Large-Scale Expansion of Umbilical Cord Mesenchymal Stem Cells with Microcarrier Tablets in Bioreactor.

Mesenchymal stem cells show great potential in tissue engineering and cell-based therapies. This protocol demonstrates the use of 3D TableTrix® microcarrier tablets for large-scale manufacturing of human umbilical cord mesenchymal stem cells (hUCMSCs) in a 5-L stirred tank bioreactor. 3D TableTrix® microcarrier tablets readily disperse into tens of thousands of porous microcarriers to simplify cell seeding, and 3D FloTrix® vivaSPIN bioreactor could automate, monitor, and control the entire culture process. 3D TableTrix® microcarriers could also be fully dissolved upon adding dissolution reagent to gently harvest the expanded cells at a high recovery rate. With this protocol, more than 109 cells could be produced in a 5-L bioreactor.

The efficacy and safety of the infiltration of the interspace between the popliteal artery and the capsule of the knee block in total knee arthroplasty: A prospective randomized trial protocol.

BACKGROUND: Total knee arthroplasty (TKA) is an established and successful surgical procedure which is the major treatment for degenerative knee joint diseases. A novel technique to address posterior knee joint pain is the infiltration of local anesthetic between the interspace between the popliteal artery and capsule of the knee (IPACK). The goal of this randomized clinical trial was to assess the efficacy and safety of adding IPACK to adductor canal block (ACB) after TKA. METHODS: This was a prospectively randomized trial that investigated the effectiveness and safety of the IPACK after TKA. Approval from Clinical Studies Ethical Committee in Qilu Hospital of Shandong University was obtained. The inclusion criteria were adult patients undergoing primary unilateral TKA and American Society of Anesthesiologists grade 1 or 2 with normal cognitive function. The patients were randomized to 1 of 2 treatment options: ACB-alone group and ACB + IPACK group. The primary outcome was the total morphine consumption during postoperative 24 hours. Secondary outcomes included postoperative pain score, time to first and total dosage of rescue morphine in postoperative 48 hours, early and late postoperative period (from postoperative day 0-3 months follow-up) performance-based test (Timed-Up and Go test, and quadriceps strength). Postoperative nausea and vomiting, length of hospital stay, patient satisfaction, and other adverse events were also evaluated. RESULTS: It was hypothesized that when combined with a control group, the IPACK block would result in a lower morphine consumption and pain score after TKA. TRIAL REGISTRATION: This study protocol was registered in Research Registry (researchregistry5765).

[Rapid screening and confirmation of 20 mycotoxins in grain products by ultrahigh performance liquid chromatography- quadrupole/electrostatic field orbitrap high- resolution mass spectrometry].

A rapid method based on ultrahigh-performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry (UPLC-HRMS) was developed for the screening and confirmation of 20 mycotoxins in grain products. The samples were extracted with acetonitrile containing 2% (v/v) formic acid, and the extracts were cleaned up on Captive EMR-Lipid columns. The analytes were separated on a Thermo Hypersil Gold C18 column (100 mm×2.1 mm, 1.9 µm), and analyzed by UPLC-HRMS. The retention time and accurate mass of the parent ion were used for fast screening in full scan mode, while the accurate masses of the fragment ions were used for confirmation in the two-stage threshold-triggered full mass scan mode. The results revealed that the 20 mycotoxins showed good linear relationships in their respective mass concentration ranges. The correlation coefficients were not less than 0.99, and the limits of quantitation (LOQs) ranged from 0.25 to 20 µg/kg. The recoveries of the 20 mycotoxins in the sample ranged from 72.9% to 117.8% with the relative standard deviations (RSDs) from 2.9% to 15.2% at three spiked levels (n=6). This method has the advantages of high sensitivity and reliability, and is thus suitable for the rapid screening and confirmation of 20 mycotoxins in grain products.

Comprehensive health status assessment of centenarians: results from the 1999 large health survey of veteran enrollees.

BACKGROUND: Information on the health status of centenarians provides a means for understanding the health care needs of this growing population. Therefore, we examined the health status of a national cohort of centenarian veteran enrollees. METHODS: Ninety-three centenarian veteran enrollees returned a complete health history questionnaire, which included questions about sociodemographic information, age-associated conditions, health behaviors, health-related quality of life as measured by the Veterans SF-36, and change in health status. RESULTS: Centenarian veteran enrollees are a group with major impairment across multiple dimensions of health-related quality of life despite having a relatively low prevalence of diseases. They had considerable physical limitations as reflected by their physical health summary scores (26.2 +/- 8.3). However, their mental health was comparatively good (mental health summary score 44.1 +/- 12.5). Compared to younger elderly veterans (ages 85-99), centenarians had a lower prevalence of hypertension, angina or myocardial infarction, diabetes, and chronic low back pain (p <.05). Centenarians had significantly worse physical functioning, role physical, vitality, and social functioning scores than did younger elderly veterans. The two groups did not differ in their general health, bodily pain, role emotional, and mental health scores. Centenarians did not perceive much decline in their physical or mental health during the preceding year. CONCLUSIONS: Centenarian veteran enrollees are a group with a low number of age-associated diseases and good mental health despite substantial physical limitations. These results support future studies of services directed toward improvement of function as opposed to those focused solely on the treatment of diseases.

No racial differences in mortality found among Veterans Health Administration out-patients.

OBJECTIVE: Health care delivery systems that offer equal access to ambulatory care may hold promise for preventing and correcting racial disparities that exist in our health care system as a whole. We examined whether racial differences in mortality rates exist among patients receiving outpatient care within the Veterans Health Administration. STUDY DESIGN AND SETTING: This study used data from the 1998 National Survey of Ambulatory Care Patients, a prospective monitoring system of patient outcomes. We used an outpatient care system in the Veterans Health Administration. We followed 25,172 Whites and 3,517 African-Americans for 48 months. The main study outcome measures were unadjusted and adjusted mortality rates over a 48-month period. RESULTS: African-Americans had significantly lower unadjusted 48-month mortality rates than Whites (33 vs. 40 deaths per 1,000 person-year, hazard ratio, 0.84; 95% confidence interval [CI], 0.75-0.95). After risk adjustment, the mortality rates became similar for African-Americans and Whites (hazard ratio, 0.99; 95% CI, 0.89-1.09). These findings were consistent across all time points evaluated during the 48-month follow-up. CONCLUSIONS: The lack of racial differences in mortality in patients receiving ambulatory care in the Veterans Health Administration is reassuring, given the emphasis on equal access within this health care system. This warrants further research to determine whether efforts to improve access in other settings have the potential to reduce racial disparities in health care.

The health status of elderly veteran enrollees in the Veterans Health Administration.

OBJECTIVES: To examine the health status of elderly veteran enrollees, stratified by age group, and compare with nonveteran populations. DESIGN: Cross-sectional study. SETTING: Outpatient. PARTICIPANTS: A total of 1,406,049 veteran enrollees were surveyed, and 887,775 returned the questionnaire (63.1%). Of these, 663,729 (74%) were aged 65 and older. MEASUREMENTS: Patient demographics, comorbid conditions, and health status, which was assessed using the Veterans 36-item short form (SF-36), a reliable and valid measure of health-related quality of life (HRQoL). RESULTS: Elderly veteran enrollees are a group with poor health status across all scales of the Veterans SF-36. Significant decline in HRQoL was found in patients grouped by increasing age (65-74, 75-84, and > or =85). Of the Veterans SF-36 scales, the role physical and role emotional scales and physical functioning presented the largest decrements by age group. The elderly veteran enrollees had poorer health status than older people enrolled in Medicare managed care, ranging from 0.5 to 1 standard deviations worse. CONCLUSION: Elderly veteran enrollees have substantial disease burden, as reflected by major impairments across multiple dimensions of HRQoL. These findings bear important implications for use of services, suggesting that the Veterans Health Administration will require considerable resources to provide care for its aging population.

Multifunctional Fe3O4@polydopamine core-shell nanocomposites for intracellular mRNA detection and imaging-guided photothermal therapy.

Multifunctional nanocomposites have the potential to integrate sensing, diagnostic, and therapeutic functions into a single nanostructure. Herein, we synthesize Fe3O4@polydopamine core-shell nanocomposites (Fe3O4@PDA NCs) through an in situ self-polymerization method. Dopamine, a melanin-like mimic of mussel adhesive proteins, can self-polymerize to form surface-adherent polydopamine (PDA) films onto a wide range of materials including Fe3O4 nanoparticles used here. In such nanocomposites, PDA provides a number of advantages, such as near-infrared absorption, high fluorescence quenching efficiency, and a surface for further functionalization with biomolecules. We demonstrate the ability of the Fe3O4@PDA NCs to act as theranostic agents for intracellular mRNA detection and multimodal imaging-guided photothermal therapy. This work would stimulate interest in the use of PDA as a useful material to construct multifunctional nanocomposites for biomedical applications.

Graphitic-phase C3N4 nanosheets as efficient photosensitizers and pH-responsive drug nanocarriers for cancer imaging and therapy.

Graphitic-phase carbon nitride (g-C3N4) nanosheets, the newly emerging two-dimensional (2D) layered nanomaterials, have been demonstrated to be promising bioimaging agents due to their high photoluminescence (PL) quantum yields, good biocompatibility and low toxicity. However, the therapeutic applications of g-C3N4 nanosheets have not been explored until now. In this study, we have proven for the first time that g-C3N4 nanosheets can be used as efficient photosensitizers for photodynamic tumor therapy and as pH-responsive nanocarriers for drug delivery. On one hand, as photosensitizers, g-C3N4 nanosheets are able to generate reactive oxygen species (ROS) and kill cancer cells efficiently under low-intensity light irradiation (20 mW cm-2). On the other hand, as nanocarriers, g-C3N4 nanosheets possess an ultrahigh drug-loading capacity owing to their high surface-to-volume ratio. More importantly, g-C3N4 nanosheets loaded with the anticancer drug doxorubicin (DOX) exhibit a pH-responsive release property which is beneficial for the delivery of DOX into cancer cells for chemotherapy. Furthermore, due to their high PL quantum yields, the fluorescent g-C3N4 nanosheets can enable visualization of the delivery. These findings demonstrated the potential of g-C3N4 nanosheets as low-toxic and biocompatible photosensitizers and pH-responsive drug nanocarriers for biomedical applications.

Glutathione-functionalized graphene quantum dots as selective fluorescent probes for phosphate-containing metabolites.

Bright blue fluorescent glutathione-functionalized graphene quantum dots (GQDs@GSH) were prepared by a one-step pyrolysis method with a fluorescence quantum yield as high as 33.6%. Futhermore, the obtained GQDs@GSH can be used as a probe to estimate the ATP level in cell lysates and human blood serum.

Highly-efficient peroxidase-like catalytic activity of graphene dots for biosensing.

In recent years, considerable efforts have been devoted to the construction of efficient enzyme mimetics, which have significant advantages of simple synthesis, good stability and design flexibility. In this paper, we described that graphene dots (GDs) possess highly-efficient peroxidase-like catalytic activity, and its activity is much higher than graphene oxide (GO) with large size. They can catalyze the oxidation of peroxidase substrate 3,3,5,5-tetramethylbenzidine (TMB) in the presence of H2O2 to produce a blue product, which can be used for H2O2 detection by measuring the absorbance change. This catalytic reaction can be also used for other analyte detection by monitoring the generation or consumption of H2O2, such as glucose and reduced glutathione (GSH). The GDs-based system permits detection of as low as 10nM H2O2, which is much lower than that of other nanomaterials-catalyzed methods. Meanwhile, the detection limit of this system is 0.5 µM for glucose and 0.5 µM for GSH, respectively. Furthermore, the proposed system also shows high selectivity and is capable of sensing in complicated biological samples such as cell lysate. Due to their high catalytic activity, high diffusion and excellent biocompatibility, GDs can be expected to be applied in various fields, such as biotechnology, medical diagnostics and environmental monitoring.

Use of risk-adjusted change in health status to assess the performance of integrated service networks in the Veterans Health Administration.

OBJECTIVE: Health outcome assessments have become an expectation of regulatory and accreditation agencies. We examined whether a clinically credible risk adjustment methodology for the outcome of change in health status can be developed for performance assessment of integrated service networks. STUDY DESIGN: Longitudinal study. SETTING: Outpatient. STUDY PARTICIPANTS: Thirty-one thousand eight hundred and twenty-three patients from 22 Veterans Health Administration (VHA) integrated service networks were followed for 18 months. MAIN MEASURE: The physical (PCS) and mental (MCS) component scales from the Veterans Rand 36-items Health Survey (VR-36) and mortality. The outcomes were decline in PCS (decline in PCS scores greater than -6.5 points or death) and MCS (decline in MCS scores greater than -7.9 points). RESULTS: Four thousand three hundred and twenty-eight (13.6%) patients showed a decline in PCS scores greater than -6.5 points, 4322 (13.5%) had a decline in MCS scores by more than -7.9 points, and 1737 died (5.5%). Multivariate logistic regression models were used to adjust for case-mix. The models performed reasonably well in cross-validated tests of discrimination (c-statistics = 0.72 and 0.68 for decline in PCS and MCS, respectively) and calibration. The resulting risk-adjusted rates of decline in PCS and MCS and ranks of the networks differed considerably from unadjusted ratings. CONCLUSION: It is feasible to develop clinically credible risk adjustment models for the outcomes of decline in PCS and MCS. Without adequate controls for case-mix, we could not determine whether poor patient outcomes reflect poor performance, sicker patients, or other factors. This methodology can help to measure and report the performance of health care systems.

Differences in health-related quality of life in rural and urban veterans.

OBJECTIVES: We sought to determine whether disparities in health-related quality of life exist between veterans who live in rural settings and their suburban or urban counterparts. METHODS: We determined health-related quality-of-life scores (physical and mental health component summaries) for 767109 veterans who had used Veterans Health Administration services within the past 3 years. We used rural/urban commuting area codes to categorize veterans into rural, suburban, or urban residence. RESULTS: Health-related quality-of-life scores were significantly lower for veterans who lived in rural settings than for those who lived in suburban or urban settings. Rural veterans had significantly more physical health comorbidities, but fewer mental health comorbidities, than their suburban and urban counterparts. Rural-urban disparities persisted in all survey subscales, across regional delivery networks, and after we controlled for sociodemographic factors. CONCLUSIONS: When compared with their urban and suburban counterparts, veterans who live in a rural setting have worse health-related quality-of-life scores. Policymakers, within and outside the Veterans Health Administration, should anticipate greater health care demands from rural populations.