Dendrimers with Human Serum Albumin: Binding Constants and Mechanisms

The interactions of nanomaterials with plasma proteins have a significant impact on their in vivo transport and fate in biological fluids. This article discusses the binding of human serum albumin (HSA) to poly(amidoamine) [PAMAM] dendrimers. We use protein-coated silica particles to measure the HSA binding constants (K_b) of a homologous series of 19 PAMAM dendrimers in aqueous solutions at physiological pH (7.4) as a function of dendrimer generation, terminal group, and core chemistry. To gain insight into the mechanisms of HSA binding to PAMAM dendrimers, we combined ^1H NMR, saturation transfer difference (STD) NMR, and NMR diffusion ordered spectroscopy (DOSY) of dendrimer−HSA complexes with atomistic molecular dynamics (MD) simulations of dendrimer conformation in aqueous solutions. The binding measurements show that the HSA binding constants (K_b) of PAMAM dendrimers depend on dendrimer size and terminal group chemistry. The NMR ^1H and DOSY experiments indicate that the interactions between HSA and PAMAM dendrimers are relatively weak. The ^1H NMR STD experiments and MD simulations suggest that the inner shell protons of the dendrimers groups interact more strongly with HSA proteins. These interactions, which are consistently observed for different dendrimer generations (G0-NH_2vs G4-NH_2) and terminal groups (G4-NH_2vs G4-OH with amidoethanol groups), suggest that PAMAM dendrimers adopt backfolded configurations as they form weak complexes with HSA proteins in aqueous solutions at physiological pH (7.4)

A novel element upstream of the Vgamma2 gene in the murine T cell receptor gamma locus cooperates with the 3 enhancer to act as a locus control region.

Transgenic expression constructs were employed to identify a cis-acting transcription element in the T cell receptor (TCR)-gamma locus, called HsA, between the Vgamma5 and Vgamma2 genes. In constructs lacking the previously defined enhancer (3E(Cgamma1)), HsA supports transcription in mature but not immature T cells in a largely position-independent fashion. 3E(Cgamma1), without HsA, supports transcription in immature and mature T cells but is subject to severe position effects. Together, the two elements support expression in immature and mature T cells in a copy number-dependent, position-independent fashion. Furthermore, HsA was necessary for consistent rearrangement of transgenic recombination substrates. These data suggest that HsA provides chromatin-opening activity and, together with 3E(Cgamma1), constitutes a T cell-specific locus control region for the TCR-gamma locus

Serum microRNA array analysis identifies miR-140-3p, miR-33b-3p and miR-671-3p as potential osteoarthritis biomarkers involved in metabolic processes.

Background: MicroRNAs (miRNAs) in circulation have emerged as promising biomarkers. In this study, we aimed to identify a circulating miRNA signature for osteoarthritis (OA) patients and in combination with bioinformatics analysis to evaluate the utility of selected differentially expressed miRNAs in the serum as potential OA biomarkers. Methods: Serum samples were collected from 12 primary OA patients, and 12 healthy individuals were screened using the Agilent Human miRNA Microarray platform interrogating 2549 miRNAs. Receiver Operating Characteristic (ROC) curves were constructed to evaluate the diagnostic performance of the deregulated miRNAs. Expression levels of selected miRNAs were validated by quantitative real-time PCR (qRT-PCR) in all serum and in articular cartilage samples from OA patients (n = 12) and healthy individuals (n = 7). Bioinformatics analysis was used to investigate the involved pathways and target genes for the above miRNAs. Results: We identified 279 differentially expressed miRNAs in the serum of OA patients compared to controls. Two hundred and five miRNAs (73.5%) were upregulated and 74 (26.5%) downregulated. ROC analysis revealed that 77 miRNAs had area under the curve (AUC) > 0.8 and p < 0.05. Bioinformatics analysis in the 77 miRNAs revealed that their target genes were involved in multiple signaling pathways associated with OA, among which FoxO, mTOR, Wnt, pI3K/akt, TGF-β signaling pathways, ECM-receptor interaction, and fatty acid biosynthesis. qRT-PCR validation in seven selected out of the 77 miRNAs revealed 3 significantly downregulated miRNAs (hsa-miR-33b-3p, hsa-miR-671-3p, and hsa-miR-140-3p) in the serum of OA patients, which were in silico predicted to be enriched in pathways involved in metabolic processes. Target-gene analysis of hsa-miR-140-3p, hsa-miR-33b-3p, and hsa-miR-671-3p revealed that InsR and IGFR1 were common targets of all three miRNAs, highlighting their involvement in regulation of metabolic processes that contribute to OA pathology. Hsa-miR-140-3p and hsa-miR-671-3p expression levels were consistently downregulated in articular cartilage of OA patients compared to healthy individuals. Conclusions: A serum miRNA signature was established for the first time using high density resolution miR-arrays in OA patients. We identified a three-miRNA signature, hsa-miR-140-3p, hsa-miR-671-3p, and hsa-miR-33b-3p, in the serum of OA patients, predicted to regulate metabolic processes, which could serve as a potential biomarker for the evaluation of OA risk and progression.Peer reviewedFinal Published versio

Conformational study of human serum albumin in pre-denaturation temperatures by differential scanning calorimetry, circular dichroism and UV spectroscopy

Thermal conformational changes of human serum albumin (HSA) in phosphate buffer, 10 mM at pH = 7 are investigated using differential scanning calorimetric (DSC), circular dichroism (CD) and UV spectroscopic methods. The results indicate that temperature increment from 25°C to 55°C induces reversible conformational changes in the structure of HSA. Conformational change of HSA are shown to be a three-step process. Interestingly, melting temperature of the last domain is equal to the maximum value of fever in pathological conditions, i.e. 42°C. These conformational alterations are accompanied by a mild alteration of secondary structures. Study of HSA-SDS (sodium dodecyl sulphate) interaction at 45°C and 35°C reveals that SDS affects the HSA structure at least in three steps: the first two steps result in more stabilization and compactness of HSA structure, while the last one induces the unfolding of HSA. Since HSA has a more affinity for SDS at 45°C compared to 35°C, It is suggested that the net negative charge of HSA is decreased in fever, which results in the decrease of HSA-associated cations and plasma osmolarity, and consequently, heat removal via the increase in urine volume

Doxorubicin-Loaded Human Serum Albumin Submicron Particles: Preparation, Characterization and In Vitro Cellular Uptake

Doxorubicin (DOX) is an effective anthracycline antibiotic drug which is commonly used in a broad range cancer therapy. However, due to dose depending side effects and toxicity to non-cancerous tissues, its clinical applications are restricted. To overcome these limitations, human serum albumin (HSA) has been investigated as a biocompatible drug delivery vehicle. In this study, human serum albumin submicron particles (HSA-MPs) were fabricated by using the Co-precipitation-Crosslinking-Dissolution technique (CCD technique) and DOX was loaded into the protein particles by absorption. DOX-HSA-MPs showed uniform peanut-like shape, submicron size and negative zeta-potential (-13 mV). The DOX entrapment efficiency was 25% of the initial amount. The in vitro release in phosphate buffered saline pH 7.4 was less than 1% within 5 h. In contrast, up to 40% of the entrapped DOX was released in presence of a protein digesting enzyme mixture (Pronase®) within the same time. In addition, in vitro cytotoxicity and cellular uptake of DOX-HSA-MPs were evaluated using the lung carcinoma cell line A549. The results demonstrated that DOX-HSA-MPs reduced the cell metabolic activities after 72 h. Interestingly, DOX-HSA-MPs were taken up by A549 cells up to 98% and localized in the cell lysosomal compartment. This study suggests that DOX-HSA-MPs which was fabricated by CCD technique is seen as a promising biopolymer particle as well as a viable alternative for drug delivery application to use for cancer therapy

25th International Congress of the European Association for Endoscopic Surgery (EAES) Frankfurt, Germany, 14-17 June 2017 : Oral Presentations

Introduction: Ouyang has recently proposed hiatal surface area (HSA) calculation by multiplanar multislice computer tomography (MDCT) scan as a useful tool for planning treatment of hiatus defects with hiatal hernia (HH), with or without gastroesophageal reflux (MRGE). Preoperative upper endoscopy or barium swallow cannot predict the HSA and pillars conditions. Aim to asses the efficacy of MDCT’s calculation of HSA for planning the best approach for the hiatal defects treatment. Methods: We retrospectively analyzed 25 patients, candidates to laparoscopic antireflux surgery as primary surgery or hiatus repair concomitant with or after bariatric surgery. Patients were analyzed preoperatively and after one-year follow-up by MDCT scan measurement of esophageal hiatus surface. Five normal patients were enrolled as control group. The HSA’s intraoperative calculation was performed after complete dissection of the area considered a triangle. Postoperative CT-scan was done after 12 months or any time reflux symptoms appeared. Results: (1) Mean HSA in control patients with no HH, no MRGE was cm2 and similar in non-complicated patients with previous LSG and cruroplasty. (2) Mean HSA in patients candidates to cruroplasty was 7.40 cm2. (3) Mean HSA in patients candidates to redo cruroplasty for recurrence was 10.11 cm2. Discussion. MDCT scan offer the possibility to obtain an objective measurement of the HSA and the correlation with endoscopic findings and symptoms. The preoperative information allow to discuss with patients the proper technique when a HSA[5 cm2 is detected. During the follow-up a correlation between symptoms and failure of cruroplasty can be assessed. Conclusions: MDCT scan seems to be an effective non-invasive method to plan hiatal defect treatment and to check during the follow-up the potential recurrence. Future research should correlate in larger series imaging data with intraoperative findings

High-performance liquid chromatography as a technique to measure the competitive adsorption of plasma proteins onto latices

Isotherms of human serum albumin (HSA), human immunoglobulin G (HIgG), and human fibrinogen (HFb) onto a polystyrene (PS)-latex were determined by depletion of protein in the solution, which was either followed by radioactivity measurements or by UV spectroscopy. Different adsorption isotherms for the same protein were obtained when either radioactivity measurements or UV spectroscopy was used as a detection technique. In order to obtain reliable results from competitive protein adsorption experiments, a method based on the use of high-performance liquid chromatography was developed. A strong preferential adsorption of HFb was observed when adsorption studies were carried out with mixtures of HSA, HFb, and HIgG. When adsorption studies were carried out with solutions containing HSA monomer and dimer, a strong preferential adsorption of HSA dimer was also observed