Implantation of Adipose-Derived Mesenchymal Stromal Cells (ADSCs)-Lining Prosthetic Graft Promotes Vascular Regeneration in Monkeys and Pigs.

BACKGROUND: Current replacement procedures for stenosis or occluded arteries using prosthetic grafts have serious limitations in clinical applications, particularly, endothelialization of the luminal surface is a long-standing unresolved problem. METHOD: We produced a cell-based hybrid vascular graft using a bioink engulfing adipose-derived mesenchymal stromal cells (ADSCs) and a 3D bioprinting process lining the ADSCs on the luminal surface of GORE-Tex grafts. The hybrid graft was implanted as an interposition conduit to replace a 3-cm-long segment of the infrarenal abdominal aorta in Rhesus monkeys. RESULTS: Complete endothelium layer and smooth muscle layer were fully developed within 21 days post-implantation, along with normalized collagen deposition and crosslinking in the regenerated vasculature in all monkeys. The regenerated blood vessels showed normal functionality for the longest observation of more than 1650 days. The same procedure was also conducted in miniature pigs for the interposition replacement of a 10-cm-long right iliac artery and showed the same long-term effective and safe outcome. CONCLUSION: This cell-based vascular graft is ready to undergo clinical trials for human patients.

Association of statin use and increase in lipoprotein(a): a real-world database research.

BACKGROUND: There is an increased concern that statins may have an unintended effect of elevated lipoprotein(a) [Lp(a)]. We conducted a large sample real-world study to test the association. METHODS: This retrospective cohort study was conducted using data from an integrated SuValue database, which includes 221 hospitals across China covering more than 200,000 of population with longitudinal follow-up to 10 years. Propensity score matching was applied to identify two comparable cohorts with statin users and non-statin users. Detailed follow-up information such as Lp(a) levels were extracted. The hazard ratio was calculated on Lp(a) changes based on the statin usage cohorts. Detailed subgroup and different characteristic cohorts' analyses were also conducted. RESULTS: After baseline propensity score matching, a total of 42,166 patients were included in a 1:1 matched ratio between statin users and non-statin users. In the case of no difference in low density lipoprotein (LDL-C), Lp(a) was increased significantly with the use of statins (adjusted HR 1.47; 95% confidence interval [CI] 1.43-1.50). Lp(a) increase was observed in various subgroup analyses and different cohorts. The dose intensity of statin was positively associated with the evaluated Lp(a) level. CONCLUSION: The use of statins was associated with an increased risk of Lp(a) elevation compared with non-statin use counterparts. The clinical relevance of these increases needs to be addressed in surrogate marker trials and/or large, cardiovascular outcomes trials.

A clinical feasible stem cell encapsulation ensures an improved wound healing.

Cell encapsulation has proven to be promising in stem cell therapy. However, there are issues needed to be addressed, including unsatisfied yield, unmet clinically friendly formulation, and unacceptable viability of stem cells after cryopreservation and thawing. We developed a novel biosynsphere technology to encapsulate stem cells in clinically-ready biomaterials with controlled microsphere size. We demonstrated that biosynspheres ensure the bioviability and functionality of adipose-derived stromal cells (ADSCs) encapsulated, as delineated by a series of testing procedures. We further demonstrated that biosynspheres protect ADSCs from the hardness of clinically handling such as cryopreservation, thawing, high-speed centrifugation and syringe/nozzle injection. In a swine full skin defect model, we showed that biosynspheres were integrated to the destined tissues and promoted the repair of injured tissues with an accelerating healing process, less scar tissue formation and normalized deposition of collagen type I and type III, the ratio similar to that found in normal skin. These findings underscore the potential of biosynsphere as an improved biofabrication technology for tissue regeneration in clinical setting.

Assessment of antibody responses against SARS-CoV-2 in unvaccinated individuals and vaccinees from Omicron-BA.2 infection in Zhaoqing, Guangdong Province, China.

Currently, the majority of the global population has been vaccinated with the COVID-19 vaccine, and characterization studies of antibodies in vivo from Omicron breakthrough infection and naive infection populations are urgently needed to provide pivotal clues about accurate diagnosis, treatment, and next-generation vaccine design against SARS-CoV-2 infection. We showed that after infection with Omicron-BA.2, the antibody levels of specific IgM against the Wuhan strain and specific IgG against Omicron were not significantly elevated within 27 days of onset. Interestingly, in this study, the levels of humoral immunity against Omicron-specific IgM were significantly increased after breakthrough infection, suggesting that the detection of Omicron-specific IgM antibodies can be used as a test criterion of Omicron breakthrough infection. In addition, we observed that serums from unvaccinated individuals and the majority of vaccinated infections possessed only low or no neutralizing activity against Omicron at the onset of Omicron breakthrough infections, and at the later stage of Omicron-BA.2 breakthrough infection, levels of neutralization antibody against the Wuhan and Omicron strains were elevated in infected individuals. The findings of this study provide important clues for the diagnosis of Omicron breakthrough infections, antibody characterization studies and vaccine design against COVID-19.

Serosurvey in SARS-CoV-2 inactivated vaccine-elicited neutralizing antibodies against authentic SARS-CoV-2 and its viral variants.

Various variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been emerging and circulating in different parts of the world. Millions of vaccine doses have been administered globally, which reduces the morbidity and mortality of coronavirus disease-2019 efficiently. Here, we assess the immune responses of individuals after two shots of BBIBP-CorV or CoronaVac inactivated vaccine. We measured neutralizing antibody responses after the second vaccination by using authentic SARS-CoV-2 and its viral variants. All the serum samples efficiently neutralized SARS-CoV-2 wild-type lineage, in contrast, a part of serum samples failed to neutralize Alpha, Beta, Gamma, Delta, or Eta lineages, and only several serum samples were able to neutralize Omicron lineage virus strains (BA.1 and BA.2) with low neutralization titer. As compared with the neutralization of SARS-CoV-2 wild-type lineage, the neutralization of all other SARS-CoV-2 variant lineages was significantly lower. Considering that all the SARS-CoV-2 mutation viruses challenged the antibody neutralization induced by BBIBP-CorV and CoronaVac, it is necessary to carry out a third booster vaccination to increase the humoral immune response against the SARS-CoV-2 mutation viruses.

Real-world economic evaluation of prospective rapid whole-genome sequencing compared to a matched retrospective cohort of critically ill pediatric patients in the United States.

There is an increasing demand for supporting the adoption of rapid whole-genome sequencing (rWGS) by demonstrating its real-world value. We aimed to assess the cost-effectiveness of rWGS in critically ill pediatric patients with diseases of unknown cause. Data were collected prospectively of patients admitted to the Nicklaus Children's Hospital's intensive care units from March 2018 to September 2020, with rWGS (N = 65). Comparative data were collected in a matched retrospective cohort with standard diagnostic genetic testing. We determined total costs, diagnostic yield (DY), and incremental cost-effectiveness ratio (ICER) adjusted for selection bias and right censoring. Sensitivity analyses explored the robustness of ICER through bootstrapping. rWGS resulted in a diagnosis in 39.8% while standard testing in 13.5% (p = 0.026). rWGS resulted in a mean saving per person of $100,440 (SE = 26,497, p < 0.001) and a total of $6.53 M for 65 patients. rWGS in critically ill pediatric patients is cost-effective, cost-saving, shortens diagnostic odyssey, and triples the DY of traditional approaches.

Disease Severity and Risk Factors of 30-Day Hospital Readmission in Pediatric Hospitalizations for Pneumonia.

Pneumonia is the leading cause of hospitalization in pediatric patients. Disease severity greatly influences pneumonia progression and adverse health outcomes such as hospital readmission. Hospital readmissions have become a measure of healthcare quality to reduce excess expenditures. The aim of this study was to examine 30-day all-cause readmission rates and evaluate the association between pneumonia severity and readmission among pediatric pneumonia hospitalizations. Using 2018 Nationwide Readmissions Database (NRD), we conducted a cross-sectional study of pediatric hospitalizations for pneumonia. Pneumonia severity was defined by the presence of respiratory failure, sepsis, mechanical ventilation, dependence on long-term supplemental oxygen, and/or respiratory intubation. Outcomes of interest were 30-day all-cause readmission, length of stay, and cost. The rate of 30-day readmission for the total sample was 5.9%, 4.7% for non-severe pneumonia, and 8.7% for severe pneumonia (p < 0.01). Among those who were readmitted, hospitalizations for severe pneumonia had a longer length of stay (6.5 vs. 5.4 days, p < 0.01) and higher daily cost (USD 3246 vs. USD 2679, p < 0.01) than admissions for non-severe pneumonia. Factors associated with 30-day readmission were pneumonia severity, immunosuppressive conditions, length of stay, and hospital case volume. To reduce potentially preventable readmissions, clinical interventions to improve the disease course and hospital system interventions are necessary.

Viral infection and transmission in a large, well-traced outbreak caused by the SARS-CoV-2 Delta variant.

The SARS-CoV-2 Delta variant has spread rapidly worldwide. To provide data on its virological profile, we here report the first local transmission of Delta in mainland China. All 167 infections could be traced back to the first index case. Daily sequential PCR testing of quarantined individuals indicated that the viral loads of Delta infections, when they first become PCR-positive, were on average ~1000 times greater compared to lineage A/B infections during the first epidemic wave in China in early 2020, suggesting potentially faster viral replication and greater infectiousness of Delta during early infection. The estimated transmission bottleneck size of the Delta variant was generally narrow, with 1-3 virions in 29 donor-recipient transmission pairs. However, the transmission of minor iSNVs resulted in at least 3 of the 34 substitutions that were identified in the outbreak, highlighting the contribution of intra-host variants to population-level viral diversity during rapid spread.

The Adaptation of a Clinic-Adjacent Parking Garage for Drive-In COVID-19 Vaccination.

PURPOSE: The distribution and vaccination of COVID-19 vaccines to billions of people worldwide will likely be one of the biggest public health undertakings in history. There has been a large focus on identifying processes to safely, efficiently, and effectively vaccinate large populations. We aimed to describe the development and operationalization of a drive-in COVID-19 vaccine site in a parking garage adjacent to outpatient clinics at University of Florida (UF) Health Physicians and how it was informed by the roll-out of SARS-CoV-2 testing and administration of respiratory vaccinations. DESIGN/METHODOLOGY/APPROACH: A technical description and analysis of a drive-in COVID-19 vaccine site. FINDINGS: We incrementally increased the number of vaccines performed per day from 300 in the first 2 weeks to 700 an additional 2 weeks later. By the end of January, we completed nearly 14 000 vaccinations. At this capacity, we estimate the site could performed 5000 vaccinations per week. PRACTICAL IMPLICATIONS: This manuscript provides step-by-step guidance how to develop, operationalize, and implement a sustainable drive-in COVID-19 vaccination site. ORIGINALITY/VALUE: To our knowledge, this is the first description of a drive-in approach to COVID-19 vaccination. Our findings can help inform other health entities as they develop or expand vaccination efforts that may serve as a template for other sites to adapt.

Network Meta-analysis of the Therapeutic Effects of Hypoglycemic Drugs and Intensive Lifestyle Modification on Impaired Glucose Tolerance.

PURPOSE: In the Guidelines for the Prevention and Control of Type 2 Diabetes in China (2017 edition), intensive lifestyle interventions are recommended for preventing the progression of impaired glucose tolerance (IGT) to type 2 diabetes mellitus. Acarbose and metformin can also be considered if intensive lifestyle modification has been ineffective for 6 months. But the effects of intensive lifestyle modification and glucose-lowering drug interventions that work best in the population with IGT are unclear. This network meta-analysis assessed the effectiveness of intensive lifestyle modification, acarbose, and metformin in treating populations with IGT. METHODS: We systematically searched both Chinese- and English-language databases, including China Knowledge, the Cochrane Library, Embase, PubMed, VIP, and Wanfang, for articles published between database inception and September 2019. Randomized, controlled clinical trials in patients with IGT treated with acarbose, metformin, and intensive lifestyle modification were assessed for eligibility. The data from all included studies were evaluated by 2 reviewers independently in accordance with the Cochrane Handbook for Systematic Reviews of Intervention version 6.0. A network meta-analysis was performed by using R software version 3.6.1. FINDINGS: The data from 53 randomized controlled trials were included in the review, with a sample size of 21,208 patients. Compared with the control group, the use of acarbose, metformin, and/or intensive lifestyle modification was associated with reduced rates of progression to diabetes (relative risks [RRs] [95% credible intervals]: acarbose, 0.37 [0.29-0.47]; metformin, 0.39 [0.30-0.50]; intensive lifestyle modification, 0.61 [0.50-0.73]). The surface under the cumulative ranking (SUCRA) value of acarbose was 88.35%, supporting that acarbose was more effective in reducing the rate of progression to diabetes compared with controls. With acarbose, metformin, and intensive lifestyle modification, the rates of achieving a normal glucose level were increased by RR = 2.1, 1.7, and 1.2, respectively when compared with control group. The SUCRA value of acarbose was 99.69%, supporting the optimal effect of acarbose in achieving a normal blood glucose level. IMPLICATIONS: In this meta-analysis in patients with IGT, compared with controls, acarbose and metformin were associated with decreased rates of progression to diabetes and increased rates of achieving a normal glucose level. Acarbose use was associated with an increased rate of achieving a normal glucose level, while intensive lifestyle modification was not.

Unsuitable use of DMSO for assessing behavioral endpoints in aquatic model species.

Dimethyl sulfoxide (DMSO) is a universally used aprotic solvent with the ability to permeate biological membranes and thus is commonly used to achieve appropriate biological availability of hydrophobic toxicants. While DMSO as a carrier medium has a reportedly low toxicity and is routinely employed in ecotoxicology, very little is known about its effect on dynamic behavioral parameters. This study presents a comparative analysis of the lethal and behavioral effects of exposures to DMSO concentrations of 0.1-10% on several test species such as: neonates of the freshwater crustacean Daphnia magna, nauplii of the marine crustacean Artemia franciscana, the marine crustacean Allorchestes compressa, embryos and larvae of the freshwater fish Danio rerio. The results demonstrated that DMSO did not cause statistically significant mortality even at concentrations close to 1% but induced clear and significant behavioral abnormalities in response to sublethal concentrations on all test species. These included hypoactivity syndrome in A. franciscana, A. compressa, D. magna and zebrafish larvae while a slight time-dependent hyperactivity response was observed in zebrafish embryos. For the majority of test species, behavioral changes such as moving distance, acceleration and burst movement were often observed during the first hours of exposure. These results indicate that caution should be exercised when using DMSO as a carrier solvent in experiments assessing behavioral endpoints.

Automatic multiple zebrafish larvae tracking in unconstrained microscopic video conditions.

The accurate tracking of zebrafish larvae movement is fundamental to research in many biomedical, pharmaceutical, and behavioral science applications. However, the locomotive characteristics of zebrafish larvae are significantly different from adult zebrafish, where existing adult zebrafish tracking systems cannot reliably track zebrafish larvae. Further, the far smaller size differentiation between larvae and the container render the detection of water impurities inevitable, which further affects the tracking of zebrafish larvae or require very strict video imaging conditions that typically result in unreliable tracking results for realistic experimental conditions. This paper investigates the adaptation of advanced computer vision segmentation techniques and multiple object tracking algorithms to develop an accurate, efficient and reliable multiple zebrafish larvae tracking system. The proposed system has been tested on a set of single and multiple adult and larvae zebrafish videos in a wide variety of (complex) video conditions, including shadowing, labels, water bubbles and background artifacts. Compared with existing state-of-the-art and commercial multiple organism tracking systems, the proposed system improves the tracking accuracy by up to 31.57% in unconstrained video imaging conditions. To facilitate the evaluation on zebrafish segmentation and tracking research, a dataset with annotated ground truth is also presented. The software is also publicly accessible.

A Millifluidic System for Analysis of Daphnia magna Locomotory Responses to Water-born Toxicants.

Aquatic toxicity testing in environmental monitoring and chemical risk assessment is critical to assess water quality for human use as well as predict impact of pollutants on ecosystems. In recent years, studies have increasingly focused on the relevance of sub-lethal effects of environmental contaminants. Sub-lethal toxicity endpoints such as behavioural responses are highly integrative and have distinct benefits for assessing water quality because they occur rapidly and thus can be used to sense the presence of toxicants. Our work describes a Lab-on-a-Chip system for the automated analysis of freshwater cladoceran Daphnia magna locomotory responses to water-born toxicants. The design combines a Lab-on-a-Chip system for Daphnia sp. culture under perfusion with time-resolved videomicroscopy and software tracking locomotory activity of multiple specimens. The application of the system to analyse the swimming behaviour of water fleas exposed to different concentrations of water-born toxicants demonstrated that Lab-on-a-Chip devices can become important research tools for behavioural ecotoxicology and water quality biomonitoring.

Fishing on chips: up-and-coming technological advances in analysis of zebrafish and Xenopus embryos.

Biotests performed on small vertebrate model organisms provide significant investigative advantages as compared with bioassays that employ cell lines, isolated primary cells, or tissue samples. The main advantage offered by whole-organism approaches is that the effects under study occur in the context of intact physiological milieu, with all its intercellular and multisystem interactions. The gap between the high-throughput cell-based in vitro assays and low-throughput, disproportionally expensive and ethically controversial mammal in vivo tests can be closed by small model organisms such as zebrafish or Xenopus. The optical transparency of their tissues, the ease of genetic manipulation and straightforward husbandry, explain the growing popularity of these model organisms. Nevertheless, despite the potential for miniaturization, automation and subsequent increase in throughput of experimental setups, the manipulation, dispensing and analysis of living fish and frog embryos remain labor-intensive. Recently, a new generation of miniaturized chip-based devices have been developed for zebrafish and Xenopus embryo on-chip culture and experimentation. In this work, we review the critical developments in the field of Lab-on-a-Chip devices designed to alleviate the limits of traditional platforms for studies on zebrafish and clawed frog embryo and larvae. © 2014 International Society for Advancement of Cytometry.

A Cost-Effectiveness Analysis between Amlodipine and Angiotensin II Receptor Blockers in Stroke and Myocardial Infarction Prevention among Hypertension Patients in China.

OBJECTIVE: Uncontrolled hypertension (HTN) results in strokes, myocardial infarction (MI), and other complications, which are the leading cause of disability, death, and severe economic consequence. We conducted an economic evaluation to determine the costs and quality-adjusted life-years (QALYs) associated with amlodipine (Norvasc) and the angiotensin II receptor blockers (ARBs) in preventing stroke and MI among Chinese HTN patients. METHODS: A cost-utility analysis was conducted from the third-party payer perspective. A Markov model was constructed to estimate 5-year costs and health consequences of amlodipine and valsartan. Effectiveness data were based on a published meta-analysis. Utility data were retrieved from the published literature. Costs of MI were retrieved from China Health Statistics Yearbook. Costs of stroke were obtained from retrospective chart review and follow-up interviews in Chinese tertiary hospitals. Costs included costs of drugs, direct medical costs of HTN management, stroke/MI treatment, and follow-up management. Discounting rate used for costs and QALYs was 3%. RESULTS: Total direct medical and drug costs of amlodipine and valsartan (ARB) users were ¥111,731,716 and ¥132,058,611, respectively; total QALYs of amlodipine and valsartan users were 30,648.5 and 30,520.8, respectively. Amlodipine is dominant with lower costs and higher QALYs. This demonstrated that compared with valsartan, amlodipine is a cost-saving therapy with better QALY outcome. When irbesartan data were used in the comparison, the magnitude of cost saving changed but the overall conclusion remained the same. CONCLUSION: Amlodipine is a cost-saving therapy compared with ARBs in preventing stroke and MI for Chinese HTN patients.