The Expression and Secretion Profile of TRAP5 Isoforms in Gaucher Disease.

BACKGROUND: Gaucher disease (GD) is caused by glucocerebrosidase (GCase) enzyme deficiency, leading to glycosylceramide (Gb-1) and glucosylsphingosine (Lyso-Gb-1) accumulation. The pathological hallmark for GD is an accumulation of large macrophages called Gaucher cells (GCs) in the liver, spleen, and bone marrow, which are associated with chronic organ enlargement, bone manifestations, and inflammation. Tartrate-resistant acid phosphatase type 5 (TRAP5 protein, ACP5 gene) has long been a nonspecific biomarker of macrophage/GCs activation; however, the discovery of two isoforms of TRAP5 has expanded its significance. The discovery of TRAP5's two isoforms revealed that it is more than just a biomarker of macrophage activity. While TRAP5a is highly expressed in macrophages, TRAP5b is secreted by osteoclasts. Recently, we have shown that the elevation of TRAP5b in plasma is associated with osteoporosis in GD. However, the role of TRAP isoforms in GD and how the accumulation of Gb-1 and Lyso-Gb-1 affects TRAP expression is unknown. METHODS: 39 patients with GD were categorized into cohorts based on bone mineral density (BMD). TRAP5a and TRAP5b plasma levels were quantified by ELISA. ACP5 mRNA was estimated using RT-PCR. RESULTS: An increase in TRAP5b was associated with reduced BMD and correlated with Lyso-Gb-1 and immune activator chemokine ligand 18 (CCL18). In contrast, the elevation of TRAP5a correlated with chitotriosidase activity in GD. Lyso-Gb-1 and plasma seemed to influence the expression of ACP5 in macrophages. CONCLUSIONS: As an early indicator of BMD alteration, measurement of circulating TRAP5b is a valuable tool for assessing osteopenia-osteoporosis in GD, while TRAP5a serves as a biomarker of macrophage activation in GD. Understanding the distinct expression pattern of TRAP5 isoforms offers valuable insight into both bone disease and the broader implications for immune system activation in GD.

ModE-RA: a global monthly paleo-reanalysis of the modern era 1421 to 2008.

The Modern Era Reanalysis (ModE-RA) is a global monthly paleo-reanalysis covering the period between 1421 and 2008. To reconstruct past climate fields an offline data assimilation approach is used, blending together information from an ensemble of transient atmospheric model simulations and observations. In the early period, ModE-RA utilizes natural proxies and documentary data, while from the 17th century onward instrumental measurements are also assimilated. The impact of each observation on the reconstruction is stored in the observation feedback archive, which provides additional information on the input data such as preprocessing steps and the regression-based forward models. The monthly resolved reconstructions include estimates of the most important climate fields. Furthermore, we provide a reconstruction, ModE-RAclim, which together with ModE-RA and the model simulations allows to disentangle the role of observations and model forcings. ModE-RA is best suited to study intra-annual to multi-decadal climate variability and to analyze the causes and mechanisms of past extreme climate events.

Monthly multidisciplinary complex spine conference: a cost-analysis utilizing time-driven activity-based costing.

PURPOSE: To understand costs and provide an initial framework associated with conference implementation as it pertains to complication prevention. METHODS: Team members' time spent on conference preparation, presentation, and follow-up tasks was recorded and averaged to determine the time required to prepare and present one patient. Using 2022 hourly wage rates based on our urban hospital setting, wage values were calculated for each personnel type and applied to their time spent. The total cost of the conference was annualized and calculated from the time spent in the three phases of the conference multiplied by the wage rate. Published data on complication rates and associated costs before and after conference implementation were used to calculate total cost reduction. RESULTS: With 3 active spine surgeons and 108 patients per year, the total time investment was 104.04 min per patient, costing $21,791 annually. Total RN equivalent value per patient was 5.25 for all three phases. Using a historical model, this multidisciplinary approach for adult spinal deformity reduced complications by 51% at 30 days, resulting in cost savings of $418,518 per year. Thus, the model demonstrates that implementation of this approach resulted in a potential total savings of $396,726/year. CONCLUSION: Implementing a cost-saving tool for managing complex spinal disorders is a responsibility of the spine team, who should lead a multidisciplinary conference. The combination of TDABC and lean methodology can effectively demonstrate the variable costs associated with this multidisciplinary effort and models provide evidence of potential cost-savings when applied to a multidisciplinary adult spinal deformity conference. These findings should encourage clinicians and administrators to allocate resources to improve patient care by reducing complications and costs.