Oxygenation heterogeneity facilitates spatiotemporal flow pattern visualization inside human blood vessels using photoacoustic computed tomography.

Hemodynamics can be explored through various biomedical imaging techniques. However, observing transient spatiotemporal variations in the saturation of oxygen (sO2) within human blood vessels proves challenging with conventional methods. In this study, we employed photoacoustic computed tomography (PACT) to reconstruct the evolving spatiotemporal patterns in a human vein. Through analysis of the multi-wavelength photoacoustic (PA) spectrum, we illustrated the dynamic distribution within blood vessels. Additionally, we computationally rendered the dynamic process of venous blood flowing into the major vein and entering a branching vessel. Notably, we successfully recovered, in real time, the parabolic wavefront profile of laminar flow inside a deep vein in vivo-a first-time achievement. While the study is preliminary, the demonstrated capability of dynamic sO2 imaging holds promise for new applications in biology and medicine.

Healthcare resource utilization and costs among patients with rheumatoid arthritis on biologic therapies in Taiwan: A 1-year mirror-image study using a national claims database.

OBJECTIVES: This nationwide population-based study aimed at evaluating healthcare resource utilization and direct medical costs among rheumatoid arthritis (RA) patients receiving biologic therapies in Taiwan. DESIGN AND SETTING: A retrospective cohort of 2,425 RA patients who had received first-line tumor necrosis factor (TNF)-α antagonist treatment for at least 6 months (the baseline period) between 2007 and 2011 was identified from the National Health Insurance Research Database in Taiwan. OUTCOME MEASURES: Healthcare resource utilization and direct medical costs of those patients were analyzed and compared 1 year before the index date and during the 1-year follow-up. RESULTS: Analytical results demonstrated that 87.7% of RA patients received the same TNF-α antagonist during the 1-year follow-up, 2.4% of the patients switched to another TNF-α antagonist after the baseline period, 7.1% of the study cohort received a second-line biologic agent, while the remaining patients discontinued use of any TNF-α antagonist. Compared to 1 year before the index date, there were significant reductions in emergency room visits and hospitalization days for RA patients treated with the same TNF-α antagonist during the 1-year follow-up. However, there was an increase of outpatient visits among those patients. For those RA patients who switched to another TNF-α antagonist or received a second-line biologic agent, they consumed more healthcare resources. Furthermore, the corresponding medication costs went up markedly during the 1-year follow-up, but nearly all total direct medical costs (biologics excluded) were significantly reduced across the study cohort. Lastly, male patients incurred slightly higher medical costs than their counterparts, albeit in a statistically insignificant fashion. CONCLUSIONS: This investigation revealed that RA patients treated with biologics utilized fewer emergency room visits and shorter hospitalization days, but incurred higher costs. In summary, this study provides meaningful information on healthcare resource utilization and medical costs of RA patients for healthcare providers and policymakers.

Low bone mineral density may be associated with long-term risk of cancer in the middle-aged population: A retrospective observational study from a single center.

BACKGROUND: It is generally understood that cancer patients are at an increased risk for osteoporosis. Additionally, recent studies have suggested a shared pathophysiological mechanism between the development of cancer and osteoporosis. The purpose of this investigation was to investigate whether low bone mineral density is associated with cancer risk. METHODS: We enrolled 8780 subjects who underwent dual-energy X-ray absorptiometry (DXA) and cancer screening from January 1, 2008-December 31, 2012 from a cohort selected from Chang Gung Health Care Center in Taiwan. The study end point was a definite pathological diagnosis of cancer or admission for cancer treatment. RESULTS: During a mean follow-up of 6.6 ± 1.5 years, 110 incident cases of cancer occurred. The overall incidence of cancer was significantly higher in those patients with a low BMD (1.3%) than in those with a normal BMD (1.0%). Multivariate Cox regression analysis showed that older age, smoking, and low BMD (hazard ratio: 1.5; 95% confidence interval: 1.0-2.3) were significant independent risk factors for cancer. CONCLUSION: Our investigation suggested that subjects with a low BMD may have a higher long-term risk of cancer compared with subjects with a normal BMD.

HIV-1 gp41 ectodomain enhances Cryptococcus neoformans binding to human brain microvascular endothelial cells via gp41 core-induced membrane activities.

Cryptococcus neoformans causes life-threatening meningoencephalitis, particularly prevalent in AIDS patients. The interrelationship between C. neoformans and HIV-1 is intriguing, as both pathogens elicit severe neuropathological complications. We have previously demonstrated that the HIV-1 gp41 ectodomain fragments gp41-I33 (amino acids 579-611) and gp41-I90 (amino acids 550-639) can enhance C. neoformans binding to HBMECs (human brain microvascular endothelial cells). Both peptides contain the loop region of gp41. In the present study, we used immunofluorescence microscopy and transmission and scanning electron microscopy to explore the underlying mechanisms. Our findings indicated that both C. neoformans and gp41-I90 up-regulated ICAM-1 (intercellular adhesion molecule 1) on the HBMECs and elicited membrane ruffling on the surface of HBMECs. The HIV-1 gp41 ectodomain could also induce CD44 and ß-actin redistribution to the membrane lipid rafts, but it could not enhance PKCα (protein kinase Cα) phosphorylation like C. neoformans. Instead, gp41-I90 was able to induce syncytium formation on HBMECs. The results of the present study suggest HIV-1 gp41-enhanced C. neoformans binding to HBMECs via gp41 core domain-induced membrane activities, revealing a potential mechanism of invasion for this pathogenic fungus into the brain tissues of HIV-1-infected patients.

HIV-1 gp41 ectodomain enhances Cryptococcus neoformans binding to HBMEC.

Cryptococcus neoformans infection has significantly increased recently, particularly in AIDS patients and immunocompromised individuals. C. neoformans has a predilection to the brain, resulting in devastating meningoencephalitis. We have previously shown the invasion of C. neoformans into the human brain microvascular endothelial cells (HBMEC), which constitute the blood-brain barrier. Here, we demonstrated that C. neoformans invasion of HBMEC was enhanced by HIV-1 gp41 protein. Peptide mapping defined its functional domain around the disulfide-bond linkage of gp41 molecule (a.a. 579-611). Recombinant protein gp41-I90 (a.a. 550-639) can also enhance the binding activity. The enhancement of C. neoformans binding to HBMEC is a strain-independent manner, suggesting that gp41 ectodomain peptide exerts its function directly on HBMEC. Importantly, the enhancement could be observed in mouse animal model. Our results suggest that HIV-1 gp41 ectodomain and C. neoformans may follow a similar invasion mechanism, possibly actin reorganization and/or membrane activation, during pathogen infections on HBMEC.