The advent of stem cell based therapies has brought regenerative medicine into an increased focus as a part of the modern medicine practice, with a potential to treat a myriad of intractable diseases in the future. Stem cells reside in a complex microenvironment presenting them with a multitude of potential cues that are chemical, physical, and mechanical in nature. Conventional techniques used for experiments involving stem cells can only poorly mimic the physiological context, and suffer from imprecise spatial and temporal control, low throughput, lack of scalability and reproducibility, and poor representation of the mechanical and physical cell microenvironment. Novel lab-on-a-chip platforms, on the other hand, can much better mimic the complexity of in vivo tissue milieu and provide a greater control of the parameter variation in a high throughput and scalable manner. This capability may be especially important for understanding the biology and cementing the clinical potential of stem cell based therapies. Here we review microfabrication- and microfluidics-based approaches to investigating the complex biology of stem cell responses to changes in the local microenvironment. In particular, we categorize each method based on the types of controlled inputs it can have on stem cells, including soluble biochemical factors, extracellular matrix interactions, homotypic and heterotypic cell-cell signaling, physical cues (e.g. oxygen tension, pH, temperature), and mechanical forces (e.g. shear, topography, rigidity). Finally, we outline the methods to perform large scale observations of stem cell phenotypes and high-throughput screening of cellular responses to a combination of stimuli, and many new emerging technologies that are becoming available specifically for stem cell applications.
The SARS-CoV-2 virus has emerged and rapidly evolved into a current global pandemic. Although bacterial and fungal coinfections have been associated with COVID-19, little is known about parasitic infection. We report a case of a COVID-19 patient who developed disseminated strongyloidiasis following treatment with high-dose corticosteroids and tocilizumab. Screening for Strongyloides infection should be pursued in individuals with COVID-19 who originate from endemic regions before initiating immunosuppressive therapy.
Objectives Effective and safe COVID‐19 vaccines have been developed and have resulted in decreased incidence and severity of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection and can decrease secondary transmission. However, there are concerns about dampened immune responses to COVID‐19 vaccination among immunocompromised patients, including people living with HIV (PLWH), which may blunt the vaccine's efficacy and durability of protection. This study aimed to assess the qualitative SARS‐CoV‐2 vaccine immunogenicity among PLWH after vaccination. Methods We conducted targeted COVID‐19 vaccination (all received BNT162b2 vaccine) of PLWH (aged ≥ 55 years per state guidelines) at Yale New Haven Health System and established a longitudinal survey to assess their qualitative antibody responses at 3 weeks after the first vaccination (and prior to receipt of the second dose of the COVID‐19 vaccine) (visit 1) and at 2–3 weeks after the second vaccination (visit 2) but excluded patients with prior COVID‐19 infection. Our goal was to assess vaccine‐induced immunity in the population we studied. Qualitative immunogenicity testing was performed using Healgen COVID‐19 anti‐Spike IgG/IgM rapid testing. Poisson regression with robust standard errors was used to determine factors associated with a positive IgG response. Results At visit 1, 45 of 78 subjects (57.7%) tested positive for SARS‐CoV‐2 anti‐Spike IgG after the first dose of COVID‐19 vaccine. Thirty‐nine subjects returned for visit 2. Of these, 38 had positive IgG (97.5%), including 20 of 21 subjects (95.2%) with an initial negative anti‐Spike IgG. Our bivariate analysis suggested that participants on an antiretroviral regimen containing integrase strand transfer inhibitors [relative risk (RR) = 1.81, 95% confidence interval (CI): 0.92–3.56, p = 0.085] were more likely to seroconvert after the first dose of the COVID‐19 vaccine, while those with a CD4 count < 500 cells/μL (RR = 0.59, 95% CI: 0.33–1.05, p = 0.071), and those diagnosed with cancer or another immunosuppressive condition (RR = 0.49, 95% CI: 0.18–1.28, p = 0.15) may have been less likely to seroconvert after the first dose of the COVID‐19 vaccine. The direction of these associations was similar in the multivariate model, although none of these findings reached statistical significance (RR integrase inhibitor = 1.71, 95% CI: 0.90–3.25, p = 0.10; RR CD4 count = 0.68, 95% CI: 0.39–1.19, p = 0.18; RR cancer or another immunosuppressive condition = 0.50, 95% CI: 0.19–1.33, p = 0.16). With regard to immunogenicity, we were able to record very high rates of new seroconversion following the second dose of the COVID‐19 vaccine. Conclusions ...
As the Coronavirus-2019 (COVID-19) pandemic continues, multiple therapies are rapidly being evaluated for efficacy in clinical trials. Clinical trials should be racially and ethnically representative of the population that will eventually benefit from these medications. There are multiple potential barriers to racial and ethnic minority enrollment in clinical trials, one of which could be that inclusion and exclusion criteria select for certain racial or ethnic groups disproportionately. In this observational cohort study at a single health care system, we examined if there were differences in eligibility for treatment with remdesivir based on clinical trial criteria for racial and ethnic minorities compared to non-Hispanic Whites. 201 electronic medical record charts were reviewed manually. Self-identified Whites were older than other racial or ethnic groups. At the time of presentation, Black, Latinx, and White participants met inclusion criteria for remdesivir at similar rates (72%, 80%, and 73% respectively), and exclusion criteria at similar rates (43%, 38% and 49% for Black, Latinx and White participants respectively). In this study, there was no difference in eligibility for remdesivir based on race or ethnicity alone.
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